Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on acetaminophen-induced acute liver injury and regeneration in rats
| Autor: | A D, Grypioti, S E, Theocharis, C A, Demopoulos, Z, Papadopoulou-Daifoti, A C, Basayiannis, M G, Mykoniatis |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Analysis of Variance Dose-Response Relationship Drug Apoptosis Platelet Membrane Glycoproteins Sensitivity and Specificity Severity of Illness Index Liver Regeneration Rats Receptors G-Protein-Coupled Disease Models Animal Lactones Random Allocation Ginkgolides Liver Function Tests Reference Values 1-Alkyl-2-acetylglycerophosphocholine Esterase Animals Chemical and Drug Induced Liver Injury Diterpenes Rats Wistar Biomarkers Acetaminophen Probability |
| Zdroj: | Liver international : official journal of the International Association for the Study of the Liver. 26(1) |
| ISSN: | 1478-3223 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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