Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on acetaminophen-induced acute liver injury and regeneration in rats.
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.
Grypioti
A D
AD
Department of Experimental Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Theocharis
S E
SE
Demopoulos
C A
CA
Papadopoulou-Daifoti
Z
Z
Basayiannis
A C
AC
Mykoniatis
M G
MG
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
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