Glutathione S-transferases of the rodent pancreas : their response to inducing agents and to manipulation of pancreatic mass

Collins, Lori Ann (1989) Glutathione S-transferases of the rodent pancreas : their response to inducing agents and to manipulation of pancreatic mass. Masters thesis, Memorial University of Newfoundland.

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Abstract

Glutathione S-transferases (GSH-T) are a family of enzymes with both detoxifying and transport capacities. Their main role is in the catalysis of detoxification pathways. The enzymes are found in many tissues, with high concentrations in the mammalian liver and the gastrointestinal tract. Significant amounts of the enzyme have also been discovered in the rat pancreas, its function there being currently unknown. Previous studies have demonstrated that GSH-T levels are inducible in the liver with oral administration of certain compounds, such as the dietary antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA). In the present study, rats, mice, and hamsters were fed a diet containing 0.75% BHA for 14 days. Pancreatic GSH-T activity and levels in response to this were significantly increased over control animals only in hamsters. It is possible that this induction may provide protection against pancreatic carcinogens. -- Three other groups of hamsters were given either 0.03 mmol a-angelica lactone (a-AL)/g of diet or 0.03 mmol coumarin (COU)/g of diet, two naturally occurring plant compounds, or 20% green coffee beans (GCB). Although all three of these are known to induce liver and small intestinal mucosal GSH-T in rats and mice, none caused any significant induction of pancreatic GSH-T in the hamster, further exemplifying the difficulty in manipulating these enzymes in the pancreas as compared to other tissues. -- In addition to these experiments, groups of rats were fed a diet containing 40% raw soya flour (RSF) for 14 or 21 days. RSF contains trypsin inhibitor (TI) which has been shown to cause pancreatic enlargement, a phenomenon attributed to increased levels of the gastrointestinal hormone cholecystokinin (CCK). Pancreatic mass increased significantly in response to RSF; however DNA content as related to body weight increased only in the animals on the 3 week feeding schedule, indicating hyperplasia or an increase in cell number in this group. The activity of GSH-T in the enlarged pancreas was not found to be significantly different from that of the control pancreas. -- In an additional study, which utilized the compound FOY-305, also a trypsin inhibitor, hamsters were gavaged with 400 mg/kg body weight of FOY-305 once daily for 14 days. Both pancreatic weight and DNA content were significantly increased in these animals with a significant reduction in GSH-T activity. This reduction may be involved in the higher incidence of pancreatic neoplasms observed when trypsin inhibitors are fed for longer periods. Total GSH-T levels in the pancreas remained unchanged in these animals. -- Finally, the CCK antagonist L-364.718 was administered orally to hamsters at 1 mg/kg body weight, twice daily for 14 days. This compound was not found to cause a reduction in pancreatic mass or DNA content, thereby indicating that CCK does not seem to be a requirement for normal pancreatic maintenance and growth in this species. Furthermore, no changes in GSH-T activity or levels were observed. -- KEY WORDS: a-Angelica Lactone; 2(3)-tert-butyl-4-hydroxyanisole; Coumarin; Detoxification; FOY-305; Glutathione S-transferases; Hypertrophy/Hyperplasia; Induction; Kahweol; L-364,718; Pancreas; Raw Soya Flour

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