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UBC Theses and Dissertations

Changes in the O-acetyl substituted sialic acids in carrageenan induced large bowel ulceration in rabbits Al-Suhail, A. Amir A. Aziz


Mucus is a glycoprotein containing viscous fluid secreted continuously, by goblet cells and by mucous glands, into the lumen of the gastrointestinal tract. Mucous forms a continuous coating over the underlying epithelium and presumably both provides protection to the sensitive mucosa and lubricates the fecal stream. Its protective properties have been attributed, in part, to the relative resistance of its glycoproteins to digestion with proteolytic enzymes. This resistance has been ascribed to the presence of terminal sialic acids residues. It is generally agreed that sialic acids bearing an O-acetyl substituents at the C₄ position are more resistant to hydrolysis with Vibrio cholera neuraminidase, and therefore it has been suggested that the presence of such substituents may protect sialic acid residues from digestion by enzymes in the fecal stream. Alterations in the large intestinal glycoproteins have been shown to be associated with ulcerative colitis, but the significance of these findings is unclear because it is not known whether the observed changes are a cause or a consequence of the disease. Furthermore, most chemical studies are difficult to interpret because the starting material could have been contaminated with connective tissue elements or products of the fecal stream. Therefore, a rational approach is to investigate changes in the glycoproteins under controlled laboratory conditions. In the present study, the carrageenan model of ulcerations has been used to investigate the effects of the large bowel ulcerations on the epithelial glycoproteins of the lower digestive tract of the rabbit. The results of this study showed that: a) There are significant regional differences in the percentage of sialic acids bearing 0-acetyl substituents on the polyhydroxy side chain in normal rabbits. Upper colon epithelial glycoproteins have the smallest percentage of O-acetyl substituted sialic acids. b) There is a significant reduction in the percentage of side chain O-acetyl substituted sialic acids and a significant increase in the percentage of sialic acids labile to digestion with Vibrio cholera neuraminidase in the epithelial glycoproteins of the ceci of the carrageenan treated rabbits, . These changes were shown to be progressive and preceded both mucosal ulceration and the presence of significant inflammatory response. c) Removal of carrageenan from the diet resulted in an apparent initial progressive recovery characterized by a progressive increase in the percentage of O-acetyl substituted sialic acid and a reduction in the percentage of sialic acids labile to digestion with Vibrio cholera neuraminidase together with gross and micro anatomical evidence of healing. These observations were particularly evident in the group of animals 12 days after removal of carrageenan from the diet. After 20 days, however, there was an exacerbation of the disease characterized by inflammation and ulceration together with reduction in the percentage of the O-acetyl substituted sialic acids. It was concluded that in this model mucosal ulceration is associated with a reduction in the percentage of O-acetyl substituted sialic acids of the epithelial glycoproteins.

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