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Kinetics of selenium metabolism in the ewe and fetal lamb Shariff, Mohammed Azamatulla 1987

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KINETICS OF SELENIUM METABOLISM IN THE EWE AND FETAL LAMB by MOHAMMED AZAMATULLA SHAJRIFF B . V . S c , A.P. A g r i c u l t u r a l U n i v e r s i t y ,  India,  M.Sc ( D a i r y i n g ) . , Kurukshetra U n i v e r s i t y ,  1979  India,  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY  in  THE  FACULTY OF GRADUATE STUDIES  (Department  of Animal  Science)  We accept t h i s t h e s i s as conforming to the required standard  THE UNIVERSITY OF BRITISH COLUMBIA March 1987 ©Mohammed Azamatulla S h a r i f f , 1987  1981  In  presenting  degree  this  at the  thesis  in  partial  fulfilment  University of  British  Columbia,  freely available for reference and study. copying  of  department publication  this or of  thesis by  for scholarly  his  or  this thesis  her  the  I agree  requirements  for  purposes  may It  be is  an  granted  by the  understood  for extensive head  that  for financial gain shall not be allowed without  Animal  Science  The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3  A p r i l 30, 1987  advanced  that the Library shall make it  I further agree that permission  representatives.  permission.  Department of  of  of  my  copying  or  my written  ii  ABSTRACT  To (Se),  investigate  the  isotope kinetic  indwelling pregnant  whole body  studies  were  undertaken  c a t h e t e r s were i m p l a n t e d  and n o n p r e g n a n t  vena cava  metabolism of in  which  i n the j u g u l a r v e i n s  ewes as w e l l  and saphenous v e i n s  selenium  as  the  of  inferior  o f 110-120 day (d) o l d  ovine  75 fetuses.  A single  administered times. of  injection  and  blood  Se-sodium  samples  A 5 d Se b a l a n c e  tracer  of  trial,  experiment,  was  selenite  were o b t a i n e d a t w h i c h commenced  also  undertaken.  was  various  on t h e The  day  plasma  75 Se s p e c i f i c kinetic  activity  parameters  transfer  rates.  d a t a were u s e d  o f Se Using  metabolism  the  net  a b s o r p t i o n and t h e f e c a l  The  fractional  individual and  and  activities.  at  determining The  effect  placental  m e t a b o l i s m was  and t r a c e r  data  of  S  e  times  utilization  after 75  tissue Se  the the  Se  manner  in ewes  tracer specific  deficiency  net absorption  i n a similar  the  calculated.  by s a c r i f i c i n g  the  transfer,  studied  placental  °f  different  the  and t h e  l o s s e s o f Se were  r a t e c o n s t a n t s and  fetuses  injection  kinetics,  Se b a l a n c e  t i s s u e s were e s t i m a t e d  the  f o r determining  on and  the tissue  by f e e d i n g  the  ewes w i t h Se d e f i c i e n t The mean plasma  rations. Se concentrations  in  the  Se  positive  and  were  142  and  than  the  187  ng/ml  nonpregnant and  were  pregnant  significantly  ewes  higher  iii  corresponding ones  values  (82 and  respectively.  positive  fetuses  different  from  irreversible weight  in  these  deficiency  both  positive  lower  Se  (ug/d) i n t h e  and  ug/d  ug/d that  The  versus  i n the the  of  i n t a k e s and  that  control  Se  Se  the  animals  tissue Se  of  fecal  that  status. Se  n o n p r e g n a n t ewes were  51%  in  for  ug/d  Se  as  the  Se  the  Se  a g a i n s t 84%  absorption  route  with  exerted  ewes.  rate constant values  positive and  27  suggested  expressed  as  increasing  Se  a  homeostatic  The  higher  in  deficient  results  decreased  than  the  turnover  Se  and  Se  fecal  ug/d  in  in  a higher  i n the d e f i c i e n t  animals  than  and B.W.  the plasma  intake)  significantly than  ug/d/kg  animals  These  net  metabolism  fractional  deficient  241  intake  c o n c e n t r a t i o n s were  25  ones.  the  Se  under  positive  the m a t e r n a l  values  and  deficient efficiency  on  and  Se  body ewes,  B.W.  11  f e t u s e s had  positive  97%  ewes were 56%  positive  deficient  corresponding  the p e r c e n t  the  indicated  Se  The  pregnant  i n the  results  (%  Se  ng/ml).  and  of  the  significantly  t o 2 ug/d/kg  20  absorption  not  and  ID v a l u e s  the  in  (53  were  that  losses  pregnant  The  deficient  Se were 7 ug/d/kg  nonpregnant  ewes i r r e s p e c t i v e  f o r net  ones.  r a t e s of  i n Se  ones and  adult  ones  values declined  These  t u r n o v e r was  272  (ID)  Se  levels  were  deficient  fetuses  respectively.  Se  ng/ml)  conditions.  deficient  Values  the  ng/ml) i n t h e  plasma  (46  disposal  (B.W.)  whereas,  than  The  69  tissue  Se  the  Se  in ones,  whereas,  were h i g h e r  the p o s i t i v e  in  ones.  iv  These  results  implied  were s i g n i f i c a n t l y and  that  dietary  the Se  The was  a  The  Se  from  deficient also  ug/d ones.  decreased  in  the  was  found  to  be  status  trace  of  mineral  the to  studies of  rates  of  ug/d  ones. reduced  supply.  conditions  t i s s u e s when  showed Se  Se  The  the  fetus  to  placenta.  fetus  declined  29  ug/d  from f e t u s  placental conditions  nutritional  have been  the  there  the  p o s i t i v e ewes t o  net  under The  to  transfer  i n the  that  across  f r o m ewe  p r e g n a n t ewes on the  in  p o s i t i v e ewes  rate  f r o m 24  deficient  concentrations  deficiency  higher  exchange  the The  maternal d i e t a r y Se  transfer  transfer  in  Se  minimal.  bidirectional  53  tissue  d e c r e a s e d under Se  was  placental  Se  the  t u r n o v e r was  intake  placental  that  the  to  ewe  12  Se of  in  transfer decreased  implications  availability  discussed.  ug/d  of  of the  V  T A B L E OF CONTENTS INTRODUCTION  1  CHAPTER  4  I . REVIEW OF THE LITERATURE  (A) S e l e n i u m animals  responsive conditions  i n sheep and  other  (B) Methods o f s e l e n i u m s u p p l e m e n t a t i o n  9  (C) M e t h o d o l o g y t o s t u d y s e l e n i u m m e t a b o l i s m (D) M e t a b o l i c f a t e  (F) S e l e n i u m CONCLUSIONS CHAPTER  metabolism  placental  of  I I I . SELENIUM METABOLISM  E x p e r i m e n t I I B: K i n e t i c s i n f e t a l lambs  of of  IN NONPREGNANT EWES  CONCLUSIONS  40  in  49 49  IN PREGNANT EWES  87  selenium  87  selenium  E x p e r i m e n t I I C: I n u t e r o p l a c e n t a l o f s e l e n i u m i n p r e g n a n t ewes SUMMARY AND  36  47  of selenium metabolism  E x p e r i m e n t I I A: K i n e t i c s i n p r e g n a n t ewes  GENERAL  transfer  i n t h e mother and t h e f e t u s  I I . SELENIUM METABOLISM  14 20  FROM THE LITERATURE REVIEW  Experiment I: K i n e t i c s n o n p r e g n a n t ewes CHAPTER  i n animals  of selenium i n animals  (E) M e t h o d o l o g y t o s t u d y trace minerals  4  metabolism metabolism  transfer  rates  125 150 172  BIBLIOGRAPHY  178  APPENDIX  202  vi  L i s t of Figures Figure  Page  1. E f f e c t of Se intake on plasma Se c o n c e n t r a t i o n i n nonpregnant ewes. 75 i n plasma Se s p e c i f i c a c t i v i t y of Se nonpregnant ewes. 75 Changes i n plasma Se s p e c i f i c a c t i v i t y of Se d e f i c i e n t nonpregnant ewes. 75 Best-fit plasma Se specific activity-time curves of Se p o s i t i v e nonpregnant ewes. 75 Best-fit plasma Se s p e c i f i c activity-time curves of Se d e f i c i e n t nonpregnant ewes. Effect of Se intake on net Se a b s o r p t i o n i n nonpregnant ewes.  61  2. Changes positive  62  3.  63  4. 5. 6.  75 7. Mean d a i l y e x c r e t i o n of Se i n u r i n e and feces of nonpregnant ewes. 8. E f f e c t of Se intake on t i s s u e Se pool s i z e s i n nonpregnant ewes. 9. E f f e c t of Se intake on plasma Se c o n c e n t r a t i o n i n pregnant ewes. 75 i n plasma Se s p e c i f i c a c t i v i t y of Se pregnant ewes. 75 Changes i n plasma Se s p e c i f i c a c t i v i t y of Se d e f i c i e n t pregnant ewes. 75 Best-fit plasma Se specific activity-time curves i n Se p o s i t i v e pregnant ewes. 75 Best-fit plasma Se specific activity-time curves i n Se d e f i c i e n t pregnant ewes. 75 Mean d a i l y e x c r e t i o n of Se i n u r i n e and feces of pregnant ewes. Effect of Se intake on net Se a b s o r p t i o n i n pregnant ewes.  64 65 71  72 75 95  10. Changes positive  96  11.  97  12. 13. 14. 15.  16. E f f e c t of Se pregnant ewes.  intake  on t i s s u e  99 100 104 107  Se pool s i z e  in  109  s p e c i f i c a c t i v i t y of  Se  134  75 17. Changes  i n plasma  Se  vn  positive  fetuses.  18. Changes i n plasma deficient fetuses.  75  Se  specific  75 19. B e s t - f i t plasma Se specific c u r v e s o f Se p o s i t i v e f e t u s e s . 75, 20. B e s t - f i t plasma ' Se specific c u r v e s o f Se d e f i c i e n t f e t u s e s . J  a c t i v i t y of  Se  activity-time activity-time  75 2 1 . Changes i n plasma Se s p e c i f i c a c t i v i t y o f Se p o s i t i v e ewes and t h e i r f e t u s e s f o l l o w i n g tracer i n j e c t i o n i n t o ewes. 75 22. Changes i n plasma Se s p e c i f i c a c t i v i t y o f Se p o s i t i v e ewes and t h e i r f e t u s e s f o l l o w i n g fetal tracer injection. 75 23. Changes i n plasma Se s p e c i f i c a c t i v i t y o f Se d e f i c i e n t ewes a n d t h e i r f e t u s e s f o l l o w i n g tracer i n j e c t i o n i n t o ewes. 75 24. Changes i n plasma Se a c t i v i t y o f Se d e f i c i e n t ewes a n d t h e i r fetuses following f e t a l tracer injection. 25. P l a c e n t a l Se transfer e f f i c i e n c i e s i n pregnant ewes.  135 136 137 160  161  162  163  165  VI 1 1  List  of Tables  Table  Page  75 e x p o n e n t i a l e q u a t i o n s o f plasma Se a c t i v i t y - t i m e c u r v e s i n n o n p r e g n a n t ewes. 75 2. C o m p a r i s o n o f a r e a s under the plasma Se s p e c i f i c a c t i v i t y - t i m e c u r v e s , p l a s m a Se c o n c e n t r a t i o n s and k i n e t i c p a r a m e t e r s i n n o n p r e g n a n t ewes. 1. B e s t - f i t specific  3. A b s o r p t i o n  and r e t e n t i o n  o f Se i n n o n p r e g n a n t  4. S t a b l e Se c o n c e n t r a t i o n s and p o o l t i s s u e s o f n o n p r e g n a n t ewes. 5. K i n e t i c p a r a m e t e r s o f t i s s u e nonpregnant ewes. 6. P h y s i o l o g i c a l intrauterine  sizes  ewes.  i n the  Se m e t a b o l i s m i n  p a r a m e t e r s o f p r e g n a n t ewes f o l l o w i n g surgery.  75 e x p o n e n t i a l e q u a t i o n s o f plasma Se a c t i v i t y - t i m e c u r v e s i n p r e g n a n t ewes. 75 8. C o m p a r i s o n o f a r e a s u n d e r t h e p l a s m a Se s p e c i f i c a c t i v i t y - t i m e c u r v e s and k i n e t i c p a r a m e t e r s i n p r e g n a n t ewes. and r e t e n t i o n  o f Se i n p r e g n a n t ewes.  10.  S t a b l e Se c o n c e n t r a t i o n and t i s s u e s o f p r e g n a n t ewes.  pool  11.  K i n e t i c parameters of t i s s u e p r e g n a n t ewes.  Se m e t a b o l i s m i n  12.  Post-surgical  13.  Best-fit specific  physiological  size  in  68  69 73 76  7. B e s t - f i t specific  9. A b s o r p t i o n  66  the  94  101 102  105 108 110  parameters of f e t u s e s .  133  75  14.  exponential activity-time  equations o f plasma curves i n fetuses  Se  75 Comparison of areas under the plasma Se specific activity-time curves and i n vivo k i n e t i c parameters i n f e t u s e s .  15.  S t a b l e Se concentration tissues of fetuses.  16.  Comparison o f the t i s s u e f e t u s and t h e ewe.  and  pool  size  i n the  Se c o n c e n t r a t i o n s o f t h e  138 139  141 143  ix  17.  K i n e t i c parameters fetuses.  of tissue  Se m e t a b o l i s m  in  144  18. Body w e i g h t s , g e s t a t i o n a l a g e , p l a s m a Se c o n c e n t r a t i o n s , i n j e c t i o n and s a m p l i n g s i t e s o f Se p o s i t i v e ewes and t h e i r f e t u s e s .  152  19. Body w e i g h t s , gestational a g e , p l a s m a Se c o n c e n t r a t i o n s , i n j e c t i o n and s a m p l i n g s i t e s o f Se d e f i c i e n t ewes and t h e i r f e t u s e s .  153  75 20. B e s t - f i t exponential specific activity-time and f e t u s e s .  equations of plasma c u r v e s i n Se p o s i t i v e  21. B e s t - f i t exponential specific activity-time and f e t u s e s .  equations o f plasma c u r v e i n Se d e f i c i e n t  Se ewes  154  75 Se ewes  75 22. A r e a s under t h e plasma Se s p e c i f i c a c t i v i t y - t i m e curves o f Se p o s i t i v e a n d Se d e f i c i e n t ewes and t h e i r r e s p e c t i v e f e t u s e s . 23. P l a c e n t a l t r a n s f e r e f f i c i e n c i e s and r a t e s o f Se t r a n s f e r i n p r e g n a n t ewes.  155  156 164  X  ACKNOWLEDGEMENTS I wish to express my h e a r t f e l t g r a t i t u d e a n d s i n c e r e t h a n k s t o my r e s e a r c h s u p e r v i s o r Dr. C R . Krishnamurti for h i s constant encouragement, c o n s t r u c t i v e c r i t i c i s m , p a t i e n c e and g u i d a n c e d u r i n g the c o u r s e o f t h i s s t u d y . I would l i k e t o thank Dr. R . I . McKay f o r s e r v i n g as my a c t i n g s u p e r v i s o r when D r . C R . K r i s h n a m u r t i was a w a y o n h i s s a b b a t i c a l l e a v e and f o r h i s a d v i c e on s t a t i s t i c a l a n a l y s i s o f t h e d a t a . I w i s h t o t h a n k D r . R. B l a i r , H e a d , Department of A n i m a l Science for letting me use the departmental f a c i l i t i e s . I would l i k e to e x p r e s s my t h a n k s t o D r s . W.T. Buckley, B.D. Mason and J.A. Shelford, members of my s u p e r v i s o r y committee, f o r t h e i r advice i n the d r a f t i n g of this thesis. I w o u l d l i k e t o e x t e n d my g r a t i t u d e t o my c o l l e a g u e s D r . Al Schaefer and D r . R. Gopinath for their valuable and t i m e l y h e l p . S i n c e r e a p p r e c i a t i o n i s e x t e n d e d t o B a r r y Wong, Shenton Tan, Dr. P a r e s h P a t t a n i f o r s h a r i n g t h e i r knowledge i n the use of computers. I would l i k e to acknowledge the t e c h n i c a l a s s i s t a n c e o f Sandy J a n s s e n s , K l a r a Shekhtman and C a r o l Dyck. Special appreciation i s extended to Dr. Al S c h a e f e r and Sandy J a n s s e n s f o r t h e i r d e d i c a t e d and s e l f l e s s assistance. I w i s h t o t h a n k P a u l W i l l i n g , Ed M i r e h o u s e and E l i z a b e t h B a z l e y f o r t h e i r c a r e and m a i n t e n a n c e o f a n i m a l s and t o Ted C a t h c a r t and G i l l e s G a l z y f o r t h e i r t e c h n i c a l h e l p . I w o u l d l i k e t o e x t e n d my t h a n k s t o n u m e r o u s f r i e n d s in V a n c o u v e r who h e l p e d me a n d my f a m i l y i n many w a y s a n d made our s t a y a memorable one. L a s t b u t n o t the l e a s t I thank my f a m i l y members b a c k i n I n d i a f o r t h e i r c o n t i n u e d s u p p o r t and e n c o u r a g e m e n t i n p u r s u i n g my o b j e c t i v e s .  xi DEDICATION I wish to dedicate this t h e s i s t o my w i f e Hamida and d a u g h t e r Rahima for their moral support and personal s a c r i f i c e without which this work would not have been c a r r i e d out.  1  INTRODUCTION  Selenium Berzelius  early  nutritional until  is a  in  the  essentiality  trace  trace  symptoms o f considered  of this  various  1934;  necrosis  as a  toxicity  Franke  in  toxicant  et  of  R o t r u c k e t a l . (1973) acts  reported  1.11.1.9),  an  h y d r o p e r o x i d e s and cell  from the  enzyme  1963).  sheep,  that  Se  peroxidase the  organic protects  of  Se  been  cattle  a p p r o v e d by t h e U.S.  swine  time  when  essentiality  supplementation of selenium  since  behind  free  1960,  administration  established  oxygen  et  been  the  to  (Oldfield  has  in  due  (Noguchi e t a l .  The  (Franke,  and t h e r e b y  for poultry  for  first  removes  established  and  was  unravelled  that  The  al.  Se  o f Se  glutathione  radicals.  1972a),  dietary  was  the  i t s involvement  of  damage  first  The mystery  f o r the  hydrogen peroxide oxidative  the  the  then  i n lambs was  action  as an i n t e g r a l component  (E.C.  the  Se  of  The r o l e  (Oldfield  mode  But  i n livestock  1935).  o f white muscle d i s e a s e  biochemical  by  alleviate  Until  because  a l . I960; Muth,  for  Se c o u l d  rats.  prevention  the  century.  reported  conditions  and P o t t e r ,  discovered  e l e m e n t was n o t e s t a b l i s h e d  quantities of  liver  only  element  nineteenth  1957 when Schwarz and F o l t z  time t h a t  in  (Se)  1974 a t a  Jenkins (Ullrey  1973), and et  has for  sheep  Hidiroglou, al.  1977).  i n the r a t i o n s f o r l i v e s t o c k Department o f Food and Drug rate  o f 0.1 ppm f o r  cattle,  (0.3 ppm f o r p r e s t a r t e r s and s t a r t e r s ) ,  poultry  2  d u c k s and 0.2  and  K e e p i n g pace w i t h studies the  were a l s o  fate  of  selenium  et  out  ingested  laboratory  livestock. subject  the n u t r i t i o n a l research,  carried  the  in  Excellent  Burk  extensively  reviews  as i n  appeared  domestic  on  this  tracers  Bopp  1983;  o f Se,  and  either  75 Se-selenomethionine  commonly employed distribution  and  or  to  Se-selenite,  study  excretion  the  of  Of l a t e s t a b l e  selenium  employed  f o r studying  Se  i n experimental  Though role  these  metabolic  of various  obtained with  in  conditions.  the  nonpregnant  and  methodology  transfer  most tissue  the b i o l o g i c a l have a l s o  been  i n humans a s et  were  a l .  well 1982).  i n d i c a t i v e of the  in  Se m e t a b o l i s m no i n f o r m a t i o n  is  to  t h e whole  of  body  kinetics  a l l the p h y s i o l o g i c a l and  animal  under  the present  pregnant to  and f e t a l  tissue  processes,  Se  turnover  different  nutritional  studies  ewes  were  undertaken  employing  investigate  m e t a b o l i s m a t two d i f f e r e n t l e v e l s placental  isotopes  (Janghorbani  plasma  Therefore,  in  metabolism  studies  integrating  absorption,  occurring  tracer  tissues regard  metabolism  namely,  animals  are  absorption,  selenium  systems.  in  administered  Shamberger,  Radioactive  75  Se  understand  (Ammerman and M i l l e r , 1974;  , 1983; NRC, 1983;  Combs and Combs, 1 9 8 4 ) .  as  as w e l l have  metabolic  to  or p a r e n t e r a l l y  animals  from time t o time  a l . 1982;  (NRC, 1 9 8 3 ) .  ppm f o r t u r k e y s  isotopic  whole  o f Se i n t a k e .  body In  Se m e t a b o l i s m were a l s o  Se  utero studied  3  under  Se  nutritional p r e g n a n t ewe  positive  and  implications for  disease i n f e t a l  the  deficiency  of  Se  supplementation  prevention  lamb have been  conditions.  of  discussed.  white  to  The the muscle  4  CHAPTER I; REVIEW OF LITERATURE  A)Selenium responsive c o n d i t i o n s i n sheep and other animals;  As a r e s u l t of domestic diets  selenium  animals  were  consuming  found  weakness.  One  to  of  (WMD) which  extent  in  cattle  reproductive  such  develop  the  n u t r i t i o n a l muscular disease  (Se) d e f i c i e n c y  most  selenium  common  1963).  i n sheep and c a t t l e  and  deficient  or  white  sheep and  In  addition  is muscle  to  some  to  NMD,  poor growth were a l s o  (Segerson e t a l .  or  afflictions  (NMD)  occurs mostly i n  problems  plants,  muscular degeneration  dystrophy  (Muth,  in  reported  1977; Andrews e t a l .  1968).  a ) N u t r i t i o n a l Muscular  Dystrophy(NMD):  N u t r i t i o n a l muscular disorders  dystrophy  and  other  have been r e p o r t e d to occur i n domestic  when the feeds consumed  are d e f i c i e n t i n  Se (20-30  related animals, ppb  or  l e s s Se) ( H a r t l e y , 1967; de Toledo and Perry, 1 9 8 5 ) .  Young  lambs and c a l v e s are u s u a l l y most s e v e r e l y a f f e c t e d .  These  lambs develop  regions  which  They become weak over a p e r i o d of  time  raised  affect their gait. and  die  from  arch  and s t i f f  starvation.  Secondary  pneumonia a l s o accompany myopathy. i s involved,  animals d i e  hind  infections  When the c a r d i a c  suddenly  showing  like muscle  degenerative  5  lesions 'I'  i n t h e e n d o c a r d i u m and  band  (myosin)  of  affected  exhibiting  skeletal  muscles  hind  the  range  necrosis replace  muscle  may  also  be d e p o s i t e d 1961;  and G r a n t , a n i m a l s NMD respond  to  Se  of  glutamate  lactate  fibers  vitamin  In  E Se  ewes  by t h e  levels  shown  to  aid in glutathione i s measured  (Thompson e t  pyruvate  and c r e a t i n i n e  (Hartley  administration.  Abnormally elevated and  salts  levels  a l . of  transaminases,  k i n a s e have  also  been  e t a l . 1969).  problems:  Andrews e t a l . Zealand  and  i n the erythrocytes  1977).  to  experimental  dependent  status o f animals  the  tends  Calcium  artificially  Se  and  coagulative  accompanied  o b s e r v e d w i t h NMD i n a n i m a l s ( B u c h a n a n - S m i t h  b)Reproductive  a  tissue  1968).  and t i s s u e  oxaloacetate  dehydrogenase  to  lymphocytes.  NMD.  t h e Se  1976; Whanger e t a l . serum  or  (GSH-Px) a c t i v i t y  assessing  pelvic  the a f f e c t e d muscles  produced  blood  diagnosis  peroxidase in  either of  in  active  Microscopically  Fibrous  and  The  commonly  Highly  degeneration  Andrews e t a l .  h a s been  Measurements the  affected.  muscle  a p p e a r a n c e o f macrophages  i s most  intercostal,  fibers.  the degenerating  a t autopsy.  damage.  (diaphragm,  from h y a l i n e  of  sarcomere  oxidative  l e g muscles) a r e a l s o  lesions  myocardium  was  embryonic m o r t a l i t y .  (1968)  reported  due t o  Se  that  infertility  deficiency  Administration  i n New  resulting  in  o f Se t o t h e ewe b e f o r e  6  mating was  shown  to  reduce  lambing percentages. percentages  might  fertilization  The have  or  infertility  resulting  been  decreased  combination of both  and  increase  due  to  in  lambing  increased  embryonic  these f a c t o r s .  increase  ova  mortality  or  Segerson and  a  Ganapathy  (1980) suggested that the improvement i n ova f e r t i l i t y i n Se and v i t a m i n E  t r e a t e d ewes was  frequency of  contractions  increase i n  the  o v i d u c t at mating. Segerson et a l . (1981) a l s o observed  that  more important than v i t a m i n E i n i n f l u e n c i n g  m o t i l i t y and the c o n t r a c t i o n  Se  has  been  reproduction. was a  migrating  the  towards  Se was  uterine  due to an  shown  velocity.  to  A c c o r d i n g to Wu  to  produce  characteristic  mid  the experimental over a  shown  sperm piece  r a t s fed  p e r i o d of  one  be  of  importance  et a l . with  (1979) Se  et a l .  1973).  cysteine rich in  rat  Se  breakage  deficiency  (<0.02 ppm)  vitamin E  shown to  nor  these  (Calvin  Smith et a l .  et  and  diets other effects  be a s s o c i a t e d with  s t r u c t u r a l p r o t e i n of m i t o c h o n d r i a l  sperm  male  i n more than 50% of  Se d e f i c i e n t  year. N e i t h e r  was  in  impaired m o t i l i t y  a n t i o x i d a n t s were e f f e c t i v e i n c o u n t e r a c t i n g (Wu  uterine  a  capsules  a l . 1981).  (1979) have reported  that i n the  the  highly  bull,  75 Se r e t e n t i o n (r=0.92)  with  demonstrated  in  sperm  epididymis  was  concentration.  that when e j a c u l a t e d  They  correlated have  bovine spermatozoa  also were  7  subjected water, was  to  Se  On  Se  the  and  study  the other  reproductive  (Heimann e t a l .  Beneficial  cows have  been  al.  1969; Julien  1984  and  Eger  of  incidence  sperm plasma in  the  they  also  were  not  concentrations in  the  i n the  et a l .  Se of  reported  et a l .  Se  Se  seminal  and  the  blood  1984).  effects  E i n r e d u c i n g the  c)Poor  as w e l l as  observed  abnormalities  the  that  between t h e  Furthermore  (1984).  distilled  components o f  c o n c e n t r a t i o n s was  c o r r e l a t e d with  in  suggesting  correlation  spermatozoal  tissues  thawing  structural  al.  the  significantly  by  with  or  without  retained placentae s e v e r a l workers  1976;  Ishak  et a l .  vitamin in  dairy  (Trinder  1983;  et  D'aleo,  1985).  growth;  New reported and  Se  and  spermatozoa  hand no  seminal  that  plasma  the  bound t o t h e  o f Heimann e t  found  freezing  remained w i t h  tightly  cell.  repeated  Zealand  workers  t h a t poor  growth was  cattle  suffering  lambs were  shown t o  diarrhea.  from  In a d v a n c e d  a  loss  of c o n d i t i o n , profuse  lambs  et  al.  have sheep  The  Se  deficient  with  or  without  were  emaciation.  d i a r r h e a and  (Andrews  1968)  al.  common p r o b l e m i n  body w e i g h t  o s t e o p o r o s i s and  cattle  et  deficiency.  stages,  exhibiting  in  Se  lose  die  reported  (Andrews  reported  Progressive  high m o r t a l i t y 1968).  to  This  were Se-  8  responsive as  syndrome  i n ruminants  unthriftiness  dietary cattle  by several workers  Rotruck  Andrews e t  et  counteracted  this  poor  immune s y s t e m .  growth shown  neutrophils  Arthur,  1979; A z i z e t a l . 1 9 8 4 ) .  animals.  i n These  Foltz,  1957),  disease  i n pigs  1970, and et  1976),  Se  other  domestic  include liver hepatosis (Trapp NMD,  a l .  1967  exudative  Poston  et  a l .  in  farm  authors  growth  (Hartley  Shamberger,  1977, 1983;  has  1970;  been  as  van  diathesis, chickens  and  and Grant, 1981;  van Vleet,  Roller  andExon,  have  been  experimental (Schwarz  heart  gizzard  myopathy  1970),  wild  (Scott  NMD,  eta l . deer  deficiency by  1986).  NRC,  poor 1976 (Brady  diseases several  McDonald e t a l . 1980;  and  e ta l .  a tlength  1961;  and  Vleet  (Poston  o f these  reviewed  (Boyne  andturkeys  NMD i n  Se  phagocytic  NMD a n d m u l b e r r y  rates i n fish  A description  animals  diseases  andScott,  a n d Combs, 1979),  1978).  Underwood,  in  that  the  as well  and  protecting the  necrosis i n rats  eta l .  a l . 1968  bacteria  dietetica,  a n d Thompson  andpoor  kill  deficiency  pancreatic degeneration  survival and  to  and  Oldfield et  proposed  t o enhance  of  i n sheep  et  syndrome b y  ability  identified  Paulson  to  Supplemental  1959;  I t h a sbeen  Se was  Many f o r m s o f  gains  (McLean e t a l .  1969).  a l .  weight  a l . 1968;  referred  1968).  eta l .  Se was shown t o i m p r o v e  1960;  al.  (Andrews  i s often  1983  1976; and  9  B)METHODS OF  SELENIUM  Prevention supplementing sufficient no  of  Se  Se  d e f i c i e n c y syndromes i s a c h i e v e d  t o the  animals.  concentrations  in  n e c e s s i t y f o r supplemental  deficient,  use  of  adequate  areas  or  required.  The  a) C h e m i c a l have been sodium  are  form used  selenate.  chemical  form of  blended  to  be  Two  be  m i x t u r e s or  al.  1969;  et a l .  1977,  and  Overnes e t a l . been u s e d  (Jenkins 1984;  and  in  Mallinson  et a l .  by  either  be  s u p p l e m e n t e d as feed  oral  or  1978;  1985  Se  and  is  a d r e n c h or as block.  concerning  Se  of  Se  Se  salts and  most commonly  used  complete  diet  with  free  licks  (Rotruck  Whanger e t  B o t h s e l e n i t e and  or p a r e n t e r a l  salt  is  to the  salt  1972a;  b) Route o f a d m i n i s t r a t i o n :  through  the  p a r e n t e r a l methods o f Se  Hidiroglou,  Se  sodium s e l e n i t e  added  mineral  also  from  supplements  types  concentrations  1985b).  be  considered  supplements l i k e Ullrey  is  below;  T h i s may  higher  in  demonstrably  to  o f Se  Sodium s e l e n i t e i s  at  present  are  known  supplementation,  Se.  is  If soils  administration  supplement:  for  Se  by  natural f e e d s t u f f s there Se.  described  of  If  feedstuffs  points  administration  or  SUPPLEMENTATION;  choice et  al.  selenate  1978 have  supplementation  Cawley  and  McPhee,  Overnes et a l . 1985a).  administered routes.  Orally  a free choice may  generally  a l s o be  Se  may  supplement placed  as  a  10  heavy p e l l e t 1981  al.  methods  in and  of  the  Hudson  1978;  et  (Jenkins  MacPherson and  in  the  salt  et a l . 1968; in their of Se disease  (WMD)  activity.  and  They  nor  on  reported  with  unsupplemented low none  of  the  evaluated  lambs when fed and  c o n t r o l ewes  that  Kuchel and  i n v e s t i g a t e d the use grazing  sheep.  deficient  ration  They  Se as  WMD  by  received  or  observed  salt containing  Se  white muscle d i s e a s e  in  Godwin,  from  that  injection  A u s t r a l i a n workers  observed  a  in  They a l s o found  1976)  of i n t r a - r u m i n a l heavy  recovered  muscle  (P<0.05)  Whanger et a l . (1978) a l s o  to t h e i r dams.  Buckley, 1969;  10 mg  of  equally e f f e c t i v e i n preventing  methods  (GSH-Px)  higher  ewes given Se  Se  (1978),  white  mild incidence  hay.  264  (Paulson  peroxidase  t h a t e i t h e r i o d i z e d or t r a c e m i n e r a l i z e d was  of  significantly  and  lambs from  p e l l e t s developed WMD.  et  to  different  sheep given  to the  Se oats  Se up  1 9 6 9 ) . Whanger et a l .  that  blood  lambs compared  slow-  that none of the  the occurrence  had  their  found  glutathione  levels  or  caused Se t o x i c i t y  sheep,  sodium s e l e n i t e drench GSH-Px  injections  H i d i r o g l o u , 1972a; Horton  and  Rotruck et a l .  administration  parenteral  v a r y i n g l e v e l s of  intake  s t u d i e s with  The  et  Chalmers, 1984).  to sheep  levels altered salt  ruminants (Hunter  1981).  include  and  Wisconsin workers fed ppm  the  al.  supplementation  r e l e a s e implants al.  r e t i c u l u m of  that the white  (Kuchel  developed  and  Se p e l l e t s  lambs  fed  muscle  a  in Se  disease  11  soon  after  the a d m i n i s t r a t i o n  Jenkins use  of  slow  control sodium in  and  loose  ewes i n mid implantation blood  Se  untreated of the  the al.  white born  to beef  that  t h e lambs  fed  of  increase times  the  were  Se  .shoulder  that  decreased in  prevented  of the the of  with another  in  deficient  Se p e l l e t s  as  abnormalities  Similarly,  Se  release  to  the  implanted  Both  to four  d i s e a s e was  i m p l a n t a t i o n of slow  neonatal  rations  by  (Hidiroglou  et  1972).  different  et  reported  al.  methods  hematological that  of  responses  and  controls.  Se  Blood  pellet Based  intramuscular  on  Se  were their  i n j e c t i o n was  evaluated  supplementation  in  b l o o d GSH-Px  animals.  (1978) Se  times higher f o r drench  control mix  ewes two  cows  the  found  o f the ewes.  muscle  o r 10 mg  respectively.  were  of  20  behind  the  ewes f o r  v e h i c l e s were  They r e p o r t e d  pathology  Horton  2.8  gestation  i n the  controls.  oily  tissue  treatments  implantation  study, calves  late  levels  muscle Se  with d i f f e r e n t  and  i n pregnant  containing either  connective  pellets.  (1972a) have i n v e s t i g a t e d  Se p e l l e t s  Pellets  selenite  the  Hidiroglou  release  o f WMD.  o f r u m i n a l Se  pregnant  injection  levels only  1.4  were 2.3  groups  i n animals  most  they  They and for  fed  salt  concluded  effective  upon  than  times h i g h e r than  studies the  based  sheep.  enzyme a c t i v i t i e s and  four  the that  followed,  12  in order,  by  the o r a l drench,  p e l l e t and  fortified  salt  mixture.  Recently  Overnes  et  al.  (1985b)  from  i n v e s t i g a t e d t h e e f f e c t o f d i f f e r e n t l e v e l s o f Se m i x t u r e s and monitored  s a l t l i c k s on t h e Se  t h e Se s t a t u s o f  m i l k Se c o n c e n t r a t i o n s 2 5 and  40 mg  m i x t u r e s and  Se/kg  supplementation inadequate  after  licks.  in  feeding  mineral  Se and  milk.  resulted  capable  c a u s i n g any  MacPherson methods  pellets, oral  husbandry system  i n t a k e of  b l o o d were  was mg  also elevated  p r e v e n t i n g white muscle d i s e a s e  without  effects.  Chalmers  (1984)  of  sodium blood sheep.  supplementation and  ease of  tested  in  methods o f  injections,  raising  Se  licks  and  c o n c e n t r a t i o n s i n c a t t l e and of  Se/kg  i n lamb's  supplementation  choice  salt  mg  and  a l l four  in  10  mineral  i n e l e v a t e d Se l e v e l s i n ewe's b l o o d  subcutaneous  effective  daily  Se s u p p l e m e n t a t i o n  They f o u n d t h a t  in  (10,  0.4  and  of  and  about  of  toxic  blood  levels  that and  They  Se d e f i c i e n c y w h i l e 2 5  i n areas w i t h extreme  Se l e v e l s  were  found  mixtures  Se/kg f o r t i f i c a t i o n p r o v i d e d a mg  three  sodium s e l e n i t e  They  i n mineral  i n sheep.  t h e ewes by m e a s u r i n g  d i e t ) of  salt  status  Norway  sheep Se  different and  supplementation  a d d i t i o n to selenite  water  solution  glutathione  depend  administration.  and were  peroxidase  They c o n c l u d e d would  cattle.  t h a t the on  cost,  13  Recently selenate Se/ml  (Deposel,  was  workers  a long  have  a  of  rate  Cawley et  reported  Several  mg S e / k g w e i g h t  into  ewes i n autumn.  that  the  large  the  muscle  around  hazard  for people  1984;  and  The (43.7%  consuming  Se  was  2-2.5  approximately The  was  recently,  implanted studied by  blood times  apparent  higher Trengove  that  afforded  muscle disease  injected  s u c h meat  Overnes  Se s t a t u s  also  there  of injection  1984;  found  and  white  at  was  concern  selenate  could  (Allen  i f  be a  i n  health  and Mallinson,  e t a l . 1985).  W/W)  The whole  controls.  site  of  o f Controlled Release  intramuscularly, sheep.  the  Mallinson  use  (90%)  residues  1985 a n d  an adequate  However,  eight  selenate  also  sheep  lambs a g a i n s t  two t o  Mallinson,  eta l .  maintained i n  and  mg  a n d t i s s u e Se  barium  (Allen  injection  i n fetal  plasma  of  selenate  s i x months  Kingdom.  within  workers  injected  animals  United  European  protection  Se  50  and c a t t l e injection  o f barium  U.K.) c o n t a i n i n g  1985b).  a tleast  preparation  blood,  M c P h e e , 1984; M a l l i n s o n  and  a l .  for  increased  i n sheep  1  Ltd.,  i n the  subcutaneous  of  barium  Rycovet  introduced  concentrations weeks  a c t i n g commercial  Se  Glasses either  (CRG)  subcutaneously  or  a l . (1981)  i n  Allen et  concentrations  i n treated animals retention  than and  of  Se  the untreated Judson  containing  (1985)  increased compared  by  by  t o the  the treated  controls. studied  More the  14 effects  of  administering  containing levels  Se i n s h e e p  and  o f Se i n b l o o d .  additional bullet  but  preventing  of  found  Though t h e i r  not toxic  was p o s s i b l e ,  suitability  orally,  supply  i tf a i l e d  glass  soluble  glass  bullets  elevated  but  variable  study  of  indicated that  Se t h r o u g h  t o demonstrate  bullets  for  the  an  glass  clearly  the  correcting  or  Se d e f i c i e n c y i n s h e e p .  C)METHODOLOGY TO STUDY S E L E N I U M M E T A B O L I S M I N A N I M A L S : The studied Se  metabolism using  Central  understanding  The Se s t a t u s  methods  which  b)  blood,  measurement i n  tissues  using  rapid  (spot)  animals  of  whole  and  man  Se  nutritional  erythrocytes,  blood,  standard  laboratory  stable i s  of  using  a  the  several  concentrations  h a i r and  tissues,  glutathione  plasma,  tests f o r glutathione  or  Se s t a t u s  i s assessed  dependent  been  o f Se m e t a b o l i s m  a ) m e a s u r e m e n t o f Se  serum,  has  labelled  the study  i n animals  include  plasma,  activity  to  of the  animal.  in  Se i n  either radioactively  compounds.  clear  of  peroxidase  erythrocytes  methods,  c)  peroxidase  and  performing  activity  i n 75  whole by  blood  o r plasma and  the red blood  a Measurement fluids  cells  of  d) m e a s u r i n g  the uptake  of  Se  i n vitro.  selenium  concentrations  i n  biological  and t i s s u e s ;  The  Se  concentrations  b e e n m e a s u r e d b y many w o r k e r s  i n  plasma  of  cattle  and l e v e l s l e s s than  20  have ng/ml  15  are  considered  to  be  indicative  of  Se d e f i c i e n c y i n  ( P e r r y e t a l . 1976; L a n e e t a l . 1982;  cattle  1983 a n d H i d i r o g l o u (1983)  have  indicate tended  indicated that  the short  to  1985).  eta l .  term  plasma  fluctuate often  Robinson and  Se c o u l d  Se s t a t u s  Fenimore  o f an  i n response  only  et a l . Thomson  be used  animal  to  because i t  t othe  dietary  Se  supply.  Whole of  little  as  blood value  similar  with  the  efficacy  of  white  Se  dams  between  hair  four  until  cows  dystrophy  lambs  less,  to  they  t h e Se  monitor  reached  a  concentration  (NMD) i n c a l v e s .  15% i n c i d e n c e i n  o r more. vary  found  Se  levels  1985).  i n  calves  hair  ranging  i n calves  The Se c o n t e n t directly 1975;  of  They  f r o m dams h a v i n g  (Hidiroglou and Spurr, and Perry,  to  1978).  t opredict the incidence  Se c o n c e n t r a t i o n  shown  and de Toledo  i n  w e e k s o f Se i n j e c t i o n .  measured  ng Se/g h a i r  h a s been  supplementation 1976;  after  used  t o 230 n g / g a n d 0% i n c i d e n c e 240  found  sheep  be  could  o f NMD i n c a l v e s  having  were  be  i n  levels  ofhair or  120  dams h a v i n g  concentrations  e t a l . (1965)  40% i n c i d e n c e  from  muscle disease  to  (Whanger e t a l .  occurred  muscular  reported  muscle disease  h a i r o f pregnant beef  110 n g / g  been  o f Se s u p p l e m e n t a t i o n  which  nutritional a  i n diagnosing  Se  Hidiroglou of  have  white  blood  plateau,  levels  blood  o r without  However,  Se  Perry  with  from of Se  e ta l .  16  The de  levels  T o l e d o and  various reach Se  Se  a plateau within  estimations  status  a n d 0.1  suggested  Se l e v e l  from  t h e same  by the  was f o u n d t o The serum  limitation  indicate short  term  as Se  of  (Andrews  Se c o n c e n t r a t i o n s  o f 1.0  ppm o r more i n t h e l i v e r Se  adequacy  0.05  ppm i n t h e  kidney  on f r e s h b a s i s  sheep.  0.02  ppm and  have  They  ppm o f  have  were also liver  b a s i s ) were t h e r e s p e c t i v e i n d i c a t o r s o f b o r d e r  line  severe  that  in  a l . 1968)  et  Se i n t h e  Se d e f i c i e n c y i n s h e e p .  glutathione  peroxidase  activity  in  blood  tissues;  Whole  blood  and  erythrocyte  d e p e n d e n t ) enzyme a c t i v i t i e s  workers t o Judson, Roller et  serum  to evaluate  a range o f 45 t o 60 ng/ml.  workers  b)Measurement o f  (Se  The  t h e r e f o r e would o n l y  that  indicative  (fresh  i n an a t t e m p t  would s u f f e r  Zealand  indicated cortex  serum have been m o n i t o r e d  i n animals.  New  and  (1985)  Perry  supplements.  p l a s m a Se a n d  and  o f Se i n b l o o d  al.  Peter  assess  the  1976; Thompson e t a l . 1983, 1976, et  glutathione  have been measured by  Se s t a t u s  in  e t a l . 1976,  cattle  a l . 1980,  Sheppard  (Wilson  Thompson e t a l .  H i d i r o g l o u e t a l . 1985)  Whanger e t a l .  peroxidase  and 1981,  and i n s h e e p (Oh  1977, A n d e r s o n e t a l . and  many  Miller,  1981).  1979, The  17  advantage perform  with  GSH-Px  compared t o  estimate  of  limitation  long of  enzyme a c t i v i t y needs a l a g  i s that  t h e Se a n a l y s i s  term  Se  GSH-Px  before  (Roller  in  that  et  the l a g period  peak Se days 35  (Zhang  (Sheppard days  (Scholz  been  respectively 1986). than  to  be  (Roller  et  British  workers  1979)  considered  The  the  storage  t h e plasma been  in  and  16-35,  enzyme reported  comparative 30  cattle  nearly  adequate  whole  i n beef  cattle  35  and >  and R i c e  (1985)  a l .  and  1979).  a l . , 1983  et  time  approximately  activities  < 15,  the  into  t o reach  and  deficient  peroxidase  The  short  has  was  1981)  Miller,  35 IU GSH-Px/g Hb would  al.  units  sheep  marginally  Hidiroglou  cattle. et  in  and H u t c h i n s o n ,  glutathione reported  It  f o r GSH-Px a c t i v i t y  and  Deficient, blood  a l . 1986).  concentrations  animals.  1984a).  c o n d i t i o n s have a l s o been shown t o a f f e c t activity  better  incorporated  a l .  to  a  t o s t a b l e Se i s t h a t  i t gets  et  i s easy  and p r o v i d e s  status  compared  i t  deteriorates i n a relatively  time  erythrocytes  estimation  mU/mg  and  suggested  have Hb  McMurray,  that  less  i n d i c a t e Se d e f i c i e n c y i n d a i r y  (Anderson e t a l . cattle  p e r ml RBC o r sheep w i t h  with  less  1978;  less  and A n d e r s o n  t h a n 15  GSH-Px  t h a n 28 u n i t s p e r ml RBC  t o be Se d e f i c i e n t .  The correlated  maximum with  reported  serum  GSH-Px a c t i v i t y  Se  concentration  i n cattle  was  that 100-120  18  ng/ml, blood  which was (Backall  1979). that  e q u i v a l e n t to 320-350  and  Scholz,  More r e c e n t l y RBC  their  which  previously  of  serum  et  al.  Se  values  for  useful  toxicity.  concentrations 6.2  reported  was  Se  upto  times higher  dairy cattle,  w e l l with the g l u t a t h i o n e peroxidase  is  g e n e r a l l y considered  Se s t a t u s  i n animals  r e p o r t s by Lane et a l . on the  contrary  0.789 than the  enzyme a c t i v i t y .  in  plasma Se  levels,  whole  that  this  point  of  recent  (1982) and H i d i r o g l o u et a l .  suggest  In  to be a b e t t e r i n d i c a t o r  than the  in  correlated  Though the a c t i v i t y of g l u t a t h i o n e peroxidase blood  whole  Hutchinson,  (1985)  activity  chronic  were approximately  reported  Scholz and  peroxidase  the d i a g n o s i s  studies  ug/ml,  Stevens  glutathione  determining  1979;  ng Se/ml of  needs  (1985) further  clarification.  c)Assay  of blood g l u t a t h i o n e  peroxidase  activity  by  rapid  tests;  A r a p i d spot t e s t peroxidase either  has  u t i l i z i n g the l e v e l s of  been introduced  adequate,  marginal  blood of ruminants (Board 1981). has  with  results  (Rice and  devised  and  Peter, 1976  and Norman et  (Ransel, Randox Labs, U.K.)  Blanchflower,  indicating  or d e f i c i e n t l e v e l s of Se i n the  A k i t f o r measuring the blood GSH-Px  been  glutathione  1986).  Radio  al.  concentration and  evaluated  Immuno Assay  (RIA)  19  (Baret  et  Assay)  (McMurray  for  assaying  Thomson of  al.  and  et  the  (1983)  GSH-Px  Cannot  1983)  al.  were  replace  cell  fluids  for  although and  more  been  Sorbent  developed  Robinson more  rapid  and assays  complementary,  measurements a  have  Immuno  GSH-Px.  useful  the  Linked  methods  remarked that  activity  biological  (Enzyme  1986)  red blood  have  totally  ELISA  of  Se  precise  in  they  tissues  assessment  and  of  Se  status.  75  d)Erythrocyte  Se  Uptake  studies  in  vitro:  75 In  vitro  studied  to  uptake  assess  workers  (Lopez  flux  rate  and  erythrocytes  the et  of  in  They concluded  useful  to  1985)  In found  Se  the  1968)  with that  erythrocytes in  technique Se  negative  been  American  the  Se  initial  by  ovine  Se  level  in  the  was  promising  and  status  A u s t r a l i a n workers  significant  that 75  of  increasing  this  has  sheep.  reported  uptake  nutritional  contrast a  by  status  vitro  decreased  assess  Se  al.  diet.  ovine.  of  in  the  (Jelinek  correlation  immature et  al.  between  the  75 erythrocyte activities. correlation  Se uptake values and erythrocyte GSH-Px Furthermore they could not demonstrate any 75 between the Se uptake and the development of  nutritional  myopathy  in  weaner  sheep.  Recently  Atroshi  et  75 al.  (1985)  was  related  studies  reported  that  to  glutathione  with  their low  and h i g h  the  uptake  of  Se  by  (GSH) c o n t e n t .  GSH F i n n  sheep,  the  erythrocytes In  their  former  group  20  exhibited  a higher erythrocyte  activity  compared  presence  to  o f more a c t i v e  Se u p t a k e and h i g h e r GSH-Px  the  latter.  T h i s suggested  detoxification  the  mechanisms i n low-GSH  animals.  D)METABOLIC  FATE OF SELENIUM IN ANIMALS:  Ingested  Se  transformations animals.  An  fate  before  by or  the  i s completely metabolized  of these use  stable.  biochemical  metabolic  of  Different  changes  isotopes,  in was  either  aspects of the metabolic  o f Se a r e d i s c u s s e d .  a)Dietary forms Se  intake of selenium:  by  animals  occurs  plant  1969;  and  Olson  et  as  and  products  Se i s i n g e s t e d i n many o r g a n i c  man  mainly  selenomethionine, and  i t  understanding  made p o s s i b l e radioactive  undergoes  through  selenocystine,  (Peterson  a l . 1970).  and  et  a l . (1984).  the major  form  for  animals  products,  i n o r g a n i c Se s a l t s  are o f t e n  used  t o supplement  1962;  plants Shrift,  on  depend  T h i s s u b j e c t has been  Gissel-Nielsen  in  to  application  etc.  selenocysteine,  o f Se p r e s e n t  including species  Butler,  food.  The amount  known  type,  and  Se-methylselenomethionine  p l a n t s may v a r y and i s soil  feeds  factors  of f e r t i l i z e r s , recently  Although  consuming (sodium  many  organic  selenite  feeds d e f i c i e n t  plant  reviewed  plants or  in  Se  and  by is plant  selenate)  i n Se.  21  b)Absorption; known t o v a r y  The with  extent  of absorption  the species  o f Se i n a n i m a l s i s  and t h e f o r m and amounts  of  75 element  ingested.  duodenum  was t h e major  was no a b s o r p t i o n from t h e rations  Studies site  stomach  of pigs 0.35  t o sheep and  Se i n d i c a t e d  of absorption  e i t h e r from  containing  selenite  with  swine  the  o f Se a n d  there  rumen o r abomasum o f sheep  (Wright  and  that  1966).  and B e l l ,  0.50 ppm Se  were f e d a s  respectively,  or  When 75 Se-  29%  about  of  75 ingested  Se was a b s o r b e d  McConnell  and  selenomethionine everted  duodenal  absorbed (1985)  mainly  i n an  transported  concentration the  actively in vitro,  by  diffusion.  i nvitro  across  study  the  gradient  vitro  such a  Se utilized  by  g e n e r a l l y found  insoluble  forms  the by  across  Arduser  that the  was  et  a l .  selenate  was  rat against  to selenomethionine.  Instead  the  selenite  Recently  of  that  1985)  a  However, failed  to  under e i t h e r  in  they  found  that  o n l y by d i f f u s i o n .  i n monogastrics  explained  whereas  mechanism f o r s e l e n i t e  was a b s o r b e d  was  transported  (Wolffram e t a l .  or i n vivo conditions.  selenite  showed  have shown  ileum  similar  same g r o u p o f w o r k e r s  demonstrate  (1965)  Cho  was sacs  i n sheep and 77% i n p i g s .  fact  to  be b e t t e r  than  in  r u m i n a n t s and  that  dietary  microbes  i n the  Se rumen  absorbed this  was r e d u c e d (Cousins  and was to and  22  1961; P e t e r s o n  Cairney,  (1968)  al.  reported  than organic forms  Se  and  that  was  a greater  converted  and the c o n v e r s i o n  than with observed  that  et  inorganic  into  insoluble  these  with  Hidiroglou  rumen  Whanger  percentage o f  was h i g h e r  roughage d i e t s .  1963).  Spedding,  s t a r c h based  et a l .  bacteria  diets  (1968b)  were  have  capable  of  75 metabolizing bacterial Ehlig  protein  et  retention selenite  inorganic  of  a l .  (1967)  have  observed  in  lambs  selenomethionine. the  minerals. pH  that of  According  to  of  recbmmended  were t h e b e s t enteric  review  forms t o absorption.  have  described  Barbezat  t h e methods  Se i n a n i m a l s  the f a c t o r s , both  have shown  workers that  et  (Combs,  including  forms.  Hence,  of  minerals enhanced  a l . (1984)  i n their  to  measure  They have  also  and e x t r i n s i c ,  that  o f Se.  1976;  the absorption  trace  they  and man.  absorption  of  affect  employed  intrinsic  from  salts  acid chelates since  of  recently  factors  inorganic  be s u p p l e m e n t e d  discussed  Cornell  in  rate  have  of the inorganic  with  than  absorption  several  amino  of  the i n t e s t i n a l  (1985)  Se  than  selenite  intestinal  absorption  affect  from  them,  into  greater  t h i s was due t o a h i g h e r  minerals that  a  selenomethionine  Se  of  it  Se-selenomethionine.  Ashmead and C h r i s t y  subject  absorption  they  the  with  changes and c o n c e n t r a t i o n  the  incorporating 75  form  excretion  reviewed  and  i n the  and reasoned  urinary  Se  of  Combs a n d P e s t i , selenite i n  chick  1976) was  23  affected and  E  by t h e d i e t a r y  concentrations  which a r e capable  added  to  the d i e t  Recently,  Mutanen  of  promoting  a t higher and  than  Mykkanen  o f v i t a m i n s A, Se  the  absorption required  (1984)  C  when  levels.  from  Finland  75 reported lower  that  i n chickens  oil)  than  al.  (1975)  in  feedstuffs  compared  diathesis  was  and f o u n d less  available  i n chicks.  absorbed,  active  for  (1984) element  sources was  exudative  bioavailability  in a  feedstuff  to a  that  biologically  f o r m , Se d e p e n d e n t g l u t a t h i o n e p e r o x i d a s e . Transport;  reported  t h a t 75-85% o f t h e Se  was  associated  peroxidase  Wisconsin  with  (GSH-Px).  erythrocytes  of  o f selenium  blood  et  o f Se  sources  of  defined  and c o n v e r t e d  c)Blood  10%  Cantor  plant  animal  the prevention  of  transported  Se from  was  sunflower  availability  t h a t 60-90% o f Se from  O'Dell  Se a s t h e f r a c t i o n  f a t (butter).  the b i o l o g i c a l  25% o f  than  duodenum  f a t (corn o i l or  f e d animal  have s t u d i e d  to  a b s o r p t i o n from  fed vegetable  i n those  biologically  of  Se-selenite  cells  rats  workers i n ovine  the  Whereas was  (Oh e t  red blood  selenoenzyme, almost  associated  was a s s o c i a t e d w i t h  (Behne a n d W o l t e r s ,  this  1979)  1974)  a l .  all  cells  glutathione  of  t h e Se i n  w i t h GSH-Px,  only  enzyme i n human r e d and 20% w i t h  GSH-Px  o f RBC i n t h e p i g ( X i a e t a l . 1 9 8 5 ) .  The similar  metabolism i n both  of  selenite  the primates  by  blood  and o t h e r a n i m a l s  in-vitro though  i s  there  24  are Px  differences  in  t h e amount  of  enzyme. The u p t a k e and r e l e a s e a l . 1969),  et  ovine  bovine  (McMurray and  sulfhydryl  groups,  plasma p r o t e i n cells  o f s e l e n i t e by human ( L e e and H i d i r o g l o u ,  1972b)  1979) e r y t h r o c y t e s  and  binding  the  was shown  1979).  w i t h GSH-  Davidson,  e t a l . 1969;  (Lee  Davidson,  (Jenkins  Se a s s o c i a t e d  t o be  of  Sandholm, 1974,  Symonds  red  to blood  1975; McMurray  (1981)  et a l .  involve  selenite  d e p e n d e n t upon  or  showed a  and  similar  75 initial  uptake and l a t e r  vivo within the  dairy  selenite (GSH)  30-60  cow. The  uptake  were f o u n d  1978a).  of  Se by 75  m i n u t e s a f t e r Na2 and  S e 0  3  the  subsequent  i n the red blood  The  erythrocytes  cells were  liver  injection  in into  metabolism  t o be d e p e n d e n t upon r e d u c e d  concentrations  Smith,  release  of  glutathione  (Gasiewicz reported  and  to  take  75 up  the  and  Se-selenite  release  either and  i t back i n t o  as  similarly  1978b).  The  erythrocytes  was  proteins  et a l .  (Lee  observed  plasma p r o t e i n s  vary  in  that  different  be  in  compound to  carry  primary  i s o l a t e d and  peroxidase  and a n o t h e r  selenide  (Gasiewicz  released  from  to  the  and H i d i r o g l o u ,  Albumin  i n cattle  of  form,  the plasma 1972b).  s e l e n i u m have been shown  species.  carriers  injection  an a l t e r e d  g e t bound  (Sandholm,  (Symonds e t a l .  1981) a n d  1975)  selenium.  identified  to  i n mice  l i p o p r o t e i n s i n man (Sandholm,  the  (1982)  the t r a c e r  reduced  1969; J e n k i n s  1 9 7 4 ) , gamma g l o b u l i n s alpha  after  the blood  l ^ S e or  Smith,  The  initially  Burk  fractions  selenoprotein  called  were f o u n d and  to  Gregory  of glutathione 75 Se-P i n p l a s m a  25  and  liver  of  rats.  They  also  reported  that  Se  75  deficiency  decreased  72 h o u r s  and  Se  incorporation  b y GSH-Px a t  3  75  after  Se-selenite  75  injection  but  increased  75  Se  incorporation  Motsenbocker  and  incorporation  of  was  Se-P. (1984)  Tappel  75  Se  that  theproportion  r e f l e c t e d the long  d)Distribution distribution  Se  term  of  Contrary have  i n t o plasma  a f f e c t e d by t h e d i e t a r y  suggested P  by  to  reported  rats.  They  o f Se i n p l a s m a  Se s t a t u s  selenium  the  75  ( Se-P) have  also  selenoprotein-  of rats.  i n  o f Se i n v a r i o u s  that  selenoprotein-P  i n  this  tissues;  animals  The  tissue  has been s t u d i e d  using  75  either was  Se o r s t a b l e  shown  to  chemical  followed pancreas  the by  element  cortex,  had  liver  muscle  sensitive  indicators  biopsy  these  of  information levels reach in  intake,  as high  a s 5-10  muscles  o f farm  a l .  Se  provide 1968).  tissues like  o f an  animals  i nliver  Se  arethe  animal  were  and kidneys  most  and t h e  diagnostic  toxic  (Maag a n d G l e n n ,  than 1977;  et a l .  valuable At  spleen, contained  more  Kincaid  Se c o n c e n t r a t i o n s ppm  kidney,  concentration  and l i v e r  status  can  (Andrews e t  o f Se  kidney  o f Se  and t h e  The  contained  1965;  content  level  bones and blood  muscle  The  organs  the  thediet.  glandular  (Wright,  Mahan a n d Moxon, 1 9 7 8 ) .  both  i n  Muscles,  Cardiac  The t i s s u e Se  thehighest  and other  l e s s Se.  skeletal  upon  of the  and p i t u i t a r y .  relatively the  be d e p e n d e n t  form  especially  Se a s t r a c e r s .  (>5  reported a n d 1-2  1967;  ppm) to ppm  Casteel  26  et  a l . 1985;  Se than  deficient  Se  1968),  i n chicks a n d sheep  in  cattle  retention possible the  animals  supplemented  observed  and  and Hopper e t a l . 1 9 8 5 ) .  (Kincaid  the  retention  Se more pattern  1963),  rats  1967;  tissue  o f Se  in  various  been  (Burk e t a l .  The  demands f o r  et a l .  has  1969)  Lopez e t a l .  Se e x c r e t i o n p a t t e r n Lopez  efficiently  This  a l . 1977).  et  greater  d i e t a r y Se l e v e l .  body  et a l .  (Muth e t a l .  reflected that  animals.  (Jensen  75  retained  increased Se. I t i s  may be a f f e c t e d  (1969)  by  measured  whole  along  with  tissues 75  urinary lambs  and  fecal  receiving different  whole body l o s s o f tissues  were  The resulted  feeding  egg  (1978)  Se  and  low  mercuric  of  75  into  diets.  The  Se i n v a r i o u s  When  Se  a l . on  (1985)  the  swine f e d as  greater  than  meal.  meal and t h e y  was  Latshaw,  1981)  levels  and  Se  in and  or f i s h  serum  poultry  Se  1976)  when  in  four  reasoned  studied  inhibition  in  and  f e d as  Mahan a n d  o f Se by m e r c u r y p r e s e n t  Bern e t  compounds  to  (Osman  Biggert,  fed fish  to the binding  More r e c e n t l y  Se i n t h e i r  resulted  or selenocystine  observed  meal  retention.  i n muscle  weanling p i g l e t s due  fish  i t  (Latshaw  selenite  of  Se a n d c o n c e n t r a t i o n  of  i n poor  concentration  75  levels  Se i n j e c t i o n  i n v e r s e l y r e l a t e d t o t h e d i e t a r y Se i n t a k e .  selenomethionine  in  Se l o s s e s f o l l o w i n g  Moxon  week o l d that fish  i t was meal.  the e f f e c t of  of  glutathione  27  peroxidase  in  inhibition was  not  of  of due  rat GSH-Px  to  enzyme  in  b i n d i n g of to  tertiary  al.  It  or  in  is  been  shown  diet  tissues.  it  to  This  site  but  the  of  Se  due  Se  moiety to  an  of  the  1985).  ingested  has  that  quarternary structure  Depending upon  before  active  mercury  metabolism;  processes  suggested  unavailability  the  e)Tissue  the  was  consequent  peroxidase  the  (Bern e t  and  simple  glutathione  alteration  liver.  is  be  was  known  its  to  chemical  undergo  utilized  by  the  converted  to  organic  demonstrated  by  form,  some  animal.  metabolic  Inorganic  forms  the  Se  in  Se the  incorporation  of  75 Se-selenite selenide acids as  (Hsieh (Olson  after  and  Palmer,  al.  1970).  selenite,  to it  intimately  formation from his  selenite colleagues  metabolic from  of  the  path +4  or  it  undergoing  (Oh e t  Ganther,  and  sources,  supplements  is  GSH-Px  selenomethionine  natural  et  into  be  to  the  been  a n d was  oxidation  selenide extensively  to  state  Se  as  of  a  (Olson that  Se  inorganic in  animals  selenite.  (1979).  six  electron  in  selenite  The  selenide  by Ganther  Ganther  in  selenite  fact  metabolism  studied  consumed  changes  largely  of  amino  present  and h y d r o g e n  by  involve of  forms  the  metabolism  reviewed  shown  Se  was  released  and  dimethyl  seleno  Se  catabolic  that  dimethyl  was  to  into  into  When  consist  evident  related  and  this,  diets  1974),  organic  postabsorptive  animal  has  other  shown  Given  is  1975) 1976).  in  was  al.  and The  reduction to  the  28  -2  level,  followed  by methylation  of s e l e n i d e as  shown  below:  (1) H  Se0  2  +  3  (2) GSSeSG  4  GSH  +  >  GSH  GSSeSG  > GSSeH  +  GSSG  +  3  H 0 2  + GSSG  OR  GSH reductase GSSeSG  (E.C. 1.6.4.2)  — — NADPH+H  NADP  +  GSH  > GSSeH  + GSH  +  reductase  (3) GSSeH  >  NADPH+H  NADP  +  H  2  S e  +  G  S  H  +  Se-methyl t r a n s f e r a s e (4) H  2  Se + 2 S-Adenosyl  > (CH ) 3  2  Se + S-Adenosyl-  methionine  i n the with  first  step,  glutathione  derivative derivative  (GSH)  homocysteine  selenite to  reacts  nonenzymatically  the  selenotrisulfide  form  (GSSeSG) and an equimolar of  GSH  (GSSG).  quantity  of d i s u l f i d e  Subsequently,  the  s e l e n o t r i s u l f i d e d e r i v a t i v e i s reduced t o a s e l e n o p e r s u l f i d e (GSSeH), e i t h e r nonenzymatically  i n the presence of  GSH or by means  the  reductase. decompose  of  the  and  The s e l e n o p e r s u l f i d e to  glutathione  of NADPH  GSH  reductase  and  enzyme,  Se.  and can  Alternatively,  can c a t a l y s e a NADPH l i n k e d  selenopersulfide  glutathione  i s q u i t e unstable  elemental  excess  t o an a c i d - v o l a t i l e Se  reduction compound,  29  hydrogen shown  selenide. to  This  be  reduction  operative  pathway  has  in erythrocytes.  been Several  75 workers taken  have up  demonstrated  by mouse,  then  released  than  GSSeSG  to  Hidiroglou,  i n an  some  pathways been  selenite.  for  cysteine.  a l .  has  been  Japanese  was r e a d i l y  bound  1969;  workers  enzymological  aspects  selenocysteine et  be  mammals  of  in  to  selenite  Se f a v o u r s  (Sunde, the  active  Selenocysteine  et  is  a l .  has a l s o  a l . been  (Bielstein  be  to  selenocysteine synthesis to  and  of  that  the  degradation review  degradation the high  of  of  reduction  hydrogen has  selenide  been  shown  glutathione  peroxidase  Ladenstein  et  shown  Jones to  et  a l . a l .  be p r e s e n t  a l . 1981).  of  studied  a recent  the  1976;  et  seems  in  Selenocysteine  1978;  there  and d e s c r i b e d  possible,  of  to  of  synthesis  release  site  (Cone e t  organelles  animals  Though  the  1984).  (Forstrom  in  selenite  extensively  mammalian t i s s u e s 1985).  in bacteria  tissue  and  of  t o be s i m i l a r  have  of  a l .  selenocysteine  instead  Jenkins  tissues,  assumed  metabolism  potential  and  rather  established,  mammalian  selenocysteine  and  et  cells  l^Se  the conversion  fully  In  selenocysteine  to  which  rapidly  1972b).  have  (Tanaka  was  possibly  u n c e r t a i n t y concerning the synthesis  from  of  form,  1979) (Lee  Se-selenite  o r human r e d b l o o d  altered  proteins  Although selenide  bovine,  (Ganther,  plasma  that  in  1979) 1979).  in  Evidence  ovine has  30  been  presented  transfer this  RNA  Tappe'l  in  this  liver  the  into  and h i s  rat  mechanism  incorporated of  by  tRNA  during  (Hawkes  (1976)  whereby  i n a preformed cysteine,  in  proposed  by selenide  the  or i t s  synthesis  possibility  specific  selenocysteine. was  a l .  found  an  1982).  i f  the  to  this  be  action and  hypothesis  sulfide  selenocysteine.  was s u p p o r t e d b y Sunde  By  Olson  alternative  equivalent,  of  for a  t r a n s l a t i o n v i a the  et  Palmer  replaced  have  for  selenocysteine  proteins  specific  coworkers  could  be  would  result  The  latter  and Hoekstra  ( 1 9 8 0 ) , who  75 demonstrated into  that  GSH-Px  the i n c o r p o r a t i o n of  by  the  isolated  decreased  by  addition of  selenite  or  selenide  addition  of  a  selenocysteine  was  conversion of  be  1982)  f)Metabolic glutathione  et  of  On  functions peroxidase  1985)  (GSH-Px)  (1973)  Se  as a  functions  defence have  CoA  system  hand,  presence not  been  was shown  and  of Clostridium  of selenium:  antioxidant  and  selenomethionine  3-hydroxybutyryl  and Sliwkowski,  other  have  (Hartmanis  while  unlabelled  the  tissues  was  nonlabelled  medium,  excess  animal  although  in  a l .  perfusion  of  to selenomethionine  in thiolase  multicomponent  Rotruck  the  rat liver  excess  effective.  in  so f a r ,  and  (Hartmanis  a  not  perfused  9-fold  100-fold  selenomethionine  present  to  of selenite  demonstrated  a  Se-selenocysteine  Stadtman, dehydrogenase kluyveri. component  as  a  within  demonstrated  to  part the  that  of of  cell. GSH-Px  31  reduces  toxic  hydrogen from  peroxide  oxidant  oxidation  damage.  both  to  reduced  mitochondria peroxide  reduce  to water,  enzymes  reported  absence  of  further  powerful  cause  peroxidase  while  excess  recently bovine  have  reviewed  and ovine  been  (Tappel,  of  is  erythrocytes  has  1982).  and  hydrogen of  both  peroxide In  which  the may a can  components.  only  time  is  to produce  cellular  isolated  (Rotruck et  and b i o c h e m i c a l  extensively 1984;  the  (OH)  the  the present  The p r o p e r t i e s  cytosol  hydrogen  anions  radical  degradation  peroxidase  oxidation  hydrogen peroxide  superoxide  hydroxy  1973).  enzyme  (Flohe,  and  formed  the  reduces  of  hydrogen  The c o m p e t i t i o n  peroxidase,  1973;  this  catalase  little  i n mammals a t  of  in  common s u b s t r a t e  selenoenzyme Flohe,  to  peroxide  oxidative  Glutathione  cytosolic  The  oxidant,  severe  reduction  anion  hydrogen  been  example,  o f membrane  be v e r y  with  have  the i n i t i a t i o n  the  glutathione  react  (both  induce  cellular  for  univalent  e  i n peroxisomes.  for to  n  that  Many  radicals,  and  biomembranes  non-enzymatic,  superoxide  glutathione  to water  identified.  and  t  the  stressors  dismutases  1975).  by  been  ^°2^  and prevent  (Fridovich,  hydroxyacids  and p r o t e c t s  reactive  Superoxide  peroxide  more  have  enzymatic  mitochondrial)  to  The p r o o x i d a n t  anion  oxygen.  was  water  generate  superoxide  these  to  i n membranes  oxidations, shown  hydroperoxides  studied  a l .  functions and  were from  Flohe,  1985).  GSH-Px  been  shown  to  contain  32  4 g atoms  o f Se p e r mole  1974).  et  a l .  of  cattle,  This  sheep,  have  a  with  four  The  r a t liver  amino in  each  with  The  reviewed  peroxide  found  was  acid  ofaction  added  to  1982;  mole the SeH).  The  glutathione the  This  (E-SeH)  with  a mole  sulfide  153  of  acids  mechanism  and  hydroperoxides  also  i n preventing  the  by  release  of  Finally  (GSSG)  next  from  of selenenic  the formation  the  i s  o f an another  resulting  i n  andselenol (E-  addition of catalytic remove  of  second  cycle  of  t h e hydrogen  t h e body  formation  in the  glutathione  t h e enzyme  helps  recently  oxidized  the  (E-SeSG).  the  studied  present  i s  of  in  after  restarts  been  the formation  resulting  released  Se  causes  reacts with  peroxide aids  of  that  and h a s been  ofoxidized glutathione  molecule  enzyme.  and  along  selenenyl  selenol  1976).  residues  while  GSH-Px h a s  Firstly  selenol  Subsequently  of glutathione formation  of  1985).  t h e enzyme  intermediate,  a l .  178 a m i n o  t o have  German w o r k e r s  alcohol  (E-SeOH).  daltons  methionine  1974),  to  1979).  substrate  corresponding  a total  cells  enzyme a s s e l e n o c y s t e i n e the  t ocontain  eta l .  by  (Flohe,  et  andthree  tissues  80,000  (Ganther  (Nakamura  mechanism  extensively  sub-units  from  Oh  a n d shown  o f approximately  twoc y s t e i n e  eta l .  e t a l . 1973;  (Flohe  a n d humans  GSH-Px w a s f o u n d  red blood  (Ladenstein  rats  weight  identical  sub-unit  bovine  enzyme  enzyme h a s b e e n p u r i f i e d  swine,  molecular  acids  of  system  and  subsequent  33  hydroperoxides  A  due  direct  to  relationship  and  the d i e t a r y  Se i n t a k e  al.  (1974).  I t was  activity  decreased  with  lowest  the  highest  Se  activity  by  Tappel,  (Godwin 1978;  et  cattle  (Anderson  Oh e t  a l . et  peroxidase  activity  diagnosing  Se d e f i c i e n c y  glutathione Burk, in  by  in  the  of  enzyme  t h e Se d e p e n d e n t  peroxidases  carry  characteristics  out  Se  a l .  et  Whanger et  a l .  The  et  et  a l .  1973,  in  sheep  a l .  1977,  used  and i n  a l .  of  Se  with  1985),  assay  often  GSH-Px  1975),  1985,  glutathione  as  metabolism  discovery  cytosol  the  a tool  in  animals.  Non-Se-GSH-Px  mitochondria,  controls  associated  Stevens  is  of  whereas,  (Noguchi  Therefore,  i n blood  peroxidase  1976).  Although  1985).  understanding  complicated  Jelinek  a l . 1978,  et  et  et  enzyme  1974).  be  a l . 1976;  1979;  that  a l .  to  i n chicks Cantor  RBC  erythrocyte et  shown  levels  by Hafeman  ppm),  the  GSH-Px  the  from  (0.05  been  1974;  a l .  that  (Hafeman  activity  Hidiroglou  The  reported  60%  a l . 1975,  Anderson et  was f i r s t  raised  has a l s o  Omaye  the t i s s u e  intake  about  GSH-Px  between  b y 18% i n r a t s  Se  increased  peroxidation.  observed  intake  supplementation  and  lipid  of  a  non-Se  (E.C.2.5.1.18) was and  shown  t h e same  as enzymes were  to  microsomes  and non-Se  further dependent  (Lawrence be of  dependent  reaction, shown  was  many  and  localized rat  liver.  glutathione of  t o be d i f f e r e n t .  their Se  3 4  d e p e n d e n t GSH-Px organic  destroys  hydroperoxides,  metabolize organic  H~0 . 2 2 o  i s  found  dependent enzyme. suggested  that  dependent the  while  present  (1983)  latter  have  has  been  proteins observed  of  (McConnell function  et  g)Excretion: and  make  has  t h e Se  at  i n  from  the  b u t n o t f r o m Se  20,000  daltons  and i n  a l .  1979)  (Pallini the  weight  semitendinosus  1972).  of cattle  animal  molecular  et a l .  1978)  Se  binding  have  been  and B a c c i ,  1979)  rat  suggesting  testis  cytosol  some  possible  r e p r o d u c t i o n and f e r t i l i t y .  and t o  excreted primarily  appear  air  depend  form  the  rest  on t h e l e v e l  through  some e x t e n t i n e x p i r e d a i r .  amounts a n d p r o p o r t i o n s t h a t  of thediet,  review  w i t h unknown f u n c t i o n s  dalton  Se i s known t o be  feces  t h e Se  to  demonstrated  to  o f Se i n m a l e  the  i n animals.  (Pedersen  15,000  not  compared  isolated  i n spermatozoa  rat (Calvin,  urine  recent  and t h e h e a r t o f n o r m a l l y f e d lambs, animals  than  greater importance  been  selenoprotein  i n a  *  towards  3  two c h a r a c t e r i s t i c s  t o be o f  10,000  and  has a higher k m  cell  a n c  does  types  A  deficient  2°2  i n fewer  tissues.  muscle  non-Se-GSH-Px  selenoproteins,  time,  H  Se-GSH-Px a n d  n o n - S e d e p e n d e n t GSH-Px  Additional  substrates  substrates than  Burk  the  GSH-Px  the  Non-Se-GSH-Px a l s o  hydroperoxide  former  both  and  i nthefeces,  of intake,  age and s p e c i e s .  The  urine  or  thenature  of  35  In  monogastric  reported  animals  t o be t h e major  Se  administration  In  ruminants,  route  excretion  irrespective  e t a l . 1972  (Burk  urinary  urinary  excretion  has  been  o f t h e route  1982).  a n d Bopp e t a l .  seems t o  depend upon  method o f a d m i n i s t r a t i o n .  Fecal  excretion  of ingested  was  than  urinary  excretion  shown  to  ruminants  1963, into  the  major  and  Lopez e t  effect  greater  (Cousins  Spedding, injected  be  sheep o r other  ruminant  1969). of  The l a t t e r  administration  Se i n and  When S e  species  (Wright  the  Peterson  a l . 1966).  et  o f Se e x c r e t i o n  a l .  route  1961;  Cairney,  and Paulson  pathway  of  and  of  was  t h e u r i n e was 1966;  and B e l l ,  workers  studied  and o f higher  the  dietary  75  Se  levels  on  Increased  the  pattern  Se l e v e l s  of  i nthediet  Se did  excretion  i n  lambs.  not substantially  affect  75  volatile, orally. levels  urinary, On t h e  of  Se  or fecal  other i n  hand  the  excretion they  diet  of  found  Se  administered  that  significantly  the  higher  increased  the  75  excretion of parenterally administered Se t h r o u g h u r i n e o r feces. Ewan e t a l . (1968) r e p o r t e d t h a t i n y o u n g lambs o f 75  8-10  weeks  synthetic than  of liquid  i n feces  rumen m i c r o b e s of  age,  Se was  Se  diet i n  o n Se  excretion.  to  theadult  be 2 t o  suggesting  e t a l . 1972).  of  was shown t o a f f e c t  Se  with  predominantly  3 days a f t e r  1967;  Burk  along  i n urine  the role  Maximum u r i n a r y  (Muth e t a l . the animal  orally  was e x c r e t e d  unlike  shown  fed  of  excretion  administration  The s e l e n i u m excretion  status  patterns.  36  In  calves  and to  rats be  (Kincaid (Burk  et  At higher  seems  be  In  the  study  the  and  a)In  or  fetal  in  mineral  study  the  kinetics  major  excretion  was  found  Se  of  excretion.  through  transfer  and  different  good  and  to  and  are  status  the  of  of  the  expired  air  trace  minerals;  commonly e m p l o y e d  fetal  metabolism  recently  reviewed  drawbacks  species  with  of  to  trace  by  Morriss  and use  various  of trace  below.  fetal by  in  a  of  (Laurell  very  inhibitors  the  1969)  loss  been  the  for  drawback  that  of  trace  slices  This  and  and Morgan, studying  binding  the  poisons  or  fetal  tissues,  it  does  not  mimic  used  of  of  this  trace  suffers or  to  enzyme  binding of it  to  iron  Though  effects on  labelled  been  1964).  has  placental  radio  a p p r o a c h has  transfer  minerals of  medium c o n t a i n i n g  metabolic placenta  uptake  incubating  compounds.  placenta  minerals  al.  the  The a d v a n t a g e s ,  vitro  tissues  trace  is  et  Se  transfer  discussed  placental  studied  method  in  Se  to  methods  has  (Lopez  method;  been  rat  vivo  (1982).  are  vitro  The  in  lambs  urinary  placental  subject  methods  elements  route  study  and  This  Caprioli  these  intakes,  placental  minerals.  1972)  major  to  vitro  1977),  proportional  animal.  E)Methodology  al.  al.  directly  to  et  from  simulate  37  the  physiological  conditions. not  many  environment  Probably  reports  placental  in  uptake  this  could  the  and  present be  the  literature  transfer  of  under  reason with  trace  in  why  there  regard  minerals  vivo are  to  the  using  this  method.  b)In  vivo  In injected  method:  this  method  into  the  appearance  in  determined  at  This the  1968, the  rabbit  Studies iron  the  different  (Douglas in  supplied is  animals  iron 1964,  several in  the  Mansour  1971,  vivo  in  several  the  fetus  in  1964a  and  maternal 1964b,  Van D i j k ,  Seal  rate  serial  rat  Larkin  et  species  have  mammals  to  et and  al.  al. in  1970).  shown  that  hemochorial  protein,  or  measure  1972)  with  is  slaughter.  (Glasser al.  are  tracer  tissues  et  while  in  endotheliochorial  erythrocytes et  of  workers  iron-transferrin  from  minerals  placental  epitheliochorial  is  1974,  by  the  following  al.  the  with  Hansard, Morgan,  to  from  placentation  used of  et  and  times  and Morgan,  done  placenta  been  trace  dam a n d  fetal  transfer  Laurell  labelled  pregnant  a p p r o a c h has placental  radio  al.  (Hoskins  1972,  and  Wong  and  labelled  cat  1981).  59 Wong  and  erythrocytes uptake  by  into the  Morgan the fetus  (1974)  pregnant (mg/d)  injected cat  and  using  Fe  calculated the  formula:  the  iron  38  % dose Fetal of  uptake  -  maternal  (fetus) X  Iron 100  (mg/d)  where  10.5  in  ml  100  More  g  hemoglobin  (Hct)  of  40%.  recently,  the  shown  that  a  synthesized  by  the  involved  in  the  transfer  of  pig  the  Furthermore,  the  et  fetal  was mg  Fe/g  studies  of  Bazer  specific  be  at  a  volume  was  coworkers  uteroferrin,  pregnant  across Roberts  shown  present standard  and h i s  of  iron 1982,  pig  Hb  to  protein,  glands  al.  X  (ml)  assumed  3.4  of  3.4  100  (Hb)  uterine  (Renegar  X  40  containing  Blood  X  X d  blood  hematocrit  have  10.5  Hct.  to  sow  the et  was  placenta  al.  1986).  incorporate  the  59 Fe-labelled injected al.  via  uteroferrin the  into  umbilical vein  of  its the  tissues  pregnant  sow  when (Buhi  et  used  to  1982). The  study  isolated,  the  approach  placental has  been  placental  transfer  van  et  Dijk  (Yudilevich, against  perfused  such  transfer  used of  al.  by  iron  of  in  vivo  and  the  lack  also  minerals.  workers (Baker  other  However, is  was  trace  several  1985)  1979). studies  placenta  study  and Morgan,  nutrients  the of  to  major  proof  of  This  in  the 1970, vitro  criticism viability  of  39  the  preparation.  In  domestic  metabolism injecting at  of the  different  and  animals.  1964, iron  sheep and  swine  1968c)  cattle  fetal  is  determined  and of  obtained  with  in  and  by  and  (Hansard  nutrients  as  some  in  vivo that  possible cannot  be has  catheterization  (Meschia  flow.  and  transfer  T h i s drawback  et  concentration blood  1968a)  these  minerals  and  Mohammed,  and  chronic  vessels  the of  the  sheep  disadvantage  trace  approach.  swine  cattle,  and  by  of  this  in  Although  minerals  certain  the  1966),  transfer  blood  exchange  studying  placental  from the  the  and O k s a n e n ,  cattle  to  fetal  Bell,  placental  veno-arterial  nutrients  transplacental  trace  particularly  the  the  and  1969).  regard  suffer  with  and u m b i l i c a l  measuring the  fluxes  dam  (Wright  (Hansard  Mohammed,  they  for  manganese  sheep  pregnant  sacrificing  1964a)  in  fetal by  ( H a n s a r d a n d Mohammed,  of  of  precisely  overcome  fetal  and  used  Hansard,  in  sheep  after  sheep  zinc  the  and studied  measuring  Jacobsson  1972),  in  in  1964b),  and  studies,  bidirectional  of  and  Hansard,  kinetics  been  1969,  into  and  been  selenium  distribution  slaughter the  radioactivity  al.  (Hansard  information and  of  (Hoskins  sulfur  compounds  has  transfer commonly  gestation  (Hansard,  and  are  of  of  1968b)  placental  elements  approach  transfer  Mohammed,  in  uptake  H i d i r o g l o u et in  the  labelled  stages  This  (Hoskins and  trace radio  placental  placental  animals  al.  1965)  differences The  well  rates as  of the  40  contribution as  well  fetal the  of  as  the  placenta  the  nutrition measured  can  be  for  studies  arterial  concentration  Furthermore, fetus  trace  the  this  are  from  be  may n o t  umbilical  of  the  employed.  the  established  be  veno-  below  techniques  normalcy to  animals  are  analytical  be to  method  whose  can  placenta  conscious  minerals  have  nutrition  the  differences  surgery  experiments  in  However  physiological  following  metabolic  on  of  the  of  determined  parameters.  limit  fetal  contribution  suitable  detection  to  ewe  and  before  the  conducted.  75  F)  Se  metabolism  a)Placental  in  the  pregnant  mother  and  in  the  transfer;  75 The use of radio labelled Se f a c i l i t a t e d the study of Se m e t a b o l i s m  as in  mother  transfer  was  and  first  fetus;  in  the  fetus.  observed  The p l a c e n t a l  by M c C o n n e l l  and Roth  selenite has the pregnant  (1964)  75  of in  Se  dogs. 75  They  found  selenite  to  suggesting was  also  bitch  that the  milk  to  reported  for  a period  incorporated pregnancy (1964)  Se  in  into  lactating be  a  that of the  (McConnell their  administered  bitch  source Se  236  subcutaneously  was d  of  Se  of  and  Roth,  studies  with  present  for  retained  after  tissues  was  in  tracer  the  the  ewes  fed  Se-  in  milk  neonate.  the  tissues  injection  pup b o r n  1964).  as  in  Wright Se  and  It of was  subsequent and  deficient  Bell hay  41  with  or  without  a  Se  supplement  demonstrated  the  transfer  of  75 Se  across  the  placenta.  They observed  that  the  total  75 kidney Se  Se  content  deficient  receiving was  ration  the  lower.  from twin  50% The  and  did  a  (McConnell Jacobsson Buck  et  to  fetal for  not  greater  of  Se  the  in  of  a  the  the  liver  for  the  of  Se  Wright  In  contrast  al.  1964;  1969;  passage  these  to  tissues  suggested the  to  found  Bell,  observations for  the  reported  were  and  the  across  fetal  H i d i r o g l o u et  barrier  also to  have  than  single  They  general  Se  the  dose/g)  tocopherol 75  workers  ewe i n 75  These  from  was  alpha  ewes  contain  of  12:1  a  content  (%  fetuses.  of  placental  from  activity  passage  1964;  sheep.  those  Se  the  1966;  consuming  to  of  amount  1981).  presence  though  Several  Roth,  al.  in  twin  affect  and Oksanen,  than  plasma  the  f r o m ewes  f e t u s e s were f o u n d 75 Se as tissues  addition  tissues  and  75  of  membranes.  maternal  contain  much  ratio  that  ration  placental that  as  22:1  demonstrated  ewe's  higher  Tissues  maternal  fetuses  was  fetuses  supplement,  singletons. the  the  Se  approximately  in  in  and the of  findings,  75 Hansson  and J a c o b s s o n  uptake  in  found and  equal  fetal  barrier due  the  to  different  pregnant  distribution  tissues  in  the  studied  mouse of  in  the  lack  of  a  the  or  with  autoradiography  tracer  The c o n f l i c t i n g  differences  intakes  Se-selenomethionine  using the  demonstrating  mouse.  species Se  (1966)  observations  regard  differential  to  and  maternal placental may  be  placentation,  placental  transfer  42  between  organic  and  inorganic  Se  sources.  In  75 another be  study  actively  gradient influx of  Se-selenomethionine  to  of  an  transported  the  tracer  human  fetus  from  mother  instantaneous  placental  function  Buck  et  against from to  al.  the fetus  measure  (Garrow,  was  of  reported a  concentration  mother's  blood.  was  as  used  fetal  to  The  an  growth  index  rate  and  1971).  (1981)  demonstrated  a  preferential  75 accumulation luteum, ewe  and  fetus Se.  of  in  the  is In  catheterized  the  maternal  al.  in  lambs 75  rapidly  The  in  pregnant  for  muscle  established.  achieved  the  of  pregnant  both  these  ewe  and  tissues  for  that  Se-selenite  in  using  they  corpus  either  chronically  demonstrated  the  the  either  to  respective  that  the fetal  ewe or  circulations. selenium  against  as  reported  study  entered  of  white  of  Se-selenite  b)Concentrations need  to  utero  administered  fetus  of  (1984) 75  permeable an  tissues  and placentome  requirement  et  fetal  intravenously  reproductive  and p i t u i t a r y g l a n d s  a normal  Shariff  placenta  such  ovary  adrenal  suggesting  direction.  or  in  non-luteal  Recently  sheep  Se  the  Se  disease In  in  following  maternal  animals  their  studies  congenital  in  form  for  fetal  the  offspring  with of  and  cattle, white  administration  of  prevention has  good  muscle Se  to  tissues;  been  of well  protection disease  pregnant  was cows  43  in  late  gestation  Hidiroglou either  et  al.  al.  selenate  successful white  in  muscle 1962  reported  the  maternal  liver ppm) and  hay.  the  0.036  of  that  Se  of  more  and  injection  of  ewes or 1961;  Burton et  to  in  pregnant  both  0.360  tissues  an  ewes  maternal  (0.650,  et al.  following  that  Se  was juvenile  Hidiroglou  Se  fetal  fed  kidney,  and  0.050  (0.214,  0.174  respectively.  workers  white  (Hartley  muscle  disease  and o f t e n  or  shortly  after  reported  that  juvenile  tissues was  al.  tissues  found  disease  disease  1964;  concentrations  6 mg  congenital died  al.  pregnant  1963).  They  et  congenital  fetal  contained  Zealand  observed  to  (Young et  al.  corresponding  ppm)  New  lambs  and  Nelson  Subcutaneous  the  increased  and muscle than  in  injection  deficient  1963;  selenite  Hamdy e t  intramuscular  al.  preventing  disease  and  et  1965).  or  (1969)  Se  (Mace  Se  lambs  in  animals  significantly  in  sheep  were  birth.  concentration of  and G r a n t ,  either  (1967)  exhibiting that  sheep  fed  a  stillborn  maternal,  than  have  o c c u r r e d as  Hartley the  lower  1961)  fetal  white of  also and  muscle unaffected  ones.  A  comparison  dystrophogenic and  their  former  hay  between showed  offspring  group  than  were in  the  that  the  about latter  tissue three  normal  Se  levels  fold  (Burton  et  higher al.  versus of  ewes  in  the  1962).  44  Following  supplementation  dystrophogenic similar  to  hay,  of  prevented.  Burton  diet  of  the  normal  retained  ewes  fed  with  Se  would by  the the  Weiss  et  selenite  daily  in  blood  from  observed  were  on  almost hay  and  offspring  also  observed  from  Se  was that  Se  injected  those  of  ewes  have  reported  of  storage  ewes  given  that  levels  (1982)  a  and  of  similar  adequate  Se  1 mg  cows.  calves Roller  in  beef  injected they  the  fetus of  Se  Hidiroglou  et  al.  Se  at  in  an  incidence  of  birth.  Se  supplementation  or  at  pellet  resulted  5 mg  concentrations  heifer  response  that  is  supply  cows  calves  reported  the  of  a decreased  in  Se  pregnant  hay were  capacity  dairy  cows w i t h  increased  when  intraruminal  dystrophy  serum  use  that  Furthermore,  Recently  pregnant  dairy  future  breeding.  fetus.  Se  al.  for  disease-producing  unsupplemented a  in  continuing  muscular  pregnant  the  a  to  plasma  nutritional  the  fetuses  tissues  reported  administration increased  in  (1969)  limited  developing have  of  levels  ewes  nondystrophogenic  (1962)  al.  time  necessitate  (1985)  those  et  muscle  that  the  of  tissues  fetal  white  suggested  al.  pregnant  hay.  in  at  to Se  NMD  concentration  Hidiroglou not  consuming  et  in  Se  tissue  congenital  concentration approached  the  those  occurrence  of  calves  sodium  significantly  birth et  of  compared  al. born  to  (1984b) to  cows  45  that  r e c e i v e d Se. A t b i r t h  0 . 2 4 2 mg/kg o f  Se i n t h e i r  from untreated  cows  whole  Itano  blood.  levels They in  that  liver  (1984)  different  methods  distribution  contained  (1985)  of  and  Se  that both  greater  injection  Se  dependent  and f e t a l  has  been  a l .  Se  concentrations  (Whanger 1979).  calves  et  i n  the  supplementaion dairy  treatments  whose  on  cows.  They  raised  the  Se l e v e l s  dams  of  at  birth  r e c e i v e d Se  by  supplementation.  shown  Flohe  tissue  higher  peroxidase  activity  i n  an i n t e g r a l  component  of  tissues;  peroxidase  between  Se  Se c o n c e n t r a t i o n s .  Serum  glutathione  glutathione et  was  whereas  o f Se  and i n j e c t i o n  for  the  investigated thee f f e c t s  amounts  b u tn o tby o r a l  c)Selenium maternal  only  their  tissues,  s e r u m Se c o n c e n t r a t i o n s o f cows. were  mg S e / k g i n  and s u c k l i n g stages.  i n periparturient  oral  those  examined  higher  cows h a d to  i n the fetuses  other  and Perry  treated compared  0.081  dolphin at fetal  to  t h eblubber  de T o l e d o  observed  had only  t h a t t h e Se l e v e l compared  sucklings  whole blood  et a l .  i nthestriped  found  the c a l v e s from  (GSH-Px)  1973). Se  t o be  (Rotruck  Highly  dependent  i n cattle  significant GSH-Px  and  a l . 1977; A n d e r s o n  Measurement  of  et  a l .  correlations  activity  sheep  were  et  a l . 1978;  GSH-Px a c t i v i t y  1973,  and  blood  established Paynter,  has therefore  been  46  recommended et  for assessing  i nanimals  (Whanger  a l . 1978) .  Roller levels They  i npregnant  blood  compared mll/mg  a l . (1984b)  et  reported  higher  beef  that  Se  GSH-Px  Hb)  higher  the  untreated  and t h e i r  activities  (144  a n d 154  (134  and  born  from  (1978)  Wong  human f e t u s  was  significantly  was p r o b a b l y  protection  glutathione  et  activity  against  peroxidase  a l . 1969;  liver  mechanism  of this  The  (30  et  Hb)  and  50  (1985)  a l .  activity at  birth  those  Emerson  isolation,  lower  from  than  dependent  and plasma  adult.  thelow a c t i v i t y of this  enzyme  t o a low requirement  i n new  to adults et  an  stress. born  Erythrocyte infants  Low  reported related  (Pinto and B a r t l e y ,  was 1967;  (Gross e t a l .  a l . 1972).  age  purification  i n  of  the  age h a s been  suggesting  Se  i n redc e l l s  activity  enzyme  that  theantioxidant  increasing with  neonatal  had  mll/mg o f  cows t h a n  an a d a p t a t i o n  t o be l o w i n c o m p a r i s o n  Bracci  found  activity  t o these workers,  the fetus  treated  calves  calves  GSH-Px  birth.  I U / g Hb v s 29 I U / g H b ) .  peroxidase  found  cows a n d t h e i r  theblood  GSH-Px  offspring at  cows  glutathione  According  and t h e i r  theblood  treated  that  i n calves  Rudolph  measured  respectively. Hidiroglou  reported  was  for  cows  t o theuntreated  of  recently  in  t h e Se s t a t u s  GSH-Px  i n  the  developmental 1977).  and k i n e t i c  properties  47  of  G S H - P x f r o m human p l a c e n t a  et  a l . (1979).  reported  that  was c a r r i e d and  not  GSH  fetus  electrophilic  drugs  a s GSH  have  thelevels  shown t h a t i nthefetal  Klassan, that not  b y Se d e p e n d e n t GSH-Px another  activity.  lung  suggested  Se  damage t o t h e f e t u s  CONCLUSIONS  than  injury  by  both  workers were  very  and Bresnick,  1976;  This  would  suggest  will  probably  added p r o t e c t i o n t o Thus  i t  c a n cause  the  fetus  has  been  more  oxidant  t o the neonate.  FROM THE L I T E R A T U R E R E V I E W :  From t h e f o r e g o i n g that  normal  Several  o f GSH S - t r a n s f e r a s e  deficiency  of  peroxides,  was a f f o r d e d  (Mukhtar  hydro-peroxides.  that  Under  o f GSH S - t r a n s f e r a s e s  be a v a i l a b l e t o p r o v i d e toxic  group  hydroperoxides,  and l i v e r  alone  the antioxidant  S-transferases.  t h e GSH-Px a c t i v i t y  there  aspects  nonpregnant  sheep.  data  with  transplacentally  survey  i s a  quantitative  available  lipids  1975 a n d P e g g a n d H o o k , 1 9 7 7 ) .  against  seen  of  and x e n o b i o t i c s  GSH-Px a s w e l l  low  o f hydroperoxides  against  from  Awasthi (1981)  S-transferases,  theprotection  by Dao  Awasthi  e x h i b i t e d GSH-Px l i k e  the  reported and  study  out i ntheplacenta by  conditions  later  thedecomposition  enzymes w h i c h  to  In a  have been  paucity  o f Se To regard  of theliterature of  metabolism be  more  information  specific  ewe  on  the  i n thepregnant and there  t o t h e a m o u n t s o f Se  from t h epregnant  i t c o u l d be  to  the  i s no  transported fetus  or  48  vice  versa  supply.  Besides  literature either  under  there  on  in  conditions  the  the  is  no  of  information  kinetic  pregnant  adequate  aspects  ewe  or  the  or  deficit  available  of  Se  growing  Se  in  the  metabolism  fetus  showing  75 quantitative  Se  exchangeable  is  Although  some  studies  on  lambs  the  pregnant  availability aimed under  at  Se  in  deficient  adequate  are or  not  her  or  in  to  in  this  from  ewes.  slaughter ewe  and  explain  how  to  changing  the  role  reports of  either  are  Se not  the  placenta  conditions.  These  background thesis  and p r e g n a n t  such  pregnant  these  deficient  the  nonpregnant  the  adapts  possible  the  reported  rations.  Se  Furthermore  provided  nonpregnant  fetus  the  in no  mostly  they  adequate  experiments  the  available  situations.  the  the  of  mother  observations  for  distribution  elucidating  Se  the  are  turnover  Similarly  available data  the  fetal  and  compartments.  information  the  uptake  ewes  on  for the  fed  Se  undertaking metabolism  of  positive  or  49  CHAPTER EXPERIMENT  II; I;  SELENIUM  Kinetics  ewes  fed  Se  METABOLISM IN  of  selenium  positive  or  NONPREGNANT  metabolism  deficient  in  EWES.  nonpregnant  rations.  INTRODUCTION  Selenium sheep  of  (Wright  et  et  1967; al.  al. Muth  that  regulating  adequate  to  investigate  at  two  al.  following  there  early  been  investigated  states  such  et  et  finding  of  A  of  Se  lactation  al.  1965;  to  and  Muth  et  study  with  et  Langlands  al.  (1967)  are  involved  ewes  improve  tissue  intake  Ehlig  1979;  knowledge  present  body  1969),  nonpregnant  necessary the  pregnancy  mechanisms  rations.  whole  levels  in  in  as  (Wright,  homeostatic  is  al.  Pope  metabolism  the  fed of  Se  these  Se  utilization  was  undertaken  metabolism  a view  to  of  Se  address  questions:  any  metabolism when  1967;  Therefore,  different  tissues  and growth  several  animal.  Se  1966)  mechanisms  the  of  Hidiroglou  deficient  by  (a) A r e  1964;  The  Se  or  regulatory  the  et  1986).  indicated in  has  varying physiological  and B e l l ,  (Paulson al.  metabolism  ewes  differences in are  the fed  Se  in  whole  the body  positive  or  kinetic  parameters  and  individual  in  deficient  rations?  and  (b) Is  there  a difference  in  the  absorption,  excretion  and  50  retention  of  Se  in  ewes  at  these  MATERIALS  (a)Animals  nonpregnant  59  +  study.  They  animals  in  ration  The  alfalfa  The in  grass of  and  Se  (0.1 BCMAF hay  mesh  mixed Feed  hays  mg  II)  in  this  with  four  a  deficient  I)  were to  at  be  been feed  five  different  15.8%  and  a  suggestion (BCMAF)  local  that 9.7%  farmer  problems  supplementing  Se  at  advice  of  samples  of  the  occasions  ground to  showed  canary  Food's  Random  t h o r o u g h l y and a l i q u o t s were  deficient  experiencing  had the  (1978).  hay  the  fed  provide  (95%  Kelowna from  to  in  fed hay  and  livestock.  contained  or  were  his  Feed a n a l y s i s  used  Se/kg,  deficient  farmer  samples  crossbred)  groups  (Group  Agriculture  selenite  on  were  two  purchased  reported  to  collected  screen.  deficient  intake?  NRC r e c o m m e n d a t i o n s  was  The  sodium  officials  analysis.  Se  Suffolk  positive  0.15  laboratory,  were  to  ewes  (Group  of  X  SEM)  Se  T h e Se  timothy)  analysis  experiment,  a  per  ewes  deficiency.  were  as  Ministry  as  fed  containing  mg S e / k g ) .  5%  +  positive  cubes,  livestock  ppm)  (mean  and were  deficient  (<0.01  (Dorset  randomly a l l o t t e d  protein  nutritional  of  of  AND METHODS  ewes  kg  Se  B.C.  whose  were  each  and  Se Se  6  hay  energy  levels  and Management;  Eight weighing  two  were pass  the  taken  for  Se  through  1  mm  the  Se  alfalfa of  during  and  crude  protein  51  respectively KJ/g).  Ewes  Se/ml)  and  with in  similar  both  groups  iodized  approximately ewes were  a  for  shorn  individual  block six  (b)Isotopic  One  tracer  day  were  to  ad  eight to  energy  separate  to  the  tracer  Parsippany,  N.J.)  implanted  were  injection  dose  of  ng fed  rations  the  cages  for  experiment,  both  Clay  jugular  and w i t h d r a w a l  approximately  (30  studies;  "PE-90", in  (17.6  being  metabolism  balance  Se  (Intramedic  bolus  these  experiments  catheters  A  on  studies.  and  water  After  and d i g e s t i b i l i t y  prior  tracer  lib.  weeks  polyethylene  facilitate  concentration  provided with  salt  a n d moved  feeding  gross  of  two Adams,  veins  to  blood.  200  uCi  (specific  75 activity;  187-919  chemicals,  Irvine,  jugular  vein.  jugular  vein  300,  360  Blood  mCi/mg  2,  5,  samples  plasma  A  samples 10,  were  heparin  was  stored  five  day  15,  -20  o  from  each  group  (Group I;  II:  ewes  998,  123  injected  45, once  in  C until  trial ewe  325)  in  Se  was  nos.  into  60,  120,  daily  the  180,  240,  thereafter. pyrex  were  conducted 99  conjunction  left right  tubes  immediately.  analyses  65,  (ICN  from the  chilled  centrifuged  balance  and  30,  placed  Se-selenite  withdrawn  and  and  at  Se  sodium  were  min p o s t i n j e c t i o n  containing  of  C a l i f o r n i a ) was  Blood at  Se)  on  and with  , The  performed.  three 100; the  ewes Group  tracer  52  experiment. of  tracer  every  The b a l a n c e  injection.  day.  Feed  Daily  measured  and  studies  were  commenced  and water  fecal  and  representative  intakes  were  urinary  aliquots  on  the  recorded  voids  of  the  day  were  same  were  o  collected  and  stored  One  ewe  from  and  999),  5  and  325)  -20  each  (65  and  998), by  Pharmaceuticals  were  C.  g r o u p was  postinjection  (Hoechst ewes  at  towel  9  (99  Ltd),  an  and  dried,  and  on d a y s  123)  administer-ing  dissected  collected,  sacrificed  weighed  20  1  (622  and  14  (100  ml  of  T-61  euthanasia  solution.  The  individual  tissues  were  and  stored  in  double  sealed  o  plastic  containers  carried  out.  (c)Analytical  at  -20  C  until  the  Se  analyses  were  methods:  75 The  plasma  automatic  gamma c o u n t e r  efficiency  of  Plasma duplicate  added  to  counted  ( P a c k a r d model  500)  with  hydride  as  per  the  10  ml  Briefly, 6^2° 2  was  concentration  using  MgfNOj^-  radioactivity  a  in  an  counting  86%. Se  spectrometry (1982).  Se  ml  dissolved of  was  generation method of in  plasma  ashing 200  ml  samples  determined atomic  of aid of  Tam (8  absorption and  Lacroix  g MgO a n d  deionized (in  in  80  water)  duplicate)  in  g  were an  53  acid  washed  glass  beaker  and  thoroughly  mixed.  The  n  and  the  contents  were  covered  with  a  beaker  II  3  X 3  piece  of c  aluminum  foil  C in  a hot  cold  muffle  (with  air  holes  oven.  furnace  on  it)  and d r i e d  The b e a k e r s and  the  were  contents  overnight  then were  at  110  transferred ashed  to  a  overnight  o  by  slowly  sample ml)  was  was  boiling  in  on  selenate an  to  35  ml  hot  with  6  (with  only  carried  the  samples.  ml  which  of  solutions  were  standardized  to by  liver.  The d e t e c t i o n  inter-  and  based  560).  on  limit a  intra-assay  (3  10  1,  above of  g  and  ppm o f along  sample of  Se  NaBH^  was in  selenide,  spectrophotometry and  standard  The method  against  the  1577  X standard  coefficients  and  100  hydrogen  Blank  sample  the  duplicate  digested g  to  diluted  procedures  gaseous  material  were  transferred  10,  (3  (5  heated  solution)  same m a n n e r .  reference  water  reduce  were  absorption  laboratory  Standards  0.1,  solution  the  was  flask  aid  ashed  contents  to  contents  aliquot  generate  in  The  Simultaneously,  the  ml  the  minutes  (containing  model  our  solution  ashing  atomic  treated  in  of  1% N a B H ^  of  sample)  ml  C.  Deionized  The  the  HCl.  500  then  volumetric  N  of  to  and  20-30  Then ml  Bureau  blank  for  One  analyzed Elmer,  HCl.  through  3 ml  (Perkin  ash  6 N  10  1% NaOH)  was  the  duplicate  were  with  temperature.  selenite.  volume  treated  room  plate  50  with  temperature  of  washed  in  the  wet  acid  standards  300  a  to  to  to  blanks  Se)  cooled  added  dissolved  to  raising  National the  deviation  was of  for  was  bovine of  5 ppb. variation  the The for  54  Se  determination  12%)  were  13%  (range  mesh  fecal  pellets  screen.  were  ground to  A representative 75  used  for  ml)  determining  Se.  measured.  samples  was  taken  and  saline  (0.9%  contamination  from  concentrations feed  the  in  samples  method  urine  of which  fecal  with  150°  C,  until  samples  during  (d)  g)  Se  blotted ml),  were  of  d r y and  any  8-  a  1  mm  1  g  was  (2  and to  of  tissue  physiological  g),  tissues  duplicate  (1982)  ii)  of  were  Se (1  as  with  loss  g) per  minor  feed  heating  prevent  concentrations  external  counted.  pre-wetting  water  urine  then  in  Lacroix  fluffy,  Se  g  in  d r y and  i)  1  in  possible  determined  included deionized  radioactivity  feces  and  ashing.  sample  thoroughly  remove  (2  Tarn  modifications samples  to  blood,  (2  through  Approximately  rinsed  NaCl),  pass  fecal  The  also  wet  (range  75  was  and  a n d 10%  respectively.  The  (1  10-15%)  and  them of  to  these  expressed  on  a  basis.  Data  The time  analysis  plasma  point  and  75  were  calculations;  Se  specific  expressed  activity  as  a  data  fraction  at  each  of  initial  Se  specific  75 dose  injected  activity-time using  the  Wagner,  per  microgram Se.  data  curve 1976).  were  peeling The  The p l a s m a  fitted computer  goodness  to  exponential  program, of  fit  AUTOAN of  the  equations (Sedman  and  exponential  55  equations  to  evaluated  75  plasma  based  on  Se  (i)the  specific squared  activity  data,  correlation  was  coefficient  2 (R  ) values  and  calculated  as  (ii)  per  the  S  S A  The  D  S  est  exponential  75  plasma  ™ Estimated  75  plasma  equations  the  overall  fit,  formula. ( S A  " Observed  A 0  following  for  -  F  where  "F" values,  obs  "  est>  S A  Se  specific  activity  Se  specific  activity  with  minimal  "F" values  2  and  2 with  the  R  values  equations.  The  calculated  by  The  of  disposal  /  o>  kinetic  from  primary  to  Se  fit were  infinity. for  the  metabolism.  (Shipley J "  -  Area  under  S.A.  the  -  Normalized  B.W.  -  Body w e i g h t  labelled  of  best  curves  used  «=  1  I.D.  time  the  1  activity-time  The  as  exponential  were  rate  (dt)  chosen  zero  parameters  B.W.)  S.A.  the  equations  (I.D.)  Se/d/kg  1 were  under  integration  i)Irreversible  (ug  areas  following  estimation  of  approaching  is pool  the  rate  which  (dt)  plasma  and  Clark,1972)  75  Se  specific  curve  dose (normalized  of does  to  loss  of  not  return  70  kg).  material to  it  from  a  during  56  the  course  Clark,  of  the  1972).  been  assumed  pool  as  In  to  blood  be  tracer  the the  plasma  experiment  present  tracee which  ie.  study stable  has  been  (Shipley  the  Se,  and  material  and  the  labelled  has  primary  with  ^Se-  selenite.  1 ii)  Pool  size (ug  (P.S)  -  (White  2  Se)  i=i  et  al.  1969)  (A. ) 1  75 where  A -  Zero  i  -  exponential  n  = number o f  exponential  quantity  unlabelled  The a  pool  In  the  amount  iii)  is  of  stable  Plasma rate  of  of no  equivalent  Se  in  material size size  the  (tracee)  (White  et  refers  blood  present  al.  to  in  1969).  the  total  plasma.  = Plasma  clearance plasma  relates  activity  I.D.  B.W.)  volume  specific  components  pool  present  Se number  pool  the  (P.C.R)  plasma  volume  the  study  of  component  clearance  (ml/d/kg  Although  intercept  known a s  current  The  time  is  rate  Se  can  be  Clark,  1972)  defined  cleared  literally  cleared,  volume  and  Cone.  nominally  the  (Shipley  per  which,  a  as unit  the time.  mathematical at  the  57  existing solute the  concentration  corresponding  specified  (Shipley  iv)  Clark,  Volume of bution  The of  is  present  study Se  The  as as was  distri-  mean  as  The using slight  total the  following  the  entire  per  et  volume  75  fecal  from  unit  time  Se 75  the  al.  to  material  al.  1969)  the  total  (tracee  1969). containing  or  In  the  all  the  distribution.  losses  Se  dose  refers  volume of  of  Body wt.  et  per  day  injected.  standard  were  calculated  and  Stable  expressed Se  nutritional  balance methods  1969).  endogenous  the  lost  (White  cone.  plasma  initial  and L o o s l i ,  Se  (White  excretion  calculated  per  of  1  distribution  i n which  and  the  amount  X  of  the  of  (Maynard  plasma)  size  Plasma  constitutes  fraction  an  irreversibly  blood  Pool  present  daily  quantity  =  pool  urinary  contains  1972).  volume  tracer)  stable  the  B.W.)  the  solute,  (e.g.,  (V.D.)  (ml/kg  volume  to  volume  and  of  fecal equation  modification  which  Se of  losses  Hansard  included  were  et  al.  use  of  calculated (1957) the  with areas  75 under curves  the (5  equation  fecal d)  as  and  plasma  numerator  respectively  Se and  instead  specific denominator of  mean  activity-time of  the specific  58  activities  of  Endogenous fecal loss  Se  the  last  two  days  of  the  AUC-Feces  Sp.  Act-time  balance  curve  (5d)  =  Average X daily  (ug/d)  where  trial.  AUC-Plasma  the  Sp.  specific  Act-time  activity  curve  of  (5d)  feces  fecal  Se  loss  and plasma  are  75 fractions  of  represents  The  the  1,  tissues  5,  9  determining  data  constants one  as  were 14  as  economy  it  was  provide  an  approximate  The was  total  derived  weight  of  skeletal weight  as  assumed  the  pool  activity fitted  the  values  that  the  turnover  (1977).  were  time  tissue.  of  Se  in  the Se  assumed  of  the  the  to  total 40%  rate  Though  curve  of  would  tissues.  individual  be  The  reasons  concentration The  on  activity-  derived. for  in  and  fractional  point  slope  organ/tissue. was  total  the  each  ewes  administration  and  the  Arnal  in  the  tissues  by m u l t i p l y i n g  tissue  sacrificing  specific  in  whole  AUC  utilization  the  at  of  Se  to  Se  muscle per  by  of  tracer  the  sacrificed  and  curve.  after  were  microgram Se,  constants  individual  well  per  obtained  specific  the  a n i m a l was  the  rate  equations of  dose  under  and  the  exponential time  area  Se  fractional  individual day  the  tissues with  weight of  of  the  the the body  59  Statistical  All were  analysis:  results  subjected  were  to  one  significance  of  by  't'test  Student's  the were  correlation  expressed way  difference (SAS,  the  means  analysis between 1985).  coefficients  c a l c u l a t e d by  as  the  variance  means  was  The r e g r e s s i o n  between  method o f  of  + SEM.  least  selected squares.  The and  data the  assessed lines  and  parameters  60  RESULTS  The 142  +  plasma Se c o n c e n t r a t i o n i n the Se p o s i t i v e ewes was 6  ng/ml, which  than i n the linear  (82 +  d e f i c i e n t ones (r=0.90)  relationship  (P <  was s i g n i f i c a n t l y higher 10 ng/ml).  A  0.01)  positive  between the Se i n t a k e and  plasma Se c o n c e n t r a t i o n was observed  (Fig.  the  1).  75  The first  plasma  24  Se  hr a f t e r  s p e c i f i c a c t i v i t y changes d u r i n g  tracer  injection  d e f i c i e n t ewes are d e p i c t e d p o s i t i v e ewes from  the  (Fig.  plasma  2)  in  an i n c r e a s e  i n the  gradually  2 and 3.  an  exponential  injection.  Se  initially  fashion  This  and  In the  t r a c e r disappeared  until  was  followed  plasma r a d i o a c t i v i t y which reached 4 hr p o s t i n j e c t i o n  peak a t approximately declining  Figs.  positive  the  approximately 1 hr a f t e r by  in  i n t o Se  the  over  several  days.  before At  finally  the peak  of  reappearance the r a d i o a c t i v i t y was 44% of that present at min  a t which time the  A similar pattern 3)  except  first  sample of blood was  was observed  that  the  r a d i o a c t i v i t y occurred a t 3 hr  2  collected.  i n Se d e f i c i e n t ewes  maximum  a  reappearance  (Fig. of  and was 49% of the  the  activity  present i n the 2 min plasma sample. The  best f i t plasma s p e c i f i c  Se  positive  and d e f i c i e n t  and  5 respectively.  The  ewes  activity-time are  shown  in  e x p o n e n t i a l equations  curves  of  Figs.  4  describing  61  160-1  140C  O C  120-  o  in  ^  IOO  80-  600  200  400  600  Se intake (pg/d)  F i g . 1. E f f e c t o f Se i n t a k e o n p l a s m a Se concentration i n n o n p r e g n a n t e w e s f e d Se p o s i t i v e ( A ) o r d e f i c i e n t (A) r a t i o n s . The r e g r e s s i o n e q u a t i o n i s Y * 79.84 + 0.13 x and r - 0 . 9 0 .  F i g . 2. Changes in plasma Se specific activity during first 24 h r after tracer i n j e c t i o n i n t o Se p o s i t i v e n o n p r e g n a n t e w e s . • , O i • » • r e f e r t o ewe nos. 6 2 2 , 6 5 , 100 a n d 99 respectively.  Fra. = Fraction  in  6 CD  o . o o o i - l  0  1  1  10  20  30  Time (Hours) F i g . 3. Changes in plasma Se specific activity during first 24 h r after tracer i n j e c t i o n i n t o Se d e f i c i e n t n o n p r e g n a n t e w e s . 9, O, u, • refer to ewe n o s . 9 9 9 , 9 9 8 , 325 a n d 123 respectively.  64  0.01 0) m  CO  CU  0.0001-f 0  1 20  1 40  1 60  Time (Hours)  — 80  F i g . 4. B e s t - f i t plasma Se specific activity-time curves of Se positive n o n p r e g n a n t e w e s . # , O, •» • r e f e r t o ewe n o s . 6 2 2 , 6 5 , 100 a n d 99 respectively. 7 5  65  O.OOOH  0  20  40 60  Time (Hours)  F i g . 5. B e s t - f i t plasma Se specific activity-time curves of Se deficient n o n p r e g n a n t e w e s . • , O, • , • r e f e r t o ewe n o s . 9 9 9 , 9 9 8 , 325 a n d 123 respectively. 7 5  Table  1.  B e s t - f i t exponential equations of plasma Se s p e c i f i c c u r v e s o f Se p o s i t i v e a n d d e f i c i e n t n o n p r e g n a n t e w e s .  Animal  Se  Se  #  A  positive  where  A  2  A  3  a  l  a  2  622  .000770  .000413  8 .5672  .0126  65  .004078  .000743  22 . 8 0 8 4  .0096  99  .000487  .000343  6 .2382  .0071  100  .001064  .000408  6 .6930  .0052  999  .005010  .002867  7 .0774  .0202  998  .003329  .002562  13 . 2 3 1 6  .0100  123  .005357  .002187  8 .6335  .0047  325  .000956  .000431  9 .3205  .0372  3  ewes • •  equation  is:  A -  plasma  a  rate  -  a  ewes:  deficient  *The  l  activity-time  a A  t Se  "  A  l  fc  1  e  specific  constant,  e -  .000281  + A e 2 +  A  -a  t 2  e  activity log  1  n  and  A e  -a  3  +  (fraction t  -  time  .0012  t 3  of  ' injected  (hr).  dose/ug  Se),  67  these curves are summarized i n were all  Required ewes  to  except  Table 1.  Two  exponentials  f i t the plasma s p e c i f i c a c t i v i t y data i n  in  one,  (#325)  which  required  three  75 exponentials. in  The plasma  Se clearance  a l l animals except ewe #325.  i s based blood  on the assumption  (pool  distributed  a) into  t r a c e r leaves  kinetics.  The  values of  and  (pool b) i n i t i a l l y .  the system  and d e f i c i e n t ewes were 1.95 respectively  The two pool k i n e t i c model  instantaneously  tissues  while the  biphasic  that the t r a c e r i n j e c t e d i n t o the  mixes the  was thus  obeying  gets After a  first'  plasma Se i n the Se + 0.44 d and 2.02  +  order positive 0.28  d  (Table 2 ) . 75  The  areas  under  the  plasma  Se s p e c i f i c a c t i v i t y -  time curves and the k i n e t i c  parameters of Se metabolism  the  in  ewes  higher  are  presented  irreversible  disposal  plasma Se c l e a r a n c e (P <^ 0.05) 0.10)  were  observed  d e f i c i e n t ones.  Table  in  of  2. Se  in  Significantly (P  _<  0.05),  and plasma Se pool s i z e Se p o s i t i v e ewes  (P<  than i n the  On the other hand the area under the plasma  75 Se  s p e c i f i c a c t i v i t y - t i m e curves was s i g n i f i c a n t l y higher  (P < 0.05)  i n the Se  d e f i c i e n t ewes than  i n the  positive  ones. The metabolic parameters of Se intake and e x c r e t i o n are g i v e n i n Table  3.  The Se intake  was s i g n i f i c a n t l y ( P  0.01) higher i n Se p o s i t i v e ewes (459 + 53 ug :  <  mean + SEM)  Table  2.  Comparison of areas under and k i n e t i c parameters o f  Se  positive  t h e c u r v e s ( A U C ) , p l a s m a Se c o n c e n t r a t i o n s Se p o s i t i v e a n d d e f i c i e n t n o n p r e g n a n t ewes.  ewes  (n»4)  Se d e f i c i e n t  ewes  Parameter Mean + S . E . M  AUC (Fraction of dose/ug Plasma  Se  0.06 Se).  Cone,  Irreversible Disposal Se ( u g S e / d / k g B . W . )  P l a s m a Se (ug Se)  Pool  142°  of  7  Rate  Size  47  734  l/2  (  d  e  r  a  a  e  1.95  )  Means w i t h i n t h e ' P < 0.10).  0.28  rows  + 6  82  + 2  2  + 10  19  + 207  258  72 + 18  Volume o f d i s t r i b u t i o n (ml/kg B.W.) T  + 0.01  b  + S.E.M + 0.07  hr (ng/ml)  Plasma Clearance (ml/d/kg B.W.)  a  Mean  differ  b  b  f  40  + 0.44  significantly(  d  2.02  a , b  P  < 0.05;  c  ,  d  P  + 10 + 0.3 + 5  + 229 + 12  + 0.28  <  0.01;  (n-4)  69  Table  3.  A b s o r p t i o n a n d r e t e n t i o n o f Se i n n o n p r e g n a n t f e d Se p o s i t i v e o r d e f i c i e n t rations.  Se Parameter  Se  intake  Fecal  Se  (ug/d) loss  (ug/d)  Endogenous f e c a l loss (ug/d) Urinary  p o s i t i v e ewes ( n - =3) Mean + S . E . M  Se  Se  loss  459  a  272  a  46  (ug/d)  Se  ewes  deficient ewes (n-3) Mean + S . E . M  + 53  44  b  + 48  25  b  + 5 + 6  + 6  24  + 9  6  d  + 1  b  + 11  35  c  + 7  186  a  + 36  20  + 7  40  + 41  44  b  + 8  97  f  + 16  152°  + 35  13  d  + 13  rows  differ  * Apparent  Se  absorption  (a)estimated (b)% Net  of Se  Se  (ug/d)  of  N e t Se (ug/d)  '  '  ( ' P a  b  Se  ®Se  (ug/d)  232  intake  51  balance^  Means w i t h i n < 0.01;  *Apparent *Net  + 20  absorption  (a)estimated (b)%  41  intake  Se  c  ,  d  P  < 0.05;  absorption  absorption=Se balance  the  = Se  ,  = Se  intake  intake  e  -  -  a  e  f  P  <  Fecal  Se  significantly  0.10).  intake (Fecal  + 11  -  Fecal  Se  loss.  loss  -  Endogenous  loss  -  Urinary  Se  Se  loss).  loss.  70  than  in  the  deficient  Measurement o f Se approximately while hay  in  higher  ones.  and u r i n e  intake  in  SEM).  30% f r o m  that water,  Se i n t a k e was  two  fecal  fold  higher  higher  from  expressed  of  as  £ 0.01) i n  ug/d  t h e Se  whereas,  deficient  was f o u n d  on  inverse  a  per  than the  Se linear  positive was  deficient  ones i t was n o t apparent  (P  _< 0.01)  expressed  Se  Se  in  absorption  the  higher  (P <^ 0.10) n e t  Se Se  low i n Se p o s i t i v e ewes,  whereas  i t was  At higher  (P  deficient  intake b a s i s the  higher  ones.  ones,  intakes  ewes  (Fig. 6).  net  was  Se  relationship  Se a b s o r p t i o n  ewes  t o be s i g n i f i c a n t l y  cent  Though  i n the d e f i c i e n t  The  of  ewes t h e  the estimated  p o s i t i v e ewes t h a n  n e t Se a b s o r p t i o n the  8%  Se d e f i c i e n t  be n o n s i g n i f i c a n t when  intake.  the  through  and  were s i g n i f i c a n t l y  ewes had a s i g n i f i c a n t l y  absorption  59%  Se p o s i t i v e  ewes t h a n  to  Se  in  Although  i n t h e Se p o s i t i v e  a per cent  were in  in  Se l o s s e s  than i n d e f i c i e n t  (ug/d)  d i f f e r e n c e s proved  ones,  whereas  Se l o s s  values  absorption  stable  than  were 5 7 % and 14% r e s p e c t i v e l y .  Se  net  +  ewes showed  ewes  o f Se p o s i t i v e ewes  significant.  in  10% o f  combined  statistically  the  : mean  from hay and  Se p o s i t i v e  The  values  endogenous  almost  as  ug  Se p o s i t i v e  ewes o n l y  respectively,  corresponding  the  +5  and 9 0 % was f r o m w a t e r . F e c a l and u r i n a r y Se l o s s e s were  feces  the  (44  Se was  i n Se d e f i c i e n t  deficient  •  intake  70% o f  significantly  Se  ones  high  between t h e Se  indicating intake  and  an the  71  F i g . 6. E f f e c t o f Se i n t a k e on n e t Se a b s o r p t i o n i n nonpregnant ewes. The r e g r e s s i o n equations are' Y 24.33  +  0.45  X  (r-0.94)  and  f o r t h e n e t Se a b s o r p t i o n , Se i n t a k e r e s p e c t i v e l y .  Y-100.80  -  0.11  X  (r—0.76)  e x p r e s s e d as ug/d and as  %  72  3-1  1  2  3  4  5  DAYS A F T E R TRACER INJECTION F i g . 7 . Mean daily excretion feces of nonpregnant ewes d e f i c i e n t rations.EEB, refer p o s i t i v e e w e s , andE&3, Z D r e f e r d e f i c i e n t ewes respectively.  of Se in urine and fed Se positive o r Se t o f e c e s a n d u r i n e o f Se t o f e c e s a n d u r i n e o f Se  Table  4. S t a b l e Se c o n c e n t r a t i o n s a n d p o o l and d e f i c i e n t n o n p r e g n a n t ewes.  Se  sizes  in  the  tissues  Pool (ug  concentration (ug/g tissue)  of  Se  positive  size Se)  Tissue Se  Liver  positive  0. 1 8  + 0.,01  a  Se  deficient  0. l l  b  Se  positive  199  e  +  15  81  £  g  +  9  131  h  1 .00  + 0.,06  0 .84  + 0..12  187  Sk.  0 .07  + 0.,01  0 .06  + 0.,01  2066  0 .21  + 0..01  0 .17  + 0..03  63  Heart  defici  + 0.,01  Kidney Muscle  Se  + 166 +  7  1623 51  +  12  +  22  + 134 +  8  Lung  0. 2 1  c  + 0..01  0. 1 2  d  + 0..01  174  e  +  7  94  f  +  11  Spleen  0. 3 9  e  + 0..01  0. 2 2  f  + 0.,02  125  a  +  14  40  b  +  6  Pancreas  0. 3 0  a  + 0..02  0. 2 0  b  + 0..02  26*  +  4  14  h  +  3  + 0..01  29  +  4  13  h  +  4  Mammary gland  Means 0.01;  with ' P  c  + 0..01  0 .10  a  different < 0.0001;  e  0 .06  g  s u p e r s c r i p t s w i t h i n t h e row d i f f e r P < 0.001; ' P < 0.05). ,  t  g  n  significantly(  a,b ' P _< t  74  The  maximum e x c r e t i o n o f  was o b s e r v e d positive  after  the  f e c e s and  tracer  On  the  other  hand  in  urine  injection  in  a 5 d  ewes and t h i s d e c l i n e d g r a d u a l l y o v e r  7).  (Fig.  day 1  on  Se t h r o u g h  Se d e f i c i e n t  Se  period  ewes  the  75  highest  Se a c t i v i t y was f o u n d  i n u r i n e on day 1 ,  whereas  75  the  daily  fecal  Se  loss  was  highest  3  d  after  the  75  tracer urine  A gradual  injection.  b u t was n o t t h e c a s e The  concentrations  entire  tissues  (1.00  ug/g)  had  concentration groups.  The  pancreas  of  higher  by  as  the Se  in  the  0.0001)  and i n t h e l u n g  in of  both  pool and and  of  the  Se  (0.84  The c a r d i a c  as  muscle o f  ewes  deficient  (P <^ 0 . 0 0 1 ) ones.  the  much  ones.  both  liver  and 0.05)  Significantly  o f t h e Se p o s i t i v e  0.01)  kidney o f Se  groups  and p a n c r e a s deficient  ewes  (P < ewes  of  Se  i n t h e ewes  (P > 0 . 1 0 ) .  i n tissues  Se  in  The c o n c e n t r a t i o n s  and d e f i c i e n t  (P < 0 . 0 0 1 ) , (P <^  Se  deficient  and c a r d i a c m u s c l e were s i m i l a r  Se p o s i t i v e  spleen  kidney  the  The  ewes was s i g n i f i c a n t l y (P _<  s i z e was s i g n i f i c a n t l y l o w e r lung  4.  times  in  in  o f Se were n o t i c e d i n t h e s p l e e n  deficient  the s k e l e t a l  three  skeletal  Se p o s i t i v e  Se  and p a n c r e a s .  concentration  concentrations  the  of  Table  i n the  spleen  approximately  than  in  sizes in  highest  in  (Fig. 7).  feces  pool  Se was o b s e r v e d  ug/g) as w e l l as i n t h e Se  higher  than  and  the  ewes f o l l o w e d  muscle  with  are presented  c o n c e n t r a t i o n was positive  decline of  The Se  s u c h as (P  liver  _<  than  0.05) in  the  Se intake (ug/d) F i g . 8 . E f f e c t o f Se i n t a k e o n t i s s u e Se p o o l s i z e i n n o n p r e g n a n t e w e s f e d Se p o s i t i v e o r d e f i c i e n t rations. The r e g r e s s i o n e q u a t i o n s a r e Y - 6 4 . 6 5 + 0.27 X , r « 0 . 8 6 , l i v e r ( A ) ; Y - 1 0 6 . 2 7 + 0 . 1 6 X , r - 0 . 8 9 , k i d n e y (ffi); and Y-1439.54 + 1.55 X, r - 0.89, skeletal muscle (•) respectively.  Table  5.  Kinetic  Tissue  parameters  of  tissue  . F r a c t i o n a l rate {Fraction/d)  Se  positive  Se  Se m e t a b o l i s m  constant  i n nonpregnant  ewes*.  **  deficient  Se  positive  Se d e f i c i e n t  Liver  0.0495  0.1201  14  6  Kidney  0.1062  0.1013  7  7  Sk.  0.0347  0.0462  20  15  Heart  0.0363  0.0557  19  12  Lung  0.0588  0.0768  12  9  Spleen  0.0927  0.1084  7  6  Pancreas  0.0591  0.0801  12  9  Mammary gland  0.0540  0.0540  13  13  Muscle  n-4 **  of  ewes  i n each  group.  Se u t i l i z a t i o n  in  individual  tissues.  77  positive  ones.  deficient positive  ewes ones  significant. found a  to  ewes Se  to  and these However, to  the  presented  utilization  than  in  the  were  generally  deficient  skeletal  be  ones.  higher  pool  were  the  muscle sizes  not  of  Se  than  the  statistically  Se  pool  size  Se  intake  dietary  was in  8).  constants  Table to  Se  muscle  utilization  in  positive  in  rate  the  tended  skeletal  lower  changes  fractional  are  have  (Fig.  indicating  and  differences  the  fashion  The  cardiac  tended  respond  linear  values  The  in  Thus, Se  Se  The  5.  higher  the  of  in the  and in  the  rate the  Se  T  tissues  Se  ewes  i/2 of  constants  of  deficient  tissue  positive  the  ewes values  than  in  the  ones.  DISCUSSION  Though were  lower  feeding long  of  enough  group  II  tissue  plasma  than  in  the  Se  to  result  ewes  Se  conditions  to of  concentrations I  this  (Table  deficient in  on  ration  this  was  4) t h e  as  ewes Se  in  followed  presumably  not  group  those  by  II the  status  Coupled in  group  d u r a t i o n of  deficient  compared to  disappearance  ewes  deficient  criterion.  marginally study  of the  2),  an a b s o l u t e  (Table be  initial  Se  group  based  levels  considered  The  the  in  with II  the  may  under group  in  be the  I.  reappearance  of  78  75  Se  after  similar  al.  to  and  1981)  3-4 h r  injection  observations in  goats have  (1981)  the  of  plasma  Se  in  (Allen  the  plasma  dairy  cows  and M i l l e r ,  reported  clearance  in  that of  the  the  played and  et  is al.  Symonds  1981).  cows  ewes  (Symonds  liver  dairy  of  a  et  role  accounted  in for  75 about  of  40%  the  Se  dose  that  is  cleared  initially  75 from the  the  plasma.  plasma  al.  took  1981) and  after  tracer  T h e maximum  place  after  3-6 h r  in  hr  1  goats  injection.  reappearance  In  in  dairy  (Allen  the  cows  and  current  of  Se  into  (Symonds  Miller,  study  et  1981)  the  highest  75 Se  activity  sample are  in  more  was  all in  observed  the  ewes.  agreement  initially The  with  results  those  of  in  the  2 min  of  the  present  Symonds  et  plasma  al.  study (1981)  75 w i t h r e g a r d t o t h e amount of plasma and w i t h those of A l l e n  Se t h a t r e a p p e a r e d i n t o the and M i l l e r (1981) w i t h r e g a r d  75 to  the  timing  at  which  Se  reappearance  occurred.  The  75 differences  in  reappearance species the  could  amounts  be  due  and p h y s i o l o g i c a l  erythrocytes  also  the  as  contributed  to  by  the  timings  the  status.  shown to  and  of  variations  The a v i d  Sandholm  initial  plasma  rapid  in  uptake  (1973)  Se  of  the Se  may  by have  disappearance  of  75 Se  from the For  an  the  assumption  were were  in at  a  plasma. purpose  of  was  made  steady  state  different  calculating that  the  condition. stages  of  the  kinetic  ewes  in  parameters  both  groups  The a n i m a l s  in  group  attaining  marginal  II Se  79  deficiency the  body  and  for  pools  (Shipley  the  were  and C l a r k ,  short  duration  assumed  to  of  the  tracer  studies  remain constant  in  size  1972).  75 The time  under  curves  higher  uptake  former.  stable  ewes  in  and  the Se  and  those  of  retention  of  may be  Se  in  the  in  due  plasma  Se 75  were  positive  Se  in  the  fact  significantly  al.  indicating  the  tissues  of  that  the  of  in  under  deficient 75  tissue Se  1967)  pool  Se  A greater  reported et  activity-  ewes  smaller  ones.  (Muth  specific  ewes  was  were  sheep  Se  to  positive  retention  conditions  plasma deficient  than  This  (cold)  than  uptake  of  (P _< 0 . 0 5 )  greater the  areas  Se  deficiency  and  in  cattle  75 (Kincaid  et  specific their  that  the  The #325 w e r e group mean in  lower  plasma  3 and  plasma  #325 w e r e  Se  specific  Se  of  levels the  period  Se  different  + SEM) a n d  Se  adequate  the 75  higher  curves  and  were  during  (Figs.  ewe  The  plasma  duration  imposed  deficient  1977).  activity-time  with  regime  al.  Se (82  level to  of  of  5).  Though  Se  concentration activity-time  (-6.53  (111 data  + 10  the  ewes  ng/ml) the  Se coupled  indicated nutritional  ewes m a r g i n a l l y  activity-time  those  than  plasma  Se  study.  from  lower  of  deficient  of  make  specific  balance  AUC  other  intake  + 8.51  those  of  ng/ml) (Figs.  ewes  in  :  of  the  ( 3 8 + 6  ug/d  its  data  3 and  the 5)  same  ug/d  mean  group mates,  and  ewe  :  + SEM) the 75  plasma indicated  Se a  80  higher be  due t o  than to  S e s t a t u s i n ewe # 3 2 5 .  plasma  her  the larger  group mates. Animal  experimentation  differences  The  irreversible  o f Se ( T a b l e  in  Se  expect  observed  intake,  than  lower  ID  decreased Se  be  plasma  Se  #325 prior  to  the  increasing  was  the  the  intake.  turnover  of  net  plasma  Se l e v e l s .  coupled feces  Therefore  metabolic  with  h i g h e r Se  a  either  could  plasma  be pool  i f this eventually  Se d e f i c i e n t  not only but  tissues  absorption  by  also  by  (Table  5).  (%  Se  a reduction i n the  and urine  t h e plasma  adaptations  s i z e was  of  and  However, the  Se h o m e o s t a s i s  As  suggest  This  limited  the efficiency  losses through  would  plasma pool would  Se  ones.  significantly  conditions  i nthe  body  the  The  0.05)  ( P _<  Se p o o l  reflecting  Se  total  the  plasma  rates  was  clearance  deficient  of  increased  higher  e n t r y o f Se i n t o  t o maintain  the turnover  addition,  Se  Se c o n t e n t .  plasma  and plasma  ones.  under  sources  of entire  decreasing  ewes,  t h a t the  was n o t r e v e r s e d  attempt  reflects  (P < 0.10)  lowered  dietary  depleted  intake)  may  o f ewe  contributed  i n the  clearance  of  fact  ewes w o u l d  In  kg)  a n d Se s t a t u s  significantly  deficient  or  by the  situation  also  than  a higher  i nthe and  the  were  i n Se p o s i t i v e  deficiency  through  have  ewes  turnover  explained  variation  d i s p o s a l (ID)  2)  positive  would  also  may  (73  size  discrepancy  observed.  rates  one  body  This  o f the  t o maintain  the  ID o f  Se,  which  entire  body,  would  81  be  a.good  adequate  indicator  values  deficient  ewes  (20 d :  present  values  1981)  o f Se  under  both  Se  (2 d ) .  study be  (iv)curve  values and  These  of  to  from those  variations  i n  experimental  (64  d :  obtained  i n ^1/2  i n the  period,  vs.  t h eobserved  i n  (i)Se status  v s . plasma  (manual  and  reported  dairy cattle  differences  counting  methods  equations  The  1969)  due t o  (whole body peeling  Se i n t h e Se p o s i t i v e  aredifferent  (ii)duration  analytical  fitting  similar.  Lopez e t a l .  could  animals,  o f plasma  were  Symonds e t a l . the  theturnover  and d e f i c i e n t c o n d i t i o n s .  The  sheep  of  (iii)the  counting)  and  computer) used  specific  of  i n  activity-time  curves.  75 In tended the  general  the  daily  t o be s l i g h t l y  higher  Se  contrary  positive to  reported the that  thefinding  Recently  thefecal  organic whether  ( F i g . 7).  o f Lopez et 7 5  excretion of Langlands  intake  of  feces  This  (1969)  a l .  Se i n t h e u r i n e  et a l .  the  Se i n  theu r i n a r y losses both i n ewes  t h ed i f f e r e n c e s observed  Se  of  (1986)  e x c r e t i o n o f Se w o u l d v a r y  matter  experimental The  than  and d e f i c i e n t  a higher  feces.  excretion  ewes. are real  have  who  than  i n  concluded  depending I t  i s  on t h e  i s not  clear  o r due t o p o s s i b l e  errors. intake  was  significantly  lower  i n  t h e Se  82  deficient relative intake  ewes t h a n  i nthe  contribution  of  ewes was  o f hay  ewes h a y p r o v i d e d a  intake,  whereas,  feces  of  Se  positive  ( P <^ 0 . 0 1 )  59  i n the  a n d 57%  respectively. the  +  that  the  fecal  those  converted 1962;  i nthe  ewes.  :  by t h e f a c t  results  was  i n t h e Se When  t o be  the feces  no  which ewes  w e r e made f o r  r e p r e s e n t e d 49  and  and d e f i c i e n t  ewes  i t may b e  does e x e r t  a  concluded homeostatic  i n t h e body.  data  i t c a n be from  these  (80%  i n rats  Peterson and Spedding,  1963)  that  et  1981).  the  intake  v a l u e s a r e much  o r g a n i c Se f r o m  Se c o m p o u n d s  seen  40-41% o f S e  : Cary  and Marcus,  that  to insoluble  Se/d)  and d e f i c i e n t  Se p o s i t i v e  route  Se i n t h e  3).  the corrections  Se  (90%) o f  there appeared  Se l o s s e s  However  Greger  ug  observed  positive  on these  balance  reported  (72%  explained  Se  excretory  Se  6  that  In  source  of stable  +  Se  o f t h e Se  Se/d)(Table  a b s o r p t i o n o f Se r a n g e d  nonpregnant  humans  than  ug  however,  Based  From t h e  than  48  o n Se m e t a b o l i s m  apparent  lower  the fecal  the intakes  control  (25  the total  portion  the primary  ewes  The  the groups.  The e x c r e t i o n  i nthe  When,  respectively.  to  (70%)  major  3).  (Table  amount e x c r e t e d t h r o u g h  endogenous l o s s  2% o f  water  a s a p e r c e n t o f Se i n t a k e  difference was  (272  ewes  expressed  ones.  ones  between  was  deficient  significantly  in  water  i nthedeficient  and  different  positive  Se  positive  lower  a l . 1973) This the  and  may feed  (Peterson and i n t h e rumen a n d  be i s  Butler, hence  83  the  absorption  recently  is  Langlands  endogenous intake)  fecal  in This  ug  observed  Se/d. in  This  fecal  Se  et  loss  wethers  study. Se/d  likely  is  in  variation  differences  in  the  endogenous  fecal  contributed ruminants  (1986)  endogenous ruminants  Se  and  the  of  could it  Se  be  contribution  the the  ug  due  to of  from l i v e r  or  that  liver  losses  in  nonruminants et  source  digestive  of  d 24  44  Langlands major  of  Se  The o r i g i n  Se in  of  17-45  be  thought  and  an  differences  could  either  However  in  a  loss  the  study.  1981)  is  on  fecal  endogenous  liver  (29%  consuming  was  the al.  of  the  Se/d  to  Very  reported  based  ewes  or  1966).  secretion  ug  Se/d  retention  to  that  14  due  now  et  reported  ug  ruminants.  have  either  losses  little  in  endogenous  duration  and Baumann,  have  be  Se  the  (Symonds  (Levander  the  could  Until  very  48  deficient  and  pancreas.  approximately  than  Se  lower  (1986)  consuming  the  from  be  al.  of  lower  losses  to  al.  of  the  tract  pancreas  is  of very  minimal.  The Se  lack  absorption  ewes  (Table  intake lost  (on  3)  coupled  as  by  Janghorbani  et  no  difference a percent  could with  endogenous  supported  indicate  of  a  (1982)  to  in  from  the  these the  the  in  of  and  Se  relatively  high  (10%)  animals.  This  human  Se  al.  apparent  net  positive  intake  and Thomson e t  between  apparent  basis)  the  percent  loss  data  difference  intake  due  lower  fecal  the al.  be  Se  between  being may  studies (1978) and  Se  be of  which net  Se  84  absorptions the  other  was  two  could  in  hand  fold be  the to  in  a  a  endogenously  discuss net  on  the  Se  than  the  results  absorption  ewes  the Se  cent  There  Se  than  reduced  per  (58%).  more  apparent  of  high  net  fed  deficient  result  with  literature  the  Se  higher  as  associated lost  human s u b j e c t s  net  of  Se  no  from  present  as  per  and  Se  intake  being data  domestic  cent  in  animals  study. of  this  intake  available  in  On  absorption  absorption  absorption  expressed  Se  dietary  are  the  1 mg S e / d .  Se  However  intake  was  75 reported  to  range  from  90-97%  (selenite/selenomethionine) al.  1978;  Griffiths  current study with those of Janghorbani  et  in  tracer  studies al.  al.  (1982)  who  found  Se)  humans  1976).  on Se d e f i c i e n t e w e s above w o r k e r s and at  et  in  (  and  (Thomson  Results  (97%) a r e variance a net  dosing et  from  the  in agreement with those of  absorption  of  68-  74 76%  in  the  present  be  man u s i n g  due  to  Se  study  the  and  as  the  that  differences  tracer.  The d i s c r e p a n c y  of  Janghorbani et  in  the  tracers  al.  between  (1982)  employed  may  and  that  74 the  stable  than  50%  latter the  Se  isotope  of  the  workers.  might  present  neglect may h a v e  of  animals  have  balance  overestimation  dose  used  of  to  Se body the  In  were  of  losses  constituting  the  purchased  it  and  is  incomplete through wool  differences.  in  the  sources  considerable  addition,  intake,  was  administered  introduced  study.  other  added  total  Se)  The h e t e r o g e n i t y  experimental  status  (  study  from  their  fecal  of  which  unknown  errors also  more  in  likely  Se the  that  collection,  and e x p i r e d  gases  85  The  Se  concentrations  positive  ewes  were  deficient  ones  (Table  the d e f i c i e n t  had  a  4).  the  Se  dietary no  positive  Se s u p p l y  by d e c r e a s i n g  or  on  to  This  nutritional  The pool  Se  by  the  their  was i n d e e d  pools  (Janghorbani  contrary  man  The  d e p l e t i o n o f Se o b s e r v e d  ewes i n d i c a t e d t h a t depots  t o meet  et  Se  that  or  was The  in  the  at  higher  to  of  Se  of the  for  the  from  the mineral  o f Se i n s k e l e t a l  the  positive Se  Se  Thomson  mobilized  the  directly  intakes  into  the  observations et  i n t h e t i s s u e s o f Se  was  Se  significantly  in  a l . 1982;  requirements  Though t h e c o n c e n t r a t i o n  4).  the  study.  tissues (Table  of  concentrations,  animals  incorporation  in  Se  in  to the short d u r a t i o n  s i z e s observed  a greater  metabolic  tissue  changes a s s o c i a t e d w i t h  various  Se i n t a k e  than  the t i s s u e s  Se  i n the present  the r f a c t  ewes d e m o n s t r a t e d  the  Se  intake  o f t h e ewes a l s o i n d i c a t e d t h a t  in  t i s s u e Se p o o l  tissue  due  regime imposed  of  influenced  there  be  t i s s u e Se d a t a  size  higher  could  the  the  the r e d u c t i o n  d e f i c i e n c y were o b s e r v e d e i t h e r i n t h e tissues.  that  t h a t t h e Se  Although  responded  pathological  in  i n t h e Se p o s i t i v e ewes  o f t h e f o r m e r ewes. ewes  than  of the f a c t  effect  deficient  clinical  higher  Because  higher  o f t h e t i s s u e s o f Se  ones i t c a n be s u g g e s t e d  direct  concentration  most  significantly  i n t a k e was s i g n i f i c a n t l y in  in  al.1978). deficient  the  tissue  (Table  m u s c l e was  5). lower  86  than  in  body  (approximately  render in  Se  other  the  pool  intake  expect  that  extent  to  Se  tissues,  Se  meet  deficiency  (Table  tissues  ones  (Table have  Se  values  into  the  However,  vulnerable  to  would  be  depleted  was  body under observed  the  would  pool  would  to  Se  deficient  ewes  tissues v  l  a  u  e  reflect and  not In  addition  4)  in  changes  a  to  greater  conditions be  the  would  logical to  to  in  of  the  case  indicated  that  than  in  exhaust  their  would  account  for  generally than  the  those  entry  the  deficient the Se the  conditions.  in  positive depots lowered  higher  the  of  ewes the  Se  from  of  in  that  ewes  were  calculated from  the  plasma tissues.  the  current kinetics  the  tissue  significanly  ones  would  at  faster  a  tended positive  tissue  fact  in  positive  These  employed  resolution this  in  deficient  retention.  protocol  to  the  also  disappearance  the  to  deficiency  than Se  be  the  both  its  permit  of  s  lowered  experimental  sizes  (Table  tissues  a  parameters  appeared  ^1/2  tissues  accurately.  under  1977)  therefore  the  mass  Arnal,  is  Se  The  lower  T^2  this  fact  muscle  It  of  metabolic  of  5).  suggesting  lower  in  -  tissue  pool  demands  of  ones  Se  BW  r=0.89).  this  which  utilization  study  the  this  ;  from  tissue  the  to  in  skeletal  5).  The the  8  the  large  40% o f  size  (Fig  the  values  cause  the  rate  and  observed  87  CHAPTER I I I ; SELENIUM METABOLISM  EXPERIMENT I I A :  Kinetics  IN PREGNANT EWES.  of selenium metabolism  ewes f e d Se p o s i t i v e  or d e f i c i e n t  i n pregnant  rations.  INTRODUCTION  Studies of mainly  on  retention  Only  tissue  these  (Wright  and  Though  these  role they  studies  not  as a whole metabolism. undertaken pregnant  aimed  and,(ii)  w i t h due  have  et a l .  concentrated  Hidiroglou were  the f a t e  al.  1969). ewes  tissue  investigation  t h e k i n e t i c s o f whole body Se  of  animal  a b s o r p t i o n and  or d e f i c i e n t  the  metabolism,  ( i ) the k i n e t i c s  the present  ewes f e d Se p o s i t i v e  and  i n elucidating  o f Se i n t h e p r e g n a n t on  and  1969).  al.  i n Se s t o r a g e o r  at determining  reason  et  Wright  i n pregnant et  helpful  either  1967;  Hidiroglou conducted  emphasis  For t h i s to study  were  1964;  of various tissues were  Muth  a l . 1969;  studies  Bell,  Se m e t a b o l i s m  in  1965;  Lopez e t  two o f  i n sheep  d i s t r i b u t i o n and whole body e x c r e t i o n  (Wright,  1964;  Bell,  Se m e t a b o l i s m  was  metabolism  rations.  MATERIALS AND METHODS  (a)Animals  and management:  Two g r o u p s o f D o r s e t X S u f f o l k  c r o s s b r e d ewes  weighing  88  60-80  kg  were u s e d  (group I, cubes  n=4)  and  barley  were  the  to  and  same as d e s c r i b e d  barley  was  purchased  ration  commenced  of  17.6  all  times.  the  the  vagina  The  bred n a t u r a l l y  with  was  moved  of for  was  1.25  feeding.  separate  after  gross energy  concentration  had f r e e  access to  in  salt  blocks at  dates  were  Approximately  was  in  from the  The ewes  to the f e t a l  cages  were  sponges  manually  breeding  the  water  a l l t h e ewes  placement.  surgery  II  respectively  their  metabolic  of the  (16.1%  kg o f hay cubes  removed  the experiment  months  CP)  cycles  were  was  Group I and g r o u p  progestagen impregnated  sponges  Intrauterine  Se were  and  The d u r a t i o n  hay (9.7%  c o n f i r m e d by l i s t e n i n g  to  The  approximately 4  5 d.  a Doppler u l t r a s o u n d machine.  to  breeding  were c o m p l e t e d .  estrous  and t h e  s i x weeks p r i o r  Se.  i t s procurement  ng Se/ml) and c o b a l t - i o d i z e d  f o u r t e e n days  Pregnancy  time  Se d e f i c i e n t  by p l a c i n g  vagina.  in  II,  deficient  on an a v e r a g e  The  synchronized  ewes ( g r o u p  The f e e d i n g o f Se  Ewes i n b o t h g r o u p s  30  (containing  NRC  locally.  contained similar  KJ/g.  per  deficient  and b a l a n c e s t u d i e s  which  as  hay  The Se  gestation  kg o f  of a l f a l f a  I (p 5 0 ) .  tracer  per day  of  ewes  i n Expt.  the experiments  CP) and 0 . 9 6  nutrients  barley deficient  until  ewes were e a t i n g  consisting  details  at  through  The Se p o s i t i v e  The Se d e f i c i e n t  hay u s e d and  continued  study.  provide  (1978).  f e d hay  deficient  this  were f e d a r a t i o n  recommendations n=3)  in  were  recorded. heart beat four  to  ewes were s h o r n  and  for performed  individual on  these  89  ewes of  to  catheterize  the  surgery  Details with  of  the  their  are  fetuses  five  before  given  are  tensions  (PCC^ and  and  temperature  neck  day  one  injection  in  Expt.  and  II  of  the  details  B  these  II  (p  126).  animals  along  C.  PC^), blood  prior  before  to  were the  300  was  was  by  blood  experiment  as  described. sides  of  facilitate  blood.  (specific  gas  hemoglobin  i n t r o d u c e d on b o t h to  The recording  pH, hematocrit,  of  given  experiments. verified  experiments  uCi  period  section)  each  withdrawal  approximately  ewe  methods  catheters  and  recovery tracer  the  Analytical  vein  Expt.  the  normalcy of  in  Jugular  vessels  status  given  of  (details  body  in  postsurgical  start  physiological  blood  Procedure:  day  the  fetal  physiological  (b)Experimental  A  the  A  bolus  the  tracer dose  activity:  of  187-919  75 mCi/mg  Se)  Irvine, Se  Se  724)  10,  Se-sodium  California)  positive  and  of  ewes  was  (group  deficient  ewes  respectively. 15,  30,  postinjection blood  45,  and once  collected  experiment  did  samples  the  from  injected I  ewes:  (group  Blood 60,  from not  selenite into  jugular  977,  982,  II  ewes:  samples 120,  180,  daily  for  each  ewe  on  36  ml.  exceed  corresponding  (ICN  vein 818  58,  were 240,  fetus  of  300  day  840)  707Y  and  and  2,  5,  360  min  The of  Simultaneous were  also  the  and  collected  3 d thereafter. the  Chemicals,  total tracer blood  collected  to  90  determine ewe  to  the  in utero  fetus  placed  (Expt.  in  placental  II  chilled  C).  transfer  A l l  pyrex  blood  tubes  immediately.  T h e p l a s m a was  Se  were  out.  A  five  day  carried  Se  tracer  injection  pellets  were  urine  was  placed Se  were  conducted  collected  separately  collected  beneath  intakes  the  the  977  also  818  were  respectively  after  of  and  T-61  (Hoechst  solution, Se  deficient  days and  and  4,  liver,  and  Subsamples  the  day  positive on  12  58,  about  spleen,  collected, 5-10  days by  g were  Feed  6,  and  subsamples  obtained  840, 41  a d m i n i s t e r i n g 20  ml  were  18  an  euthanasia  by  laparotomy.  sacrificed  T h e ewes w e r e  towel  and  and  delivered  lung  and  when  982,  14,  the  outputs  as  nos.  the  funnel  prevented  fecal  of  Fecal  experiment  Ltd.),  7 0 7 Y a n d 725  respectively.  heart,  were  were  and  day  fecal  tracer  ewes,  injection  fetuses nos.  of  until  a  urine. and  and  tray while  urine,  urinary  Pharmaceuticals  kidney,  of  Se  This  urinary  Daily  tracer  the  (gastrocnemius)  on  the  through  and  were  ewes.  a meshed  feces  sacrificed  ewes,  6,  in  from  -20° C  on  the  A l i q u o t s of  noted.  collected.  on  Se  heparin  at  commencing  cages.  the  day.  kept  pail  the  with  collected  were  a  metabolic  between  along  were  volumes  were  into  recorded every  voided,  trial  was  contamination  water  balance  of  samples  containing  centrifuged analyses  rate  and  dissected  skeletal  dried from  on  and  muscle weighed.  each  of  the  75 tissues  for  Se  r a d i o a c t i v i t y measurements  and  rest  were  91  stored the  in  Se  double  sealed  analyses  (d)Analytical  were  determined  base  with  recording  blood  calibrated  of by  (Radiometer, recorded venous were  data 52) .  as  were  bubbling  was  until  acid-  pHM  72,  and  electrodes  Copenhagen)  respectively.  The  gas  mixture of  COj  through using  at  bubbles/min)  electrodes.  and  high  The  pH  Stable  radioactive same  machine once  the  following respective  Se  analytical  as  described  pH  were  injection  of  electrodes  methods under  for  standards  T h e P C C ^ , PC»2 a n d p H v a l u e s the  a  were  and C ^ , c o r r e c t e d  the  low  (12-15  for PCO^,  a  gas  were  digital  electrodes  samples  the  pH  blood  calibrated.  were  PC^) and  The  completely  and  Whole  C.  calibrated  blood  Hematocrit  maintained  pressure  on  pH  the  procedure.  Radiometer model  to  Houston).  and  modules  pressures  displayed  analysis  C  thermostatically  Copenhagen).  whole  a  POj and  37.5°  barometric  electrode  using  individual PCC^,  Inc.,  (PCC<2  (Radiometer,  known p a r t i a l  daily  (Hycel  tensions  pH e l e c t r o d e s  temperature  -20  according  microhematocrit  anerobically  equipped  with  the  gas  analyzer  PC>2 a n d  determined  method  by  (venous)  determined  at  performed.  was  cyanomethemoglobin  blood  containers  Methods:  Hemoglobin  was  plastic  and  Expt.  I.  the (p  92  Statistical  All  analysis:  results  were  p l a s m a and t i s s u e two way a n a l y s i s and  t h e sheep  remaining  employed the  were  't'  test  as  The  be t h e main one  means A least  The  a  ration  analysis  The of  significance  of  was d e t e r m i n e d  by  squares  method was  o f t h e r e g r e s s i o n e q u a t i o n s and  c o e f f i c i e n t s when c o m p a r i n g  parameters.  The  effects. way  statistical  1985).  f o r the c a l c u l a t i o n  SEM.  u s i n g SAS ( 1 9 8 5 ) .  treatment  (SAS,  means +  d a t a were a n a l y s e d by  subjected to  1985).  between  correlation  between  of variance  were assumed t o  (SAS,  differences Students  Se c o n c e n t r a t i o n  data  variance  expressed  the r e l a t i o n s h i p  93  RESULTS  The to  Se c o n c e n t r a t i o n s I ewes  group  respectively.  The  mean  pregnant are  physiological  ewes  f e d Se  presented  during  surgery. positive 0.0001) positive  6.  The ewes  (187  higher  than  +  concentration  Se  between  values  Se  of  deficient  the  rations  were  recorded  5 days  commenced  was  i n  after  the  significantly  Se  ( P <^  (69 + 14 n g / m l ) .  ones  t h e Se i n t a k e ( F i g . 9,  had  respectively.  concentration  20 n g / m l )  was o b s e r v e d  mg/kg  fed mg/kg  barley  These v a l u e s  i nt h ed e f i c i e n t  correlation  and  or  period which  plasma  0.22  and  parameter  positive  i n Table  theexperimental  hay  a n d 0.04  mg/kg  cubes and b a r l e y  mg/kg  deficient  o f 0.01  concentrations  0.23  were Se  i n alfalfa  A  a n d t h e p l a s m a Se  0.53).  r =  75  Following  thesingle  injection of  Se-sodium  selenite 75  into  t h e Se  radioactivity During  the  positive  pregnant  ewes  showed a c h a r a c t e r i s t i c  initial  half  an  hour  t h e plasma  pattern  of  after  Se  clearance.  the  tracer  75  injection exponentially  the plasma Se radioactivity declined f o l l o w e d b y a n i n c r e a s e d u r i n g t h e n e x t 3-4 h . 75  The  highest  plasma  Se a c t i v i t y  was o b s e r v e d  i nthe i n i t i a l  75  2 min  sample,  systemic peak  7  whereas  the  c i r c u l a t i o n w a s maximum  ^Se  radioactivity  plasma  Se t h a t  around  4 h (Fig.  observed  at  3-4  reentered 10). h  The was  Table  6.  Physiological  parameters  Se  of  positive  Se  positive  and d e f i c i e n t  (n-9)  Se  pregnant  deficient  Parameter Mean + S . E . M  Blood  pH  -  7.50  Mean + S . E . M  + 0.01  7.44  + 0.04  (mm Hg)  28.3  + 1.2  26.6  + 0.8  (mm Hg)  25.4  + 1.9  25.1  + 1.3  Hemoglobin  (g  13.0  + 0.7  13.0  + 0.4  Hematocrit  (%)  33.0  + 1.2  34.9  + 1.1  Blood  PC0  Blood  PC»2  Blood  2  samples  %)  were  obtained  from  the  jugular  vein.  ewes.  (n-6)  95  F i g . 9 . E f f e c t o f S e i n t a k e o n p l a s m a Se c o n c e n t r a t i o n i n p r e g n a n t e w e s f e d Se positive ( A )or d e f i c i e n t (A) r a t i o n s . The r e g r e s s i o n e q u a t i o n i s Y - 74.48 + 0.22 X r-0.53.  F i g . 10. Changes during first 24 p o s i t i v e pregnant 8 1 8 , 8 4 0 , 977 a n d  specific activity in plasma Se i n j e c t i o n i n t o Se hr after tracer r e f e r t o ewe nos. ewes. • , o» •/ • 982 respectively.  97  O.Ol-i  0.00010  10  20  Time (Hours)  Fig. 11. Changes in plasma Se during f i r s t 24 h r after tracer deficient pregnant ewes. • , o, o 5 8 , 707Y a n d 725 respectively.  specific injection refer to  activity i n t o Se ewe nos.  98  approximately  61%  of  A  similar  postinjection. the  Se  deficient  lasted of  ewes  approximately  the  the  activity  phenomenon was  i n which  radioactivity  present  min  a l s o observed  t h e peak  3-4  f o r about  at 2  present  of  i n  reappearance  h and accounted  2 min  i n the i n i t i a l  55%  for  sample  75  11).  (Fig.  thereafter  The  plasma  g r a d u a l l y over  Se  radioactivity  s e v e r a l days  i n both  declined  groups.  75  The curves  best  i n t h e Se 12  Fig.  two  all  these  curves  i n the  the the  were  ewes a n d  (4  similar  in  of  specific  and d e f i c i e n t The  are  given  both  in  dj i n both  these  groups  equations 7.  Table  i n  obtain the  A  sum  best f i t  This  indicated  t h e p l a s m a was b i p h a s i c i n  that approximately  each o f  ewes a r e g i v e n  groups.  Se f r o m  activity-time  exponential  required to  ewes o f  clearance  lost  Se  respectively.  e x p o n e n t i a l s was  equations that  positive  13  and  describing of  f i t plasma  equal  phases.  amounts  The T^^  °f  2  of S  e  Se w  a  s  8).  (Table 75  The curves the  under  the plasma  (AUC) a n d t h e k i n e t i c  ewes a r e p r e s e n t e d  deficient the  areas  ewes was  Se p o s i t i v e  Se s p e c i f i c  parameters  significantly  ones  8.  i n Table  indicating  activity-time  o f Se m e t a b o l i s m T h e AUC  higher  i n  the  (P < 0.001)  a greater plasma  i n  than  Se i n  retention  75 of  Se.  of  the cold  the  total  This  could  be due  Se i n t h e p l a s m a  plasma  Se p o o l  to  the  smaller  of the d e f i c i e n t  observed  in  the  pool  ewes. present  size Infact, study  99  F i g . 12. B e s t - f i t plasma Se specific activity-time c u r v e s i n Se p o s i t i v e p r e g n a n t e w e s . • , O / • » • refer t o ewe n o s . 8 1 8 , 8 4 0 , 977 a n d 982 respectively. 7 5  100  O.Ol-i  GO fciC  a  0) o  cc  o.ooH o  <:  d CO CC  6 0.000H 0  20  40  60  Time (Hours)  75, activity-time Fig. 1 3 . B e s t - f i t p l a s m a '"Se specific o, • refer c u r v e s i n Se d e f i c i e n t p r e g n a n t e w e s . • t o ewe n o s . 5 8 , 7 0 7 Y a n d 7 2 5 respectively.  Table  7.  B e s t - f i t exponential equations c u r v e s of pregnant ewes.  Ewe  Se  Se  #  positive  of  A  plasma  Se  specific  activity-time  &2  a^  2  ewes:  818  .000825  .000701  5.9871  .0127  840  .000909  .001107  9.0355  .0149  977  .000505  .000671  8.2206  .0169  982  .000595  .000519  14.8482  .0131  58  .002218  .002375  8.4231  .0133  707Y  .002038  .001586  10.7979  .0125  725  .001741  .001187  5.3791  .0086  deficient  *The where  equation  ewes:  A -  A^. - A e " l 1 75 plasma Se s p e c i f i c  a  rate  -  is:  a  A  constant,  e  e  -  fc +  2  A  e  "V'  activity  log  1  n  and  ( f r a c t i o n of t  «  time  dose/ug  (hr).  Se),  Table  8.  Comparison of areas under Se p o s i t i v e a n d d e f i c i e n t  Se  positive  the c u r v e s (AUC) and pregnant ewes.  ewes  (n=4)  Se  kinetic  parameters  deficient  ewes  (n-3)  Parameter Mean  AUC (fraction of dose/ug Se).  0.05  a  7  Plasma Clearance (ml/d/kg B.W.)  39  Pool  Plasma  Cone,  Se  Rate  l/2  (  d  C  725  Size  (ng/ml)  Volume of distribution (ml/kg B.W.) T  187  c  e  56  4.42  )  + 0.01  a  0.15  + S.E.M + 0.02  b  + 1  2  + 2  26  + 93  279  + 20  69  + 4  e  i  d  d  f  45  + 0.49  Means w i t h . d i f f e r e n t superscripts within < 0.001; P < 0.01; P < 0.0001). c  Mean  hr  Irreversible Disposal o f Se ( u g S e / d / k g B . W . )  P l a s m a Se (ug Se)  + S.E.M  4.40  the  row d i f f e r  + 0.2 + 3 + 36 + 14 + 7 + 0.92  significantly(  P  of  103  was  significantly  ewes  than  in  the  irreversible positive present to  be  Se  and in  disposal  deficient  the  II  <  former  lower  ones. (ID)  the  this  (P  >  Se  Se  deficient  difference  between  higher  group  However,  significant  the  The p l a s m a  in  the  observed  with  group.  in  A significant was  ewes  higher  ewes.  statistically  0.01)  positive  slightly  group  (P  the  in Se  value  being  clearance  tended  I  than  in  the  difference  was  not  0.10).  75 The pregnant given  in  excretory  patterns  ewes  Se  fed  Fig.  patterns  were  14.  of  Se  positive When  examined  the  it  was  into  feces  and u r i n e  and d e f i c i e n t overall found  (5  that  d)  rations Se  the  of are  excretion  daily  urinary  75 of  Se l o s s t e n d e d t o t h e t r i a l i n Se  be h i g h e r t h a n p o s i t i v e ewes.  the f e c a l On the  l o s s on a l l 5 d other hand in  75 Se  deficient  higher  than  time  the  fecal  loss.  the  it  urine  of  the  daily  urinary  urinary  examined and  ewes  Se  loss  If  the  was  observed  Se  positive  daily  to  the  other  deficient  ewes  the  daily  1,  balance The  while  the  fecal  Se  except  excretion  compared  day  fecal  was  Se  on  day  slightly  excretion 75  that ewes  the  Se  were  days. urinary 75 Se  loss  was 1  which than  patterns losses  maximum  peaked  at  greater  on  the were  into  on day  On the other 75 Se l o s s was  loss  generally  feces 1  as  hand i n  Se  maximum  on  day  2 of  the  of  the  Se  trial. balance  data  showing  the  details  6  F i g . 1 4 . Mean daily excretion of Se in urine and feces of pregnant ewes f e d Se p o s i t i v e o r deficient r a t i o n s .LZ3, E H r e f e r t o f e c e s a n d u r i n e o f Se p o s i t i v e e w e s a n d E S , [ZD r e f e r t o f e c e s a n d u r i n e o f S e deficient ewes respectively. 7 5  105  Table  9.  A b s o r p t i o n a n d r e t e n t i o n o f Se i n p r e g n a n t Se p o s i t i v e a n d d e f i c i e n t rations.  Se  Se  Parameter  p o s i t i v e ewes ( n - =8) Mean + S . E . M  intake  430  Fecal  Se  (ug/d) loss  (ug/d)  Endogenous f e c a l l o s s + (ug S e / d ) Urinary  Se  Apparent  Se  Net  of Se  Se  it  b  Se  + 11  + 28  27  b  +  2  52  c  + 10  14  d  +  4  45  e  +  8  8  f  +  2  189  e  + 36  64  f  + 11  43  e  +  5  67  f  +  5  241  e  + 36  78  f  +  11  56^  +  5  84  h  +  3  145^  +  35  56  u  +  10  rows  differ  intake 7  of  Se  (ug/d)  intake  Se  ab,cd,ef,gh a  b  ewes  absorption "  Apparent (ug/d)  ( ' P  91  a  (ug/d)  (ug/d)  (a)estimated (b)%  40  fed  absorption^  (a)estimated (b)%  +  deficient (n= =6) Mean + S.  241  Se  loss  a  Se  ewes  M  balance  e  a  n  < 0.0001;  balance  for  g  w  C  '  t h i n  i  P  d  ewe  the  < 0.05; #58  was  e  ,  f  P  significantly  < 0.001;  from a  4 d  <  0.01).  collection  only.  g  '  h  P  """Endogenous f e c a l Se l o s s was c a l c u l a t e d f r o m d a t a o f tracer i n j e c t e d (n=4 f o r Se p o s i t i v e a n d n=3 f o r Se d e f i c i e n t ) ewes The t o t a l number i n c l u d e s f e t a l t r a c e r i n j e c t e d ewes a l s o . $ ""Apparent  #N e t  Se  absorption  absorption=Se  "Apparent  balance  = Se  intake = Se  -  intake (Fecal  intake  -  -  Fecal  loss  Fecal  -  loss  Se  loss.  Endogenous -  Urinary  Se  loss)  Se  loss.  106  metabolism was  trial  are  significantly  ewes t h a n water  found  respectively deficient  primary  t h e Se  (P < 0 . 0 0 1 )  ewes  Se  o f Se i n t a k e  in  ewes  the  loss  fed  absorption  rates  in  o f Se  Se p o s i t i v e  ewes.  observed (ug/d),  between  of Se  intake  intake  The  rates  i n t h e Se p o s i t i v e  apparent  respectively  Se  negative  15).  (Fig.  Se in  A  balance t h e ewes  intake i n Se water 18  for  significantly and u r i n a r y  Se  positive  The a p p a r e n t  Se  absorption  were  group were  I  and  group  expressed  as  net  rations. the  When  apparent  Se a b s o r p t i o n  rates  i n t h e g r o u p I and  relationship (r=0.89) and  n e t Se  expressed as  well  significantly  ewes t h a n values f e d Se  group was  absorption  relationship (r=-0.66)  apparent  a  43 and 67% r e s p e c t i v e l y  and d e f i c i e n t  intake  were  and  Se  and n e t Se a b s o r p t i o n  absorption  0.001) The  the  whereas, a  between  linear  barley  the  the  resulting  A positive  positive  i n t a k e was  Se l o s s e s were added t o  the  intake  hay a c c o u n t e d  in  were 241 and 78 u g / d r e s p e c t i v e l y II  hay,  0.05)  When t h e s e  the values  endogenous f e c a l  t h e Se  Se  Interestingly,  (P <  ones.  ug/d  respectively.  in  respectively.  i n the d e f i c i e n t  percent  the  ewes.  were a l s o o b s e r v e d  r a t e s were 189 and 64  The  11% and 22% o f Se  source  intake  9.  Alfalfa  67%,  t o t h e Se p o s i t i v e  endogenous f e c a l  ewes t h a n  II  higher  w h e r e a s , b a r l e y and Se d e f i c i e n t  higher loss  Table  ones.  to provide  ewes t h e  7% o f  and  in  _< 0 . 0 0 0 1 )  (P  i n the d e f i c i e n t  were  (75%)  given  existed  as p e r cent as  the net  higher  (P _<  i n the d e f i c i e n t  ones.  were  145  positive  and and  56  ug/d  deficient  107  Se intake (pg/d) F i g . 1 5 . E f f e c t o f Se i n t a k e o n n e t Se absorption in p r e g n a n t ewes. The r e g r e s s i o n e q u a t i o n s a r e Y-23.75 + 0.52 X ( r - 0 . 8 9 ) and Y=85.91 - 0 . 0 6 X ( r — 0 . 6 6 ) f o r the n e t Se a b s o r p t i o n , e x p r e s s e d a s pg/d and as % Se intake respectively.  Table  10.  S t a b l e Se c o n c e n t r a t i o n a n d ^ p o o l and d e f i c i e n t p r e g n a n t ewes .  Se  size  in  the  tissues  Concentration (ug/g)  Pool (ug  of  Se  positive  size Se)  Tissue Se  positive  Liver  0.37  Kidney  1.09  c  Sk.  0.13  a  Heart  0.31  a  Lung  0.31  a  Spleen  0.57  Muscle  a  a  Se  deficient  + 0.02  0.11  + 0.06  0.87  d  + 0.01  0.06  b  + 0.02  0.17  b  + 0.02  0.14  b  + 0.03  0.26  b  positive  + 0.02  347  + 0.06  184  + 0.01  3664  + 0.02  b  Se  a  e  9  76°  + 0.02  200  + 0.03  l l l  C  e  Se  deficient  +  29  102  b  +  13  137  f  + 332  1709  h  +  8  50  d  +  24  103  d  +  24  50  f  +  11  +  14  + 145 +  4  +  12  +  9  a Means w i t h . d i f f e r e n t 0.0001; ' ° P < 0.01; C  *n-6  ewes  in  each  6  superscripts P < 0.05; ,  t  group.  g  w i t h i n t h e row d i f f e r < 0.001). ,  n  significantly(  b '  P <  5000  •  •  Se intake (ug/d) F i g . 1 6 . E f f e c t o f Se i n t a k e o n t i s s u e Se p o o l s i z e i n p r e g n a n t ewes f e d Se p o s i t i v e or deficient rations. The r e g r e s s i o n e q u a t i o n s a r e Y - 7 5 . 4 7 + 0.53 X , r - 0 . 7 6 , l i v e r ( A ) ; Y-1477.35 + 4.55 X , r - 0 . 7 1 , s k e l e t a l muscle (•); Y - 4 3 . 3 7 + 0.08 X , r - 0 . 7 1 , h e a r t (a) and Y - 2 8 . 3 9 + 0.23 X , r - 0 . 7 6 , s p l e e n ($).  Table  11. K i n e t i c parameters d e f i c i e n t pregnant  oftissue ewes.  Se m e t a b o l i s m  i n Se p o s i t i v e a n d  Fractional rate constant (Fraction/d) Tissue Se  *of  positive (n=4)  Se  deficient (n-3)  Se  positive (n-4)  Se  deficient (n-3)  Liver  0.0439  0.1245  16  6  Kidney  0.0618  0.1488  11  5  Sk.  0.0122  0.0320  57  22  Heart  0.0273  0.0760  25  9  Lung  0.0534  0.1143  13  6  Spleen  0.0139  0.1313  50  5  Muscle  Se u t i l i z a t i o n  i n the  individual  tissues.  Ill  rations  The Se  tissue  positive  10.  Se  higher  spleen of  in  deficient  positive  the  ones.  stable  liver  I ewes  Se p o o l s  and  the  muscle, heart tissue  Se  than  values  turnover  o f Se.  tended than  t o have  than  sizes  Se  stable  Se  positive  ewes  the  skeletal  muscle,  sizes  in  the  slightly  other higher  was  i n the  heart  ewes.  the  Se  skeletal  parameters of  11.  The  utilization a  i n the  Se rate higher  Se p o s i t i v e  values  and  higher  II  liver,  ones i n d i c a t i n g  hand t h e  <  Se p o o l  _< 0 . 0 5 )  Table  (P  A  than  kinetic  higher  positive  Table  ones.  between  of  the  l u n g and  the group  relationship  are given  On t h e  of  (Fig. 16).The  in  heart,  i n deficient total  pool  of  significantly  muscle,  had g e n e r a l l y  the d e f i c i e n t  presented  than  linear  and s p l e e n  constant  are  i n the t i s s u e s  tissue  ewes  pool  had s i g n i f i c a n t l y (P  metabolism  deficient  of  Similarly  T h e r e was a p o s i t i v e intake  skeletal ewes  and  were  (P <^ 0 . 0 1 )  higher  o f group  ewes  concentrations in liver,  Se  significantly observed  Se c o n c e n t r a t i o n s  and d e f i c i e n t  The  0.0001)  lung  P <^ 0 . 0 5 ) .  and were s i g n i f i c a n t l y d i f f e r e n t (  ewes tissues  ones.  DISCUSSION  The parameters those  values  of  observed  various  post-operative  i n the  ewe  r e p o r t e d by o t h e r  workers  were  physiological  i n agreement  (Anand e t a l . 1 9 7 9 ;  with  Hodgson  112  et  a l . 1980;  and  Krishnamurti,  had  c h r o n i c a l l y implanted  with  the  Kitts  fact  and  1984)  of  ewe had r e c o v e r e d tracer  ewes  vascular ewes  bearing  This  to  the surgery  Schaefer  fetuses  catheters.  started  2 d after  amounts o f f e e d w i t h i n the  for  that the  1982;  Krishnamurti,  that  coupled  eat  normal  indicated  from t h e s t r e s s o f s u r g e r y  that  a t the time  experiment.  75  The for  plasma  about  the  Se s p e c i f i c  half  an hour  Se d e f i c i e n t  reappearance gradually  ewes.  which  over  activity  initially  i n t h e Se p o s i t i v e as w e l l  T h i s was f o l l o w e d  lasted  several  declined  by  an  as  in  increased  f o r about 6 hr b e f o r e d e c l i n i n g  days.  This  type  of  characteristic  75  plasma  Se c l e a r a n c e  ewes f e d similar  Se p o s i t i v e  phenomenon  i n goats  was  reported  (Allen  that  in  a l s o observed  and d e f i c i e n t  (Sandholm, 1 9 7 3 ) ,  mice and  was  also  noted  by  other  1  within  I).  workers  A in  (Symonds e t a l . 1 9 8 1 )  1981).  and M i l l e r ,  nonpregnant  r a t i o n s (Expt  i n dairy cattle  mice  i n the  min  (1973)  Sandholm after  the  tracer  75  injection taken be  50% o f  up  by t h e  released  within  intravenously erythrocytes  from e r y t h r o c y t e s  15 min p o s t t r a c e r  administered (RBC).  Se  and t a k e n  injection  at  was  had t h e h i g h e s t  Se  activity.  was  found  to  up by  the  which  time  the  (1973)  also  75  liver  Se dose  Sandholm  liver  75  suggested that from the l i v e r  t h e r e was an e x p u l s i o n o f Se t a k i n g p l a c e i n t o the plasma around 1 h r a f t e r the t r a c e r 75  injection  a t which time the plasma  Se  was  found  to  be  113  gradually  increasing.  transport due  to  due  the  speculated  from e r y t h r o c y t e s  contrast,  clearance  the  was  to  liver  albumin-glutathione-Se  In  to  Se  an  1973). that  of  It  action  Symonds  of  Se  of  liver  in  cells  the  could  be  complex  (Sandholm,  al.  (1981)  suggested  blood  plasma  et  from the  that  cattle.  It  was  was  mainly reported  75 that  the  Se  was  greater  the  rapid  radioactivity  than  in  the  showed  that  injection  75  the  bound  Se  phase  the of  a  portal venous  and  that  venous  plasma  plasma  during  the  liver  was  75  removal of injected 3 Symonds et al. (1981) S  re-entered  to  the  hepatic  distribution  a c c o u n t i n g f o r 40% of the plasma. The s t u d y  in  the  plasma  plasma  within  component  e  from also  0  1 hr  after  probably  a  r-  plasma  was  75 globulin. found  to  50% o f  The peak occur  the  (Symonds  et  al.  injection  the is  more  with  and in  tracer  occur  these the  regard in  Miller(1981) reappearance  On  other  the  to  the  the with into  in  were  plasma  and  regard plasma  to  took  hand  of  2 min  the  higher taken  Se with  place.  sample 75  peak  Se  of  goats tracer  than  those after  1981).  study  et  Our al.  (1981)  radioactivity  that time  being  immediately  Symonds 75  of  the  activity  following  Miller,  that  amount  the  initial  hr  even  and  the  and plasma  3-6  samples  with  the  blood  around  into  with  in  (Allen  agreement  Se  present  initial  injection  in  reappeared  1981).  to  of  postinjection  concentrations  reported  observed  1 hr  radioactivity  reappearance were  at  reappearance  of at  Allen which  Differences  that and  maximum in  the  114  plasma to  Se r e a p p e a r a n c e a c t i v i t i e s  ( i ) the  protein  components  variations and  differences that  the  bind  in different  initial  reappearance  the  be due  of  plasma  to  Se  and  ( i i )  by t h e  liver  species.  decline  of  could  synthesis  i n t h e r a t e o f p l a s m a Se c l e a r a n c e  erythrocytes  An  in  and t i m i n g s  followed tracer  by  into  an  increased  the  systemic  64 circulation  was a l s o o b s e r v e d  p r e g n a n t ewes i n  with  Cu i n j e c t e d i n t o  the p l a c e n t a l t r a n s f e r  studies of  the  copper  64 (Sansom e t a l . 1 9 7 9 ) . the  p l a s m a was  (in  fact  much  during  Since longer  the  e x p e r i m e n t ) and t h e f a c t shorter to  (12 h r ) , t h e s e  account  for  radioactivity.  the In  o f p l a s m a samples  the p e r i o d o f (10-24  entire that  Cu r e e n t r y  hr) a f t e r  duration  of  the h a l f l i f e  injection  the 64  of  tracer  Cu was  workers a p p l i e d a c o r r e c t i o n over-estimates  the present  in  study  (3 d) and t h e c u r v e  the  into  mean  the longer  much  factor specific  collection  p e e l i n g of the  plasma  75 Se ' r a d i o a c t i v i t y (AUTOAN, Sedman correction  for  specific  activity  curves during  by non-linear regression methods and Wagner, 1976) f a c i l i t a t e d the 75  over-estimates  and e x p o n e n t i a l the  course  automatically equations of  tracer  disappearance  lost.  Thus  the  biological  the  very  e a r l y phase  during  in and  with  fitting  followed  by  the  plasma  Se  resulted i n  best  fits.  the  However  characteristic  reappearance  significance  smooth  of  (hump) Se  is  transport  following tracer injection  may  115  a l s o be  missed. In order  to obtain  simulated curves more powerful (Simulation,  Analysis  physiologically  kinetic  programs  And Modeling)  Berman and Weiss ( 1 9 7 8 ) .  Ramberg  were  et a l .  best  like  SAAM  developed  (1973)  used  by SAAM  along with the deconvolution a n a l y s i s to study the i n u t e r o p l a c e n t a l t r a n s f e r and the i n v i v o metabolism o f c a l c i u m i n pregnant lately  sheep.  The  f o r the  SAAM program  has a l s o  been  development o f k i n e t i c models  describing  the metabolism o f v a r i o u s n u t r i e n t s such as glucose et  al.  1983),  copper (Weber e t a l .  phosphorus (Schneider  (Wastney  and c a l c i u m and  1983)  1985)  et a l .  used  i n sheep  and  zinc  ( F o s t e r e t a l . 1 9 8 4 ) i n humans.  Symonds e t a l . 64 d i n d a i r y  reported a T^^ °f approximately  (1981)  2  cows that were  injected intravenously  with  75  S e - s e l e n i t e . The discrepancy between our study and t h a t o f Symonds e t a l . duration  could be the r e s u l t o f  (1981)  o f the present study  s m a l l e r as compared to those al.  (1969)  ration  which  (3 d ) .  ppm  The T.^ values were 2  reported i n sheep by Lopez e t  were approximately  containing 0 . 2 6  Se  fed a Se d e f i c i e n t  20  d  f o r lambs fed  and approximately  lambs  Se.  The values i n the study of Lopez e t a l . based  v a r i o u s times  on the  f o r 14 d  69  a d  r a t i o n c o n t a i n i n g 0 . 0 1 ppm  for  calculated  the s h o r t e r  whole body counting  (1969)  were  o f lambs a t  a f t e r the t r a c e r i n j e c t i o n and  this  might have c o n t r i b u t e d to the d i s c r e p a n c y to some e x t e n t . As  pointed  out by  Hansen  and K r i s t e n s e n  (1979),  in  116  prolonged  s t u d i e s o f Se a  c o u n t i n g w o u l d be due the  hair  for  a l l practical  l/2  *  can  be  T  s  o r wool  D a s e a  -  o  to  although  the  being  a  an  assumption be  valid  first  order  depend on on  the  growth  the metabolic  Moreover with  regard  Under  processes  there  of  1.5  t o 8.0  in  mice -  (Furchner 1969);  monkeys -  et  al.  many of  65  cattle d  et a l .  1975).  factors  animals,  amount  life  may n o t  counting  64 d  (Bielstein 1975);  than  °f values  2  S  literature observed  e  are:  i n rats -  13 d ( B l i n c o e , 1 9 6 0 ) ,  i n sheep -  would  rather  i n the  and K r i s t e n s e n , 1979) -  20-69d  (Symonds e t  et a l .  1984)  and i n dogs -  The v a r i a t i o n s such  o r wool t h e  and 50-59 d (Thomson and S t e w a r t ,  a l . 1975);  i n dairy  (Furchner  e t a l . 1972),  14 d (Hansen et  half  of biological  v a r i o u s s p e c i e s . The r e p o r t e d T ^  (Ewan e t a l . 1968)  hair  o r wool  controversy  in  d (Burk  (blood  circumstances  body  hair  an  o c c u r r i n g i n the animal.  is a  t o the values  into  i n whole  rate  body  with  pool  such  the b i o l o g i c a l  the decrease  in  biological  reaction  the c e n t r a l  i s incorporated  for calculating as  estimation of  a t t a i n e d between  element  Se  that the e l i m i n a t i o n process  o r p l a s m a ) and a l l t h e o r g a n s . where  of  body-  e l i m i n a t e d from t h e  The  *-he a s s u m p t i o n  n  concentration  i t was  purposes.  d e s c r i b e d by  equilibrium  g r e a t e r p r o p o r t i o n o f whole  2  dose  d  (Lopez e t  a l .  a l . 1981);  in  and  46-53  d  (Furchner  c o u l d be due t o  a s s p e c i e s , d i e t a r y Se l e v e l s , of tracer  d  1973);  and 17-18  46 t o 60 d  i n the T ^  43  administered,  Se  status  route  of  117  administration, analytical in  the  A  duration  methods  curve  peeling  i n the  f o r m e r ewes. of  Se  a  (manual v s .  higher  Se  ones s u g g e s t i n g  greater  p o s i t i v e ewes u n l i k e i n the  Se  intake  deficient ewes were  found  to  different  metabolic  p l a s m a Se  turnover  losses net Se  Se  through  (%  Se  transfer  (Expt.  II  ultimate  aim  all  deficient an  ewes  optimum  reflect  the  The higher  was  C).  It  these  o f Se  feces  (Table  may  be  the  i n the  Se  the  i n Se  Though  the  lower  in  homeostasis  9),  i)  metabolic increased  iv) increased  plasma  Se of  the  in  the  was  p o s i t i v e ewes on  level Se  body o f p r e g n a n t  trial.  The  combined u r i n a r y  Se  Se  that  adjustments  urine  tissue  placental  suggested  ID  by  decreased  i i i )  net  Se  deficient  at  would  ewes.  generally all 5 d  of  5  d  75  the  entry the  the  plasma  through  the  of  reduced  decreased  maintain  turnover  i n the  ii)  metabolic  Therefore  of  ones.  included  basis),  v)  level.  excretion  than  8),  urine  and  to  plasma p o o l  Se  which  in  greater  0.0001)  their  intake  11)  the  was  deficient  o f Se  p o s i t i v e ones,  (Table and  <  (P  adaptations  (Table  of  i n t o the  maintain  feces  absorption  turnover  i n the  by  deficient  significantly  ewes t h a n  d i s p o s a l o f Se  turnover  explained  d i e t a r y sources  in  differences  t h a n i n the  plasma  be  the  errors  computer) methods.  ewes  Se  was  period,  irreversible  positive  This could  f r o m the  experimental  (whole body c o u n t i n g ) and  significantly  observed  of  l o s s e s over  a  118 period in  Se  of  the  accounted positive dose  that  the  of  the  for  approximately  ewes,  whereas  administered.  urinary  and  in  lambs.  were  in  agreement  almost  study  75  fecal  respectively  The  (14%)  employed  lower  (5  be  d)  as  dose  losses  were  al.  losses  were  of  results  from  the  Se  those  losses  to  against  12  d of  9%  reported 5%  Se-selenite present Lopez  observed  shorter  about  31% a n d 75  of  the  injected  (1969)  dose  with  due  On t h e o t h e r h a n d i n Se were generally higher  Se  et  the  injected The  urinary  could  fecal  Lopez  intravenously  (1969).  the  14% o f  in  study et  al.  the  current  collection  period  Lopez  et  al. 75  (1969).  d e f i c i e n t ewes t h e f e c a l Se l o s s e s than the urinary losses. The 75  cumulative  fecal  approximately  7 and  were  in  (1969) lost  contrast who  in  source  positive Se  in Se  and d e f i c i e n t  (22%)  > barley  (75%)  was  the  in  major  and  hay  (7%).  were  significantly  injected.  reported  equal of  the was  by  amounts  Se  found In  Se  order  in Se  estimated  reduced  in  Se  ones vary  hay Se  fecal  et  tracer  al.  to  be  the  Se  sheep. in  (Table  9).  The  between  the  ewes  dietary  the  (67%)  by  > ones  barley  and u r i n a r y  deficiency  results  Lopez  deficient  followed  were  These  lower  positive of  whereas, of  to  losses  of  deficient  positive  ewes.  source  The  Se  significantly  the  (11%),  dose  those  was  than  were  the  and u r i n e  dietary  sources  urinary  almost  intake  ewes  of  with  feces  Se  deficient  3% o f  observed  the  The  and  (Table  Se 9).  Se  water water (18%) losses When  119  the  fecal  basis  Se  the  losses  values  deficient  ewes  Se  fed  positive  suggested the  that  Se  recently in  intake  urinary  a  be  due  primarily  t h r o u g h the Levander  The  P e t e r s o n and  1981)  9%  and  This  et  al.  of  the  Se  Se  control (1983)  homeostasis studies  excretion  is  (Cousins  and  ruminants 1963)  whereas i t i s  (Bopp  indicating  a  respectively.  Swanson  Spedding,  on  ewes  a  in  on  in  exert  i n monogastrics  al.  expressed  d i f f e r e n c e s between t h e s e  feces  the  deficiency.  d i d not  that  and  control  Se  were 11  regulation  fact  the  urine  et  Contrarily  the  1961;  of  l o s s e s were  route  intake  positive  homeostatic  values  Se  renal  through  Cairney,  Se  to  Se  the  retention.  reported  a  Se  Se  indicated that  deficient rations  p r e g n a n t women.  could  the  basis  the  in  conditions  urinary  and  a percent  This  exerted  under  percent  on  tract  when the  Se  33%  and  respectively.  metabolism  However  58  were  gastrointestinal Se  were e x p r e s s e d on  et  1982,  al.  a species  variation in  metabolism.  The reduced  endogenous i n Se  positive fecal  ones Se  pancreatic  (52  ug/d)  would  of  injected) 1966)  Se  had  and  (Table  be  secretions of  Baumann,  Se  d e f i c i e n t ewes  secretion dose  fecal  losses (14  ug/d)  9).  The  either  entering been and  very  as  significantly  compared  origin  of  t h r o u g h the the  duodenum.  shown t o variable minimal  were  be in  (0.6%  very rats  to  the  endogenous biliary The  or  biliary  little (Levander  of dose i n j e c t e d )  (1-2% and in  120  ruminants in  thebile  h a d b e e n shown  arsenic  compounds  1966).  Se  was  by  the pancreas  to  be r e a b s o r b e d 1980).  al.  and only  shown  from  source  theliver  of  50%  of that  percent  reported  Se  intake  increase  the  conditions  The higher ones  (Table  absorption Se  whose  ducts  Se  fecal  Se  was An  observed  48  ug Se/d  intake  was  i s  Se v a l u e  earlier  mechanism o p e r a t i n g Se  of  approximately  a l . (1986)  et  of  ruminants  14 u g S e / d w a s  As discussed  efficiency  using  secretions.  Se d e f i c i e n t ewes  basis.  et  reported  i n  The e n d o g e n o u s f e c a l  Se a b s o r p t i o n  the  Se p o s i t i v e  9).  This  rates  by  indicated  the  rates ewes  ( u g / d ) was d i r e c t l y  consumed  absorption  a n d was f o u n d  a l . (1986)  endogenous  loss of  Baumann,  on  the  this  could  i n t h e ewes  utilization  to under  of deficiency.  apparent i n  et  when  (Lake-Bakaar  the biliary  by Langlands  be d u e t o a h o m e o s t a t i c  enzymes  pancreatic  the  through  i nthe  and  p a n c r e a s was minimum  1986).  et a l .  14 u g / d o b s e r v e d  of  ligated  Se d e f i c i e n t w e t h e r s  excretion  i n t o t h e duodenum  i n man  Langlands  endogenous f e c a l  (Langlands  t o be s e c r e t e d  and r e c i r c u l a t e d  without  Se  (Levander  i n t h e form o f p r o t e i n  thecontribution of  estimated in  were a d m i n i s t e r e d also  or  t h emajor  However,  t o be g r e a t l y e n h a n c e d o n l y  Contrarily  wethers with that  1981).  (Symonds e t a l .  that  than  significantly  i nthe deficient  the rate  proportional  ewes.  were e x p r e s s e d  were  When  as percent  o f a p p a r e n t Se  to  the  the  amount  apparent  Se  o f Se i n t a k e  the  121  values  43 a n d  were  positive  and d e f i c i e n t  absorption  o f Se i n  monogastric and  Se p r e s e n t  Spedding other to  c o u l d be a s i n  by  the the  be  absorbed  feed  absorption Se  15; as  study  against  were  humans  and  ones. the  A  Se  percent  fecal  respectively rations. absorption deficient  i n  i n  intake  On a  the  Se was  Se  losses the  ewes.  the  were  These  Se p o s i t i v e  an  and  the  net  to  net i n  values  was  Se the  were i n the observed  Se a b s o r p t i o n ( F i g r a t e s were  the values  percentage  intake  basis  significantly ones.  56  were  positive  i n the positive  added  ewes t h a n  f e d Se  ewes t h a n  found  Reasbeck  resulting  relationship  intake  were  the  g r a d i e n t by  ewes  values  and  On  and Cho, 1 9 6 5 ,  values  linear  o f Se  insoluble  rate.  deficient  higher  organic  (Peterson  the organic  (McConnell  of  Se a b s o r p t i o n .  a concentration  i n  eta l .  into  rumen  Se  (Thomson  (Robinson  1969) the  than  rats  of conversion  r = 0 . 8 9 ) . When t h e n e t S e a b s o r p t i o n a  i n  91-97%  i n  lower  r a t e s w e r e 2 4 1 a n d 78 u g / d r e s p e c t i v e l y  significantly  between  apparent  i n  Se a b s o r p t i o n  positive  deficient  for  animals  When t h e e n d o g e n o u s apparent  These v a l u e s  i n lowered  a l . 1981) a t a faster  the  fed  (Shrift,  bacteria  transport process  ewes  a result  resulting  (1963)  i n the  were  and 66-75%  hand i n monogastric  active et  rations.  the present  1973)  This  compounds  respectively  species which  Stewart,  1978).  67%  and the  higher This  expressed and  84%  deficient net i n the  higher  Se Se  n e t Se  122  absorption  (%) i n S e d e f i c i e n t  adaptation  t o increase  the  animal  under  The  apparent  0.05)  higher  deficient  58%  t h e Se a v a i l a b i l i t y  conditions balance  i n Se  positive  respectively rations.  significant ewes were  (P  Se i n t a k e  retaining  Se  supply. (P £  ug/d) than  i n  However  when t h e s e  were  basis  t h e v a l u e s were  f e d Se  indicating  more Se  to thetissues of  dietary  differences  0.01)  _<  metabolic  (145  i n t h e ewes These  be a  was s i g n i f i c a n t l y  ewes  ug/d).  on a percent  deficient  o f reduced  or retention  (56  ones  expressed and  Se  ewes m i g h t  positive  were that  i nspite  and  statistically  t h e Se  of  32  their  deficient  lowered  Se  intake.  The in  tissue  Se p o s i t i v e  This  indicated  was  directly  the  ration  Se c o n c e n t r a t i o n s ewes t h a n that  spleen  hand  i n  c o n c e n t r a t i o n s were > lung  observed  and t h e l i v e r  other  > liver.  by  (1968a)  i n lambs.  the  after  sequential  The  obtaining  slaughter  total  i n  highest  Se  the  of kidney  (1967)  tissues  present  ewes.  ewes  10).  (Table  followed  positive  v a l u e s were  b y Maag a n d G l e n n  The  thekidney  deficient  reported  determined  i n  i ntheorder  These  o f Se  t h e ewes.  i n t h e Se Se  ones  higher  o f Se i n t h e  b y t h e amount  consumed  significantly  i nthedeficient  theconcentration  influenced  c o n c e n t r a t i o n was  were  by t h e On  the  tissue  Se  > spleen  >  heart  i n agreement w i t h  those  i n ewes a n d P a u l s o n  tissue  Se  theindividual o f t h e ewes  at  pool  et a l .  sizes  tissues different  were  following times.  123  The Se  tissue  Se  positive  pool  ewes t h a n  explained  by  in  positive  the  9).  Se  the  skeletal  Though  the of  information For  the  this  in  positive the  Se  T  equations  w  e  to  Se  and  Se  e  the  could  they  metabolism  (Table  in  the  16).  (Fig.  values  were  (Hartley  do  be  observed  size  ewes  the  higher  ones  pool  spleen  the  1981)  in  was  concentration  of  r  This  deficient  fractional  i / 2  ones.  relationship  s t a t u s of  the  higher  significantly  total  tissue  kinetics  and  the  heart  reason  utilization  i n t a k e s were  liver,  Se  the  significantly  deficient  Underwood,  on  exponential  Se  i n t a k e and  1961;  Grant,  the  a linear Se  were  ewes t h a n  muscle,  indicative  in  t h a t the  Indeed,  between  sizes  and  not  provide  i n the  tissues.  rate constants  determined  after  individual  (whole)  of  Se  fitting tissue  75 Se  specific  indicated  activity  t h a t the  data  turnover  11).  (Table  of  Se  was  c o n d i t i o n s . However  these  out  i n the  previous  w i t h nonpregnant  I),  would  Se  into/from  represent  approximation turnover pools  the  ewe  of  coupled  i n the  faster  the  rates of  tissues  the  and  actual tissue  with  the  deficient  ewes  (Table  from  the  d e p l e t i o n of and  both  her  Se  f e t u s t o Se  values,  2  e n t r y and  pointed  ewes  (Expt.  disappearance are  turnover.  This  significantly  tissues  lower  would and  in  as  therefore  10)  data  generally higher  deficiency  experiment  T^^  These  only  d e f i c i e n c y syndromes.  an  increased tissue  result  might  of  in  Se a  predispose  124  A  direct  nonpregnant  comparison  ewes  and  is  the  time  and  physiological  duration  of  similar.  On t h e  0.05) ug/d). and in  other  higher This  is  apparent  hand  the  also  ewes  several  the  varibles  i n the  ug/d)  was  reflected in  in  3 and 9 ) .  intake  net  was  pregnant  ewes  Se  the  (P  ewes  _< (44  absorption  pregnant  When  of  group  nonpregnant  higher  as  status  significantly  Se d e f i c i e n t  (Tables  of  vs  such  Se  T h e Se  Se p o s i t i v e  Se c o n s u m p t i o n (91  prior  animals.  corresponding  Se b a l a n c e  nonpregnant  of  ewes  rations  than  with  i n pregnant  experimentation,  condition  and nonpregnant  Se d e f i c i e n t  Se m e t a b o l i s m  confounded  pregnant  fed  of  ewes  final  than slopes  75 of  plasma  found  to  Se be  higher  corresponding increasing tissue  clearance in  requirements  of of  were  Se p o s i t i v e  nonpregnant  demands  curves  Se the  examined,  pregnant  ewes.  This  by the  pregnant  growing  may  be  ewes  than  attributed  ewes  conceptus.  they  to  meet  were the to the  125  EXPERIMENT  I I B: K i n e t i c s o f s e l e n i u m  positive  or deficient  fetal  metabolism lambs  i n Se  i n utero. r  INTRODUCTION  Early use  of  s t u d i e s on f e t a l  n u t r i e n t metabolism  e i t h e r acute  surgical  comparative Colorado of  this  utero the et  developed  chronic  and  slaughter  fetal  paved  vascular  the  i n conscious metabolism  a l .  1981;  ewes.  was s t u d i e d  catheters  Using  of various  fetal such  for  Schaefer fetus.  1965)  et a l . studies  chronic  1982)  i n  placement  metabolic  and K r i s h n a m u r t i ,  i n t h e sheep  the  (Meschia  such  1983;  or  Researchers  substrates  (Lemons and S c h r i e n e r , 1984)  procedures  way f o r t h e  Kitts  preparations  techniques.  surgical  involved the  i n  preparations  as glucose and  and  (Hay  aminoacids  Krishnamurti,  Although  the  recovery  75  of  Se  i n the  accompanied demonstrated  by the  1964;  Jacobsson  1969),  there  Se  Se  utero.  slaughter  i n  maternal at  and  Oksanen,  i n  Se  the fetus study  1966;  tracer  injection  different  p l a c e n t a l Se t r a n s f e r  the present  metabolism  following  i s no i n f o r m a t i o n  utilization  Therefore  fetus  (Wright  times and  Hidiroglou  Bell, et a l .  a v a i l a b l e on t h e k i n e t i c s under  was d e s i g n e d  i n utero  conditions.  to investigate  positive or deficient  of  sheep  fetus  the i n  1 2 6  M A T E R I A L S AND METHODS  Animals, as  feeding  described  i n Expt.  (a)Surgical  110-120 "PE-90  (Intramedic  silastic  blood  the  surgery  The 36 The  hr  and  ewes were prior  were  ml/kg wt,  ewe a n d  by K i t t s  post-operative  catheters  Adams, P a r s i p p a n y , N . J . ) surgically  the fetus  care  into  according  (1979).  et a l .  deprived  o f food,  given  maleate  2-3  an  of the  the  to the  The d e t a i l s animals  washed  thoroughly was  intravenous  induced  of are  by slow  Laboratories)  and t h e  (1 m l o v e r  o f sodium  a t a dose  dose  24size.  injection  t o prevent  iodine  for  rumen  procedures.  coarse  with  injection  the  Ayerst), at a  preparative  was  anesthesia  reduce  the surgery  t h e abdomen was c l i p p e d  but n o twater  intramuscular  (Atravet,  hr before  pre-operative  to  over  Abbott  Clay  introduced  t o surgery  were  acepromazine  min)  same  below:  ewes  during  gestation polyethylene  and PE-50",  of the  reported  described  the  I I A.  d of  tips  vessels  procedure  were  Procedures;  Around  with  a n d management d e t a i l s  of  of 0.01  excitement The  wool  operative  site  soap.  General  a period  thiopental  of  1-2  (Pentothal,  o f 20 m g / k g b o d y w e i g h t .  An  127  effective reflex  anesthesia  and  intubated Ayerst) with  the  and a  mandibular mixture  i n oxygen  the  was e n s u e d  ewe  i n  was a d m i n i s t e r e d  drip  to  surgery.  replace  (0.06  subcutaneously surgery heart  t o prevent beat  and  frequently over the  mg/kg)  the  during  was  site  washed  below the umbilicus through  the  palpated to  the  least the  the  exterior vascular  hooves  incision suture around  fetal  of amniotic  exteriorized  by  of  the  fluid. cutting  The  wool  clipper  and  (Surgidine,  incision  the  w a s made  by  cutting  horn  limbs  incision.  A  A  exposing  purse  (Ethicon)  the fetal  and t h e  through  brought  was c h o s e n a n d a  catgut  The h i n d  was  f e t u s were  of cotyledons,  including  handling  monitored  uterine  uterine wall.  chromic  The  were  abdominal  devoid hind  surgery.  was e x p o s e d  The g r a v i d  the  the  soap  skin  given  before  a fine  iodine  limbs the  by  during  was  of surgery.  cm m i d l i n e  through  the u t e r i n e opening the  during  rate  with  limbs  2-0  losses  hour  salivation  hind  area,  a  fluid  an  and t h e uterus  made o n  with  facilitate leakage  again  of the fetal  was  half  dextrose  intravenously  was removed w i t h  peritoneum.  and  and  course  A 10-15  Ingram and B e l l ) .  A sterile  animal  respiration  the  the operative area  position.  (BDH p h a r m a c e u t i c a l s )  excessive  was  anesthesia  the  sulfate  animal  f o rmaintaining  electrolyte  Atropine  The  corneal  (Fluothane,  used  to  the  1.0-1.5% h a l o t h a n e  the supine  saline  checking  movement.  of  was  by  small string  was  membranes  prevention of the fetus fetal  made to of were  membranes  128  carefully. the  hock  locate  The w o o l  joint  saphenous  HCl  (Duracaine,  were  with  the external  the  vein  By  vein  the  t i p of  vena  cava.  pedal  a  blunt  A small  the  incision  catheter  was  hind  overnight  i n  solution  catheters  were  to  with  rinsed  saline  the fetal  0 silk  cidex  blood  skin  4-0  catheterization  catheter  instill  The  uterus  vein  silk  back  suture.  the  Ayerst)  the uterus  antibiotic was c l o s e d  along  i n  them  Canlab).  The  with  sterile introduction  were  with  anchored  a braided  i n a continuous  Following the  fetal  uterus.  was c l o s e d .  with  keeping  their  limbs  into  inferior  catheterized.  by  was i n s t i l l e d  during  the  were a l s o  The c a t h e t e r s  hind  into  o f 20 cm s o t h a t  and o c c a s i o n a l l y t h e  before  ( T y g o n ) was i n t r o d u c e d  to  and  s k i n was c l o s e d  ( 5 0 0 mg,  before  the  external  w a s made o n t h e v e i n  filled  and anchoring  carefully  ampicillin cavity  on  anesthetic  for  (Surgicos,  U/ml)  lidocaine  the  sterilized  vessels.  and the f e t a l  a braided  placed  (50  to  a n d was i s o l a t e d  limb  and  to  parallel  local  located  saphenous  were  the fetal  An i n c i s i o n  sterile  above  was c l e a n e d  dissection  catheters  into  clipped  was i n s e r t e d t o a d i s t a n c e  a r t e r y on t h e other  heparinized  was  made a n d a f e w d r o p s o f  The e x t e r n a l  fetal  vein.  was c l e a r e d o f f a s c i a  PE-90 c a t h e t e r  The  was  limbs  and t h e area  Rogar/STB),  catheterization. a  scissors saphenous  instilled.  saphenous  over the hind  An the  the  fashion vascular  hind  limbs  The  antibiotic,  into  the amniotic  amniotic amniotic  the postoperative the fetal  2-  membranes  were  fluid cavity period. using  129  2-0  chromic  was  then  damaging  catgut  buried the  (Ethicon)  into  cotyledons  catheters  were  through  the  peritoneum,  side  the  of  s k i n were  ewe.  respectively. bandage the  was  individual  plus  (100  metabolic 5 ml  Rogar/STB)  of  daily  instilled fluid  Ayerst) into  catheter  uneventfully after  the  the  long  and  acting  with  A  2 ml  containing amniotic  the  the  cavity  feeding  moved  of G  heating  Penlong-S 250  and  mg  administered solution  Ampicillin  The  to  (Penlong-S  through the  f o r 3 days.  sterile  infrared  was  mg  using  catheters  were  ml  Both  ewe  of A m p i c i l l i n  100  sterile  abdomen.  Penicillin Each  and  fashion  with  ewes  antibiotic  days.  right  (Ethicon)  the  Penicillin  resumed n o r m a l  surgery.  the  daily  The  i.u.  once d a i l y  under  patency of  provided  The 3  for  (Penbritin,  Proline-0  intramuscularly.  dihydrostreptomycin. once  and  them  U/ml).  crates  200,000  contained  a continuous  catheterized in  filling  saline  were g i v e n  plus,  by  made  the  in  The  The  tunnel  s k i n on  were t u c k e d  tubing.  without  abdominal muscles  t h e wound a r o u n d  were  which  suture.  a small  peritoneum,  catheters  (PE-90)  maintained  heparinized  and  The  second  via  Plain-0  veins  polyethylene  a  separately  a p p l i e d over  jugular  with  suture  musculature  f l a n k m u s c l e s and  The  sutured  a continuous  uterine  exteriorized  Ethiflex-O,  using  the  as  ewes  within  was amniotic  recovered 2  days  130  (b)Experimental  Following  procedure;  the  intravascular  allowed  to recover q u i e t l y  stress.  The p o s t s u r g i c a l  by  recording  hematocrit Expt. of  blood and  gas  for  tensions  70  (  were  days from the s u r g i c a l  p C 0  2  a n o  was  -  verified P '  2^'  p 0  H  as p e r t h e methods d e s c r i b e d  t o each t r a c e r  approximately  five  the f e t u s e s  normalcy of the f e t u s  hemoglobin  IIA p r i o r  surgery  experiment.  uCi ( s p e c i f i c  A  bolus  activity:  in dose  187-919  75  mCi/mg  Se)  Irvine,  of  C a l i f o r n i a ) was  Se p o s i t i v e 665  fetuses  and 707W)  725,  sodium  909  and  Se-selenite injected  240,  300  360  and  min  thereafter  for 3  fetus  the 6 hr p e r i o d  over  exceed  18  were  also  placental Blood  ml.  Blood  transfer  s a m p l e s were k e p t The  30,  blood  from  collected  Se p o s i t i v e  60,  and  fetuses: from  the  120,  180,  once  withdrawn  daily  from  the  the c o r r e s p o n d i n g  simultaneously  frozen  45,  654,  on t h e day o f e x p e r i m e n t d i d  samples  and  samples  postinjection  for  o f Se f r o m t h e f e t u s  were  heparin  15,  587,  (group I I  Blood  10,  The t o t a l  obtained  samples  containing  d.  5,  Chemicals,  vena cava o f  572,  fetuses  respectively.  were c o l l e c t e d a t 2 ,  fetus  inferior  (group I f e t u s e s :  and Se d e f i c i e n t 1000)  into  (ICN  into  centrifuged  ewes  determining  the  t o ewe  (Expt.  IIC).  chilled  pyrex  tubes  immediately.  at -20° C for further ewes were  not  sacrificed  Se on  Plasma  analysis. days 7  (#  131  654),  9  killed  on d a y s 5  after  (#  587)  tracer  delivered fetus  and 23 (#  572)  909),  and t h e d e f i c i e n t ewes  7 (#  i n j e c t i o n i n t o the  1000)  collection.  dried,  Liver,  21  kidney, were  724)  The f e t u s e s  under E x p t .  heart,  were  (#  for  s p l e e n and  collected,  were  I I A.  w e i g h e d and d i s s e c t e d  (gastrocnemius)  w e i g h e d and s t o r e d  and  fetuses.  by l a p a r o t o m y as d e s c r i b e d  was t o w e l  muscle  (#  The  tissue  skeletal  towel  dried,  a t - 2 0 ° C.  75  Stable of  Se  and  and t h e k i n e t i c  d a t a were t h e same as d e s c r i b e d All  fetal  the r e s u l t s  plasma  two way a n a l y s i s the  under E x p t .  were e x p r e s s e d  and t i s s u e  were combined w i t h  and  Se a n a l y s i s  Se  I.  as means +  (stable)  analysis  SEM.  concentration  s h e e p were  using  assumed  SAS  t o be  (1985).  t h e main  subjected  to  variance  1985).  Student's  ' t ' t e s t was u s e d  significance of difference  two g r o u p s o f  fetuses.  between  way  effects.  were  the  one  the  by  a  The r a t i o n  remaining data (SAS,  data  t h e m a t e r n a l d a t a and were a n a l y s e d  of variance  The  analysis  means  to of  The of test the  132  RESULTS  The  mean  positive  and  12.  These  period  physiological deficient values  which  fetuses  were  commenced  parameter are  recorded  values  presented  during  5 days a f t e r  of  Se  i n  the  Table  experimental  surgery.  75 Following inferior  vena  the cava  injection  of the  of  Se-selenite  fetuses  there  was a n  into  the  exponential  75 decline  i n  contrast  the plasma  to  the  Se r a d i o a c t i v i t y  adult  ewe  ( F i g 17).  the reappearance  In  ( h u m p ) o f Se 75  into  the  plasma  was  into  the  injected disappeared relatively  minimal. Se  deficient  e x p o n e n t i a l l y from smaller  Similarly  fetuses  the plasma  reappearance  of  when the  (Fig.  the  Se  was  tracer  18) w i t h  tracer  into  a the  plasma. 75 The of  the  Figs.  best Se  Two  to  positive  19  equations  f i t plasma  a n d 20  Se s p e c i f i c  and d e f i c i e n t  respectively.  d e s c r i b i n g these  four  exponentials  curves were  activity-time  fetuses  curves  are presented  The  best  are  given  f i t  i n  exponential  i n  Table  required to obtain  the  13. best  75 fit the  curves o f the plasma Se positive fetuses  biexponential (# 572  and  clearance  pattern of 587)  patterns  Se r a d i o a c t i v i t y d a t a . (# 707, 654 a n d 665) 75 Se c l e a r a n c e  exhibited  a  while  t r i - and  respectively.  A biphasic  Three of showed a  the other  two  tetraphasic pattern  of  Table  12.  Physiological  Se  parameters  positive  of  Se  positive  (n=9)  and d e f i c i e n t  Se  deficient  fetuses.  (n=6)  Parameter Mean + S . E . M  B l o o d pH  7.35  Blood  PCC»2  (mm Hg)  Blood  PC<2 (mm Hg)  Hemoglobin  (g  Hematocrit  (%)  Blood  %)  samples  were  Mean + S . E . M  + 0.02  7.37  + 0.02  37.1  + 1.0  35.6  + 1.2  10.1  + 0.7  12.3  + 0.4  11.4  + 0.6  13.4  + 0.4  34.0  + 1.3  35.1  + 0.9  obtained  from the  inferior  vena  cava.  134  O.l-i  CD  CO ton  B  E  O . O O l i  0  1  1  '  10  20  30  Time (Hours) F i g . 17. Changes in plasma ^Se specific activity during first 24 h r after tracer i n j e c t i o n i n t o Se positive fetuses, o i • > O » • > refer to fetus nos. 654, 707W, 6 6 5 , 572 a n d 587 respectively. 7  A  135  F i g . 18. C h a n g e s i n plasma Se specific activity during f i r s t 24 h r after tracer injection i n t o Se d e f i c i e n t f e t u s e s . O , • , O r e f e r t o f e t u s nos. 909, 724 and 1000 respectively.  136  m 0)  o  00. 1 CJ  d  oo CO  o.oon  20  0  40  60  Time (Hours)  F i g . 19. B e s t - f i t plasma S e specific * tivity-time curves of Se p o s i t i v e f e t u s e s . O » Bfl to f e t u r n o L 6 5 4 , 707W, 665, 572 and 587 r e s p e c t i v e l y . 7 5  P  c  137  Time (Hours) 7  F  i  g  .  2  I  .  »  S^/oS"...  .  W  1  )  J  1  ^Se  »  specific  activity-time refer to D  !000  respective!*.  Table  13.  Fetus  Se  Se  Best-fit exponential curves of fetuses.  #  positive  A  l  A  equations  2  3  A  of  A  plasma  4  a  Se  specific  l  a  activity-time  2  a  .019508  .010324  3.3279  .0187  654  .016472  .015369  1.3235  .0127  665  .014707  .008532  3.3662  .0529  572  .015218  .008985  .006662  587  .025661  .006159  .003542  .002687  6.2326  .4906  .0082  35.0147  .0421  .2938  deficient fetuses: 724  .020478  .010593  4.6987  .0192  909  .051408  .021717  6.2838  .0158  1000  .032005  .018706  5.3916  .0197  ^"The e q u a t i o n  is: A  A -  plasma  a  rate  -  a  4  fetuses:  707W  where  3  f c  - v "\ t  Se  specific  constant,  e «  +  "V ~V +  2  A  e  activity  log.  n  +  A  and  3  (fraction t  -  A e A  e  time  of  4  e  ~  dose/ug  (hr).  a  t  4 Se),  .0027  Table  14.  Comparison of a r e a s u n d e r t h e c u r v e s (AUC) a n d p a r a m e t e r s o f Se p o s i t i v e a n d d e f i c i e n t fetuses.  Se  positive  (n»4)  in-vivo  Se  kinetic  deficient  (n»3)  Parameter  AUC ( f r a c t i o n of dose/ug Se).  Plasma Clearance (ml/d/kg B.W.) Plasma (ug)  Se  Pool  Plasma  Se  Cone,  Rate  Size  (ng/ml)  Volume of d i s t r i b u t i o n (ml/kg B.W.) l/2  (  d  Mean  + S.E.M  0.79  + 0.20  0.96  + 0.24  20  with  different  + 9  11  + 3  444  + 157  301  + 91  30  + 1  22  + 5  a  46 310  6.10  )  ' Means 0.10).  + S.E.M  hr  Irreversible Disposal o f Se ( u g S e / d / k g B . W . )  T  Mean  + 4 + 41 + 1.74  superscripts  within  b  53  + 10  232  + 64  3.08  the  row d i f f e r  + 0.26  significantly(P  <  140  Se  clearance  was  observed  in  all  the  three  Se  deficient  fetuses.  The curves  areas  and  deficient  the  under in  vivo  fetuses  are  the  plasma  kinetic  specific  parameters  presented  in  of  Table  activity-time Se  14.  positive  and  Although  the  75 area Se  under  the  deficient  the  plasma  Se  fetuses  positive  ones,  specific  tended  a  to  be  statistical  Irreversible  disposal  values  were  Se  positive  Se  ones  and these  significant. Se  positive  in  the  _<  0.10)  and  d  and  with  3.08  The fetuses  the  of  higher  + 0.26  are  highest  deficient  d  values  of  Se 310  that  differed  SEM)  respectively  of  in  not  be  clearance than  in  in  ml/kg  was  well  pool  size  significantly  (P  Se  the  Se  the not  a n d 232 Se  observed  values  in  distribution  The p l a s m a  being  than  statistically  were  tissues.  could  of  in  Se  are Se  6.10  positive +  positive  1.74 and  fetuses.  tissue  followed  (+  volumes  groups  higher  fetuses  were  fetuses  curve  and plasma  indicated  fetal  both  T h e mean  deficient  the  into  these  fold  deficient  differences  deficient  and  fetuses  fetuses.  in  The a p p a r e n t  respectively distributed  lower  two  significance  established. of  activity-time  by  Se  concentration  presented Se  in  Table  concentration  liver  fetuses  and the  15. was  spleen. kidney,  and  pool In  size  Se  positive  observed On t h e  liver  and  data  in  the  other  hand  spleen  had  of  the  fetuses kidney in  Se  almost  Table  15.  S t a b l e Se c o n c e n t r a t i o n and d e f i c i e n t fetuses .  Se  and p o o l  size  in  the  tissues  Concentration (ug/g)  Pool (ug  of  Se  positive  size Se)  Tissue Se  positive  Se  deficient  Liver  0.29  a  + 0.02  0.15  b  + 0.02  Kidney  0.45°  + 0.06  0.17  d  + 0.06  Sk.  0.10  + 0.01  0.03  f  f  Muscle  e  Heart  0.20  e  + 0.02  0.07  Spleen  0.29  c  + 0.03  0.15  Means w i t h d i f f e r e n t 0.001; ' P < 0.01; C  n=6  d  fetuses  i n  6  each  '  d  Se  positive  Se  deficient  +  4.0  14.  0  +  2.0  2.7  h  + 0.4  + 12.3  31.6  b  + 5.1  29.6  C  8.1«  + 0.01  96.2  + 0.02  5.4  + 0.03  2.1*  a  C  s u p e r s c r i p t s w i t h i n t h e row d i f f e r P < 0.0001; P < 0.05). £  group.  g  ,  n  d  + 1.1  +  1.2  1.5  d  + 0.2  +  0.3  l . l  h  + 0.3  significantly(  '  P <  142  equal  c o n c e n t r a t i o n o f Se.  general than  were  s i g n i f i c a n t l y higher  i n the deficient  muscle  Se  positive  (P  ones.  examined,  the  When  and spleen  positive  and  Se  kidney  twice  tended  differences  this  be  difference,  Se p o o l  lower however,  the maternal  liver both  than  where  skeletal  groups.  be l o w e r  Se  utilization  were  higher 16).  t h a t t h e Se  i n the  17. were  i n t h e Se d e f i c i e n t  maternal  The e x c e p t i o n  of  tissue  The e x c e p t i o n was l i v e r  ones  Se c o n c e n t r a t i o n s  was  Se was p r e s e n t  Se m e t a b o l i s m  of  i n  not  of  i n Table  than  <  statistically  The  a r e presented  (P  i n thepositive  concentration  parameters  i n the  i n Se d e f i c i e n t  hepatic  kinetic  were  muscle  fetuses  i t was f o u n d  (Table  sizes  (P > 0.10)  constants  to  similar  statistically  t h e f e t a l and maternal  fetuses  both  data  significantly  i n thefetus  o f t h e Se  was o b s e r v e d  was  compared w i t h  tissues  i n t h e Se  pool  size  than  When t h e f e t a l t i s s u e  was  Se  value  significant.  concentration  were  o f Se d e f i c i e n t  The l i v e r  to  than  were  t h e Se c o n c e n t r a t i o n o f Se  (P < 0.05),  heart  fetuses  fetuses  and spleen  total tissue  (P < 0.01)  ones.  positive higher  a s i g n i f i c a n t l y lower  (P < 0.05),  fetuses  the  positive  i n  The c a r d i a c a n d t h e s k e l e t a l  of  liver,  fetuses and these  significant.  0.10)  The  Se c o n c e n t r a t i o n s  i n Se  0.0001)  <  fetuses had almost  deficient  kidney  ones.  concentrations  significantly deficient  The t i s s u e  The  where  f e t u s e s than  tissues.  i n the  fractional  almost  i n  similar  t h evalue  rate i n tended  i nthe positive  Table  1 6 . C o m p a r i s o n o f t h e t i s s u e Se c o n c e n t r a t i o n s  Se  Tissue  concentration  o f t h e f e t u s a n d t h e ewe.  (ug/g  tissue)  Se p o s i t i v e  Se d e f i c i e n t  Fetus  (n-6)  Ewe ( n - 6 )  Fetus ( n - 6 )  Liver  0.29  a  +  0.02  0.37  b  + 0 .02  0.15  Kidney  0.45  c  +  0.06  1.09  d  + 0 .06  0.17  c  +  0.06  0.87  d  +  0.06  Sk.  0.10  a  +  0.01  0.13  b  + 0 .01  0.03  a  +  0.01  0.06  b  +  0.01  Heart  0.20  e  +  0.02  0.31  f  + 0 .02  0.07  e  +  0.02  0.17  f  +  0.02  Lung  0.21  g  +  0.02  0.31  h  + 0 .02  0.07  a  +  0.02  0.14  b  +  0.02  Spleen  0.29  c  +  0.03  0.57  d  + 0 .03  0.15  a  +  0.03  0.26  b  +  0.03  Muscle  ' differ  '  '  y  Means w i t h  significantly( ' P a  D  different < 0.05;  +  0.02  superscripts within c  ' P d  < 0.0001;  e  ,  £  P  Ewe ( n - 6 ) 0.11  +  0.02  t h e rows o f e a c h  < 0.001;  g  '  n  P <  group  0.01).  Table  17.  K i n e t i c parameters, o f deficient fetuses .  tissue  Se m e t a b o l i s m  in  the  Fractional rate constant (Fraction/d)  Tissue  Se  positive  Se  deficient  Se p o s i t i v e  T (<  Se  positive  Se  deficient  Liver  0.1000  0.0595  7  12  Kidney  0.0480  0.0518  14  13  Sk.  0.0954  0.0761  7  9  0.0612  0.0793  11  9  Muscle  Heart  *n-3  fetuses  i n each  **of  Se u t i l i z a t i o n  group. i n the  individual  tissues.  and  145  ones.  When t h e  these in  values  the  higher  jy2  v  *  a  u  e  were a l m o s t  liver  than  T  of  s  w  e  r  examined  e  similar  Se d e f i c i e n t  i t was f o u n d  i n both  that  groups  except  f e t u s e s which tended  to  be  i n the p o s i t i v e ones.  DISCUSSION  The  values  of  parameters observed reported  by o t h e r  et a l .  1984)  indicating  stress tracer  of  researchers  that  the  surgery  clearance  deficient  adult  1981)  of  7  with  and g o a t s  GSH-Px  indicates  1978;  at  Schaefer, from  the  the time  i n the  activity  an  age  selenoprotein.  d e p e n d e n t GSH-Px was  the  of  1981)  Miller,  fetus at this in  stage  the neonatal by  Pinto  Furthermore in  a  in  (Symonds e t a l . not  have  of gestation.  liver and  that  A  increased (1977)  Bartley  lower the  release  observed  may  r e l a t e d developmental  reported  physiological  as  I and I I A ) , c a t t l e and  positive  u p t a k e and l a t e r  and t h e e r y t h r o c y t e s  (Expts. (Allen  p l a s m a o f Se that  i n the i n i t i a l  age has been r e p o r t e d  suggesting this  and  recovered  anesthesia  ^ S e from the  fetuses  sheep  yet developed low  Krishnamurti  f e t u s has  and t h e  t h e Se by t h e l i v e r  the  those  ( B a t t a g l i a and M e s c h i a ,  1981;  Silver,  mechanisms i n v o l v e d of  physiological  experiment.  The and  post-operative  i n t h e f e t u s a r e i n agreement w i t h  1979;  Kitts  various  mechanism  of  amount  Se  of  erythrocytes  of  146  the  human  fetus  infants  (Gross e t a l .  et  1972)  al.  and Wong, 1 9 7 8 )  (Rudolph  than  1967;  i n the a d u l t s .  functional  selenoproteins  t i s s u e s may  thus  mechanisms and 7  ^Se  decay  account  an a l m o s t  significantly  positive  f e t u s e s (30  suggest  either  reduced  metabolic  the ID  a  14)  differences because  smooth a p p e a r a n c e  ug)  than  Se  deficiency support o f Se  volume  that  of  regulatory  of the  fetal  plasma  the  statistically  animal v a r i a t i o n s placental  Se  tissue  ones  in  i n Expt.  Although  of  were  the  distribution  fetus,  the  these probably  parameters. and  ewe  the  in  I I C (p 8 1 )  t h e r e i s an i n c r e a s e d  fetus  a  to  these  to  or  an a d v a n t a g e  efficiencies  the f e t u s  would  in  significant  transfer  data of the Se p o o l s  of  Se  both  t h e Se d e f i c i e n t  c o n d i t i o n s observed  tissue  be  volume  were  from  deficient  Se d e f i c i e n c y .  in  transfer  o f the  distribution  would  i n t h e f e t u s when t h e m a t e r n a l  the  the  combination  were l o w e r not  the  of a  The l a t t e r  the hypothesis that  The  of  in  p l a s m a Se c o n c e n t r a t i o n s  c l e a r a n c e and  of large  of  in  c l e a r a n c e or  However t h e r e d u c e d rate  absence  synthesis  h i g h e r p l a s m a Se p o o l s i z e  reduced  fetuses.  plasma  (Table  Emerson  a s GSH-Px  f o r the  f e t u s under c o n d i t i o n s o f ,  1969;  et a l .  The r e d u c e d  such  ug) c o u p l e d w i t h s i m i l a r  deficient  newborn  curves.  The  (22  Bracci  and t h e  Se  would  retention  Se s u p p l y i s l o w .  ( T a b l e 15)  significantly  indicated larger  in  147  Se  positive  accounted to  the  shown by  fetuses  for  by  fetus later  the  fetuses than  than  the  observation  that  that  significantly  higher  the  fetal  The lambs  as  the  limited  may b e  discussed  known  at  the  other  either utilize the  that for  et  Se  is or  the  to  al.  be  to  Se  of  Se  was  the  contained those  in  the that  retention  it  selenide This  the  in  the  the  fetal  in  be  as  functional  Though i t  is  which  assumed  in  the  an  is  that  Se  inorganic  fetus  could  be  to  The a c t i v i t y  could  s t i l l  argued  from  liver of  On form  B  synthase,  selenocysteine  fetal  not  Se  seleno-aminoacids.  cystathionine  selenide  present  into  can  in  mechanisms,  form  transferred  of  the  Se  organic  enzyme,  1976).  deficient  Se  observed  of  the  fetus  Se.  conversion  Se  indicated  much  mineral.  time  as  selenite  reported  (Sturman  if  selenite  the  fact  required been  hand  than  This  as  the  this  present  probably  the  as  confirmed  interest  Se  16).  incorporate  ewe  of  ewe  ewes  tissues of  absence  store  from the  as  of  the  to  that  transferred  the  to  positive  Of  have  from the  be  ones.  retention  before,  transferred is  maternal  due  selenoproteins  not  may  concentrations  ones.  (Table  Se  This  further  maternal  group do  Se  tissues lower  ones. of  was  concentrations  tissues  capability  the  the  either  in  This  positive  observation  of  transfer  significantly  the  deficient  placenta  IIC.  in  fetuses  the  Expt.  contained  the  increased  across  in  in  and  has  kidney  cystathionine  148  synthase and  kidney  rapidly  than  after  was  birth  and  i nthefetal  a n d was shown t o be  reaching  theadult  GSH-Px  have closer to  than  incorporation  and of  into  peroxidase this  selenite  actually  Apart  selenocysteine formation  formation  theplacenta.  the  conversion  (Sturman e t  acids,  A  similar selenide  of  incorporated enzyme  from  or  (1980)  pathway,  that the  study  was  into  the  i nthefetus.  selenide  or  selenite,  i nthefetus either  from by i t s  However  similar  to  methionine transfer  thelast  cystathionase  fetal  a l . 1970)  v i a  enzyme  of  required f o r  w e l l as i nthe  of  and  this  the  the  tissues as humans  by  from  o f c y s t a t h i o n i n e t o c y s t e i n e was f o u n d  the  or  glutathione  present  selenomethionine,  pathway,  transsulfuration  i n  the  cysteine  the  of  t o thesuggestion  a l s o be p r e s e n t  from  transsulfuration  absent  and  of  across  i n  i t ssynthesis  could  active site  b y Sunde a n d H o e k s t r a  c o m p o n e n t o f GSH-Px  from  i s  labelled moiety  support  used  metabolized  selenocysteine  mother  added  compounds  selenite  selenomethionine.  selenocysteine  Studies  seleno-amino  radioactively  give  Se  that  the  was d e m o n s t r a t e d  would  labelled  of  at the  1976).  theselenocysteine  either  selenocysteine  selenite  suggested  liver  decreasing  levels  on i n c o r p o r a t i o n o f v a r i o u s  GSH-Px  metabolically  its  t o be h i g h e r  i ntheadult  (1984)  Tappel  into  and  found  o f 2 weeks p o s t n a t a l l y (Sturman e t a l .  age by  enzyme  led  t o be  placenta to  the  149  suggestion the  that  fetus  was  (Sturman e t  1973)  Gaull,  although  reported  cystathionase and  was  from  Se  t h a t the  Se  the  at  a  faster  in  was Se  would  ewe.  selenocystathionine the  be  essentiality  of  established until  1)  s e l e n i t e to  parameters r a t e o f Se and  2)  selenocysteine  the  of  tissue  utilization  form i n  deficient  almost  pool  would  deficiency.  from  a  lowered the  ewe  a disadvantage  p r e c i p i t a t e the  to  the  Se  17).  s i z e s noted  be  depleted Se  supply  placental transfer  t o the  These m e t a b o l i c  similar  (Table  r a t e under c o n d i t i o n s o f d e c r e a s e d Indeed  which  metabolism  fetuses  15)  (Table  Se  was  r e d u c e d t i s s u e Se  fetuses  observed  w o u l d be  not  reaction  mother t o f e t u s i s d e t e r m i n e d .  significantly  deficient  from the  However,  s e l e n i d e or  positive  However t h e in  of  fetus  cystathionase  elimination  precursor  f e t u s can  f r o m the  kinetic  indicated  Se  i n the  sheep  if  selenocysteine  because  i s known q u a n t i t a t i v e l y and  transported  the  the  sulphide Even  i n the  adequate  the  1985).  al.  The  in  be  from  1969).  al.  1972;  et a l .  cysteine  present  not  catalyse  c o n t r i b u t i o n of  synthesis  of  selenocystathionine  to  selenocysteine  Gaull  et  t o be  may  selenohomocysteine,  (Tanaka e t  the  formation  there  e s s e n t i a l amino a c i d f o r  1970;  al.  i s assumed  found  i s an  (Braunstein  placenta  formation  of  cyst(e)ine  fetus  of  (Expt.  IIC)  changes d i s c u s s e d  above  deficient  fetus  and  d e f i c i e n c y symptoms a t a f a s t e r  rate.  150  EXPERIMENT Se  IIC:  i n pregnant  In utero  placental  transport  rates  of  e w e s f e d Se p o s i t i v e o r d e f i c i e n t r a t i o n s .  INTRODUCTION  Whole  body  influenced occurring extent Se.  Se  not  only  within  of  the  of  utero  sampling  separately. have  the To  resorted  ewes  fetal  and  placental Bell,  1982). the  of  i s confronted  with  and  this  ewe a n d  placental Se t r a n s f e r 1964;  et  i n addition of  several  the  exchanges  across  difficult  to  to  the  metabolism  of  of  drawback the  the expense  placenta,  determine  pregnant  recovery  1969;  the  Se  i n  the  effective  1966;  Wright  Buck  et a l .  involved  animals  the  workers  the  indicate  that  compartments  radioactive  their  experimental  two  difficulty  several  of  a l .  to  latter  the  ( J a c o b s s o n and Oksanen,  Hidiroglou  slaughter from  tissues  by  fetal  slaughter  measuring  also  the  problem  i s  processes  but  fetal  the administration  However,  suffers  and  placental  ewes  metabolic  compartment  to the sequential  compounds t o t h e  pregnant  determination  overcome  following  i n  the  transfer  The q u a n t i t a t i v e i n  by  maternal  placental  parameters  and  metabolism  this  i n  method  bidirectional i f  quantitatively.  Se  any,  are  Preliminary  75 studies  (Shariff  selenite  injected  placenta  i n either  et  a l .  into the  1984)  indicated  ewe o r  direction.  With  the fetus the  that  Se-  crossed  the  advent  of  the  151  chronic 1965)  fetal  catheterization  i t i s now  possible  nutrient  transfer  substrate  utilization  in  as  has  ewes f e d Se  measure  as  the  separately  the radioisotope  transfer  to  well  u n a n e s t h e t i z e d ewes.  with  technique  Using  under  (Meschia the  been q u a n t i t a t i v e l y positive  or  and  i nutero  d i l u t i o n technique  fetal  conditions  i n  conjunction  the placental  determined  i n  rations  i n the  deficient  a l .  transplacental  placental  t h i s approach  et  Se  utero  i n  present  study.  M A T E R I A L S AND METHODS  Animals injections described status  and feeding, and blood  i n  s u r g i c a l procedures,  sampling  experiments  protocol  I I A and I I B .  o f t h e ewes a n d t h e i r f e t u s e s  injection  and  18  respectively  a n d 19  sampling  details for  t h e Se  radiotracer  were The  t h e same  physiological  along with  the  tracer  i n  Tables  are presented positive  as  and  deficient  groups.  (a)Data  analysis:  75  The and  of  plasma the  injections exponential  Se s p e c i f i c a c t i v i t y - t i m e d a t a  fetus  (in  following both  equations  (Sedman a n d Wagner,  maternal  the  groups)  (Tables  1976).  as  20  The a r e a s  well  were  and  21)  under  of the  ewe  as  fetal  fitted  to  using these  AUTOAN curves  152  T a b l e 18. Body w e i g h t s , g e s t a t i o n a l age, plasma Se c o n c e n t r a t i o n s , i n j e c t i o n and s a m p l i n g s i t e s o f Se p o s i t i v e ewes and t h e i r f e t u s e s • Body weight (kg)  Animal #  818  73.6  Ewe (T)  Fetus  Fetus  (T)  Ewe  982  (T)  Ewe (T)  ,57 2 Ewe  587  (S)  Ewe (S)  Ewe (T)  665  Ewe (S)  7 07W Ewe (S)  Ewe  IVC  Fetus  JV(R)  JV(L)  SV  255  116  JV(L)  JV(R) SV  50  1.90 114  JV(R)  181 31  3.39  115  —  32  117  + 1  2.3 + 0.2  SV  —  36 115  JV(R)  IVC  128  2.72  SV  —  55 113  JV(R)  IVC  175  1.90  SV  —  56 116  JV(R)  IVC  286  1.44  SV  IVC  149  3.18  • Inferior  SV  50  71 + 3  Fetus  JV(R)  JV(L)  251  1.47  59.1  Fetus Mean + SEM  115  72.7  Fetus  SV  63  79.6  Fetus  JV(F)  JV(L)  118  2.85  77.3  Fetus 654  117  88.2  Fetus  Sampling site  44  60.5  Fetus  Injection site  144  2.13  59.1  Fetus  Plasma Se Cone, (ng/ml)  116  69.1  84 0 Ewe  977  Gestational age (d)  JV(R) SV  IVC  187  a  + 20  .  46  D  + 4  ——  '  1  ——  vena cava, SV - Saphenous v e i n , JV » J u g u l a r v e i n .  (S) - S i n g l e f e t u s , F e t u s  (T) - Twin  "'^Mean plasma Se c o n c e n t r a t i o n s d i f f e r e d  fetus. significantly  (P < 0.0001).  153  Table  19. Body w e i g h t s , g e s t a t i o n a l age, plasma Se c o n c e n t r a t i o n s , i n j e c t i o n and s a m p l i n g s i t e s o f Se d e f i c i e n t ewes and t h e i r f e t u s e s .  Animal #  58  Body w e i g h t (kg)  Ewe  42.7 (S)  Fetus  Fetus  (S)  4  (S)  Ewe  909  (S)  (T)  Fetus Mean + SEM  113  3.29 116  3.63 116  2.17 77.2  Ewe (T)  Ewe  115  2.15 65 + 5  Fetus  Injection site  Sampling site  JV(L)  JV(R)  97  SV JV(L)  82  JV(R) SV  82  2.95  62.7  Ewe Fetus  1000  117  66.2  Fetus  Plasma Se Cone, (ng/ml)  32  3.23  72.7  Ewe Fetus  72  116  65.5  707Y Ewe  725  Gestational age (d)  116  2.9 + 0.3  + 1  JV(L)  90  JV(R)  88  SV  18  JV(R)  36  IVC  90  —  39  IVC  36  —  41  IVC  SV JV(R) SV JV(R) SV  69 + 14 —  53 + 10  • i  IVC  - Inferior  Fetus  vena cava, SV - Saphenous v e i n , JV - J u g u l a r v e i n .  (S) - S i n g l e f e t u s ,  F e t u s (T) » Twin  fetus.  154  Table  20.  B e s t - f i t exponential equations o f plasma c u r v e s i n Se p o s i t i v e ewes and f e t u s e s .  Animal #  A  818 Ewe (j )  A  l  2  2  .0149  16 .5294  .0561  6.2206  .0169  .000021  .000034 -.000114 ,.000101 19 .9807  .2963  .000595  .000519  —  14 .8482  .0131  —  e .8617  .0424  .000036  .000671  .000054  3.3279  .0187  - .000120  .000120  —  .2172  .0015  587 F e t u s ( | ) .025661  .006159  .003542 ,.002687 35 .0147  .0421  .000028  .000028  .1319  .0016  665 F e t u s H ) .014707  .008532  3.3662  .0529  - .000013  -.000053  16 .2693  .0937  654 F e t u s ( J ) .016472  .015369  1.3235  .0127  .000096  .000096  .1678  .0074  572 F e t u s ( J ) .015218  .006985  6 .2326  .4906  .000061  .000061  .1532  .0007  Ewe  Ewe indicates The  l  equation  Se0  3  is:A  t  7 5  where A - plasma a - rate  7 5  Se  (tracer) - h^e  .000066  .006662  injection + A e ~ 2  i n t o ewe or  either 8  t 2  + A e ~ 3  specific activity (fraction  constant, e - l o g . -  and  a  t 3  + A e 4  .2938  .0051  .0082  fetus. -  *  t 4  r  o f dose/ug S e ) ,  t - time ( h r ) .  4  .0004  .0008  —  Ewe  a  .0012  .1391  .010324  Ewe  3  .0066  707 F e t u s ( \ ) .019508 Ewe  activity-time  a  9.0355  .000074  .001107  .000015 -.000039  Fetus  a  l  .0759  977 Ewe ( | ) .000505 982 Ewe(\)  a  20 .1604  .000008 -.000028  Fetus  4  .0127  .000909  Fetus  A  .000701  .000021 -.000053  840 Ewe(,)  3  5.9871  .000825  Fetus  A  Se s p e c i f i c  .0027  Table  21.  B e s t - f i t exponential equations o f plasma c u r v e s i n Se d e f i c i e n t ewes a n d f e t u s e s .  Animal #  58  707Y  725  724  A  1000  U> 1  The  A  2  A  3  l  a  a  2  8.4231  .0133  15.2593  .0547  10.7979  .0125  19.2293  .0323  5.3791  .0086  20.1687  .0090  4.6987  .0192  9.1067  .0482  .021717  6.2838  .0158  .000761  .000761  .0701  .0219  Fetus(|)  .032005  .018706  5.3916  .0197  Ewe  .000087  -.000796  32.3683  .0365  Ewe(\)  .002218  .002375  Fetus  .000033  -.000095  Ewe(J)  .002038  .001586  Fetus  .000006  -.000026  Ewe(|)  .001741  .001187  Fetus  .000016  -.000032  Fetus(\)  .020478  .010593  - .000320  -.000633  Fetus(\)  .051408  Ewe  Ewe 909  l  Se s p e c i f i c  75  indicates  equation  S  0  (tracer)  3  i s : A - A e ~  where A - plasma a  e  f c  x  .000032  .000048  .000953  .000883  injection a  either 3  l  Se s p e c i f i c  - rate constant,  .000128  f c +  A  2  e  "  fc  2  activity  e - l°9in  a n c  *  + A +  A  i n t o ewe o r 3  e  _  e  (fraction fc  a  fetus.  fc  3  '  o f dose/ug S e ) ,  " time ( h r ) .  activity-time  a  3  .0003  .0014  .0009  .0064 •  .0150  Table  2 2 . A r e a s under t h e plasma Se s p e c i f i c a c t i v i t y - t i m e c u r v e s (AUC) Se p o s i t i v e and d e f i c i e n t . e w e s and t h e i r c o r r e s p o n d i n g f e t u s e s ( F r a c t i o n o f d o s e , ug Se . h r ) .  Se p o s i t i v e  group  Se d e f i c i e n t  of  group  Parameter Mean + S.E.M  Maternal  Fetal  Injection: ±  .02  .17  +  .13  .20  .96  +  .24  .02  .07  +  .04  AUC (Ewe)  .05 +  .01  AUC  .09  +  .06  .79  +  .04  +  a  (Fetus)  .15  b  Injection: AUC  (Fetus)  AUC (Ewe) a b ' Means w i t h <  Mean + S.E.M  0.001).  different  s u p e r s c r i p t s w i t h i n t h e same row  differ significantly(P  157  (AUC)  22),  (Table  equations  from time  determining efficiency  rates  in  ewe)  f r o m ewe  Se  transfer  rate  Placental  Se t r a n s f e r  in  ewe  and  1985):  =  X AUC-Ewe a f t e r  fet.  transfer  Se t r a n s f e r  from f e t u s  Irreversible X  rate  100  Inj.  disposal  (I.D.) o f Se i n the  ewe  e f f i c i e n c y and  t o ewe were  AUC-Ewe a f t e r  calculated:  fet.  Inj X  fetus =  (% o f I.D.  fetus)  and t h e  AUC-Fetus a f t e r m a t . l n j  placental  rates  from  for  (from Expt. IIA)  transport  to  et a l . (1982;  ewe t o f e t u s  Similarly  used  as p e r the formulae  Se/d)  efficiency  rates  were  efficiency  e f f i c i e n c y from  f r o m ewe t o fetus(ug  transfer  Placental =  infinity,  Se t r a n s p o r t  Se  (% o f I.D.  Placental  the e x p o n e n t i a l  Se t r a n s f e r .  Se t r a n s f e r  efficiency  time  were c a l c u l a t e d  by Donoghue  Placental  fetus  the p l a c e n t a l  placental  transport  to  zero to  of placental  The  reported  o b t a i n e d by i n t e g r a t i n g  A U C - F e t u s a f t e r mat.  Inj.  100  158  Placental transfer from  Se  Placental  rate  fetus  »  transfer  e f f i c i e n c y from  to  fetus  Irreversible disposal X  rate  t o ewe  (from Expt. IIB)  areas  means + SEM.  under  The AUC  the curves data  and  analysed  of  differences  between t h e means was t e s t e d  (SAS, 1 9 8 5 ) .  variance  were  (AUC) were e x p r e s s e d  analysis  test  o f Se i n  the fetus  ewe(ug Se/d)  The  (I.D.)  the  by  a  one  significance by a S t u d e n t ' s  as way of 't'  159  RESULTS  When  Se-selenite  positive  ewes,  the  and  entered the  the  transplacental  fetus  the  tracer  The  were made  the  tracer  injection. Similarly,  when the  maternal blood c i r c u l a t i o n i n l e s s  than  well  ( F i g . 23).  fetus  to  the  conditions  The  transfer the  fetus  transfer  permeable to Se  A similar ewe  (Fig.  was  In  ewes in  experimental 3 d  after  injected  i t appeared i n 2 min  the  indicating  f e t a l side  of Se t r a n s f e r  ewe  was  29 ug  Se/d  Se d e f i c i e n t  group  the  transfer  under  Se  as  from  the  deficient  e f f i c i e n c i e s of Se  positive to the 24  to the ewe  rates  r e s p e c t i v e l y with a net  rates and  Se  rate from the ewe  of  placental  the  increased  the  on the  observed  transfer  23.  to the  pattern  also  to  24).  placental  given i n Table  ewe  t r a c e r was  fetus  was  indicating  between 1 and  i n f e r i o r vena cava of the  placenta  readily  Se d e f i c i e n t  6 hr of  began to d e c l i n e  Se  a l s o observed when the  i n t o the  first  and  that  2 min  tracer concentration gradually  period  i n t o the  then  from  This phenomenon was  f e t a l blood d u r i n g the  into  crossed the p l a c e n t a  t r a n s f e r of Se  maternal i n j e c t i o n s 22).  injected intravenously  f e t a l c i r c u l a t i o n within  ( F i g . 21).  (Fig.  was  of  ewes the p l a c e n t a l  f e t u s was  ug/d  53 ug/d  resulting  fetus. to f e t u s Se  are  were  On  and  in  a  Se  from net  the other hand i n  and 29  t r a n s f e r of 17 ug/d  fetus and  to 12  from the  ewe ug/d  ewe  to  8  Time (Hours) P i g . 21. Changes in plasma Se specific activity of Se p o s i t i v e e w e s ( c l o s e d s y m b o l s ) a n d t h e i r c o r r e s p o n d ing fetuses (open symbols) after maternal tracer injection. • , • , • , • r e f e r t o ewe n o s . 8 1 8 , 840, 977 a n d 982 respectively. ,D  Plasma  75 , , v Se Activity in ewe (cpm/ml)  n  ON H-TJ CO tn 3 O CD r*vQ » CD Q a O * O cn r r a 01 N> Cf\ H - v Q rr • ui o r  *  3  <n  • CD cn < fD 3* - J • CD 0» tsJ CO M> 3 CD \Q rr CD fl) C oi a o 01 CD H» Ul CD 0) 3  3  -s>0  O 1 — I-l ^ c/> l_> at CD • O 01  3 oi 3 CT fD Al O a  w T5 CD  n * t-< rr  w o» m ~ CO < fD 3 fD fD ffc cr fD CU O on •< 1 Ml i—a r r 0) fD r r fD — O O «i 0) Ht H- n  3 r-h o ruan  r r fD C r r rr oi Oi 3* fl* M H O H- rr 3  o 01 •  <  rr O r r - J n -1 »< o Or if »J O fD 01 O  cn -  Plasma  191  75  Se Activity in fetus (cpm/ml)  Plasma  Se Activity in fetus (cpm/ml)  ftH-  1  »  75  i  3  •o o  vQ  a• i»  (» (9 lt»Ml to n i n rr • rr O • HC < • tn <o a (0 <v 3 3* CO rr 01 3 o f0 03  * T3  •  3  *  l»  <D  a  01  01 — «—  n •< O 3 H 3 H Hi  ro 1  cr o  O cn H (ft tn Q.  —  TJ H  QI  0)  tn 3 0» "< » 3 rr Or -J (0 (D O ui < n H W <D tn fo  rr O  M»  3 3 0)ft»0» rr 3 »o <0 Q. (0 n O ui 3 rr H 00 01 3* rt» O  01  -  M (D H H- O  O 3  Q>  •~J<-»- O O *  (9 Q cr  o n rt n <  0* (0 H3 O ot rr a 3 TJ K O  to  Ul  3  o ao  Plasma  291  75  Se Activity in ewe (cpm/ml)  Plasma o o n rr TJ cn ^ co i-i o » H iO o> 01 3 T3 O Q. Q> •  CD CD o M 3 rr • ifl  75  Se Activity in ewe (cpm/ml)  o  b  ft-*  O  P N*  "•  a  H i (O H- A  0 • <• < it n CO  fD  fD 3 3* Bl rr » 3 MlvQ  *— CD fD Oft  »  co at  H-  n c  P0 -  3 fD 3 cn  CO  0>  T3  — M 3 O Of O" t— « rr 0 O 3 O H- cn fl» cn fD — a -4 co cn rr c 01 cn(Dca at MI 3 rr CT 3 fD O 01 O n (-"O at 01 fD H» ^- r> fD M« to rr 01 M i fl> 3 H -  cw o  C  -I  .CiO.  Mao  vo 3 O U vo'fl O 0» rr 3 a O 3 H*  3" Of fD O H«- rr  cn -  M H-  < O H» O rr  M *< M  O fD O O 01 O O Ml I Ml  cn  Plasma  £91  75  Se Activity in fetus (cpm/ml)  o o o o  Table  23.  P l a c e n t a l t r a n s f e r e f f i c i e n c i e s and r a t e s Se p o s i t i v e and d e f i c i e n t ewes. Se p o s i t i v e  Parameter P l a c e n t a l Se Efficiency  ewes  o f Se t r a n s f e r i n  Se  deficient  transfer  Ewe t o f e t u s (% o f m a t e r n a l i r r e v e r s i b l e Se d i s p o s a l )  11  17  F e t u s t o ewe (% o f f e t a l i r r e v e r s i b l e Se disposal)  80  44  Ewe t o F e t u s (ug Se/d)  53  29  F e t u s t o Ewe (ug Se/d)  24  12  29  17  Placental rates:  Se  transfer  Net Se t r a n s f e r (ug Se/d) .  to fetus  ewes  165  Fig. ewes  25. fed  P l a c e n t a l Se t r a n s f e r e f f i c i e n c i e s Se p o s i t i v e o r d e f i c i e n t rations.  LZ2 EWE TO FETUS  in  pregnant  E S FETUS TO EWE  166  the  fetus.  positive  The p l a c e n t a l  and d e f i c i e n t  efficiencies  of  fetus  fetus  and the  maternal  I I A and  positive  rations.  and  ewe  44% o f  to  are Se  the  given transfer ewe  the  the  the  fetus  and  the  and f e t a l  I I A and I I B )  in  Fig.  from the 11  in  25.  ewe  The  to  the  80%  rates  of (from  ewes  fed  Se  in  ewes  fed  Se  transfer  fetus  Se  the  hand Se  of  and  disposal  other  placental  efficiencies  were  irreversible  On  maternal  Expts.  transfer  I I B ) respectively  rations,  the  (from  to  fetal  Expts.  from  ewes  placental  and  deficient  Se  to  irreversible  the  efficiencies ewe w e r e  disposal  17  rates  respectively.  DISCUSSION  The fetus  higher  t o t h e ewe  ewes i n d i c a t e d and  that  deficient  amount  of  of Se  maternal  the  a  slaughter  adequate  Se d e f i c i e n c y  Se  storing  experiments. placental  ones  Se s u p p l y  conditions.  i n Se  indicated  i ntransfering  On  transfer  ( F i g . 25) o b s e r v e d  placenta  t oensure  limited  was h i g h  w a s made b y H i d i r o g l o u e t  i n t h ep o s i t i v e the  p o s i t i v e and d e f i c i e n t  higher  ewe t o f e t u s  ewes t h a n  role  of  from t h e  o f Se i n t h e f e t u s  t i s s u e s had only  hand  from  active  under  theturnover  on t h eb a s i s  other  efficiency  t h e Se  A similar observation  (1969)  the  transfer efficiencies  i nboth  that  thefetal  capability. al.  placental  the  greater  t othe  fetus  167  The Se  examination  i n plasma  their  of  o f Se  respective  the concentrations  positive fetuses  18 a n d 1 9 ) .  (Tables  fetal  Se c o n c e n t r a t i o n  0.0001)  than  maternal  maternal  ratio  being  indicate  that  is  concentration hand  gradient  i n Se d e f i c i e n t  plasma  i sequal  close  one (0.98  the  of  placenta  availability. the  active  to  of  of  sulphur  to  be  maternal  data  indicating  any  of  along  the  the  other  o f Se i n  fetal  On  greater  fetal  by an plasma  gradient  (Gaull  e t a l . 1973).  unique  i n t h e sense  ratio  or there  placental transfer Methionine  transfer other are  some  was f o u n d  i n man  a  from  threefold amino  acids  C o n t r a r i l y c y s t ( e ) i n e was f o u n d  t o be  that  other  Se  processes  process  t o most  Se  available i n  utero  against  an  across  active transport  similar  being  thelimited  i n  i n  of  mechanism  However  o f selenoaminoacids.  than  i ssuggestive  the selenoaminoacids  on t h e i nu t e r o  tranferred  concentration  fetus  overcome  the  the placenta.  analogs  to  ewe t o t h e  We a r e n o t a w a r e o f a n y r e p o r t s  compounds a c r o s s available  to  to might  fetal  transport  the fetus  literature  processes  Se  This  ( P _<  This  t o be s l i g h t l y to  the  fetal  + 0.04).  theconcentration  0.25).  lower  diffusion  t h e maternal +  and  interesting  the  the p l a c e n t a .  across  o r tended  plasma w i t h  involvement  with  from the  simple  ewes  maternal to  some  l e s s t h a n one (0.27  a  ewes  i ss i g n i f i c a n t l y  concentration  by  stable  I n Se p o s i t i v e e w e s ,  t h e t r a n s f e r o f Se  accomplished  deficient  revealed  differences plasma  and  of  i t sconcentration  i nthe  mother  168  was  equal  or  Furthermore, be  fetal  decreasing  therefore  the  More almost  blood  of  with  the  who  equal  our  process  placenta  from  gradient.  This  1.5  maternal 1959).  to 3 blood  et  Finnish  of  authors, of  active  process,  ratio  was n o t  by t h e  and  their  that  mother  et a l .  their  This  along (1980)  Se  i n Se  give  added  Se i s t r a n s f e r r e d b y i n Se d e f i c i e n c y . transfer  of a  Se  has been  This  concentration  found  the placenta 1984;  an  to the  be s u b s t a n t i a t e d  Se c o n c e n t r a t i o n i n  and  of  fetuses  against  phenomenon c o u l d  i n the  Robinson  concentrations  initial  study  reported  o f Se a r e p r e s e n t  to fetus  higher  (1984)  p r e g n a n t women  and  hypothesis  (Korpela  a l .  Thomson  women  I n thepresent  cyst(e)ine  transfer  u g / 1 ; Mean + S D ) .  similar  fold  i n the  These  concentration  Korpela  the  the  1973).  an  t o one.  from mother  be e x p l a i n e d  of  to  and  was o b s e r v e d  mediated  concentrations  pregnant  that  plasma.  only)  the placental  carrier  found  active  from  a  or equal  to  fact  et  fetal/maternal  support  could  of cyst(e)ine  + 12 V s . 61 + 14  also  fetal  cyst(e)ine  that  studies  deficient  -  a l .  Se d e f i c i e n t  (58  fetuses  the  (Gaull  recently  that  i n  concentration  was  than  that  t h ematernal  suggested  cyst(e)ine  greater  (L  concentration  p l a s m a when  wherein  than  p l a c e n t a l t r a n s f e r o f c y s t ( e ) i n e was f o u n d  stereospecific  increasing  was  greater  by to  than  Hadjimarkos  theconcentration  the range  i n the et  a l .  o f Se i n t h e  169  placenta  1.3  was  (69  m a t e r n a l plasma transferred  found  t o be  placenta 1984)  and  humans  ng/ml).  from  concentration  (90  times  the  In the  placenta  gradient.  Since  operating  in  present  study  also  i n the  hemochorial  et  and  i t indicates that  ( i ) the  fetus  i n Se  i s not  deficiency  governed  placenta  has  by  the  type  a definite  second  step,  type  type  was  process type  (Roller  al.  placenta  in  and  Robinson,  specific  of p l a c e n t a t i o n  and  i n the  of  et  a c t i v e t r a n s f e r of  role  is  of  Thomson  regulatory  Se  the  the  of  species  in  fetus along  in cattle  1984;  al.  than  epitheliochorial  i n the  (Korpela  higher  t o the  this  the  1980)  not  ng/g)  Se  to  the  and  also  (ii)  that  transfer  of  Se.  The  (0.081  calves their  whole  blood mg  Se/kg)  dams ( 0 . 0 5 2 mg  (Roller  workers  transferred  to higher  maternal  blood  s u g g e s t e d an can  of  this  the  i n the  Se  or  the  calf  Se  f r o m the  t h a t the  for  trace  the  and  and  the  Se  and dam,  fetus  face  can  of  low  Furthermore  they  a Se  maternal  This  cattle  the  the  t o meet i t s f u t u r e element.  beef  than  effectively  f e t u s of  low  higher  is dam  in  neonatal  whole b l o o d  concentrations.  s t o r i n g Se  essential  t o be  neonatal  Se  of the  deficient  on  that  fetus  hypothesis  Se  Based  amounts o f  compensate  concentrating  in  concluded  sequester  dam  were r e p o r t e d  a l . 1984b).  et  concentrations  Se/kg)  GSH-Px c o n c e n t r a t i o n s these  Se  deficient  blood  Se  by  requirement  hypothesis  does  170  not  appear  to  be t r u e  storage  capability  study.  Furthermore 29  of the  t o 17  from  observed  i nthe current  the  would  lamb over  thelight  fetus  quite  i nthe  ug/d during study  thelimited i n  the  (12  deficiency  affect  of thegestation  Se  present  netplacental  Se  ug/d)  a t 115 d  f r o m ewe t o f e t u s  significantly  the rest  of  observed  the decrease  transfer  gestation  i n  of  t h e Se s t a t u s  of  and consequently  at  of  i n  birth.  A  decreased  general  from  several  1975;  such or  for  a l .  and  1982),  uterine  decreased decreased the a  to  flow  study plasma  The r o l e  be e s t a b l i s h e d  t o be (1)  (Wilkening  i n Se  The m a j o r under  decreased  nutrient (Crandell  cardiac 1982),  t o the fetus ewes i nthe  output and  1984).  (Rosenfeld,  concentration factors  transfer  circulation  Se d e f i c i e n t  o f other  1983).  et al.  Se t r a n s f e r  or  Widdowson,  maternal  irrigation  netplacental  decreased  ng/ml).  found  by  and  nutrient  decreased  placental  present  Munro e t a l .  reported starvation  (Young  i n thematernal  (2)  blood  maternal  placental  were  nutrients  has been  during  1980;  levels  fetus  deficiencies  et al.  conditions  transfer  to  occur  decreased  metabolite  et  to  nutritional  Morriss  causes  mother  workers  maternal  placental  The  observed i n  could  be due t o  ewe ( 1 8 9  enumerated  (3)  vs  69  above h a s y e t  i n Se d e f i c i e n c y .  Though p l a c e n t a l  transfer  o f Se  has been  reported  by  171  several  workers  in  (Jacobsson  and Oksanen,  various 1966;  (McConnel  and R o t h ,  1964);  and  Roller  al.  1985;  this  appears  knowledge, transfer in  the  the  to  be  that in  theirs.  It could  both  the  positive it  was  a  storing  found  to  of  and  of  has  dog  al.  1972  Perry,  1985),  best  species by data  from the Se  the  of  our  been  deficient  that  the  fetal  Se  differences employed  other  with  experiment  demonstrated pregnant lambs  in  workers  directly  present  Se  capability.  1964);  However  the  our  and  sheep  transplacental  studies  concluded  and  Toledo  time  compare  transfer  Furthermore Se  to  and B e l l ,  reported.  transfer  be  bidirectional  been  including  ( H i d i r o g l o u et de  first  techniques  Se  that  limited  the  difficult  Se  cattle  1984b;  has  experimental  it  Wright  quantitation  utero  placental  render  et  species  have  in  ewes. only  172  GENERAL SUMMARY AND  Although well  the n u t r i t i o n a l  established  very  little  f o r sheep  attention  metabolism  i n t h e whole  absorption  and t i s s u e  CONCLUSIONS  essentiality and  other  was p a i d animal  of  domestic  with  regard  utilization.  pregnant  rations.  ewes  The  fed  either  bidirectional  of  Se e x c h a n g e s a c r o s s  The  major  to  Therefore  Se  positive  Se  present  nonpregnant  or  deficient  and  quantitation  t h e p l a c e n t a were a l s o  investigated.  accomplishments  transfer  of  kinetics,  the  in  been  animals,  t o the t r a n s a c t i o n s  s t u d y was u n d e r t a k e n t o a d d r e s s t h e s e p o i n t s and  Se had  of  the current  study  were  as  follows:  1.  The  isotope  dilution  technique,  involving  a  single  75 injection  of  Se-selenite,  kinetic  parameters  disposal  rate,  volume o f well the  Se  distribution  as i n p r e g n a n t f a c t whether  the d e f i c i e n t  were  The  I and  in  size  and  nonpregnant  as  I I A ) . Regardless  of  pregnant or not  i n those  the  irreversible  p l a s m a Se p o o l  determined  ewes ( E x p t  ewes were  to determine  metabolism.  plasma c l e a r a n c e ,  t u r n o v e r was h i g h e r in  of  was employed  f e d Se p o s i t i v e  the plasma rations  Se than  ones.  75 2.  A  characteristic  involved by  a  very  an i n c r e a s e  plasma rapid  Se  disappearance  i n the plasma  clearance initially  radioactivity  f o r 3-4  which followed hr  after  173  the  tracer  both  injection  nonpregnant  was  (Expt.  demonstrated I ) and  f o r the  pregnant  first  (Expt.  time  I I A)  in  ewes.  75 This  suggested  erythrocytes tissues Se  may  an and  be  was  uptake  that  the  involved  i n the very  interest  avid  in  Se  proteins the  early period  the  of  by  the  synthesized  transport  and  following tracer  finding that  such  liver  and  by  those  metabolism  of  injection.  a mechanism  Of  of  plasma  i n the  fetuses  75 Se  clearance I I B).  (Expt. fetal  proteins 3.  The  may  the  intake  (%  Se  net  and  amount  intake was  i n the  the  as  that  f a c t o r which to both  the  of  ewes  Se  and  specific  and  (r=0.90  radiotracer  Se  absorption. and  Se  Se  net  intake  was  ewes.  As  of net  and  absorption  r=0.89  in  the  However  the  (ug/d) i n c r e a s e d  dietary  the  pregnant  respectively).  linear  metabolism.  the  of  efficiency  the  those  intake  percent  that  mechanisms  transport  the  a  absorbed  the  basis the  coupled with  the  exhibiting a positive  mineral  Se  nonpregnant  pregnant  the  c a l c u l a t i o n of net  decreased  o f Se  concluded  major  plasma  increased,  intake)  nonpregnant  synthesis  expressed  both  on  yet developed  r e l a t i o n s h i p between  observed  pronounced  explained  technique  enabled  absorption  Se  be  as  have  i n the  balance  inverse  may  the  involved  Se  not  not  for  methodology An  This  tissues  responsible  was  with  relationship. intake  regulated  the  availability  pregnant  and  nonpregnant  the  Se  Thus  i t  ( u g / d ) was of  this  ewes.  the trace  174  4. T h e tool  Se  in  assessing  pathways to  balance  the  namely overall  significantly  Se  metabolism.  reduced  control  on  both  pregnant  of  the  fecal  Se  Se  utilization  organ/tissue examining  quantitative tissues  of  tissues  manner.  exerted  of  the Se  would  be  exhausted  drastically  reduced.  employing  the  in  and  a  when  Se  Se  the  kidney  losses  supply  were  was  low  homeostatic conditions  rate  from  Se  in  a  was  the  tissues higher  rate  dilution,  whole  method  in  ewes  stored  dietary  constant  the  nonpregnant  faster the  isotope  and  individual of  Thus  at  excretory  provided  turnover  deficiency.  major  a major  values  Se  valuable  fractional  data  pregnant  fecal  a  ewes.  i/2  of  tract  be  deficiency  tissue T  to  the  dietary  under  the  The  syndromes  By  route  and  deficiency  6.  the  metabolism  both  conditions  when  radioactivity  the  The  and nonpregnant  of  of  intestinal  metabolism  calculation  proved  contribution  gastro  that  Si T h e  the  also  the  showing  the  technique  Se  of in  a the  under in  the  leading  to  intakes  are  involving  a  single  chronic  vascular  75 injection  of  Se-selenite,  catheterization  techniques  the  Se  kinetics  lambs the  in  utero.  values  generally  of  of higher  and it  metabolism  The k i n e t i c these than  in  the was  possible  to  quantitatively  in  parameters  parameters the  adult  were  in ewes.  the  determine the  fetal  calculated fetuses  Therefore,  it  and were was  175  suggested  that  the  fetal  Se  turnover  was  higher  than  in  the  of  the  adult.  7.  The  fetus  comparison a n d ewe  capability lower the  Se  fetal  The  fetal  the  provided a  of  the  tissues to  of  the  maternal  radioisotope  a  Se  of  concentrations  assessing  tissues. in  the  limited  Se  the  The  Se  storage  significantly  fetus  indicated  storage  that  capability  as  adult.  placement and  means  values  have  the  tissue  individual  concentration  compared  8.  of  chronic  blood  experiments  indwelling  catheters  vessels  coupled  facilitated  the  in  with  the the  investigations  75 on  placental  either and  into  Se  ewe  appeared  transfer.  or  fetus,  in  the  respectively.  of  the  the  across  first  the  Se-selenite  tracer  crossed  corresponding  compartments Se  When  placenta  Thus in  the  utero  fetal  was the  placenta  or  maternal  bidirectional was  injected  transfer  demonstrated  for  time. 75  Kinetic data  permitted  rates  from  transfer ug/d the  analysis the  ewe  from  respectively corresponding  deficient  ones.  the  plasma  calculation  to  ewe  of  fetus  to  fetus in  the  values The  net  of  the  and v i c e and  fetus Se  were  Se  specific  placental versa.  The  to  were  ewe  positive 29  placental  and Se  Se  transfer  rates 53  ewes,  12  activity  ug/d  transfer  of  Se  and  24  whereas, in from  the ewe  176  to  fetus  declined  in  t h e d e f i c i e n t ones.  to  influence  demonstrated  results of  that  conditions,  a)  b) t h a t  t o fetus  l o w and c) that  was  lower  prevent  than  the fetal  i ntheadult,  was  reported  Furthermore  maternal  Se t r e a t m e n t  NMD  the  i n  capability  lamb.  of the  supplementation storage  of  occurrence similar  and  of  these  white  injected  the  workers  of  to  ?"  be  needs  suggesting  Se s t a t u s  i n Expt.  ewes  with  selenium  at of  late  of the  Hidiroglou that  of  limited  et the  juvenile  Se  storage  IIB,  t h e Se  tissues to  adequate  prevent  i n t h e neonate.  Hidiroglou  pregnant  the supplementation  ewe i n  limited retention  with  to  suggested  disease  intake  capability  ewe may n o t e n s u r e  fetal  muscle  the  from  q u e s t i o n - "How  the occurrence  observed  i nthe  o f Se  d i e t a r y Se  Hamdy e t a l . 1 9 6 3 ;  t i s s u e s w a s made b y  studies  However,  fetus  rate  o f t h e pregnant  view  deficiency  t i s s u e Se s t o r a g e  increase  clearly  concentrations Se  transfer  maternal  prevented In  mineral  tissue  thebasic  o f t h e pregnant  observation  fetal  their  to  was f o u n d  study have  i ntheoffspring  (Young e t a l . 1961; 1969).  al.  when  ug/d  ewe t o f e t u s .  under  theplacental  Se s u p p l e m e n t a t i o n  gestation fetus  fetal  reduced  Se d e f i c i e n c y  answered.  from  Se s t a t u s  thepresent  the  was r e d u c e d  was  the  Thus t h e m a t e r n a l  significantly  ewe  i n p o s i t i v e e w e s t o 17  t h e n e t Se t r a n s f e r  Though t h e  were  29 u g / d  from  et a l .  the A  o f Se i n (1969)  i n  f e d dystrophogenic hay the  time  of  the pregnant  breeding. ewe  would  177  enhance  the  observed gland in  storage  i n  has been  1969),  goat  and  I n thepresent the  the maternal  and  selenium  study  pregnant  from  sheep  cows  mammary  blood  t o milk  (Hidiroglou beef  (de Toledo  the radioactivity ewes  (#  818)  as  The  1981),  Miller,  and d a i r y  tissues  16).  (Table  1964),  Roth,  1984b)  1985).  of  study  (Allen  et a l .  one  i n  shown t o t r a n s f e r  (Roller  of  Se  thepresent  dog (McConnell  al.  of  et  cattle  and P e r r y ,  i nthe  which  milk  received  75  Se-selenite monitored  injection  daily.  and  Though t h i s  delivered  result  normally  was n o t r e p o r t e d  was under 75  the  experimental  radioactivity 41 d a f t e r could  Se  i nthemilk  tracer  be a s o u r c e  warranted  practical neonate neonate  method  to  compounds.  either  be  prevent  the  Further  that  suggested  Based  that  thedeficiency  or  i n the on t h e  the  best  o f Se i n t h e  t h e dam o r a l t e r n a t i v e l y parenterally  milk  studiesare  o f mammary g l a n d terms.  Se  as long as  i t appears  i nquantitative  i t may  that  t o be p r e s e n t  Therefore  t h e importance  i s t o supplement itself  continued  found  o f Se f o r t h e n e o n a t e .  o f neonate  findings  i t was  injection.  t o assess  nutrition  present  section  orally  treat  the  with  Se  178  BIBLIOGRAPHY A l l e n , J . C . and W.J. M i l l e r . 1981. Transfer o f selenium from b l o o d t o milk i n goats and n o n i n t e r f e r e n c e o f c o p p e r w i t h s e l e n i u m m e t a b o l i s m . J . D a i r y S c . 64:814-821. A l l e n , W.M., P.R. Moore and B.F. Sansom. 1981. Controlled Release Glasses (CRG) f o r s e l e n i u m supplementation. In " T r a c e e l e m e n t m e t a b o l i s m i n man and a n i m a l s " , TEMA 4, J.M. Gawthorne, J.M. H o w e l l and C L . W h i t e ( e d s . ) Pp. 195, Springer-Verlag, Berlin. A l l e n , W.M. a n d C.B. M a l l i n s o n . 1984. P a r e n t e r a l methods o f s u p p l e m e n t a t i o n w i t h c o p p e r and s e l e n i u m . V e t . R e c . 114:  451-454.  Anand, R.S., M.A. Sperling, S. Ganguli and P.W. Nathanielsz. 1979. Bidirectional placental transfer of g l u c o s e and i t s t u r n o v e r i n f e t a l and m a t e r n a l sheep. P e d i a t r . R e s . 13:783-787. A n d e r s o n , P.H., S. Berrett and D.S.P. Patterson. 1978. G l u t a t h i o n e p e r o x i d a s e a c t i v i t y i n e r y t h r o c y t e s and m u s c l e s o f c a t t l e a n d sheep and i t s r e l a t i o n s h i p t o s e l e n i u m . J. Comp. P a t h o l . 88:181-189. A n d e r s o n , P.H., S. B e r r e t t and D.S.P. P a t t e r s o n . 1979. The b i o l o g i c a l selenium status of livestock i n B r i t a i n as indicated b y sheep erythrocyte glutathione peroxidase a c t i v i t y . V e t . R e c . 104:235-238. Andrews , E.D., W.J. H a r t l e y and A.B. G r a n t . 1968. Selenium r e s p o n s i v e d i s e a s e s o f a n i m a l s i n New Z e a l a n d . N.Z. V e t . J .  16:3-17.  A r d u s e r , F., S. Wolffram and E. a b s o r p t i o n o f s e l e n a t e by r a t ileum.  S c h a r r e r . 1985. Active J . N u t r . 115:1203-1208.  A r n a l , M. 1977. M u s c l e p r o t e i n t u r n o v e r i n lambs t h r o u g h o u t development. Publ. E u r . A s s n . Anim. P r o d . 22:35-37. Ashmead, D. a n d H. C h r i s t y . 1985. intestinal absorption of minerals.  13.  Factors i n t e r f e r i n g with Anim. N u t r . H l t h . 40:10-  A t r o s h i , F., S. S a n k a r i and P. K a i p a i n e n . 1985. and l i v e r characteristics in l o w and h i g h Finnsheep. Pharmacol. R e s . Commun. 17:23-32  Erythrocyte glutathione  A w a s t h i , Y.C., D.D. Dao, A.K. L a i and S.K. S r i v a s t a v a . 1979. P u r i f i c a t i o n and p r o p e r t i e s o f g l u t a t h i o n e peroxidase from human placenta. Biochem. J . 177:471-476. A w a s t h i , Y.C.  and D.D.  Dao. 1981.  Glutathione-mediated  179  detoxification (suppl.)  mechanisms  3:289-301.  o f human  placenta.  Placenta  A z i z , E.S., P.H. K l e s i u s and J.C. Frandsen. 1 9 8 4 . Effects of selenium on polymorphonuclear leukocyte function i n goats. Am. J . V e t . Res. 4 5 : 1 7 1 5 - 1 7 1 8 . Backall, K.A. and R.W. S c h o l z . 1 9 7 9 . Reference values for a field test to estimate inadequate glutathione peroxidase a c t i v i t y and selenium s t a t u s i n the blood of c a t t l e . Am. J . V e t . Res. 4 0 : 7 3 3 - 7 3 8 .  Baker, E. and E.H. Morgan. 1 9 7 0 . Iron t r a n s f e r the perfused rabbit placenta. L i f e S c i . 9 : 7 6 5 - 7 7 2 .  across  Barbezat, G . O . , C E . Casey, P.C Reasbeck, M.F. Robinson and C D . Thomson. 1 9 8 4 . Absorption and malabsorption of mineral n u t r i e n t s Selenium. In, Current topics i n n u t r i t i o n and d i s e a s e , Eds. N.W. Solomons and I.H. Rosenberg, V o l . 1 2 , pp 2 3 1 - 2 5 8 , Alan R. L i s s Inc., New York. Baret, A., R.A. C o u r t i e r e and A.M. Michelson. 1983. Determination o f g l u t a t h i o n e peroxidase in circulating blood c e l l s : Use of a r a d i o immuno assay. Molecular P h y s i o l . 4: 3 1 3 - 3 2 2 B a t t a g l i a , F . C and G . Meschia. 1 9 7 8 . P r i n c i p a l of f e t l metabolism. P h y s i o l . Rev. 5 8 : 4 9 9 - 5 2 7 .  substrates  Behne, D. and W. Wolters. 1979. Selenium content and glutathione peroxidase activity i n the plasma and erythrocytes of non-pregnant and pregnant women. J . C l i n . Chem. C l i n . Biochem. 1 7 : 1 3 3 - 1 3 5 . Bern, E.M., K. M a i l e r and C M . E l s o n . 1 9 8 5 . I n f l u e n c e o f mercury(II), cadmium (II), methylmercury, and phenylmercury on the k i n e t i c p r o p e r t i e s of rat liver g l u t a t h i o n e peroxidase. Can. J . Biochem. C e l l B i o l . 6 3 : 1 2 1 2 1216.  Berman, M. and M.F. Weiss. 1 9 7 8 . S i m u l a t i o n , A n a l y s i s And M o d e l l i n g (SAAM) manual, U.S. Department o f Health, Education and Welfare publication no. (NIH) 78-180, Washington, D.C. B i e l s t e i n , M.A., M.J. T r i p p and P.D. Whanger. 1981. Evidence f o r s e l e n o c y s t e i n e i n ovine t i s s u e o r g a n e l l e s . J . Inorg. Biochem. 1 5 : 3 3 9 - 3 4 7 . Bielstein, M.A.J.A. B u t l e r and P.D. Whanger. 1984. Metabolism of S e - s e l e n i t e by rhesus monkeys. J . Nutr. 5  114:1501-1509.  B l i n c o e , C.  1 9 6 0 . Whole-body  turnover of  selenium  i n the  180  r a t . Nature, 1 8 6 : 3 9 8 .  Board, P.G. and D.W. Peter. 1 9 7 6 . A simple test f o r g l u t a t h i o n e peroxidase and selenium d e f i c i e n c y . Vet. Rec. 99:144-145.  Bopp, B.A., R.C. Sonders and J.W. Kesterson. 1982. M e t a b o l i c f a t e o f s e l e c t e d selenium compounds i n l a b o r a t o r y animals and man. Drug Metab. Rev. 1 3 : 2 7 1 - 3 1 8 . Boyne, R. and J.R. A r t h u r . 1 9 7 9 . A l t e r a t i o n s o f n e u t r o p h i l f u n c t i o n i n selenium deficient cattle. J . Comp. P a t h o l . 89:151-158.  B r a c c i , R. , E. C o r v a g l i a , P. P r i n c i , F. B e t t i n i and C. P i n d i n e l l i . 1 9 6 9 . The r o l e of GSH-peroxidase d e f i c i e n c y i n the increased s u s c e p t i b i l i t y to Heinz body formation. I t a l i a n J . Biochem. 1 8 : 1 0 0 - 1 1 3 . Brady, P.S., L . J . Brady, P.A. Whetter, D.E. U l l r e y and L.D. Fay. 1 9 7 8 . The e f f e c t of d i e t a r y selenium and v i t a m i n E on biochemical parameters and s u r v i v a l of young among w h i t e - t a i l e d deer (Odocoileus virginianus). J. Nutr. 1 0 8 : 1 4 3 9 - 1 4 4 8 . B r a u n s t e i n , A.E., E.V. Goryachenkova and N.D. L a c . 1 9 6 9 . Reactions c a t a l y s e d by s e r i n e s u l f h y d r a s e from chicken liver. Biochim. Biophys. Acta, 1 7 1 : 3 6 6 - 3 6 8 . Buchanan-Smith, J.G., E.C. Nelson and A.D. T i l l m a n . 1969. E f f e c t o f v i t a m i n E and selenium deficiencies on lysosomal and cytoplasmic enzymes i n sheep t i s s u e s . J . Nutr. 99:387-394.  Buck, E.L., J.A. S c h m i t z and L.V. Swanson. 1981. Incorporation of Se into endocrine glands and r e p r o d u c t i v e t i s s u e s of the prepartum ewe and f e t u s . In symposium "Selenium i n biology and medicine", J.E. Spallholz, J . L . M a r t i n and H.E. Ganther (Eds.), Pp 5 1 4 5 2 0 . AVI Publ. Co., Westport, Conn. 7  Buhi, W.C., C A . Ducsay, F.W. Bazer and R.M. Roberts. 1982. Iron t r a n s f e r between the purple phosphatase, uteroferrin, and t r a n s f e r r i n , and i t s p o s s i b l e r o l e i n i r o n metabolism of the f e t a l pig. J. Biol. Chem. 257: 1712-1721.  Burk, R.F., R. Whitney, H. Frank and N. Pearson. 1968. T i s s u e selenium l e v e l s during the development of d i e t a r y l i v e r necrosis i n rats fed torula yeast d i e t s . J . Nutr. 95:420-428.  Burk, R.F., D.G. Brown, R.J. Seely and C.C. S c a i e f . 1 9 7 2 . I n f l u e n c e of d i e t a r y and i n j e c t e d selenium on whole body  181  retention, route of e x c r e t i o n and t i s s u e i n the r a t . J . Nutr. 1 0 2 : 1 0 4 9 - 1 0 5 6 .  0  r e t e n t i o n of  Se  3  B u r k R.F. and P.E. Gregory. 1 9 8 2 . Some characteristics of Se-P, a s e l e n o p r o t e i n found i n r a t l i v e r and plasma, and comparison of i t with selenoglutathione peroxidase. A r c h . Biochem. Biophys. 2 1 3 : 7 3 - 8 0 . 5  Burk, R.F. 1 9 8 3 . B i o l o g i c a l a c t i v i t y of selenium. Ann. Nutr. 3 : 5 3 - 7 0 .  Rev.  Burton, V., R.F. K e e l e r , K.F. Swingle and S. Young. 1 9 6 2 . N u t r i t i o n a l muscular dystrophy i n lambs: The e f f e c t of a d m i n i s t e r i n g selenium to pregnant ewes. Am. J . V e t . Res. 22:416-418.  Calvin, A.I. 1 9 7 8 . Selective i n c o r p o r a t i o n of selenium-75 i n t o a p o l y p e p t i d e of the r a t sperm t a i l . J . Exp. Z o o l . 204:445-452.  C a l v i n , A . I . , G.W. Cooper and E. Wallace. 1981. Evidence t h a t selenium i n r a t sperm is associated with a cysteine-rich structural protein of the m i t o c h o n d r i a l c a p s u l e s . Gamete Res. 4 : 1 3 9 - 1 4 9 . Cantor, A.H., M.L. S c o t t and T. Noguchi. 1 9 7 5 . B i o l o g i c a l availability of selenium i n feedstuffs and selenium compounds for prevention of exudative diathesis i n c h i c k s . J . Nutr. 1 0 5 : 9 6 - 1 0 5 . Cary, E.E., W.H. Allaway and M. M i l l e r . 1 9 7 3 . U t i l i z a t i o n of d i f f e r e n t forms of d i e t a r y selenium. J . Anim. S c i . 3 6 : 2 8 5 292.  C a s t e e l , S.W., G.D. Osweiler, W.O. Cook, G. D a n i e l s and R. Kadlec. 1 9 8 5 . Selenium t o x i c o s i s i n swine. J . Am. V e t . Med. Assoc. 1 8 6 : 1 0 8 4 - 1 0 8 5 . Cawley, G.D. and I . McPhee. 1 9 8 4 . T r i a l s with a long acting p a r e n t e r a l selenium p r e p a r a t i o n i n ruminants:Sheep. V e t . Rec.  114:565-566.  Combs, G.F. J r . 1 9 7 6 . D i f f e r e n t i a l e f f e c t s of high dietary l e v e l s of v i t a m i n A on the v i t a m i n E-Selenium n u t r i t i o n of young and a d u l t c h i c k e n s . J . Nutr. 1 0 6 : 9 6 7 - 9 7 5 . Combs, G.F. Jr. a s c o r b i c a c i d on the Nutr. 1 0 6 : 9 5 8 - 9 6 6 .  and G.M. Pesti. 1 9 7 6 . Influence selenium n u t r i t i o n of the c h i c k .  of J.  Combs, G.F. J r . and S.B. Combs. 1 9 8 4 . The nutritional b i o c h e m i s t r y of selenium. Ann. Rev. Nutr. 4 : 2 5 7 - 2 8 0 . Cone, J.E.,  R.M.  del  R i o , J.N.  Davis and  T.C.  Stadtman.  182  1976. Chemical characterization of the s e l e n o p r o t e i n component of C l o s t r i d i a l g l y c i n e reductase: Identification of s e l e n o c y s t e i n e as the organo-selenium moiety. Proc. N a t l . Acad. S c i . 7 3 : 2 6 5 9 - 2 6 6 3 . Cousins, F.B. and I.M. Cairney. 1 9 6 1 . Some aspects o f selenium metabolism i n sheep. Aust. J . A g r i C i Res. 12:927942.  C r a n d e l l , S.S., P.A. Palma and F.H. Morriss. 1982. E f f e c t of maternal serum i n s u l i n on u m b i l i c a l extraction of glucose; and l a c t a t e i n fed and f a s t e d sheep. Am. J . Obstet. Gynecol. 1 4 2 : 2 1 9 - 2 2 4 . D'aleo, L. 1984. P r a c t i c a l sulphur-selenium metabolic interactions i n dairy c a t t l e . M.Sc. T h e s i s , U n i v e r s i t y o f B r i t i s h Columbia, Vancouver, Canada. de Toledo, L.R.A. and T.W. Perry. 1 9 8 5 . D i s t r i b u t i o n o f supplemental selenium i n the serum, h a i r , colostrum, and fetus of parturient dairy cows. J . D a i r y S c i . 6 8 : 3 2 4 9 3254.  Donoghue, S., D.W. Richardson, D. Sklan and D.S. Kronfeld. 1 9 8 2 . Placental t r a n s p o r t o f r e t i n o l i n sheep. J . Nutr. 1 1 2 : 2 1 9 7 - 2 2 0 3 . Donoghue, S., D.W. Richardson, D. Kronfeld. 1 9 8 5 . Placental transport of fed high i n t a k e s of v i t a m i n A. J . Nutr.  Sklan and D.S. retinol i n ewes 115:1562-1571.  Douglas, T.A., J.P. Renton and C. Watts. 1 9 7 1 . Placental t r a n s f e r of i r o n i n the r a b b i t . Br. J . Haematol. 2 0 : 1 8 5 - 1 9 4 . Eger, S., D. D r o r i , I. Kadoori, N. Miller and H. Schindler. 1 9 8 5 . Effects o f selenium and v i t a m i n E on i n c i d e n c e of r e t a i n e d p l a c e n t a . J . Dairy S c i . 68:21192122.  E h l i g , C.F., D.E. Hogue., W.H: Allaway and D.J. Hamm. 1 9 6 7 . Fate o f selenium from s e l e n i t e or seleno-methionine, w i t h or without v i t a m i n E, i n lambs. J . Nutr. 9 2 : 1 2 1 - 1 2 6 . Emerson, P.M., D.Y. Mason and J.E. Cuthbert. 1972. Erythrocyte glutathione peroxidase content and serum tocopherol l e v e l s i n newborn i n f a n t s . Br. J . Haematol. 22:667-680.  Ewan, R . C , C A . Baumann and A.L. Pope. 1 9 6 8 . R e t e n t i o n o f selenium by growing lambs. J . A g r i c . Food Chem. 1 6 : 2 1 6 - 2 1 9 . Fenimore, R.L., D.S.- Adams and R. P u i s . 1 9 8 3 . Selenium l e v e l s of beef c a t t l e i n southeastern British Columbia relative t o supplementation and type of p a s t u r e . Can. V e t .  183  J.  24:41-44.  Flohe, L., W.A. Gunzler and H.H. Schock. 1973. G l u t a t h i o n e peroxidase: a seleno-enzyme. FEBS L e t t . 3 2 : 1 3 2 134.  Flohe, L. 1 9 8 2 . G l u t a t h i o n e peroxidase brought i n t o focus. In "Free r a d i c a l s i n b i o l o g y " , W.A. Pryor (ed.) V o l . 5 , Pp. 2 2 3 - 2 5 4 , Academic Press, New York. Flohe, L. 1985. The g l u t a t h i o n e peroxidase reaction: Molecular b a s i s o f the a n t i o x i d a n t f u n c t i o n of selenium in mammals. In "Current topics i n cellular regulation", S. S h a l t i e l and P.B. Chock (eds.,) V o l . 2 7 , Pp. 4 7 3 - 4 7 8 , Academic Press, New York. Forstrom, J.W., J . J . Zakowski and A.L. Tappel. 1978. Identification of the c a t a l y t i c site of r a t liver glutathione peroxidase as s e l e n o c y s t e i n e . Biochemistry, 17:2639-2644.  F o s t e r , D.M., M.E. Wastney and R.I. Henkin. 1 9 8 4 . Zinc metabolism i n humans: A kinetic model. Mathematical Biosciences, 7 2 : 3 5 9 - 3 7 2 . Franke, K.W. 1 9 3 4 . A t o x i c a n t o c c u r r i n g n a t u r a l l y i n c e r t a i n samples of plant f o o d s t u f f s . I. Results obtained i n p r e l i m i n a r y feeding t r i a l s . J . Nutr. 8 : 5 9 6 - 6 0 8 . Franke, K.W. and V.R. P o t t e r . 1 9 3 5 . A new toxicant occurring naturally i n certain samples of plant f o o d s t u f f s . IX. Toxic e f f e c t s of o r a l l y ingested selenium. J . Nutr. 1 0 : 2 1 3 - 2 2 1 . Fridovich, Biochem.  I. 1 9 7 5 .  44:147-159.  Superoxide  dismutases.  Ann.  Rev.  Furchner, J.E., J . E . London and J.S. Wilson. 1975. Comparative metabolism of r a d i o n u c l i d e s in mammals-IX. R e t e n t i o n of Se i n the mouse, r a t , monkey and dog. Health Physics,  29:641-648.  Ganther, H.E., D.G. Hafeman, R.A. Lawrence, R.E. Serfass and W.G. Hoekstra. 1976. Selenium and glutathione peroxidase i n health and disease - A review. In "Trace elements i n human h e a l t h and d i s e a s e " , A.S. Prasad (ed.) V o l . 2 , Pp. 1 6 5 - 2 3 4 , Academic Press, New York. Ganther, H.E. 1 9 7 9 . Metabolism o f hydrogen s e l e n i d e methylated s e l e n i d e s . Adv. Nutr. Res. 2 : 1 0 7 - 1 2 8 .  and  Garrow, J.S. 1 9 7 1 . Selenomethionine uptake t e s t as a sensitive i n d i c a t o r of placental function i n the l a s t trimester of pregnancy. In "Dynamic studies with  184  radioisotopes i n medicine, Pp Atomic Energy Agency, V i e n n a .  83-92,  International  G a s i e w i c z , T.A. and J . C . S m i t h . 1978a. The m e t a b o l i s m of s e l e n i t e by i n t a c t r a t e r y t h r o c y t e s i n v i t r o . Chem. Biol. I n t e r a c t . 21:299-313. G a s i e w i c z , T.A. and J . C . S m i t h . 1978b. P r o p e r t i e s of the cadmium and s e l e n i u m complex formed i n r a t p l a s m a i n v i v o and i n v i t r o . Chem. Biol. Interact. 23:171-183. G a u l l , G.E., J.A. Sturman and N.C.R. Raiha. 1972. D e v e l o p m e n t o f mammalian sulfur metabolism: Absence of cystathionase in human fetal tissues. P e d i a t . Res. 6:538-547. G a u l l , G.E., N.C.R. R a i h a , S. S a a r i k o s k i and J.A. Sturman. 1973. Transfer of cyst(e)ine and m e t h i o n i n e across the human p l a c e n t a . Pediat. R e s . 7:908-913. Gissel-Nielsen, G., U.C. Gupta, M. Lamand and T. W e s t e r m a r c k . 1984. S e l e n i u m i n s o i l s and p l a n t s and i t s importance i n l i v e s t o c k and human n u t r i t i o n . Adv. Agron. 37:397-460. G l a s s e r , S.R., C. W r i g h t and R.M. H e y s s e l . 1968. T r a n s f e r o f i r o n a c r o s s t h e p l a c e n t a and f e t a l membranes i n t h e r a t . Am. J . P h y s i o l . 215:205-210. Godwin, K.O., C.N. F u s s and R.E. K u c h e l . 1975. G l u t a t h i o n e peroxidase activities i n sheep and r a t m u s c l e and some effects of selenium deficiency. Aust. J. Biol. S c i . 28:251-258. Greger, J . L . and R.E. M a r c u s . 1981. E f f e c t of dietary p r o t e i n , phosphorus, and s u l f u r amino acids on selenium metabolism of adult males. Ann. N u t r . Metab., 25:97108. G r i f f i t h s , N.M., R D.H. S t e w a r t and M.F. Robinson. 1976. The m e t a b o l i s m o f Se-selenomethionine i n f o u r women. B r . J . N u t r . 35:373-382. 5  G r o s s , R.T., R. Bracci, N. R u d o l p h , E. S c h r o e d e r and J.A. K o c h e n . 1967. H y d r o g e n p e r o x i d e t o x i c i t y and d e t o x i f i c a t i o n i n the erythrocytes of new born i n f a n t s . Blood, 29:481493. H a d j i m a r k o s , D.M., C.W. B o n h o r s t and J . J . M a t t i c e . 1959. The selenium c o n c e n t r a t i o n i n p l a c e n t a l t i s s u e and f e t a l cord b l o o d . J . P e d i a t . 54:296-298. Hafeman, D.G., R.A. Sunde and W.G. H o e k s t r a . 1974. Effect of d i e t a r y s e l e n i u m on e r y t h r o c y t e and l i v e r glutathione  185  peroxidase  i n the r a t . J . Nutr.  104: 580-587.  Hamdy, A.H., W.D. Pounden, A.L. Trapp, D.S. B e l l and Lagace. 1 9 6 3 . E f f e c t on lambs o f s e l e n i u m a d m i n i s t e r e d p r e g n a n t ewes. J . Am. V e t . Med. A s s o c . 143:749-751.  A. to  Hansard, S.L., H.M. Crowder and W.A. Lyke. 1957. The b i o l o g i c a l a v a i l a b i l i t y of calcium i n feeds f o r c a t t l e . J. Anim. S c i . 16:437-443. H a n s a r d , S.L. and A.S. Mohammed. 1968a. u t i l i z a t i o n of sulfate s u l f u r by t h e g r a v i d 96:247-254. Hansard, S.L. and transfer of zinc in (Abstr.).  Maternal-fetal ewe. J . N u t r .  A.S. Mohammed. 1968b. Placental the bovine. J . Anim. S c i . 27:301,  H a n s a r d , S.L. and A.S. Mohammed. 1968c. Maternal-fetal u t i l i z a t i o n o f z i n c by s h e e p . J . Anim. S c i . 2 7 : 8 0 7 - 8 1 3 . H a n s a r d , S.L. and A.S. Mohammed. 1 9 6 9 . A b s o r p t i o n , e x c r e t i o n and m a t e r n a l - f e t a l u t i l i z a t i o n o f s u l f a t e by t h e b o v i n e . J . A n i m . S c i . 28:283-287. Hansard, S.L. 1972. Physiological behaviour of manganese i n g r a v i d c a t t l e , sheep and s w i n e . In, Isotope studies on t h e p h y s i o l o g y of domestic animals, IAEA156/19, pp 351-365, International Atomic Energy Agency, Vienna, A u s t r i a . 75  Hansen, J . C . and P. K r i s t e n s e n . 1979. The k i n e t i c s o f Ses e l e n i u m i n r e l a t i o n t o dose and mode o f a d m i n i s t r a t i o n to m i c e . J . N u t r . 109:1223-1233. 75  H a n s s o n , E. and S.O. Jacobsson. selenomethionine i n the t i s s u e s whole body autoradiography. 115:285-293.  1966. Uptake o f Seo f t h e mouse studied by Biochim. Biophys. Acta,  H a r t l e y , W.J. and A.B. G r a n t . 1961. A review responsive diseases o f New Zealand l i v e s t o c k . 20:679-688.  of selenium Fed. Proc.  Hartley, W.J. 1967. Levels of selenium in animal tissues and methods of selenium a d m i n i s t r a t i o n . In symposium, S e l e n i u m i n b i o m e d i c i n e , O.H. Muth ( e d . ) , Pp 7 9 96, AVI P u b l . Co., W e s t p o r t , C o n n e c t i c u t , U.S.A. H a r t m a n i s , M.G.N, and T.C. S t a d t m a n . 1982. Isolation of a selenium-containing thiolase from Clostridium kluyveri: I d e n t i f i c a t i o n o f t h e s e l e n i u m m o i e t y as selenomethionine. P r o c . N a t l . A c a d . S c i . , U.S.A. 7 9 : 4 9 1 2 - 4 9 1 6 .  186 Hartmanis, M.G.N. and M.X. Sliwkowski. 1985. Selenomethionine containing thiolase and 3hydroxybutyryl-Co A dehydrogenase from C l o s t r i d i u m kluyveri. In " Current t o p i c s in cellular r e g u l a t i o n " S. Shaltiel and P.B. Chock (eds.) V o l . 2 7 , Pp. 4 7 9 - 4 8 6 , Academic Press, New York. Lyons and A.L. Tappel. 1982. selenocysteine - s p e c i f i c aminoacyl rat liver. Biochim. Biophys. Acta  Hawkes, W.C., D.E. I d e n t i f i c a t i o n of a transfer RNA from 699:183-191.  Hay, W.W., J.W. S p a r k s , B . J . Q u i s s e l l , F.C. B a t t a g l i a and G. M e s c h i a . 1981. S i m u l t a n e o u s measurements o f u m b i l i c a l uptake, fetal utilization rate, f e t a l turnover rate o f g l u c o s e . Am. J . P h y s i o l . 240:E662-E668. Heimann, E.D., M.F. Smith, J.S. Morriss, T.J. Gall, R.G. E l m o r e and R.E. Morrow. 1984. R e l a t i o n s h i p s among s p e r m a t o z o a l a b n o r m a l i t i e s and t h e s e l e n i u m c o n c e n t r a t i o n o f b l o o d plasma, semen, and r e p r o d u c t i v e tissues i n young b u l l s . Anim. R e p r o d . S c i . 7:315-321. H i d i r o g l o u , M., R.B. C a r s o n and G.A. B r o s s a r d . 1965. I n f l u e n c e o f s e l e n i u m on t h e s e l e n i u m c o n t e n t s o f h a i r a n d on t h e i n c i d e n c e o f n u t r i t i o n a l m u s c u l a r disease i n beef c a t t l e . C a n . J . Anim. S c i . 45:197-202.  H i d i r o g l o u , M., R.B. Carson and G.A. B r o s s a r d . 1968a. Problems a s s o c i a t e d with selenium d e f i c i e n c y i n beef c a l v e s . Can. J .  Physiol.  Pharmacol.  46:853-858.  H i d i r o g l o u , M., D.P. Heany and K.J. Jenkins. 1968b. Metabolism of i n o r g a n i c selenium i n rumen b a c t e r i a . Can. J . Physiol.  Pharmacol.  46:229-232.  H i d i r o g l o u , M., I . Hoffman and K.J. Jenkins. 1969. Selenium d i s t r i b u t i o n and r a d i o t o c o p h e r o l metabolism in the pregnant ewe and f e t a l lamb. Can. J . Physiol. Pharmacol.  47:953-962.  H i d i r o g l o u , M., K.J. J e n k i n s , J.M. Wauthy and J.E. P r o u l x . 1972. A note on the p r e v e n t i o n of n u t r i t i o n a l muscular dystrophy by winter s i l a g e f e e d i n g of the cow or selenium i m p l a n t a t i o n o f the c a l f . Anim. Prod. 1 4 : 1 1 5 - 1 1 8 . H i d i r o g l o u , M. and D.T. Spurr. 1 9 7 5 . I n f l u e n c e o f c o l d exposure and d i e t change on the t r a c e element composition o f h a i r from shorthorn cattle. Can. J . Anim. S c i . 5 5 : 3 1 . (Abstr.) Hidiroglou, M., J . Proulx and J . Jolette. 1985. I n t r a r u m i n a l selenium pellet f o r control of n u t r i t i o n a l muscular dystrophy i n c a t t l e . J . Dairy S c i . 6 8 : 5 7 - 6 6 .  187  Hodgson, J . C , D.J. M e l l o r and A . C F i e l d . 1 9 8 0 . Rates of glucose p r o d u c t i o n and u t i l i z a t i o n by the foetus in c h r o n i c a l l y c a t h e t e r i z e d sheep. Biochem. J . 1 8 6 : 7 3 9 - 7 4 7 . Hopper, S.A., A. G r e i g and C H . McMurray. p o i s o n i n g i n lambs. Vet. Rec. 1 1 6 : 5 6 9 - 5 7 1 .  1985.  Selenium  Horton, G.M.J., W.L. Jenkins and R. Rettenmaier. 1 9 7 8 . Haematological and blood chemistry changes i n ewes and lambs f o l l o w i n g supplementation with v i t a m i n E and selenium. B r . J . Nutr. 4 0 : 1 9 3 - 2 0 3 . Hoskins, F.H. and S.L. Hansard. 1 9 6 4 a . P l a c e n t a l t r a n s f e r and f e t a l t i s s u e i r o n u t i l i z a t i o n i n sheep. J . Nutr. 83:1014.  Hoskins, F.H. and S.L. Hansard. 1 9 6 4 b . P l a c e n t a l t r a n s f e r o f i r o n i n swine as a f u n c t i o n of g e s t a t i o n age. Proc. Soc. Exp. B i o l . Med. 1 1 6 : 7 - 1 1 . Hsieh, H.S. and H.E. Ganther. 1 9 7 5 . A c i d - v o l a t i l e selenium formation c a t a l y z e d by g l u t a t h i o n e reductase. Biochemistry, 14:1632-1636.  Hudson, D.R., R.A. Hunter and D.W. Peter. 1 9 8 1 . S t u d i e s with the i n t r a r u m i n a l selenium p e l l e t . I I . The e f f e c t o f grain size of selenium on the f u n c t i o n a l l i f e of p e l l e t s i n sheep. Aust. J . A g r i c . Res. 3 2 : 9 3 5 - 9 4 5 . Hunter, R.A., D.W. Peter, D.R. Hudson and B.S. Chandler. 1 9 8 1 . S t u d i e s with the i n t r a r u m i n a l selenium pellet. I. Some factors influencing the e f f e c t i v e n e s s o f the p e l l e t f o r selenium supplementation of sheep. Aust. J . A g r i c . Res. 3 2 : 9 2 7 - 9 3 3 . Ishak, M.A., L.L. Larson, F.G. Owen, S.R. Lowry and E.D. Erickson. 1 9 8 3 . E f f e c t s of selenium, v i t a m i n s and r a t i o n f i b e r on p l a c e n t a l r e t e n t i o n and performance of d a i r y c a t t l e . J . Dairy S c i . 6 6 : 9 9 - 1 0 6 . Itano, K., S. Kawai, N. M i y a z a k i , R. Tatsukawa and T. Fujiyama. 1 9 8 4 . Mercury and selenium l e v e l s a t the f e t a l and s u c k l i n g stages o f s t r i p e d dolphin, Stenella coeruleoalba. A g r i c . B i o l . Chem. 4 8 : 1 6 9 1 - 1 6 9 8 . Jacobsson, S.O. and H.E. Oksanen. 1 9 6 6 . P l a c e n t a l t r a n s m i s s i o n of selenium i n sheep. Acta Vet. Scand. 7 : 6 6 - 7 6 . Janghorbani, M., M.J. C h r i s t e n s e n , A. Nahapetian Young. 1 9 8 2 . Selenium metabolism in healthy Quantitative aspects u s i n g the s t a b l e isotope Am. J . C l i n . Nutr. 3 5 : 6 4 7 - 6 5 4 .  7  and V.R. ^adul|s: SeO,  188  Jelinek, P.D., P. S t e e l e , H.G. M a s t e r s , J.G. Allen, M.D. C o p e l a n d and D.S. Petterson. 1985. Erythrocyte selenium-75 u p t a k e as a measure o f s e l e n i u m s t a t u s i n weaner s h e e p , and its relationship to erythrocyte glutathione peroxi-dase a c t i v i t y . A u s t . V e t . J . 62:327-331. J e n k i n s , K.J. and M. Hidiroglou. 1972a. A review selenium/vitamin E responsive problems in livestock. c a s e f o r s e l e n i u m as a feed a d d i t i v e i n C a n a d a . Can. A n i m . S c i . 52:591-620.  of A J.  J e n k i n s , K . J . and M. Hidiroglou. 1972b. Comparative metabolism of Se-selenite, Se-selenate, and Seselenomethionine i n bovine e r y t h r o c y t e s . Can. J . Physiol. P h a r m a c o l . 50:927-935. J e n s e n , L.S., E.D. W a l t e r and J . S . D u n l a p . 1 9 6 3 . Influence o f d i e t a r y v i t a m i n E and s e l e n i u m on d i s t r i b u t i o n o f Se i n t h e c h i c k . P r o c . S o c . Exp. Biol. Med. 112:899-901. J o n e s , J.B., G.L. D i l w o r t h and T.C. Stadtman. 1979. Occurrence of selenocysteine i n the selenium dependent formate dehydrogenase of Methanococcus v a n n i e l i i . Arch. B i o c h e m . B i o p h y s . 195:255-260. Julien, W.E., H.R. C o n r a d and A.L. Moxon. 1976. S e l e n i u m and v i t a m i n E and i n c i d e n c e of retained placenta in parturient cows. II. Prevention i n commercial herds w i t h prepartum treatment. J . D a i r y S c i . 5 9 : 1 9 6 0 - 1 9 6 2 . K i n c a i d , R.L., W.J. M i l l e r , M.W. N e a t h e r y , R.P. G e n t r y and D.L. Hampton. 1977. Effect o f added d i e t a r y selenium on m e t a b o l i s m and tissue distribution of radioactive and s t a b l e s e l e n i u m i n c a l v e s . J . Anim. S c i . 44:147-151. K i t t s , D.D., CR. K r i s h n a m u r t i and W.D. K i t t s . 1979. P o s t s u r g i c a l changes i n b l o o d parameters of the ovine f e t u s in u t e r o . Can. J . Anim. S c i . 59:265-271. Kitts, D.D. and CR. Krishnamurti. Substrate metabolism and i n t e r r e l a t i o n s h i p s i n t h e f e t u s i n u t e r o . Can. J . Anim. S c i . 62: 397-408.  1982. ovine  Klassan, C D . 1975. Biliary excretion of drugs: Role of ligandin i n new-born immaturity and i n the a c t i o n of m i c r o s o m a l enzyme inducers. J. Pharmacol. Exp. Therap. 195:311-319. Roller, L.D., P.J. South, J.H. Exon and G.A. Whitbeck. 1983. Selenium d e f i c i e n c y of beef cattle in I d a h o and W a s h i n g t o n and a p r a c t i c a l means o f p r e v e n t i o n . C o r n e l l V e t . 73:323-332. Roller,  L.D.,  P.J.  South,  J.H. Exon,  G.A.  Whitbeck  and  J.  189  Maas. 1984a. C o m p a r i s o n o f s e l e n i u m l e v e l s and g l u t a t h i o n e peroxidase a c t i v i t y i n bovine whole b l o o d . Can. J . Comp. Med. 48:431-433. Roller, L.D., G.A. Whitbeck and P.J. South. 1984b. Transplacental transfer and c o l o s t r a l concentrations of selenium i n beef c a t t l e . Am. J . V e t . Res. 45: 2 5 0 7 - 2 5 1 0 . R o l l e r , L.D., and J.H. Exon. 1986. The two f a c e s o f s e l e n i u m - d e f i c i e n c y and t o x i c i t y - a r e s i m i l a r i n a n i m a l s and man. Can. J . V e t . R e s . 50:297-306. R o r p e l a , H., R. Loueniva, E. Yrjanheikki and A. Kauppila. 1984. Selenium c o n c e n t r a t i o n i n maternal and umbilical cord blood, placenta and a m n i o t i c membranes. I n t e r n a t . J . V i t . N u t r . R e s . 54:257-261. R r i s h n a m u r t i , C R . and A . L . S c h a e f e r . 1984. E f f e c t o f a c u t e maternal starvation on t y r o s i n e metabolism and protein s y n t h e s i s i n f e t a l sheep. Growth, 48: 391-403. Kuchel, R.E. and R.A. Buckley. 1969. The p r o v i s i o n of s e l e n i u m t o sheep by means o f h e a v y p e l l e t s . A u s t . J . A g r i c . Res. 20: 1099-1107. K u c h e l , R.E. and R.O. Godwin. 1976. The p r e v e n t i o n and cure o f white muscle d i s e a s e i n lambs by means o f selenium pellets. Proc. Aust. S o c . Anim. P r o d . 11:389-392. L a d e n s t e i n , R., 0. Epp, K. B a r t e l s , A. J o n e s , R. Huber and A. W e n d e l . 1 9 7 9 . S t r u c t u r e a n a l y s i s and m o l e c u l a r model of the selenoenzyme g l u t a t h i o n e p e r o x i d a s e a t 2.8 A r e s o l u t i o n . J . M o l . B i o l . 134:199-218. Lake-Bakaar, C , CE. R u b i o , S. McRavanagh and J.A. Summerfield. 1980. The d e c a y o f e n d o g e n o u s l y labelled Se-selenomethionine labelled proteins in duodenal juice: Evidence for recirculation in man. H e p a t o g a s t r o e n t e r o l o g y , 27:484-487. L a n e , H.W., A.I. Barraso, S . J . D u t r i c k , D.A. E n g l e r t and B.V. M a c F a y d e n . 1982. In, " T r a c e e l e m e n t m e t a b o l i s m i n man and a n i m a l s " , TEMA 4, J.M. Gawthorne, J.M. H o w e l l and C L . W h i t e ( E d s . ) Pp 30, S p r i n g e r - V e r l a g , B e r l i n . Langlands, J.P., J.E. B o w l e s , G.E. Donald Smith. 1986. S e l e n i u m e x c r e t i o n i n s h e e p . A u s t . Res. 37:201-209. Larkin, E.C, L.R. Iron transport across P h y s i o l . 218:7-11.  and A . J . J. Agric.  W e i n t r a u b and W.H. Crosby. rabbit allantoic placenta.  1970. Am. J .  190  Latshaw, J.D. and M.D. B i g g e r t . 1 9 8 1 . I n c o r p o r a t i o n selenium i n t o egg p r o t e i n s a f t e r f e e d i n g selenomethionine sodium selenite. Poult. S c i . 6 0 : 1 3 0 9 - 1 3 1 3 .  of or  L a u r e l l , C.B. and E. Morgan. 1 9 6 4 . Iron exchange between t r a n s f e r r i n and the p l a c e n t a i n the r a t . Acta P h y s i o l . Scand. 62:271-279.  Lawrence, R.A. and R.F. Burk. 1 9 7 6 . G l u t a t h i o n e peroxidase i n selenium d e f i c i e n t r a t l i v e r . Biochem. Biophys. Res. Commun. 71:952-958. 75  Lee, M., A. Dong and J . Yano. 1 9 6 9 . Metabolism of Ses e l e n i t e by human blood i n v i t r o . Can. J . Biochem. 4 7 : 7 9 1 - 7 9 7 . Lemons, J.A. and R.L. Schreiner. 1983. Amino acid metabolism i n the ovine f e t u s . Am. J . P h y s i o l . 2 4 4 : E 4 5 9 - E 4 6 6 . Levander, O.A. and C A . Baumann. 1966. Selenium metabolism. V I . E f f e c t of a r s e n i c on the e x c r e t i o n of selenium i n the b i l e . T o x i c o l . Appl. Pharmacol. 9:106115.  Levander, O.A., B. Sutherland, V . C M o r r i s s and J.C. King. 1981. Selenium balance i n young men d u r i n g selenium d e p l e t i o n and r e p l e t i o n . Am. J . C l i n . Nutr. 3 4 : 2 6 6 2 - 2 6 6 9 . Lopez, P.L., R.L. Preston and W.H. Pfander. 1968. uptake of selenium-75 by red blood cells immature ovine d u r i n g v a r y i n g selenium intakes. 94:219-226.  In v i t r o from the J . Nutr.  Lopez, P.L., R.L. Preston and W.H. Pfander. 1 9 6 9 . Whole-body retention, tissue distribution and e x c r e t i o n of selenium75 after o r a l and intravenous a d m i n i s t r a t i o n i n lambs f e d v a r y i n g selenium i n t a k e s . J . Nutr. 9 7 : 1 2 3 - 1 3 2 . Maag, D.D. and M.W. Glenn. 1 9 6 7 . T o x i c i t y of selenium: animals. in Symposium "Selenium i n Biomedicine" O.H. (ed.), P p . 1 2 7 - 1 4 0 , AVI Publ. Co., Westport, Conn.  Farm Muth  Mace, D.L., J.A. Tucker, C.B. B i l l s and C.J. F e r r e i r a . 1 9 6 3 . Reduction i n i n c i d e n c e of b i r t h of premature, weak or dead c a l v e s f o l l o w i n g sodium s e l e n i t e d-alpha t o c o p h e r y l therapy i n pregnant cows. C a l i f o r n i a State Dept. A g r i c . Bull. 52:21-28. MacPherson, A. supplementation  and J.S. Chalmers. 1 9 8 4 . Methods of of ruminants. Vet. Rec. 1 1 5 : 5 4 4 - 5 4 6 .  selenium  Mahan, D.C. and A.L. Moxon. 1 9 7 8 . E f f e c t s of adding i n o r g a n i c or o r g a n i c selenium sources to the d i e t s of young swine. J . Anim. S c i . 4 7 : 4 5 6 - 4 6 6 . M a l l i n s o n , C.B., W.M.  A l l e n and B.F.  Sansom. 1 9 8 5 .  Barium  191  selenate injections i n cattle: c o n c e n t r a t i o n s i n plasma and l i v e r i n j e c t i o n . V e t . Rec. 1 1 7 : 4 0 5 - 4 0 7 .  Effects on selenium and r e s i d u e s a t s i t e o f  Mansour, M.M., A.R. Schulert and S.R. Glasser. Mechanism o f p l a c e n t a l iron t r a n s f e r i n the r a t . Physiol.  222:1628-1633.  Maynard, L. and J.K. L o o s l i . Animal N u t r i t i o n . 1969. Nutrition. S i x t h e d i t i o n , McGraw-Hill Co., New York.  1972. Am. J . Animal  McConnell, K.P. and D.M. Roth. 1 9 6 4 . Passage o f selenium a c r o s s the p l a c e n t a and a l s o i n t o the milk of the dog. J . Nutr. 8 4 : 3 4 0 - 3 4 4 . McConnell, K.P. and G.J. Cho. 1 9 6 5 . Transmucosal selenium. Am. J . P h y s i o l . 2 0 8 : 1 1 9 1 - 1 1 9 5 .  movement o f  McConnell, K.P., R.M. Burton, T. Kute and P. H i g g i n s . 1 9 7 9 . S e l e n o p r o t e i n s from rat testis cytosol. Biochim. Biophys. Acta, 5 8 8 : 1 1 3 - 1 1 9 . McDonald, D.W., R.G. C h r i s t i a n , G.R. Whenham and J . Howell. 1976. A review of some aspects of v i t a m i n E-selenium responsive diseases with a note on t h e i r possible i n c i d e n c e i n A l b e r t a . Can. V e t . J . 1 7 : 6 1 - 7 1 . McLean, J.W., G.G. Thomson and J.H. C l a x t o n . 1 9 5 9 . responses to selenium i n lambs. Nature, 1 8 4 : 2 5 1 - 2 5 2 .  Growth  McMurray, C.H. and W.B. Davidson. 1979. In v i t r o metabolism of s e l e n i t e i n sheep blood: Factors c o n t r o l l i n g the d i s t r i b u t i o n of selenium and the l a b e l l i n g of plasma p r o t e i n . Biochim. Biophys. Acta 5 8 3 : 3 3 2 - 3 4 3 . McMurray, C.H., W.B. Davidson, H.J. B a l l and D. Todd. 1 9 8 6 . C h a r a c t e r i s a t i o n of an antiserum and development o f an ELISA f o r g l u t a t h i o n e peroxidase. V e t . Res. Commun. 1 0 : 2 6 9 - 2 8 1 . Meschia, G., J.R. C o t t e r , C.S. Breathnach and D.H. Barron. 1 9 6 5 . Hemoglobin, oxygen, carbon d i o x i d e and hydrogen i o n c o n c e n t r a t i o n s i n the u m b i l i c a l bloods of sheep and goats as sampled v i a i n d w e l l i n g p l a s t i c c a t h e t e r s . Q u a r t e r l y J . Exp. Physiol.  50:185-195.  M o r r i s s , F.H., C R . Rosenfeld, S.S. C r a n d e l l and E.W. Adcock. 1 9 8 0 . E f f e c t s o f f a s t i n g on u t e r i n e blood flow and s u b s t r a t e uptake i n sheep. J . Nutr. 110:2433-2443. M o r r i s s , F.H. and R.M. Caprioli. 1 9 8 2 . Techniques and i n v e s t i g a t i o n of trace element metabolism i n the mother and fetus. in, Animal models in fetal medicine, P.W. N a t h a n i e l s z (ed.), pp. 1 5 0 - 1 9 4 , E l s e v i e r Biomedical P r e s s , Amsterdam.  192  Motsenbocker, M.A. and A.L. Tappel. 1 9 8 4 . E f f e c t of dietaryselenium on plasma selenoprotein P, selenoprotein Pi and g l u t a t h i o n e peroxidase i n the r a t . J . Nutr. 1 1 4 : 2 7 9 - 2 8 5 . Mukhtar, H. and E. B r e s n i c k . 1976. Glutathione transferase activity during development and hepatectomy. Cancer Res. 3 6 : 9 3 7 - 9 4 0 . Munro, H.N., S.J. P i l i s t i n e and M.E. Fant. p l a c e n t a i n n u t r i t i o n . Ann. Rev. Nutr. 3 : 9 7 - 1 2 4 .  S-epoxide partial 1983.  The  Mutanen, M.L. and H.M. Mykkanen. 1 9 8 4 . E f f e c t of d i e t a r y f a t on plasma g l u t a t h i o n e peroxidase levels and intestinal a b s o r p t i o n of Se-labeled sodium s e l e n i t e i n c h i c k s . J. Nutr. 1 1 4 : 8 2 9 - 8 3 4 . Muth, O.H. myopathy.  1 9 6 3 . White muscle d i s e a s e , a selenium-responsive J . Am. Vet. Med. Assoc. 1 4 2 : 2 7 2 - 2 7 7 .  Muth, O.H., H.W. Pendell, CR. Watson, J.E. O l d f i e l d and P.H. Weswig. } § 6 7 . Uptake and retention of parenterally administered Se i n ewes on d i f f e r e n t selenium regimens.  Am.  J . Vet.  Res.  28:1397-1406.  Nakamura, W., S. Hosoda and K. Hayashi. 1974. Purification and p r o p e r t i e s of r a t l i v e r g l u t a t h i o n e p e r o x i d a s e . Biochim. Biophys. Acta 3 5 8 : 2 5 1 - 2 6 1 . Nelson, F . C , M. Hidiroglou and H.A. Hamilton. 1 9 6 4 . The e f f e c t of p r o p h y l a c t i c treatment of pregnant beef cows on the i n c i d e n c e of n u t r i t i o n a l muscular dystrophy. A f i e l d trial. Can.  Vet.  J.  5:268-273.  Noguchi, T., A.H. Cantor and M.L. S c o t t . 1 9 7 3 . Mode of a c t i o n of selenium and v i t a m i n E i n p r e v e n t i o n of exudative diathesis i n chicks. J . Nutr. 103: 1502-1511. Norman, B.B., H.J. S e g a l l , W.H. Johnson, M.N. Oliver and J.R. Dunbar. 1 9 8 1 . Modification of a glutathione peroxidase blood spot t e s t to d e t e c t selenium-responsive calves i n northern C a l i f o r n i a . In, "Selenium in biology and medicine". J.E. S p a l l h o l z , J.L. M a r t i n and H.E. Ganther (eds.) AVI Publ. Co., Westport, Conn. NRC, U.S. 1 9 8 3 . Selenium in nutrition, N a t i o n a l Academy Press, Washington, D.C. O ' D e l l , B.L. Rev.  1984.  42:301-308.  B i o a v a i l a b i l i t y of  Revised  edition,  t r a c e elements.  Nutr.  Oh, S.H., H.E. Ganther and W.G. Hoekstra. 1974. Selenium as a component of g l u t a t h i o n e peroxidase isolated from ovine e r y t h r o c y t e s . Biochemistry, 1 3 : 1 8 2 5 - 1 8 2 9 .  1 9 3  Oh, S.H., A . L . Pope and W.G. Hoekstra. 1976. selenium requirement o f sheep fed practical-type a s s e s s e d by t i s s u e g l u t a t h i o n e p e r o x i d a s e and o t h e r J . Anim. S c i . 42:984-992.  Dietary diet as criteria.  O l d f i e l d , J.E., O.H. Muth and J.R. Schubert. 1960. S e l e n i u m and v i t a m i n E a s r e l a t e d t o growth and w h i t e m u s c l e disease. Proc. S o c . Exp. B i o l . Med. 103:799-800. O l s o n , O.E., E . J . Novacek, E.I. Whitehead and I.S. P a l m e r . 1 9 7 0 . I n v e s t i g a t i o n s on s e l e n i u m i n wheat. Phytochemistry, 9:1181-1188. O l s o n , O.E. and I . S . P a l m e r . 1976. Selenoamino acids i n tissues of rats administered inorganic selenium. Metabolism, 25:299-306. Omaye, S.T. and A.L. Tappel. s e l e n i u m on g l u t a t h i o n e p e r o x i d a s e 104:747-753.  1974. E f f e c t of dietary i n the c h i c k . J. Nutr.  Osman, M. and J.D. Latshaw. 1976. B i o l o g i c a l potency of selenium from sodium selenite, selenomethionine and s e l e n o c y s t i n e i n the c h i c k . P o u l t . S c i . 55:987-994. O v e r n e s , G., K. Moksnes and A. Froslie. 1985a. Barium s e l e n a t e : A l o n g - a c t i n g selenium p r e p a r a t i o n f o r subcutaneous injection. A c t a V e t . S c a n d . 26:164-168. O v e r n e s , G., K. Moksnes., A. F r o s l i e , J.G. N o r s t e b o and J . Flaat. 1985b. The e f f e c t of d i f f e r e n t l e v e l s of selenium i n m i n e r a l m i x t u r e s and s a l t l i c k s on s e l e n i u m s t a t u s i n s h e e p . A c t a V e t . S c a n d . 26:405-416. P a l l i n i , V. and E. bound t o a s t r u c t u r a l C y t o l . 11:165-170.  Bacci. protein  1979. B u l l sperm-selenium is of mitochondria. J. Submicros.  P a u l s o n , G.D., C A . Baumann and A . L . Pope. 1 9 6 6 . F a t e o f a p h y s i o l o g i c a l d o s e o f s e l e n a t e i n the l a c t a t i n g ewe: Effect of sulfate. J . Anim. S c i . 25:1054-1058. P a u l s o n , G.D., G.A. Broderick, C A . Baumann and A.L. Pope. 1968. E f f e c t of feeding sheep selenium fortified trace mineralized salt: Effect o f t o c o p h e r o l . J . Anim. S c i . 27:195-202. P a y n t e r , D.I. 1979. G l u t a t h i o n e p e r o x i d a s e and s e l e n i u m i n sheep. I . E f f e c t of i n t r a r u m i n a l selenium p e l l e t s on tissue glutathione peroxidase activities. Aust. J. Agric. Res. 30:665-702. Pedersen,  N.D.,  P.D. Whanger, P.H. Weswig  and O.H. Muth. 1972.  194  Selenium b i n d i n g p r o t e i n s i n t i s s u e s of normal and seleniumresponsive myopathic lambs. B i o i n o r g . Chem. 2 : 3 3 - 4 5 . Pegg, D.G. and J.B. Hook. 1 9 7 7 . G l u t a t h i o n e S - t r a n s f e r a s e s . An e v a l u a t i o n o f t h e i r r o l e i n r e n a l o r g a n i c anion t r a n s p o r t . J. Pharmacol. Exp. Therap. 200:65-74. Perry, T.W., D.M. C a l d w e l l and R.C. Peterson. 1 9 7 6 . Selenium content of feeds and e f f e c t of d i e t a r y selenium on h a i r and blood serum. J . D a i r y S c i . 5 9 : 7 6 0 - 7 6 3 . Peter, D.W., P.G. Board and M.J. Palmer. 1 9 8 0 . Selenium supplementation of g r a z i n g sheep. I. E f f e c t s o f selenium drenching and other factors on plasma and erythrocyte glutathione peroxidase activities and blood selenium c o n c e n t r a t i o n s o f lambs and ewes. Aust. J . Agric. Res. 31:991-1004.  Peterson, P.J. and G.W. B u t l e r . 1 9 6 2 . The uptake and a s s i m i l a t i o n o f s e l e n i t e by higher p l a n t s . Aust. J . B i o l . S c i . 15:126-146.  P e t e r s o n , | . J . and D.J. Spedding. 1963. The e x c r e t i o n by sheep o f Se i n c o r p o r a t e d i n t o red c l o v e r : The chemical nature o f the excreted selenium and i t s uptake by three p l a n t s p e c i e s . N. Z. J . A g r i c . Res. 6 : 1 3 - 2 3 . 7  Pinto, R.E. and W. B a r t l e y . 1 9 7 7 . The e f f e c t of age and sex on g l u t a t h i o n e reductase and g l u t a t h i o n e peroxidase a c t i v i t i e s and on a e r o b i c g l u t a t h i o n e o x i d a t i o n i n r a t liver homogenates. Biochem. J . 1 1 2 : 1 0 9 - 1 1 5 . Pope, A.L., R.J. Moir, M. Somers, E . J . ynderwood and C L . White. 1 9 7 9 . The e f f e c t of sulphur on Se a b s o r p t i o n and retention i n sheep. J . Nutr. 109:1448-1455. 7  Poston, H.A., G.F. Combs, J r . and L. Leibovitz. 1976. V i t a m i n E and selenium i n t e r r e l a t i o n s i n the d i e t of A t l a n t i c salmon (Salmo s a l a r ) : Gross, histological and b i o c h e m i c a l d e f i c i e n c y s i g n s . J . Nutr. 1 0 6 : 8 9 2 - 9 0 4 . Poston, H.A. and G.F. Combs, J r . 1 9 7 9 . Interrelationships between requirements f o r d i e t a r y selenium, v i t a m i n E, and L - a s c o r b i c a c i d by A t l a n t i c salmon (Salmo s a l a r ) fed a semip u r i f i e d d i e t . F i s h H l t h . News, 8 : v i - v i i . Ramberg, C.F., M. Delivoria-Papadopoulos, E.D. Crandall and D.S. Kronfeld. 1 9 7 3 . Kinetic a n a l y s i s of c a l c i u m t r a n s p o r t across the p l a c e n t a . J . A p p l . Physiol. 35:682-688. Reasbeck, P.G., C O . Barbezat, M.F. Thomson. 1 9 8 1 . Selenium a b s o r p t i o n from Aust. NZ. J . Surg. 5 1 : 3 9 4 - 3 9 5 .  Robinson and C D . the canine jejunum.  195  Renegar, R.H., F.W. Bazer and R.M. Roberts. P l a c e n t a l t r a n s p o r t and d i s t r i b u t i o n of u t e r o f e r r i n f e t a l p i g . B i o l . Reprod. 2 7 : 1 2 4 7 - 1 2 6 0 .  1982. i n the  R i c e , D.A. and C.H. McMurray. 1 9 8 6 . Use of sodium hydroxide t r e a t e d selenium d e f i c i e n t b a r l e y to induce v i t a m i n E and selenium d e f i c i e n c y i n y e a r l i n g c a t t l e . Vet. Rec. 1 1 8 : 1 7 3 176.  Rice, D.A. and W.J. B l a n c h f l o w e r . 1 9 8 6 . E v a l u a t i o n of a new t e s t k i t f o r measuring whole blood g l u t a t h i o n e peroxidase u s i n g c a t t l e blood. Vet. Rec. 118:479-480. Roberts, R.M., T . J . Raub and F.W. Bazer. 1 9 8 6 . Role of uteroferrin i n t r a n s p l a c e n t a l i r o n t r a n s p o r t i n the p i g . Fed. Proc. 4 5 : 2 5 1 3 - 2 5 1 8 . Robinson, M.F., H.M. Rea, G.M. F r i e n d , R.D.H. Stewart, P.G. Snow and C D . Thomson. 1 9 7 8 . On supplementing the selenium i n t a k e of New Zealanders. 2 . Prolonged metabolic experiments with daily supplements of selenomethionine, s e l e n i t e and f i s h . Br. J . Nutr. 3 9 : 5 8 9 - 6 0 0 . Robinson, M.F. and C D . Thomson. 1 9 8 3 . The r o l e of selenium i n the d i e t . Nutr. Abst. Rev. 5 3 : 3 - 2 6 . Rosenfeld, CR. 1984. Consideration of the uteroplacental circulation i n i n t r a u t e r i n e growth. Seminars in Perinatol.  8:42-51.  Rotruck, J.T., A.L. Pope, C A . Baumann, W.G. Hoekstra and G.D. Paulson. 1 9 6 9 . E f f e c t of long-term f e e d i n g of s e l e n i z e d s a l t to ewes and t h e i r lambs. J . Anim. S c i . 2 9 : 1 7 0 (Abstr.) Rotruck, J.T., A.L. Pope, H.E. Ganther, A.B. Swanson, D.G. Hafeman and W.G. Hoekstra. 1 9 7 3 . Selenium: Biochemical role as a component of g l u t a t h i o n e peroxidase. Science, 179:588590.  Rudolph, N. and S.L. Wong. 1 9 7 8 . Selenium and g l u t a t h i o n e peroxidase a c t i v i t y i n maternal and cord plasma and red c e l l s . Pediatr.  Res. 1 2 : 7 8 9 - 7 9 2 .  Sandholm, M. 1 9 7 3 . The i n i t i a l of i n t r a v e n o u s l y administered Toxicol. 3 3 : 1 - 5 . Sandholm, M. 1974. plasma. A c t a Pharmacol.  fate of a t r a c e amount s e l e n i t e . Acta Pharmacol.  Selenium carrier proteins Toxicol. 35:424-431.  i n mouse  Sandholm, M. 1 9 7 5 . Function o f e r y t h r o c y t e s i n selenite-Se onto s p e c i f i c plasma p r o t e i n s . Acta  attaching Pharmacol.  Toxicol.  36:321-327.  196  Sansom, B.F., H.W. Symonds and P.J. T a y l o r . 1 9 7 9 . The t r a n s f e r of copper from ewes with Border d i s e a s e t o t h e i r lambs. J . Comp. P a t h o l . 8 9 : 3 6 1 - 3 6 6 . SAS. 1 9 8 5 . User guide, Cary, N C , USA.  S t a t i s t i c s , V e r s i o n 5 , SAS  Institute,  Schaefer, A.L. and C R . K r i s h n a m u r t i . 1 9 8 4 . Whole body and tissue fractional p r o t e i n s y n t h e s i s i n the ovine fetus i n u t e r o . Br. J . Nutr. 5 2 : 3 5 9 - 3 6 9 . Schneider, K.M., J.H. Ternouth, C.C. Sevilla and R.C. Boston. 1 9 8 5 . A short term study o f calcium and phosphorus a b s o r p t i o n i n sheep fed on d i e t s high and low i n c a l c i u m and phosphorus. Aust. J . A g r i c . Res. 3 6 : 9 1 - 1 0 5 . S c h o l z , R.W. and L . J . Hutchinson. 1 9 7 9 . Distribution g l u t a t h i o n e peroxidase a c t i v i t y and selenium i n the blood d a i r y cows. Am. J . Vet. Res. 4 0 : 2 4 5 - 2 4 9 .  of of  Schwarz, K. and C M . F o l t z . 1 9 5 7 . Selenium as an i n t e g r a l part of factor 3 against dietary necrotic l i v e r degeneration. J . Am. Chem. Soc. 7 9 : 3 2 9 2 - 3 2 9 3 . Scott, M.L., G. Olson, L. Krook and W.R. Brown. Selenium-responsive myopathies of myocardium and o f muscle i n the young p o u l t . J . Nutr. 9 1 : 5 7 3 - 5 8 3 .  1967. smooth  S e a l , U.S., A.A. Sinha and R. Doc. 1 9 7 2 . P l a c e n t a l iron t r a n s f e r : Relationship to placental anatomy and phylogeny o f the mammal. Am. J . Anat. 134:263-269. Sedman, A . J . and J.G. Wagner. 1 9 7 6 . AUTOAN: A d e c i s i o n making pharmacokinetic computer program. Michigan: P u b l i c a t i o n distribution service. Segerson, E . C , F.A. Murray, A.L. Moxon, D.R. Redman and H.R. Conrad. 1977. Selenium and v i t a m i n E: Role i n f e r t i l i z a t i o n o f the bovine ova. J . Dairy S c i . 6 0 : 1 0 0 1 - 1 0 0 5 . Segerson, E.C. and S.N. Ganapathy. 1 9 8 0 . F e r t i l i z a t i o n of ova i n selenium/vitamin E t r e a t e d ewes maintained on two planes of n u t r i t i o n . J . Anim. S c i . 5 1 : 3 8 6 - 3 9 4 . Segerson, E . C , G. R i v i e r e , T.R. B u l l o c k , S. Thimaya and S.N. Ganapathy. 1 9 8 1 . U t e r i n e c o n t r a c t i o n s and e l e c t r i c a l a c t i v i t y i n ewes t r e a t e d with selenium and v i t a m i n E. B i o l . Reprod. 23:1020-1028.  Shamberger, R.J. 1 9 8 3 . Biochemistry of selenium. Plenum P r e s s , New York. Shariff, Heindze.  M.A., 1984.  C R . Krishnamurti, A.L. Schaefer and A.M. Bidirectional transfer of selenium across  197  the  sheep  placenta  i n utero.  (suppl.):252-254.  Can. J . Anim.  S c i . 64  Sheppard, A.D. and K.R. Millar. 1981. S t a b i l i t y of g l u t a t h i o n e peroxidase i n ovine blood samples under various storage c o n d i t i o n s and the response of t h i s enzyme to d i f f e r e n t methods o f selenium supplementation. N. Z. V e t . J.  29:77-80.  S h i p l e y , R.A. and R.E. C l a r k . 1 9 7 2 . Tracer methods f o r i n v i v o k i n e t i c s : Theory and a p p l i c a t i o n s . Academic Press, New York. S h r i f t , A. 1 9 6 9 . Aspects of selenium metabolism i n p l a n t s . Annu. Rev. Plant P h y s i o l . 2 0 : 4 7 5 - 4 9 4 .  higher  Silver, M. 1981. An assessment of the c h r o n i c a l l y catheterized fetal p r e p a r a t i o n i n sheep and other species. In, Placental transfer: Methods, and i n t e r p r e t a t i o n P l a c e n t a ( s u p p l . 2 ) , M. Young, R.D.H. Boyd, L.D. Longo and G. Telegdy (eds.), W.B. Saunders Co., P h i l a d e l p h i a . Smith, D.G., P.L. Senger, J.F. McCutchan and C A . Landa. 1979. Selenium a n d g l u t a t h i o n e peroxidase d i s t r i b u t i o n i n bovine semen and Se r e t e n t i o n by the t i s s u e s o f the r e p r o d u c t i v e t r a c t i n the b u l l . B i o l . Reprod. 2 0 : 3 7 7 - 3 8 3 . 7  Stevens, J.B., W.G. Olson, R. Kraemer and J . Archambeau. 1 9 8 5 . Serum selenium c o n c e n t r a t i o n s and g l u t a t h i o n e peroxidase activities in cattle grazing forages of v a r i o u s selenium c o n c e n t r a t i o n s . Am.  J . V e t . Res.  46:1556-1560.  Sturman, J.A., G.E. G a u l l and N.C.R. c y s t a t h i o n a s e i n human f e t a l l i v e r : Science,  169:74-76.  Raiha. 1 9 7 0 . Absence o f Is c y s t i n e e s s e n t i a l ?  Sturman, J.A., G.E. G a u l l and W.H. Niemann. C y s t a t h i o n i n e s y n t h e s i s and degradation i n brain, and kidney of the developing monkey. J . Neurochem.  1976. liver 26:457-  463.  Sunde, R.A. and W.G. Hoekstra. 1980. Incorporation of selenium from s e l e n i t e and s e l e n o c y s t i n e into glutathione peroxidase i n the i s o l a t e d perfused rat liver. Biochem. Biophys. Res. Commun. 9 3 : 1 1 8 1 - 1 1 8 8 . Sunde, R.A. 1 9 8 4 . Am. O i l Chem. Soc.  The b i o c h e m i s t r y  of selenoproteins.  J.  61:1891-1900.  Swanson, C A . , D.C. Reamer, C. V e i l l o n , J.C. King and O.A. Levander. 1983. Quantitative and q u a l i t a t i v e aspects o f selenium u t i l i z a t i o n i n pregnant and nonpregnant women: an a p p l i c a t i o n o f s t a b l e isotope methodology. Am. J . C l i n . Nutr. 38:169-180.  198  Symonds, H.W., B.F. Sansom, D.L. Mather and M.J. Vagg. 1981. Selenium metabolism i n the d a i r y cow: The i n f l u e n c e o f the l i v e r and the e f f e c t of the form of Se s a l t . Br. J . Nutr. 45:117-125.  Tam, G.K.H. and G. L a c r o i x . 1 9 8 2 . Dry ashing, hydride g e n e r a t i o n atomic absorption spectrometric determination of arsenic and selenium in foods. J . Assoc. O f f . Analy. chem. 6 5 : 6 4 7 - 6 5 0 . Tanaka, H., N. E s a k i and K. Soda. 1 9 8 5 . S e l e n o c y s t e i n e metabolism i n mammals. In, "Current topics in cellular r e g u l a t i o n " , V o l . 2 7 , S. S h a l t i e l and P.B. Chock ( e d s . ) , Pp 4 8 7 - 4 9 5 , Academic Press, New York. Tappel, A.L. 1 9 8 4 . Selenium - glutathione peroxidase: P r o p e r t i e s and s y n t h e s i s . In, "Current t o p i c s i n c e l l u l a r regulation", V o l . 24, B.L. Horecker and E.R. Stadtman ( e d s . ) , Pp 8 7 - 9 7 , Academic Press, New York. Thompson, J.N. and M.L. S c o t t . 1 9 7 0 . Impaired l i p i d and v i t a m i n E a b s o r p t i o n r e l a t e d to atrophy of the pancreas i n s e l e n i u m - d e f i c i e n t c h i c k s . J . Nutr. 100:797-809. Thompson, K.G., A . J . Fraser and B.M. Harrop. 1981. G l u t a t h i o n e peroxidase a c t i v i t y and selenium concentration in bovine blood and liver as i n d i c a t o r s of d i e t a r y selenium i n t a k e . N. Z. V e t . J . 2 9 : 3 - 6 . Thompson, R.H., C.H. McMurray and W.J. Blanchflower. 1976. The l e v e l s o f selenium and g l u t a t h i o n e peroxidase a c t i v i t y i n blood of sheep, cows and p i g s . Res. V e t . Sci. 20:229-231.  Thomson, 7 § ' * R.D.H. Stewart, studies of Se-Selenomethionine and r a t . B r . J . Nutr. 3 0 : 1 3 9 - 1 4 7 . C  a n c  5  1973. Metabolic S e - s e l e n i t e i n the  Thomson, C D . , C E . Burton and M.F. Robinson. 1978. supplementing the selenium intake of New Zealanders. Short term experiments with large doses of s e l e n i t e selenomethionine. Br. J . Nutr. 3 9 : 5 7 9 - 5 8 7 .  On 1. or  Thomson, C D . and M.F. Robinson. 1980. Selenium i n human h e a l t h with emphasis on those aspects p e c u l i a r to New Zealand. Am. J . C l i n . Nutr. 3 3 : 3 0 3 - 3 2 3 . Trapp, A.L., K.K. Keahey, D.L. Whitenack and C K . W h i t e h a i r . 1 9 7 0 . V i t a m i n E-selenium d e f i c i e n c y i n swine: Differential d i a g n o s i s and nature of the f i e l d problem. J . Am. V e t . Med. Assoc. 1 5 7 : 2 8 9 - 3 0 0 . Trengove, CL. supplementation  and G.J. Judson. of sheep: E v a l u a t i o n  1 9 8 5 . Trace of v a r i o u s  element copper  199  supplements and a s o l u b l e glass b u l l e t containing c o b a l t and selenium. Aust. Vet. J . 6 2 : 3 2 1 - 3 2 4 .  copper,  T r i n d e r , N. , C D . Woodhouse and C P . Renton. 1 9 6 9 . The e f f e c t of v i t a m i n E and selenium on the i n c i d e n c e of retained placentae i n d a i r y cows. V e t . Rec. 8 5 : 5 5 0 - 5 5 3 . U l l r e y , D.E., P.S. Brady, P.A. Whetter, P.K. Ku and W.T. Magee. 1 9 7 7 . Selenium supplementation o f d i e t s f o r sheep and beef c a t t l e . J . Anim. S c i . 4 5 : 5 5 9 - 5 6 5 . U l l r e y , D.E., M . R . L i g h t , P.S. Brady, P.A. Whetter, J . E . Tilton, H.A. Henneman and W.T. Magee. 1 9 7 8 . Selenium supplements i n s a l t f o r sheep. J . Anim. S c i . 4 6 : 1 5 1 5 - 1 5 2 1 . Underwood, nutrition,  E . J . 1 9 7 7 . Trace elements i n human and 4th e d i t i o n , Academic Press, New York.  Underwood, livestock,  E.J. 19.81. The mineral nutrition of 2 n d e d i t i o n , Commonwealth A g r i c . Bureaux, U.K.  animal  van D i j k , H.P. 1 9 8 1 . Active t r a n s f e r of the plasma bound compounds c a l c i u m and i r o n across the p l a c e n t a . I n , Transfer a c r o s s the primate and non-primate p l a c e n t a - P l a c e n t a (Suppl. 1 ) , H.C.S. Wallenberg, B.K. van K r e e l and J.P. van D i j k ( e d s . ) , W.B. Saunders Co., P h i l a d e l p h i a . van Dijk, J.P., B.K. van Kreel and J.W.A. Heeren. 1985. S t u d i e s on the mechanisms i n v o l v e d i n i r o n transfer across the i s o l a t e d guinea p i g p l a c e n t a by means o f bolus experiments. J . Dev. P h y s i o l . 7 : 1 - 1 6 . van V l e e t , J.F., W. Carlton and H.J. Olander. 1970. Hepatosis d i e t e t i c a and mulberry heart d i s e a s e a s s o c i a t e d with selenium deficiency i n Indiana swine. J . Am. V e t . Med. Assoc. 1 5 7 : 1 2 0 8 - 1 2 1 9 . van V l e e t , J.F., G . Ruth and V.J. Ferrans. 1976. Ultrastructural alterations i n skeletal muscles of p i g s w i t h selenium-vitamin E d e f i c i e n c y . Am. J . Vet. Res. 3 7 : 9 1 1 - 9 2 2 . van V l e e t , J . F . 1 9 8 0 . Current knowledge of selenium-vitamin E deficiency i n domestic animals. J . Am. Vet. Med. Assoc. 176:321-325.  Wastney, M.E., J . E . Wolff, R. B i c k e r s t a f f e , C F . Ramberg and M. Berman. 1 9 8 3 . Kinetics of glucose metabolism i n sheep. Aust. J . B i o l . S c i . 3 6 : 4 6 3 - 4 7 4 . Weber, K.M., R.C. Boston and D.D. Leaver. 1 9 8 3 . The e f f e c t of molybdenum and s u l f u r on the k i n e t i c s of copper metabolism i n sheep. Aust. J . A g r i c . Res. 3 4 : 2 9 5 - 3 0 6 . Weiss, W.P.,  V.F. Colenbrander  and M.D.  Cunningham.  1982.  200  I n t e r a c t i o n between selenium supplementation of c a l f . J . Dairy S c i . 65:116(Abstr.)  the dam and  Whanger, P.D., P.H. Weswig and O.H. Muth. 1 9 6 8 . Metabolism of Se-selenite and Se-selenomethionine by rumen microorganisms. Fed. Proc. 27:418, (Abstr.). Whanger, P.D., P.H. Weswig, J.A. Schmitz and J.E. Oldfield. 1977. E f f e c t s o f selenium and vitamin E on blood selenium l e v e l s , t i s s u e g l u t a t h i o n e peroxidase a c t i v i t i e s and white muscle d i s e a s e i n sheep fed p u r i f i e d or hay d i e t s . J . Nutr. 1 0 7 : 1 2 9 8 - 1 3 0 7 . Whanger, P.D., P.H. Weswig, J.A. Schmitz and J.E. O l d f i e l d . 1 9 7 8 . E f f e c t s o f v a r i o u s methods o f selenium administration on white muscle disease, glutathione peroxidase and plasma enzyme a c t i v i t i e s i n sheep. J . Anim. S c i . 4 7 : 1 1 5 7 1166.  White, R.G., J.W. S t e e l , R.A. Leng and J.R. Luick. 1969. E v a l u a t i o n of three isotope dilution techniques for studying the kinetics of glucose metabolism i n sheep. Biochem. J . 1 1 4 : 2 0 3 - 2 1 4 .  W i l k e n i n g , R.B., P.A. Palma and F.H. M o r r i s s . 1982. Effect of maternal serum i n s u l i n on u m b i l i c a l e x t r a c t i o n of g l u c o s e and l a c t a t e i n f e d and f a s t e d sheep. Am. J . Obstet. Gynecol. 142:219-224.  Wilson, P.S. and G.J. Judson. 1 9 7 6 . Glutathione peroxidase a c t i v i t y i n bovine and ovine e r y t h r o c y t e s i n r e l a t i o n t o blood selenium c o n c e n t r a t i o n s . Br. V e t . J . 1 3 2 : 4 2 8 - 4 3 4 . Wolffram, S., F. Arduser and E. S c h a r r e r . 1985. i n t e s t i n a l a b s o r p t i o n o f s e l e n a t e and s e l e n i t e .  In v i v o J . Nutr.  115:454-459.  Wong, C.T. and E.H. Morgan. 1 9 7 4 . Source of f o e t a l i r o n the c a t . Aust. J . Exp. B i o l . Med. S c i . 5 2 : 4 1 3 - 4 1 6 .  in  Wright, E. 1 9 6 5 . The d i s t r i b u t i o n and e x c r e t i o n r a d i o s e l e n i u m i n sheep. N. Z. J . A g r i c . Res. 8 : 2 8 4 - 2 9 1 .  of  Wright, P.L. and M.C. B e l l . 1 9 6 4 . Selenium-75 metabolism i n the gestating ewe and fetal lamb: E f f e c t s of dietary t o c o p h e r o l and selenium. J . Nutr. 8 4 : 4 9 - 5 7 . Wright, P.L. and M.C. B e l l . 1 9 6 6 . Comparative metabolism o f selenium and t e l l u r i u m i n sheep and swine. Am. J . P h y s i o l . 211:6-10.  Wu, S.H., J . E . O l d f i e l d , P.D. Whanger and P.H. Weswig. 1973. Effect of selenium, v i t a m i n E and a n t i o x i d a n t s on t e s t i c u l a r f u n c t i o n i n r a t s . B i o l . Reprod. 8:625-629.  201  Wu, S.H., J.E. O l d f i e l d , L.R. S h u l l and P.R. Cheeke. Specific effect of selenium d e f i c i e n c y on r a t sperm. R e p r o d . 20:793-798. X i a , Y., J . E . O l d f i e l d , M.A. Bielstein 1985. M e t a b o l i s m o f o r a l l y administered p i g . N u t r . Res. 5:545-553.  7 5  1979. Biol.  a n d P.D. Whanger. S e - s e l e n i t e by the  Young, S., W.W. Hawkins, J r . and K.F. Swingle. 1961. N u t r i t i o n a l muscular dystrophy in lambs The e f f e c t of administering selenium to p r e g n a n t ewes. Am. J . Vet. Res. 22:416-418. Young, M. and E.M. Widdowson. 1975. The i n f l u e n c e of diets d e f i c i e n t i n energy, or i n p r o t e i n , on c o n c e p t u s w e i g h t , and the p l a c e n t a l t r a n s f e r of a non-metabolizable amino a c i d in t h e g u i n e a p i g . B i o l . N e o n a t e , 27:184-191. Yudilevich, D.L., B.M. Eaton, A.H.A. Short and H.P. L e i c h t w e i s s . 1979. G l u c o s e c a r r i e r s a t t h e m a t e r n a l and fetal s i d e o f the t r o p h o b l a s t i n the g u i n e a p i g p l a c e n t a . Am. J. P h y s i o l . 237:C205-C212. Zhang, W.R., P.K. Ku, E.R. Miller and D.E. Ullrey. 1986. S t a b i l i t y of glutathione peroxidase in swine plasma samples under various storage conditions. Can. J . Vet. Res. 50:390-392.  202  APPENDIX  203  A p p e n d i x 1 . Plasma Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug Se) changes i n Se p o s i t i v e and d e f i c i e n t nonpregnant ewes.  Time after tracer injection 2 5 10  min it  n  n  Se p o s i t i v e ewes 622  65  99  Se d e f i c i e n t  ewes  100  999  998  123  325  .000952  .002818  .000709  .001398  .007013  .004709  .006178  .001408  .000753  .001396  .000709  .000918  .005579  .003848  .005029  .001224  .000575  .001060  .000451  .000751  .004351  .002937  .003377  .000900  .000476  .000853  .000387  .000626  .003737  .002431  .002730  .000739  30  M  .000396  .000569  .000290  .000438  .002764  .001924  .001724  .000623  45  II  .000377  .000465  .000322  .000438  .002506  .002177  .001796  .000600  60  It  .000396  .000543  .000339  .000417  .002611  .002177  .001868  .000623  .000416  .000827  .000387  .000501  .002815  .002886  .002371  .000693  .000436  .000879  .000387  .000438  .002918  .002686  .002443  .000716  .000436  .000879  .000435  .000501  .002764  .002836  .002514  .000670  .000416  .000853  .000419  .000501  .002662  .002684  .002443  .000646  .000436  .000827  .000387  .000522  .002713  .002582  .002299  .000670  .000416  —  —  —  .002559  —  —  —  .000416  —  —  —  .002303  —  —  —  .000396  —  —  —  .002355  —  —  —  .000377  —  —  —  .002201  —  —  —  .000377  —  —  —  .002150  —  —  —  .000377  —  —  —  .002150  —  —  —  d  .000297  .000440  .000242  .000313  .001689  .001671  .001940  .000485  n  —  .000388  .000193  .000271  —  .001266  .001796  .000323  n  —  .000310  .000161  .000229  —  .001063  .001581  .000300  4  it  —  .000284  .000161  .000229  —  .001013  .001293  .000254  5  ti  .000259  .000145  .000188  —  .000861  .001149  .000231  6  tt  —  —  .000129  .000167  —  —  .001149  .000254  7  tt  —  —  .000129  .000167  —  —  .001006  .000231  8  tt  —  —  .000113  .000146  —  —  .001006  .000231  9  tt  —  —  .000113  .000146  —  —  .001006  .000208  —  —  —  .000146  —  —  —  .000208  15  2 3 4 5 6 7 8 9 10 11 12 1 2 3  10  hr n n n n n n tt  n ti  n  n  11  tt  —  —  —  .000146  —  —  —  .000208  12  ti  —  —  —  .000146  —  —  —  .000185  13  ti  — •  —  —  .000125  —  —  —  .000185  —  —  —  .000104  —  —  —  .000185  14  n  204  A p p e n d i x 2 . Plasma Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug Se) changes i n Se p o s i t i v e and d e f i c i e n t p r e g n a n t ewes.  Time after tracer injection 2 5 10 15 30 45 60 2 3 4 5 6  min n n n n n n  hr fl n  n n  Se p o s i t i v e 977  818  840  .001127  .000897  .001400  .001846  .000935  .000682  .001192  .000794  .000548  .000961  .000756  .000460  .000602  58  ewes  707  725  .004144  .002990  .002593  .003474  .002533  .002285  .001291  .002865  .001900  .001959  .000856  .001051  .002499  .001513  .001632  .000357  .000614  .000856  .002133  .001196  .001325  .000551  .000389  .000590  .000901  .002133  .001478  .001248  .000499  .000421  .000648  .000976  .002133  .001442  .001152  .000628  .000548,  .000683  .001051  .002377  .001689  .001133  .000653  .000571  .000729  .001186  .002560  .001724  .001210  .000717  .000563  .000741  .001261  .002438  .001724  .001210  .000692  .000555  .000729  .001156  .002438  .001724  .001191  .000653  .000516  .000810  .001126  .002377  .001689  .001133  .000451  .000721  .001585  .001020  .000883  .000540  .001097  .000774  .000711  .000405  .000975  .000668  .000653  d  .000410  .000309  2  n  .000295  .000286  .000243  .000175  3  Se d e f i c i e n t  982  1  n  ewes  ** .000266  **  ** B l o o d samples hemolysed and t h e r e f o r e plasma r a d i o a c t i v i t y determined.  c o u l d n o t be  205  A p p e n d i x 3. Plasma Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug Se) changes i n Se p o s i t i v e and d e f i c i e n t f e t u s e s .  Time after tracer injection 2 5 10 15 30 45 60 2 3 4 5 6 1 2 3  min n n n n n n  hr tl n n n  d n M  Se p o s i t i v e f e t u s e s 572  587  654  665  Se d e f i c i e n t 707  724  909  fetuses 1000  .023414  .026520  .029413  .061782  .045813  .018621  .025341  .023734  .055535  .039082  .030521  .016593  .022591  .019657  .039106  .032134  .008085  .025162  .014749  .018073  .017036  .032164  .026706  .014542  .006508  .021434  .011062  .013751  .012522  .025685  .020627  .012906  .005522  .020735  .009956  .013162  .010629  .023371  .018238  .011452  .005324  .019571  .009771  **  .010775  .021288  .018673  .009634  .004338  .019338  .007559  **  .009610  .020594  .018455  .008907  .004338  .016076  .007006  .011001  .009610  .020825  .018455  .007816  .003944  .011416  .006084  .009626  .010338  .020594  .018890  .007089  .003747  **  .005715  .008447  .009465  .020594  .017153  .006544  .003155  **  .005347  .007858  .009173  .018743  .015633  .005453  .002564  .008853  .002581  .005500  .005533  .011338  .008902  .004362  .002366  .007688  ***  .003536  .004077  .009024  .006297  .003817  .002169  .0067561  ***  .003143  .002912  .008330  .005428  .028901  .020706  .019631  .012226  .018177  .009268  .017813  .031220  **  ** B l o o d samples hemolysed and t h e r e f o r e plasma r a d i o a c t i v i t y c o u l d not, be d e t e r m i n e d . *** C a t h e t e r s  q u i t and hence no b l o o d samples were c o l l e c t e d .  206  A p p e n d i x 4 . Plasma Se s p e c i f i c a c t i v i t y ( f r a c t i o n of dose/ug Se) changes i n Se p o s i t i v e and d e f i c i e n t f e t u s e s f o l l o w i n g m a t e r n a l t r a c e r injection.  Time a f t e r maternal tracer injection 2 5 10 15 30 45 60 2 3 4 5  min n it n H  n n  hr ft n n  Se p o s i t i v e f e t u s e s  Se d e f i c i e n t  fetuses  982  818  840  .000027  .000009  .000014  .000005  .000020  .000005  .000010  .000021  .000009  .000016  .000006  .000022  .000007  .000012  .000020  .000011  .000013  .000008  .000025  .000005  .000012  .000023  .000011  .000015  .000007  .000045  .000006  .000012  .000020  .000014  .000023  .000009  .000063  .000005  .000013  .000027  .000015  .000024  .000012  .000036  .000006  .000015  .000033  .000014  .000031  .000011  .000035  .000008  .000016  .000032  .000018  .000037  .000013  .000039  .000009  .000020  .000038  .000019  .000028  .000013  .000038  .000007  .000022  .000047  .000023  .000031  .000014  .000042  .000009  .000017  .000051  .000025  .000032  .000013  .000010  .000019  977  58  **  725  707  6  n  .000044  .000027  .000038  .000015  .000051  .000009  .000015  1  d  .000096  .000038  .000066  .000028  .000102  .000019  .000020  .000099  .000052  .000049  .000034  .000122  .000030  .000046  .000094  .000046  .000044  .000030  .000115  .000023  .000038  2 3  n tt  1  ** Plasma ~*^Se r a d i o a c t i v i t y c o u l d not be d e t e r m i n e d a s a r e s u l t o f hemolysis.  207  A p p e n d i x 5. Plasma Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug Se) changes i n Se p o s i t i v e and d e f i c i e n t ewes f o l l o w i n g f e t a l t r a c e r i n j e c t i o n .  Time a f t e r fetal tracer injection  Se p o s i t i v e 572  587  ewes  654  665 **  Se 707  d e f i c i e n t ewes  724  909  1000  2 min  .000007  .000003  5  "  .000006  **  10  "  .000007  .000003  .000004 .000015  15  "  .000009  .000004  .000004 .000011  .000008 .000272 .000049  .000081  30  "  .000009  .000003  .000006  .000009 .000213  .000074  45  H  .000009  .000002  .000004 .000010  .000016 .000265 .000078 .000079  60  "  .000012  .000005  .000014 .000017  .000017 .000251  2  hr  .000015  .000007  .000020 .000023  .000050 .000324 .000084 .000125  3  "  .000014  .000009  .000031  .000046  .000353  .0001B7 .000179  4  "  .000024  .000013  .000032 .000032  **  .000466  .000151  5  "  .000032  .000013  .000051 .000034  **  .000473  .000122 .000171  6  "  .000040  .000014  .000061  .000034  .000087 .000467 .000112 .000163  1  d  **  .000027  .000080 .000053  .000117 .000602 .000428 .000283  2  "  .000059  .000026  **  .000052  .000110 .000658 .000293  .000433  3  "  .000054  .000019  .000056  .000046  .000101 .000612 .000151  .000297  .000003  .000004 .000019  .000012  .000028  .000005 .000208 .000052 .000070 .000007 .000201 **  .000196  B l o o d samples hemolysed and t h e r e f o r e plasma r a d i o a c t i v i t y be d e t e r m i n e d . Catheters quit  and hence no b l o o d  samples were  collected.  .000057 .000084 .000054 .000074  .000056  .000064 .000092  .000165  could not  Appendix 6 .  Tissue Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug Se/whole t i s s u e ) of the Se p o s i t i v e and d e f i c i e n t nonpregnant ewes.  Se p o s i t i v e  ewes  Se d e f i c i e n t ewes  Tissue 622(1)  65(5)  999(1)  998(5)  123(9)  Liver  .063357  .073988  .040981  .037820  .145598  .155491  .138462  .028950  Kidney  .065668  .039201  .020142  .017459  .342729  .142651  .240378  .069782  Skeletal muscle  .083720  .190352  .140608  .155131  .412112  .516230  .574994  .216103  Heart  .010119  .007381  .006369  .006235  .022100  .015792  .030706  .008443  Lung  .025288  .029269  .017851  .012962  .081880  .083359  .117573  .026096  Spleen  .007541  .008367  .006853  .028620  .021847  .033451  .037472  .004938  Pancreas  .004889  .002902  .002234  .002235  .009994  .010538  .012921  .003168  Mammary gland  .005920  .005085  .002561  .003332  .005559  .002580  .015768  .006900  Day o f s a c r i f i c e a f t e r each animal.  99(9)  tracer  100(14)  injection i s indicated  325(14)  i n brackets  against  * Weight of s k e l e t a l muscle was assumed to be 40% of body weight 1977).  (Arnal,  Appendix 7 . Tissue tissue)  75  Se s p e c i f i c a c t i v i t y ( f r a c t i o n of dose/ug Se/whole o f the Se p o s i t i v e and d e f i c i e n t pregnant ewes.  Se p o s i t i v e  ewes  Se d e f i c i e n t ewes  Tissue 982(6)  840(14)  977(18)  818(41)  58(4)  707(6)  725(12)  Liver  .080844  .063958  .040817  .017735  .223557  .084227  .067095  Kidney  .061905  .023028  .024614  .006134  .318863  .127485  .081264  Skeletal muscle  .169488  .097120  .088673  .093744  .331873  .244737  .239904  Heart  .008092  .006488  .006633  .003143  .014843  .014565  .008396  Lung  .037652  .026950  .015724  .005833  .095377  .059264  .035622  Spleen  .011239  .005555  .010674  .005934  .026606  .026181  .009983  Day o f s a c r i f i c e a f t e r t r a c e r each animal.  injection i s indicated  i n brackets against  * Weight of s k e l e t a l muscle was assumed t o be 40% o f body weight  (Arnal,  1977).  Ewe #818 gave b i r t h t o l i v e , healthy twin lambs and was l a c t a t i n g a t the time of s a c r i f i c e .  Appendix 8 . Tissue Se s p e c i f i c a c t i v i t y ( f r a c t i o n o f dose/ug t i s s u e ) of the Se p o s i t i v e and d e f i c i e n t f e t u s e s .  Se p o s i t i v e  fetuses  Se/whole  Se d e f i c i e n t  fetuses  Tissue 909(5)  1000(7)  .015078  .128048  .097421  .025112  .165513  .187594  .026669  .013631  .009837  .182707  .031110  .028298  .223293  .277506  .057174  .024250  .004042  .003546  .009917  .009015  .003768  654(7)  587(9)  Liver  .167627  .003899  Kidney  .757988  Skeletal muscle Heart  572(23)  724(21)  Day o f s a c r i f i c e a f t e r t r a c e r i n j e c t i o n i s i n d i c a t e d i n b r a c k e t s each animal. T i s s u e s from fetuses 6 6 5 , 707 were not c o l l e c t e d .  against  * Weight of s k e l e t a l muscle was assumed to be 40% o f body weight  (Arnal,  1977).  

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