Non-steroidal anti-inflammatory drugs (NSAID) are extensively used in the clinic for their anti-inflammatory, analgesic, anti-thrombotic and anti-pyretic activity. However, the major limitation of their use are the serious gastrointestinal side effects such as hemorrhage, ulceration and even perforation. In this review, we attempted to summarize the recent advances in the physiology and patophysiology of a new class of molecules, the nitric oxide (NO) donating drugs, and their ability to counteract the gastrointestinal injury caused by native NSAID. These NO-donating drugs originally described almost 10 years ago, were proved by reserchers and clinical investigators to exert gastrointestinal, renal and cardiovascular safety and a broad anti-inflammatory activity. Addition of NO moiety to classic NSAID such as aspirin or to other NSAID, has resulted in molecules that maintain their effects on cyclooxygenase (COX)-1 and COX-2 but are devoid of cardiovascular, kidney and gastrointestinal toxicity. NO-aspirin was shown to exhibit a beneficial effect on gastric mucosa attenuating acute gastric lesions induced by necrotizing agents such as ethanol and those evoked by stress and ischemia-reperfusion and, in contrast, to native aspirin and other classic NSAID, NO- releasing aspirin failed to delay the healing of chronic gastric ulcerations. These experimental results with NO- donating compounds are very promising in terms of recognition of new avenues that are effective against NSAID gastropathy and being considered as a new approach to discover safer NSAID able to spare the gastrointestinal tract in conditions, where activity of both, COX-1 and COX-2 enzymes can be inhibited.
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