Effect of platelet‐activating factor (PAF) receptor antagonist (BN52021) on acetaminophen‐induced acute liver injury and regeneration in rats

Liver International - Tập 26 Số 1 - Trang 97-105 - 2006
A.D. Grypioti1,2, Stamatios Theocharis3, Constantinos A. Demopoulos2, Zeta Papadopoulou‐Daifoti1, A. C. Basayiannis4, Michael G. Mykoniatis1
1Department of Experimental Pharmacology, Medical School,
2Faculty of Chemistry
3Department of Forensic Medicine and Toxicology, Medical School, National and Kapodistrian University of Athens,
4Department of Biochemistry, General Hospital of Patision, Athens, Greece

Tóm tắt

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.Conclusion: 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.

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Liver International

Tập 26 Số 1

97-105

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