LIPID-PEROXIDATION IN GASTRIC-MUCOSAL LESIONS INDUCED BY INDOMETHACININ RAT

The peroxidation of lipids and changes in the activities of related en zymes in the gastric mucosa were studied in a rat model of gastric muc osal injury induced by the nonsteroidal anti-inflammatory drug indomet hacin. The area of gastric erosion and the amount of thiobarbituric ac id reactive substances (TBARS) in gastric mucosa were significantly in creased beginning Ih after administration of indomethacin, Xanthine ox idase (XOD) activity in the gastric mucosa also increased immediately after administration of the drug, Although XOD activity was significan tly suppressed by allopurinol treatment, the induction of gastric muco sal injury and the increase of TEARS in the gastric mucosa were not. M yeloperoxidase (MPO), a marker enzyme of leukocytes, was unaffected by indomethacin administration, But the depletion of polymorphonuclear l eukocyte (PMN) counts induced by an injection of anti-rat PMN antibody inhibited both the injury and the increase in TEARS. Indomethacin act ivated PMN in peripheral blood at 30 mg/kg per os and enhanced release of oxygen radicals from PMN in peripheral blood. As compared with the XOD system, the generation of oxygen free radicals mag derived mainly from activated PMN. On the other hand, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reduced by the administration of indomethacin. Decreases in SOD and GSH-px activity in gastric mucosa may aggravate mucosal injury by free radicals and lipid peroxidation.