Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors

Abstract

The influence of different nonsteroidal anti-inflammatory drugs (NSAIDs) and of a proton pump inhibitor on the healing parameters of a chronic gastric ulcer was evaluated. Wistar rats were used after the induction of a chronic acetic acid ulcer. The animals were treated orally for 8 and 15 days, twice daily, with the conventional NSAID, piroxicam (0.35 mg/kg), the non-narcotic analgesic, metamizol (33 mg/kg), the selective cyclooxygenase-2 inhibitor, celecoxib (1.8 mg/kg) and the proton pump inhibitor, omeprazole (0.35 mg/kg). Macroscopic ulcer index, myeloperoxidase activity and prostaglandin E 2 content (both biochemical parameters were evaluated in ulcerated and in intact tissue) as well as histological and immunohistochemical evaluations were carried out at 8 and 15 days. Omeprazole accelerated ulcer healing at 8 and 15 days ( P<0.05), while celecoxib delayed healing significantly at 15 days ( P<0.01). At 8 days, the prostaglandin E 2 content decreased with all NSAIDs at the ulcer site as well as in intact tissue. The same happened at 15 days except for celecoxib, which only diminished prostaglandins in intact mucosa. Immunohistochemistry showed differences in the location of cyclooxygenase-2 and -1. The highest cyclooxygenase-2 expression was found with piroxicam and the lowest expression was with celecoxib. Conclusions: Down-regulation of cyclooxygenase-2 expression as well as a possible involvement of the chemical structure of celecoxib, a 1,5-dirarylpirazole with a sulphonamide moiety, may account for the delay in ulcer healing.