Role of antioxidants in gastric mucosal damage induced by indomethacin in rats

Reactive oxygen species play a role in the formation of gastric lesions ind uced by nonsteroidal antiinflammatory drugs. The present study was undertak en to determine whether endogenous antioxidants in gastric mucosa can prote ct ii against the damaging effects of oxygen free radicals. This study exam ined oxygen free radical production (superoxide anions and hydrogen peroxid e), gastric mucosa antioxidant defense mechanisms (glutathione, catalase, s uperoxide dismutase), the lesion-inducing effects of the generated oxygen f ree radicals (vascular permeability, lipid peroxidation) and gastric ulcera tion in mrs treated orally with indomethacin at 10 mg/kg at 2 and 6 h after drug administration. Two hours after administration of the antiinflammator y drug, there was a sharp increase in production of oxygen free radicals in the gastric mucosa with no alteration in other parameters examined. Six ho urs after indomethacin administration the production of oxygen free radical s returned to basal levels, but there was a high degree of gastric ulcerati on and a significant increase in lipid peroxidation and vascular permeabili ty together with decreases of 45% in glutathione concentration and 30% in c atalase relative to the control group. These results suggest that like plas ma, the gastric mucosa has an antioxidant capacity and only when this capac ity is exhausted are the lesive effects of the oxygen free radicals manifes ted. (C) 1998 Prous Science. All rights reserved.