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 examined 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. Severe 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 plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.
Yamasaki
K
K
Department of Biosignal Analysis, Osaka City University Medical School, Japan. yamasakik@ohq.otsuka.co.jp
Arakawa
T
T
Takaishi
O
O
Higuchi
K
K
Kobayashi
K
K
Kuroki
T
T
D000208:Acute Disease; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D005756:Gastritis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007213:Indomethacin / Q000633:toxicity*; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009853:Omeprazole / Q000494:pharmacology; D010477:Perfusion; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D015363:Quinolones; D002927:Cimetidine; D002374:Catalase; D013482:Superoxide Dismutase; D009853:Omeprazole; C052785:rebamipide; D000409:Alanine; C031049:geranylgeranylacetone; D007213:Indomethacin