GASTRIC-MUCOSAL DAMAGE IN EXPERIMENTAL DIABETES IN RATS - ROLE OF ENDOGENOUS GLUTATHIONE

Background & Aims: Spontaneous gastric damage occurs in diabetic vats, but the mechanism is unknown. The aim of this study was to assess the role of glutathione metabolism and gastric mucosal blood flow (GMBF) in the development of such spontaneous gastric damage. Methods: Mucosa l damage, GMBF, glutathione metabolism, and lipid peroxidation were me asured in the stomach of diabetic and control vats. Results: Spontaneo us gastric damage occurred in fasted diabetic rats 4 weeks after strep tozotocin administration or pancreatectomy. This was accompanied by a 50% decrement in mucosal content of glutathione; 48 hours after strept ozotocin, the decrement of glutathione was only of 25% and no gastric damage was observed. Fed diabetic rats (4 weeks after streptozotocin) had normal glutathione levels and no damage; however, a 30% glutathion e depletion achieved by buthionine-sulfoximine administration promoted significant damage. Gastric glutathione synthetic rate, levels of ade nosine triphosphate, oxidized glutathione, and malonyldialdehyde were similar in all groups, whereas cysteine concentration was reduced in f asted diabetic animals. Exogenous cysteine attenuated the gastric dama ge. GMBF was not influenced by diabetes. Conclusions: Spontaneous gast ric damage in fasted diabetic vats seems to be related to glutathione depletion as a result of limited availability of cysteine and not to i ncreased glutathione oxidation. GMBF changes are not involved.