EFFECTS OF CIMETIDINE ON ACUTE GASTRIC-MUCOSAL INJURY-INDUCED BY ISCHEMIA-REPERFUSION IN RATS

We investigated the effects of cimetidine on acute gastric mucosal inj ury induced by ischemia-reperfusion in rats. Under pentobarbital anest hesia, the celiac artery was clamped for 30 min and reperfused for 60 min. Cimetidine, famotidine and omeprazole caused a dose-dependent sup pression in the total area of erosions that were induced by ischemia-r eperfusion, Whereas, none of them inhibited the increase in thiobarbit uric acid-reactive substances in the stomach, as an index of lipid per oxidation. The inhibitory effect of intraperitoneally administered cim etidine on mucosal damage was abolished by continuous luminal perfusio n with HCl solution (pH 1.5, 1 ml/min) during ischemia-reperfusion, wh ile luminal perfusion with the solution containing HCl and cimetidine (3 mmol/l) significantly reduced the total area of erosions compared t o luminal perfusion with HCl solution alone. Cimetidine (3 mmol/l) inh ibited hydroxyl radical-induced lipid peroxidation of human erythrocyt e membranes by 60% in vitro. These results indicate that cimetidine po ssesses a protective effect against acute gastric mucosal injury induc ed by ischemia-reperfusion not only due to the suppression in gastric acid secretion, but also due to the antioxidant action when it is pres ent at a high concentration in the intragastric environment.