[Changes in ulcerogenic response to non-steroidal anti-inflammatory drugs (NSAIDs) in adjuvant arthritic rats].
Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammatory disorders. It is known that rheumatoid arthritic (RA) patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritis on gastric mucosal integrity in adjuvant-induced arthritic rats. The gastric mucosal lesions induced by indomethacin, one of conventional NSAIDs, were markedly aggravated in arthritic rats. Likewise, the healing of chronic gastric ulcers induced by thermal cauterization was significantly delayed in arthritic rats. The underlying mechanisms of these phenomena observed in arthritic rats may be attributable to the enhancement of iNOS/NO pathway in the former and the less expression of various growth factors in the ulcerated mucosa, such as basic fibroblast growth factors (bFGF) or insulin-like growth factors (IGF-1) in the latter. In addition, we recently found that cyclooxygenase-2 (COX-2) selective inhibitors, such as rofecoxib or celecoxib, induced apparent gastric lesions in arthritic rats, suggesting that a caution should be paid on the use of COX-2 selective inhibitors in RA patients.
Kato
S
S
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001169:Arthritis, Experimental / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006133:Growth Substances; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat