N-acetylcysteine and glycyrrhizin combination:Benefit outcome in a murine model of acetaminophen-induced liver failure  

作　　者：Charlotte Minsart Sandrine Rorive Arnaud Lemmers Eric Quertinmont Thierry Gustot 

机构地区：[1]Laboratory of Experimental Gastroenterology,Erasme Hospital,UniversitéLibre de Bruxelles,Brussels 1070,Belgium [2]Department of Pathology,Erasme Hospital,UniversitéLibre de Bruxelles,Brussels 1070,Belgium [3]DIAPATH-Center for Microscopy and Molecular Imaging,UniversitéLibre de Bruxelles,Gosselies 6041,Belgium [4]Department of Gastroenterology,Hepato Pancreatology and Digestive Oncology,Erasme Hospital,UniversitéLibre de Bruxelles,Brussels 1070,Belgium [5]Inserm Unité1149,Centre de Recherche sur l’inflammation,Paris 75006,France [6]UMR S_1149,UniversitéParis Diderot,Paris 75006,France

出　　处：《World Journal of Hepatology》2020年第9期596-618,共23页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by the Bourse du Conseil Médical de l’hôpital Erasme,Fonds E.et S.Jacobs and Novartis Grant;The CMMI is supported by the European Regional Development Fund and Wallonia

摘　　要：BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries.Substantial progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic window.Thus,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced hepatotoxicity.Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HMGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various diseases.AIM To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity.METHODS Eight-week-old C57BL/6J wild-type female mice were used for all our experiments.Mice fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:Glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/glycyrrhizin.In all groups,mice were sacrificed 12 h following acetaminophen administration.The assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase.Hepatotoxicity was also evaluated by histological examination of hematoxylin and eosin-stained tissues sections.Survival rates were compared between various groups using Kaplan-Meier curves.RESULTS Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis score.Glycyrrhizin administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury.Thus,the co-administration of glycyrrhizin and N

关 键 词：ACETAMINOPHEN Acute liver injury GLYCYRRHIZIN N-ACETYLCYSTEINE Nacetylcysteine/glycyrrhizin combination Murine model High mobility group box 1 

分 类 号：R575.3[医药卫生—消化系统]