GASTRIC INJURY-INDUCED BY ETHANOL AND ISCHEMIA-REPERFUSION IN THE RAT- DIFFERING ROLES FOR LIPID-PEROXIDATION AND OXYGEN RADICALS

This study determined the role that oxygen-derived free radicals playe d in the production of gastric injury in rats challenged orally with c oncentrated ethanol or subjected to vascular compromise. In the ethano l study, rats were pretreated with a variety of free radical scavenger s or enzyme inhibitors prior to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic damage to the glandular gastri c mucosa was quantified. In separate studies, the effects of ethanol o n gastric mucosal levels of enaldehydes (malondialdehyde and 4-hydroxy nonenal) were examined as an index of lipid peroxidation. Superoxide d ismutase and catalase pretreatment were without benefit in reducing in jury in our ethanol model, excluding potential contributory roles for the superoxide anion or hydrogen peroxide, respectively. Dimethyl sulf oxide and desferoxamine were likewise without protective capabilities, eliminating a role for the hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no protection under acute conditions, even though partial protection was noted when administered chronically. Fu rther, enaldehyde levels were not increased over control levels in alc ohol-exposed mucosa, indicating no enhanced lipid peroxide formation. In contrast, in animals in which ischemia to the stomach was induced f ollowed by reperfusion, marked gastric injury was observed in combinat ion with enhanced enaldehyde levels. Prevention of enaldehyde formatio n by a 21-aminosteroid concomitantly prevented injury induced by ische mia-reperfusion. These findings support the conclusion that ischemia-r eperfusion injury to the stomach is an oxygen-derived free radical pro cess whereas ethanol-induced injury clearly involved some other proces s. Although allopurinal was partially protective against ethanol damag e when administered chronically, observations in other models of injur y suggest that this action is independent of its inhibitory effect on xanthine oxidase.