Effects of anti-ulcer agents on ethanol-induced gastric mucosal lesions in D-galactosamine-induced hepatitis rats.
Patients with hepatic injury have an increased incidence of gastric ulcers and erosions. In this study, the effect of D-galactosamine(GalN)-induced hepatitis on ethanol-induced gastric mucosal lesions and the protective effect of anti-ulcer agents in rats were examined. Subcutaneous injection of GalN (1 g/kg) remarkably increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities suggesting induction of hepatic injury. Gastric mucosal lesions induced by ethanol were significantly aggravated in GalN-induced hepatitis rats. Orally administered ecabet (CAS 86408-72-2; 20-200 mg/kg) dose dependently inhibited ethanol-induced gastric mucosal lesions in GalN-induced hepatitis rats. Sucralfate (CAS 54182-58-0) tended to inhibit the gastric mucosal lesions at a dose of 200 mg/kg but teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and rebamipide (CAS 90098-04-7) had little effect. All anti-ulcer agents had no effect on the serum ALT and AST activities increased by GalN pretreatment. These results indicate that the gastric mucosa of GalN-induced hepatitis rats is more susceptible to injury induced by luminal irritants such as ethanol. Ecabet potently inhibited gastric mucosal lesions suggesting its clinical utility for the gastric mucosal damage in patients with hepatic injury.
Taniguchi
Hiroyuki
H
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan. h-tani@tanabe.co.jp
Yomota
Eiji
E
Nogi
Koji
K
Onoda
Yuichi
Y
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005688:Galactosamine; D005753:Gastric Mucosa / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D045784:Abietanes; D000897:Anti-Ulcer Agents; D002492:Central Nervous System Depressants; D004224:Diterpenes; C061681:ecabet; D000431:Ethanol; D005688:Galactosamine