NEW CONCEPTS REGARDING ULCEROGENIC MECHANISM OF
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Non-steroidal anti-inflammatory drugs
(NSAIDs) produce gastroduodenal, mucosal and vascular lesions. Research work
carried out so 434g63e far showed that NSAIDs increase basal acid secretion and produce
vascular disorders having as a consequence a reducing of gastric mucosal blood
flow. Our recent studies showed that NSAIDs activate carbonic anhydrase (CA) I,
isozyme involved in vascular modifications.(I.Puscas,Am.J.of Hypertens,1997,10,(1),
124-28). The same research showed that NSAIDs activate CA II, a cytozol
enzyme involved in secretory processes (I.Puscas,
J.Pharmacol.
AIM: we studied the effect of certain NSAIDs, upon CA I,II,and IV isozymes.
MATERIAL AND METHOD: in vitro, we researched the effect of piroxicam (PXC), naproxen (NPX), diclofenac (DCF), phenylbutazone (PBZ) and Na salicylate (NaS) on human gastric mucosa CA I, II and IV, according to dose-response relationship at concentrations between 10-8-10-4M. Fundic gastric mucosa was obtained by gastric resection. Differentiation between CA I and CA II activity was achieved by the test with nicotinates (I.Puscas, Int.Conf.on CA, Oxford, 1995). CA IV was separated according to the technique described by Maren (1993). CA activity was asessed by the stopped-flow method.
DISCUSSION AND CONCLUSIONS: NSAIDs activate CA I, II and IV isozymes. CA II activation (a cytosol enzyme) and CA IV activation (a membrane parietal cell isozyme) produce an H+ excess having consequences on elevating acid secretion values. CA I activation (enzyme located in vascular walls) is accompanied by a reducing of gastric microcirculation. The results suggest that by secretory and vasculary modifications NSAIDs produce both lesions and gastro-duodenal hemorrhages, by a direct mechanism. The decreasing of cyclo-oxygenase activity and of prostaglandins synthesis could be secondary to pH modifications produced by CA activation through NSAIDs.
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