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.
Gambero
Alessandra
A
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av São Francisco de Assis 218, Bragança Paulista, 12916-900, SP, Brazil. alessandragambero@saofrancisco.edu.br
Maróstica
Marta
M
Becker
Tagliane Liza
TL
Pedrazzoli
José
J
D000818:Animals; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects*; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007052:Ibuprofen / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007509:Irritants; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D004008:Diclofenac; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; D015232:Dinoprostone; C012655:nimesulide; D019331:NG-Nitroarginine Methyl Ester; D000077239:Meloxicam; D007052:Ibuprofen