Lipid peroxidation in gastric mucosal lesions induced by indomethacin in rat.
The peroxidation of lipids and changes in the activities of related enzymes in the gastric mucosa were studied in a rat model of gastric mucosal injury induced by the nonsteroidal anti-inflammatory drug indomethacin. The area of gastric erosion and the amount of thiobarbituric acid reactive substances (TBARS) in gastric mucosa were significantly increased beginning 4h after administration of indomethacin. Xanthine oxidase (XOD) activity in the gastric mucosa also increased immediately after administration of the drug. Although XOD activity was significantly suppressed by allopurinol treatment, the induction of gastric mucosal injury and the increase of TBARS in the gastric mucosa were not. Myeloperoxidase (MPO), a marker enzyme of leukocytes, was unaffected by indomethacin administration. But the depletion of polymorphonuclear leukocyte (PMN) counts induced by an injection of anti-rat PMN antibody inhibited both the injury and the increase in TBARS. Indomethacin activated PMN in peripheral blood at 30mg/kg per as and enhanced release of oxygen radicals from PMN in peripheral blood. As compared with the XOD system, the generation of oxygen free radicals may 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.
Tanaka
J
J
Pharmacology Dept., Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Yuda
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000633:toxicity*; D000906:Antibodies / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014969:Xanthine Oxidase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D000493:Allopurinol; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D007213:Indomethacin