title: Influence of a platelet-activating factor antagonist on severe pancreatitis in two experimental models.
abstract: This study investigates the role of platelet-activating factor (PAF) in experimental pancreatitis. The concentration of PAF quantified in ascites of bile-induced pancreatitis by radioimmunoassay (RIA) ranged from 3.67 +/- 0.39 pmol/mL 2 h to 0.954 +/- 0.39 pmol/mL 10 h after injection of taurocholate. Administration of a potent PAF antagonist, WEB-2170, prior to injection of taurocholate prolonged mean survival time in rats receiving i.v. camostate and albumin (46.4 h, n = 15, vs controls 38.3 h, n = 13). However, the survival rate after 72 h was not improved. The histologically estimated severity of pancreatitis and pancreatic enzymes in blood, tissue, or ascites was not affected. WEB-2170 had no effect on survival when injected simultaneously with taurocholate into the pancreatic duct or given i.v. after induction of pancreatitis (1, 0.1, or 0.01 mg/kg WEB-2170 vs controls). Subcutaneous injection of 10 mg/kg WEB-2170 also did not improve survival in pancreatitis induced by choline-deficient, ethionine-supplemented diet in mice. It is concluded that administration of a PAF antagonist after the onset of severe experimental pancreatitis does not influence its outcome, although activation of PAF may play a role in the pathogenesis of pancreatitis.
authors.affiliation: Department of Medicine, University of Göttingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Leonhardt
authors.forename: A
authors.initials: A
authors.lastname: Fayyazzi
authors.forename: F
authors.initials: F
authors.lastname: Seidensticker
authors.forename: F
authors.initials: F
authors.lastname: Stöckmann
authors.forename: H D
authors.initials: HD
authors.lastname: Söling
authors.forename: W
authors.initials: W
authors.lastname: Creutzfeldt
mesh_terms: D000818:Animals; D001201:Ascites / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology*; D008297:Male; D010195:Pancreatitis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C063964:bepafant