NSAID-induced small intestinal damage - Role of COX inhibition

Indomethacin, the nonselective COX inhibitor, decreased mucosal PGE(2) content and caused damage in the intestine within 24 hr, accompanied by increase in intestinal motility, bacterial number, and MPO as well as iNOS activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither SC-560 nor rofecoxib alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not rofecoxib, caused intestinal hypermotillty, bacterial invasion and COX-2 as well. as iNOS mRNA expression, yet the NOS and MPO activity was increased only when rofecoxib was also administered. Although SC-560 inhibited the PG production, the level of PGE(2) was recovered, in a rofecoxib-dependent manner. These results suggest that inhibition of COX-1. despite causing intestinal hypermotility. bacterial invasion and iNOS expression., up-regulates the expression of COX-2, and the the COX-2/PGE(2) counteracts deleterious events and maintains the mucosal integrity.