Pathogenesis of non-steroidal anti-inflammatory drug gastropathy.
Although non-steroidal anti-inflammatory drugs (NSAIDs) may impair the defensive ability of the gastric mucosal barrier through topical actions, recent evidence suggests that microcirculation disturbance plays a pivotal role in the genesis of gastric mucosal damage. In particular, attention has been drawn to the role exerted by those cytokine (TNF alpha and IL-1 beta) and adhesion molecules (LFA-1, Mac-1, ICAM-1) that regulate interactions between leukocyte and endothelial cells leading to gastric microvessels occlusion and ischaemic/hypoxic endothelial-epithelial cell damage. In recent years the role of prostaglandin synthesis inhibition in the pathogenesis of NSAID-gastropathy has been reconsidered, highlighting the immunomodulatory and pro-inflammatory consequences of prostanoids suppression. The awareness that mucosal damage is due to the non-discriminatory effect of NSAIDs on cyclo-oxygenase (COX) isoenzymes, has lead to the development of more selective, safer, COX-2 inhibitors. On the other hand, the observation that NO exerts a predominant physiological role in the maintenance of mucosal integrity has raised the opportunity to develop a new generation of NO-releasing NSAID derivatives with a reduced gastrointestinal toxicity.
Fiorucci
S
S
Department of Clinical and Experimental Medicine, University of Perugia, Italy. gastro1@unipg.it
Antonelli
E
E
Morelli
O
O
Morelli
A
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015415:Biomarkers; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015289:Leukotrienes; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1