Effect of different cyclooxygenase inhibitors on gastric adaptive cytoprotection induced by 20% ethanol.

In this study, we evaluated the effect of two different dosages of therapeutically prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen, diclofenac, nimesulide, meloxicam, and celecoxib (ED80 for COX-1 and COX-2) on normal gastric mucosa and mucosa, previously exposed to 20% ethanol. At COX-2-inhibiting dosages, the NSAIDs tested were nonulcerogenic, and the same response profile was observed in "adapted" stomachs. Interestingly, low doses of nimesulide and celecoxib increase the levels of Prostaglandin E(2) and COX-2, and protect against subsequent 100% ethanol exposition, suggesting that these drugs may act as "mild irritants" to gastric mucosa. The ulcerogenic response to NSAIDs was prevented by the previous 20% ethanol exposition, probably the result of nitric oxide synthesis, because PGE(2) levels in gastric mucosa were reduced by these agents and a concomitant nitric oxide blockade reversed this protection.