title: Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on acetaminophen-induced acute liver injury and regeneration in rats.
abstract: BACKGROUND
  Platelet-activating factor (PAF) is an endogenous lipid mediator that plays a key role in catalyzing various pro-inflammatory processes associated with acute liver injury. In the present study, the possible influence of PAF-R antagonist (BN52021) on the protection of liver injury after 4-hydroxyacetanilide, N-acetyl-p-aminophenol, paracetamol (APAP) intoxication was investigated.
  
  
  METHODS
  Thereby, one group of rats was treated with a toxic dose of APAP (3.5 g/kg body weight (b.w.). The animals were killed at 56, 66, 72, 84 and 96 h after treatment.
  
  
  RESULTS
  APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase) and liver histopathological (degree of necrosis and apoptosis) indices, which was followed by liver regeneration, evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). The protective effects of BN52021 were qualified during post-treatment time by: (1) significant reduction of hepatic injury as showed by all biochemical and histological parameters, (2) high decrease of regenerating activity showed by three regenerative markers and (3) remarkable increase of PAF-acetylhydrolase (PAF-AH) activity.
  
  
  CONCLUSIONS
  These results suggest that PAF may play an important role in APAP-induced liver injury and regeneration, and PAF-R antagonist (BN52021) attenuates liver damage.
authors.affiliation: Department of Experimental Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: A D
authors.initials: AD
authors.lastname: Grypioti
authors.forename: S E
authors.initials: SE
authors.lastname: Theocharis
authors.forename: C A
authors.initials: CA
authors.lastname: Demopoulos
authors.forename: Z
authors.initials: Z
authors.lastname: Papadopoulou-Daifoti
authors.forename: A C
authors.initials: AC
authors.lastname: Basayiannis
authors.forename: M G
authors.initials: MG
authors.lastname: Mykoniatis
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000082:Acetaminophen; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D000082:Acetaminophen; C045856:ginkgolide B; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase