薬理と治療

Abstract

We previously reported that gastric ulcerogenic responses to non－steroidal anti－inflammatory drugs（NSAIDs）and highly selective cyclooxygenase－2（COX－2）inhibitors were markedly increased in arthritic rats. In the present study, we examined the effect of irsogladine on aggravation of gastric damage induced by meloxicam, a preferential COX－2 inhibitor, in adjuvant arthritic rats. Arthritis was induced in male DA rats by a plantar injection of Freund’s complete adjuvant. Two weeks after the adjuvant injection, the animals were given meloxicam （3 and 10 mg／kg, p.o.）, and 4 h later the gastric mucosa was examined for damage, myeloperoxidase（MPO）activity, and lipid peroxidation. In normal rats, meloxicam at 3 mg／kg did not cause any damage in the stomach but at 10 mg／kg produced only slight damage. In arthritic rats, however, this agent provoked apparent damage in the stomach even at 3 mg／kg and at 10 mg／kg produced severe hemorrhagic damage. The severity of meloxicam－induced gastric damage in arthritic rats was ameliorated by irsogladine, in a dose－dependent manner. Similar effect was also observed by omeprazole and teprenone. Likewise, the increase in MPO activity and lipid peroxidation after the administration of meloxicam was significantly suppressed by irsogladine, omeprazole, and teprenone. These findings suggest that meloxicam, a preferential COX－2 inhibitor, although showed only minimum gastric ulcerogenecity in normal rats,caused severe hemorrhagic damage in the arthritic rat stomach. Irsogladine prevented meloxicam－induced gastric damage in arthritic rats, similar to omeprazole and teprenone. It is assumed that irsogladine can be used as a prophylactic against meloxicam－induced gastric toxicity in arthritic patients.