Alteration of gastric ulcerogenic and healing responses in rats with adjuvant-induced arthritis.
Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of inflammatory disorders. It is known that rheumatoid arthritic patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritic conditions on gastric ulcerogenic response to NSAID and healing response of chronic gastric ulcers in rats. Gastric lesions induced by indomethacin, one of the conventional NSAIDs, were markedly aggravated in arthritic rats. This increased ulcerogenic response in arthritic rats was attributable to nitric oxide production due to up-regulation of inducible nitric oxide synthase. In arthritic rat stomachs, cyclooxygenase (COX)-2 was also up-regulated, where COX-2 selective inhibitors such as rofecoxib or celecoxib provoked gross lesions, although they caused no damage in normal rats. In addition, the healing of chronic gastric ulcers was also delayed in arthritic rats because of less expression of various growth factors such as basic fibroblast growth factors or insulin-like growth factors. Based on these findings, it is concluded that arthritic conditions alter the mucosal ulcerogenic and healing responses in the stomach. Especially, caution should be paid on the use of COX-2 selective inhibitors in rheumatoid arthritic patients.
Kato
Shinichi
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashima, Japan. skato@mb.kyoto-phu.ac.jp
Takeuchi
Koji
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D007527:Isoenzymes / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D013276:Stomach Ulcer / Q000209:etiology / Q000473:pathology*; D014945:Wound Healing
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases