Author(s): HotzBehofsits C, Simpson RJ, Walley M, Bjarnason IT
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Abstract OBJECTIVE: It is widely thought that cyclooxygenase 1 (COX-1) inhibition with consequential decreases in mucosal prostaglandins, along with concomitant inhibition of COX-2, is pivotal in nonsteroidal anti-inflammatory drug-induced (NSAID) enteropathy. We examined the role of COX-1, COX-2 and topical effects of drugs in NSAID enteropathy. MATERIAL AND METHODS: We quantified small intestinal damage and prostaglandin E(2) levels in wild-type, COX-1 and COX-2 deficient mice after administration of R-2-phenylpropionic acid (which has the same topical characteristics as conventional NSAIDs but does not affect the COX enzymes), the conventional NSAIDs flurbiprofen and the selective COX-2 inhibitor celecoxib. We also measured intestinal permeability and inflammation in rats given the selective COX-1 inhibitor SC-560 and NSAIDs. The parameters were assessed at baseline and after administration of the drugs. RESULTS: R-2-phenylpropionic acid caused small intestinal damage in COX-2(-/-) and wild-type mice given celecoxib, but not in wild type or COX-1(-/-) mice. PGE(2) levels in mice dosed with R-2-phenylpropionic acid were elevated. Indomethacin raised permeability and caused inflammation in rats. CONCLUSIONS: The combination of COX-2 absence (or inhibition) and the topical effect of NSAIDs lead to changes characteristic of NSAID enteropathy without concomitant COX-1 inhibition and/or associated decreases in mucosal prostaglandins. COX-2 appears to be more important for maintaining small bowel integrity than COX-1.
This article was published in Scand J Gastroenterol
and referenced in Pharmaceutica Analytica Acta