Influence of rebamipide on indometacin-induced gastric hemorrhage in rats under restraint stress

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl ] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examine d in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Sev ere gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide ( 3. 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin pl us restraint stress, being more effective than teprenone or cimetidine. Pre treatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemo rrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., whi ch caused depletion of circulating neutrophils, also suppressed the hemorrh age induced by indometacin plus restraint stress. Thus reactive oxygen spec ies derived from neutrophils may play a role in the occurrence of the hemor rhage during acute gastritis induced by indometacin with restraint stress.