ROLE OF ACTIVE OXYGEN, LIPID-PEROXIDATION, AND ANTIOXIDANTS IN THE PATHOGENESIS OF GASTRIC-MUCOSAL INJURY-INDUCED BY INDOMETHACIN IN RATS

The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric eros ions and concentration of lipid peroxides in the gastric mucosa increa sed with time after administration of indomethacin (20 mg/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significant ly decreased and the activity of glutathione peroxidase, an important enzyme to scavenger of lipid peroxides, was inhibited by the administr ation of indomethacin. Treatments with superoxide dismutase and catala se inhibited the increases in gastric mucosal erosions and lipid perox ides in the gastric mucosa, and the reduction of serum alpha-tocophero l. Treatment with these scavengers did not improve the decreased gluta thione peroxidase activity. These findings suggest that active oxygen species and lipid peroxidation play an important part in the pathogene sis of gastric mucosal injury induced by indomethacin, and that the de creased glutathione peroxidase activity aggravated the injury due to a ccelerated accumulation of hydrogen peroxide and lipid peroxides in th e gastric mucosal cell.