Dissecting the molecular pathophysiology of drug-induced liver injury

作     者：Hui Ye Leonard J Nelson Manuel Gómez del Moral Eduardo Martínez-Naves Francisco Javier Cubero 

作者机构：Department of ImmunologyOphtalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12)Madrid 28041Spain Institute for BioEngineering(Human Liver Tissue EngineeringFaraday BuildingThe University of EdinburghThe King BuildingsMayfield RoadEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Cell BiologyComplutense University School of MedicineMadrid 28040Spain 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2018年第24卷第13期

页      面：1373-1385页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：Supported by the Spanish Ministerio de Economía y Competitividad(MINECO),No.RyC 2014-15242 No.SAF2016-78711 to Martinez-Naves E and Cubero FJ.Martinez-Naves E Cubero FJ are part of the UCM group"Lymphocyte Immunobiology",Ref.920631(imas12-associated,Ref.IBL-6) Chinese Scholarship Council fellow to YeH 

主　　题：signaling pathways acetaminophen Drug-induced liver injury cell death reactive oxygen species 

摘      要：Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.