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Abstract

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 weeks. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 to 8 weeks. The control groups comprised rats not injected with STZ, which were either Mn-deficient or Mn-sufficient. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copper-zinc superoxide dismutase (CuZnSOD) in kidney, in non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Pancreas weights were significantly lower in Mn-deficient, compared to Mn-sufficient rats. Also, Mn-deficient, diabetic rats were significantly more hyperglycemic in response to a glucose load than Mn-sufficient, suggesting that they may have been more severely diabetic. Surprisingly, plasma and hepatic vitamin E levels increased progressively with the duration of diabetes. Lipid peroxidation, as measured by H₂O₂ -induced production of thiobarbituric acid reactive substances in erythrocytes, plasma lipoperoxides, and renal adipose tissue fluorescence, also increased concomitant with decreased liver and kidney glutathione levels. The effect of vitamin E-deficiency on Mn-deficient, diabetic rats was also investigated. Predictably, vitamin E-deficient rats were almost entirely depleted of plasma and liver vitamin E after 12 weeks on the deficient diets (4 weeks after STZ treatment). Consistent with this, tissue lipid peroxides were elevated compared to vitamin E-sufficient rats. Superimposing vitamin E-deficiency on manganese deficiency failed to add any further deficits in tissue antioxidant status. Higher glycosylated hemoglobin levels were observed in vitamin E-deficient, compared to vitamin E-sufficient, diabetic rats. These findings demonstrate for the first time an interactive effect between manganese deficiency and STZ-diabetes resulting in amplification of tissue antioxidant changes seen with either manganese deficiency or STZ-diabetes alone. This effect of cofactor deprivation in experimental diabetes raises the question of adequacy of the nominally Mn-sufficient diet in insulin-dependent diabetes mellitus.