Role of active oxygen species and lipid peroxidation in mepirizole-induced duodenal ulcers in rats.
The role of active oxygen species and lipid peroxidation in the pathogenesis of duodenal ulcers induced by mepirizole was investigated in rats. Oral administration of mepirizole (200 mg/kg) resulted in ulcer lesions in the proximal duodenum. Thiobarbituric acid-reactive substances (TBA-reactive substances), an indicator of lipid peroxidation, also significantly increased in the duodenal mucosa. Myeloperoxidase (MPO) activity in the duodenal mucosa, a sign of polymorphonuclear leukocyte (PMN) accumulation, significantly increased. Combination treatment with polyethylene glycol-modified Serratia Mn-SOD and catalase significantly decreased the size of the ulcers and TBA-reactive substances in the duodenal mucosa. Allopurinol, a xanthine oxidase inhibitor, also reduced the size of duodenal ulcers. Both the size of the ulcers and the increase in TBA-reactive substances in the duodenal mucosa were significantly lower in PMN-depleted rats. Mepirizole increased the surface expression of adhesion molecule CD18 on PMNs in vitro. These results suggest that lipid peroxidation, mediated by active oxygen species generated from xanthine oxidase and PMNs, plays an important role in the pathogenesis of duodenal ulcers induced by mepirizole.
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
S
S
Iinuma
T
T
Yoshikawa
N
N
Yoshida
Y
Y
Naito
M
M
Kondo
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D018821:CD18 Antigens / Q000032:analysis; D002374:Catalase / Q000494:pharmacology; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004840:Epirizole / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018821:CD18 Antigens; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004840:Epirizole; D011092:Polyethylene Glycols; D000493:Allopurinol; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D014969:Xanthine Oxidase