Oral but Not Parenteral Aspirin Upregulates COX-2 Expression in Rat Stomachs

Abstract

Aim: We compared the ulcerogenic effects of aspirin (ASA) and indomethacin in the rat gastric mucosa depending on the route of administration, together with the expression of COX-2. Methods: Animals fasted for 18 h were given ASA or indomethacin, either p.o. or s.c., and the stomach was examined 4 h later. Results: Indomethacin decreased mucosal PGE₂level, increased gastric motility, and caused gastric lesions with the up-regulation of COX-2 expression, irrespective of the route of administration. ASA induced both damage and COX-2 expression in the stomach when given p.o. but not s.c., despite decreasing the PGE₂ level similarly via either route of administration. Gastric motility was temporarily increased and gastric potential difference (PD) was markedly decreased by ASA given p.o. PGE₂ and atropine, although preventing ASA-induced gastric lesions as well as hypermotility, affected neither the COX-2 expression nor PD reduction induced by p.o. ASA. By contrast, the COX-2 expression induced by indomethacin was prevented by both PGE₂ and atropine. Conclusion: ASA given p.o. caused damage in the stomach, together with the up-regulation of COX-2 expression, and this expression may be due to the topical irritative action, rather than being a result of PG deficiency. The expression of COX-2 after indomethacin is associated with gastric hypermotility due to PG deficiency.