Role of lipid peroxidation in gastric mucosal lesions induced by ischemia-reperfusion in the pylorus-ligated rat.
The peroxidation of lipids and changes in the activities of related enzymes, such as xanthine-xanthine oxidase (XOD), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in the gastric mucosa were studied in rat model of ischemia-reperfusion with pylorus ligation. Myeloperoxidase (MPO), a marker enzyme of leucocytes, was also studied. Thiobarbituric acid reactive substances (TBA RS) in gastric mucosa were significantly increased by clamping the celiac artery for 30 min and reperfusion for 60 min after 3 h of pylorus ligation. XOD activity in gastric mucosa increased with the development of gastric mucosal injury. Allopurinol significantly suppressed XOD activity but did not inhibit mucosal injury or the increase in TBA RS. MPO activity in the gastric mucosa was significantly increased by gastric mucosal injury. Famotidine significantly inhibited the increase in MPO activity in gastric mucosa, while allopurinol did not. SOD and GSH-px activities in the gastric mucosa were decreased significantly by gastric mucosal injury. SOD activity was normal following treatment with famotidine and allopurinol. Moreover, GSH-px activity recovered to the normal level with famotidine and allopurinol treatment. These findings suggest that oxygen radicals and lipid peroxidation can cause gastric mucosal injury by ischemia-reperfusion in the pylorus-ligated rat. The generation of oxygen free radicals may be derived mainly from activated polymorphonuclear leukocytes (PMN), and the decrease in SOD and GSH-px activity in gastric mucosa seems to aggravate mucosal injury by free radicals and lipid peroxidation.
Tanaka
J
J
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Yuda
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015738:Famotidine / Q000494:pharmacology; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008026:Ligation; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011708:Pylorus; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D015738:Famotidine; D000493:Allopurinol; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase