Involvement of platelet-activating factor (PAF) in endotoxin- or ischaemia-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 ischaemia-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 mucosa. 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. Pretreatment of the rats with allopurinol also resulted in similar protection except that the free radical scavenger was unable to inhibit the increase in PAF levels after ischaemia, suggesting that oxidative reagents are implicated in this pathology to a much greater extent than PAF.
Defaux
J P
JP
Institut Henri Beaufour, Les Ulis, France.
Thonier
F
F
Baroggi
N
N
Etienne
A
A
Braquet
P
P
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D008297:Male; D010539:Permeability / Q000187:drug effects; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D001381:Azepines; D004731:Endotoxins; D016166:Free Radical Scavengers; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D058924:Thienopyridines; D014230:Triazoles; D000493:Allopurinol; D014969:Xanthine Oxidase; C067429:Setipafant