Gambero Alessandra, Maróstica Marta, Becker Tagliane Liza, Pedrazzoli José
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av São Francisco de Assis 218, Bragança Paulista, 12916-900, SP, Brazil.
Dig Dis Sci. 2007 Feb;52(2):425-33. doi: 10.1007/s10620-006-9487-4. Epub 2007 Jan 17.
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.
在本研究中，我们评估了两种不同治疗剂量的非甾体抗炎药（NSAIDs），即布洛芬、双氯芬酸、尼美舒利、美洛昔康和塞来昔布（COX - 1和COX - 2的ED80）对正常胃黏膜以及先前暴露于20%乙醇的胃黏膜的影响。在COX - 2抑制剂量下，所测试的NSAIDs不具有致溃疡作用，并且在“适应”的胃中观察到相同的反应模式。有趣的是，低剂量的尼美舒利和塞来昔布可提高前列腺素E2（Prostaglandin E(2)）和COX - 2的水平，并预防随后的100%乙醇暴露，这表明这些药物可能对胃黏膜起“轻度刺激物”的作用。先前20%乙醇暴露可预防对NSAIDs的致溃疡反应，这可能是一氧化氮合成的结果，因为这些药物会降低胃黏膜中的PGE(2)水平，而同时进行一氧化氮阻断可逆转这种保护作用。
