INVOLVEMENT OF PLATELET-ACTIVATING-FACTOR (PAF) IN ENDOTOXIN-INDUCED OR ISCHEMIA-INDUCED INTESTINAL HYPERPERMEABILITY IN THE RAT

We have investigated the influence of BN 50727, a PAF antagonist, and allopurinol, a free radical scavenger, on the damaging effects of isch aemia-reperfusion and endotoxin in the small intestinal mucosa. Using a rat experimental model, we determined the alterations in intestinal permeability and mucosal levels of PAF and lysoPAF following ischaemia or intravenous administration of endotoxin. Both of these treatments increased intestinal permeability and enhanced PAF levels in the mucos a. Preventive oral or intraduodenal administration of BN 50727 reduced both of these effects, by decreasing mucosal PAF formation, probably as a result of neutrophil infiltration and activation reduction. Pretr eatment of the rats with allopurinol also resulted in similar protecti on except that the free radical scavenger was unable to inhibit the in crease in PAF levels after ischaemia, suggesting that oxidative reagen ts are implicated in this pathology to a much greater extent than PAF.