Nitric oxide‐releasing non‐steroidal anti‐inflammatory drugs: A novel approach for reducing gastrointestinal toxicity
作者:
J. L. WALLACE,
B. K. REUTER,
G. CIRINO,
期刊:
Journal of Gastroenterology and Hepatology
(WILEY Available online 1994)
卷期:
Volume 9,
issue S1
页码: 40-44
ISSN:0815-9319
年代: 1994
DOI:10.1111/j.1440-1746.1994.tb01300.x
出版商: Blackwell Publishing Ltd
关键词: neutrophils;nitric oxide;non‐steroidal anti‐inflammatory drug;prostaglandin;ulcer.
数据来源: WILEY
摘要:
AbstractThe use of non‐steroidal anti‐inflammatory drugs (NSAID) for treatment of inflammatory conditions is significantly limited by the untoward effects of these compounds on the gastrointestinal tract. While the pathogenesis of ‘NSAID‐gastropathy’ is not completely understood, there is good evidence that the process is directly linked to suppression of prostaglandin synthesis and possibly to neutrophil adherence to the vascular endothelium. Pretreatment of rats with a nitric oxide (NO) donor (sodium nitroprusside) was found to significantly reduce the extent of gastric injury induced by flurbiprofen. We therefore tested the effects of a novel derivative of flurbiprofen. This compound contains a moiety similar to the NO‐releasing moieties found in many organic nitrates. This compound suppressed gastric prostaglandin synthesis as effectively as flurbiprofen, but caused significantly less haemorrhagic damage. The compound was also found not to induce small intestinal injury. Since the compound was found to exert anti‐inflammatory effects comparable with flurbiprofen, NO‐releasing NSAID may represent a novel class of drugs with markedly reduced gastrointe
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