Release of platelet-activating factor (PAF) and accelerated healing induced by a PAF antagonist in an animal model of chronic colitis.
The role of platelet-activating factor as a mediator of inflammation was examined using a rat model of colitis. Release of platelet-activating factor by samples of colonic tissue, as measured by bioassay, was determined at various times after induction of inflammation by intracolonic administration of trinitrobenzene sulfonic acid. At the same times, colonic damage was scored and the extent of neutrophil infiltration was assessed by measuring tissue levels of myeloperoxidase activity. Platelet-activating factor release from normal colon averaged 46 +/- 17 pg/g, while not being detectable in samples taken 24 h after induction of inflammation, a time when neutrophil infiltration was maximal. However, substantial release of platelet-activating factor (12-16 times control levels; p less than 0.05) was observed in samples from rats sacrificed 1-3 weeks after induction of inflammation. In a second series of experiments, the effects of treatment with BN52021, a specific platelet-activating factor receptor antagonist, were assessed using this model. Treatment with BN52021 during either the 1st or 2nd weeks after induction of colitis resulted in significant (p less than 0.05) reductions of colonic damage scores and the wet weight of the distal colon. These results demonstrate that platelet-activating factor release is significantly elevated during the chronic phase of colitis in this animal model, and that inhibition of the action of platelet-activating factor, through receptor antagonism, leads to a significant reduction of colonic inflammation and ulceration. These observations are therefore consistent with a role for platelet-activating factor as an inflammatory mediator in chronic inflammation of the rat colon.
Wallace
J L
JL
Department of Physiology, Queen's University, Kingston, Ont., Canada.
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014302:Trinitrobenzenesulfonic Acid
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014302:Trinitrobenzenesulfonic Acid; C045856:ginkgolide B