Role of antioxidants in gastric mucosal damage induced by indomethacin in rats.
Reactive oxygen species play a role in the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs. The present study was undertaken to determine whether endogenous antioxidants in gastric mucosa can protect it against the damaging effects of oxygen free radicals. This study examine oxygen free radical production (superoxide anions and hydrogen peroxide), gastric mucosa antioxidant defense mechanisms (glutathione, catalase, superoxide dismutase), the lesion-inducing effects of the generated oxygen free radicals (vascular permeability, lipid peroxidation) and gastric ulceration in rats treated orally with indomethacin at 10 mg/kg at 2 and 6 h after drug administration. Two hours after administration of the antiinflammatory drug, there was a sharp increase in production of oxygen free radicals in the gastric mucosa with no alteration in other parameters examined. Six hours after indomethacin administration the production of oxygen free radicals returned to basal levels, but there was a high degree of gastric ulceration and a significant increase in lipid peroxidation and vascular permeability together with decreases of 45% in glutathione concentration and 30% in catalase relative to the control group. These results suggest that like plasma, the gastric mucosa has an antioxidant capacity and only when this capacity is exhausted are the lesive effects of the oxygen free radicals manifested.
Hassan
A
A
Pharmacology Unit, Faculty of Medicine, University of Barcelona, Spain.
Martin
E
E
Puig-Parellada
P
P
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000502:physiology; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000502:physiology; D007213:Indomethacin / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D007213:Indomethacin