Effect of acetaminophen on stress-induced gastric mucosal lesions in rats.
The effects of acetaminophen (APAP) on stress-induced gastric mucosal lesions were investigated in rats treated with water-immersion restraint stress (WIR) for 3 hours. Three-hour WIR caused both significant increase in gastric lesions in terms of ulcer index and lipid peroxide levels and decrease in prostaglandin E2 (PGE2) levels in the stomach, compared with prestress control levels. When APAP (500mg/kg) was intraperitoneally (i.p.) administered into rats 2 hours before WIR, the stress-induced changes were significantly inhibited. Whereas, three-hour WIR markedly decreased total glutathione levels in the liver, but not in the stomach and plasma and simultaneously reduced glutathione (GSH) levels in the liver and stomach were markedly decreased. In addition to the enhancement of decrease in liver total glutathione levels, APAP pretreatment caused significant decrease in gastric and plasma total glutathione levels compared with prestress control levels. Moreover, co-administration of indomethacin (5mg/kg, i.p.) with APAP almost abolished the protective effects of APAP against the stress-induced ulceration. These results suggest that APAP may protect gastric mucosa from stress-induced ulceration, probably through the promoted production of PGE2 in the gastric mucosa without restoring glutathione levels.
Omura
H
H
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Kamisaki
Y
Y
Kawasaki
H
H
Itoh
T
T
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004338:Drug Combinations; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications
D004338:Drug Combinations; D008054:Lipid Peroxides; D000082:Acetaminophen; D005978:Glutathione; D015232:Dinoprostone; D007213:Indomethacin