Metabolic derivatives of alcohol and the molecular culpritsof fibro-hepatocarcinogenesis:Allies or enemies?  

作　　者：Alex Boye Yu-Hong Zou Yan Yang 

机构地区：[1]Department of Pharmacology and Institute of Natural Medicine,Anhui Medical University,Hefei 230032,Anhui Province,China [2]Department of Medical Laboratory Science,College of Allied Health Sciences,University of Cape Coast,Cape Coast 25064,Ghana [3]Department of Biology,School of Science,Center for Regenerative Biology and Medicine,Indiana University-Purdue University Indianapolis,Indianapolis,IN 46202,United States

出　　处：《World Journal of Gastroenterology》2016年第1期50-71,共22页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China,No.81374012 and No.81573652

摘　　要：Chronic intake of alcohol undoubtedly overwhelms the structural and functional capacity of the liver by initiating complex pathological events characterized by steatosis,steatohepatitis,hepatic fibrosis and cirrhosis.Subsequently,these initial pathological events are sustained and ushered into a more complex and progressive liver disease,increasing the risk of fibrohepatocarcinogenesis.These coordinated pathological events mainly result from buildup of toxic metabolic derivatives of alcohol including but not limited to acetaldehyde(AA),malondialdehyde(MDA),CYP2E1-generated reactive oxygen species,alcohol-induced gut-derived lipopolysaccharide,AA/MDA protein and DNA adducts.The metabolic derivatives of alcohol together with other comorbidity factors,including hepatitis B and C viral infections,dysregulated iron metabolism,abuse of antibiotics,schistosomiasis,toxic drug metabolites,autoimmune disease and other non-specific factors,have been shown to underlie liver diseases.In view of the multiple etiology of liver diseases,attempts to delineate the mechanism by which each etiological factor causes liver disease has always proved cumbersome if not impossible.In the case of alcoholic liver disease(ALD),it is even more cumbersome and complicated as a result of the many toxic metabolic derivatives of alcohol with their varying liver-specific toxicities.In spite of all these hurdles,researchers and experts in hepatology have strived to expand knowledge and scientific discourse,particularly on ALD and its associated complications through the medium of scientific research,reviews and commentaries.Nonetheless,the molecularmechanisms underpinning ALD,particularly those underlying toxic effects of metabolic derivatives of alcohol on parenchymal and non-parenchymal hepatic cells leading to increased risk of alcohol-induced fibrohepatocarcinogenesis,are still incompletely elucidated.In this review,we examined published scientific findings on how alcohol and its metabolic derivatives mount cellular attack on each hepatic cell aChronic intake of alcohol undoubtedly overwhelms the structural and functional capacity of the liver by initiating complex pathological events characterized by steatosis,steatohepatitis,hepatic fibrosis and cirrhosis.Subsequently,these initial pathological events are sustained and ushered into a more complex and progressive liver disease,increasing the risk of fibrohepatocarcinogenesis.These coordinated pathological events mainly result from buildup of toxic metabolic derivatives of alcohol including but not limited to acetaldehyde(AA),malondialdehyde(MDA),CYP2E1-generated reactive oxygen species,alcohol-induced gut-derived lipopolysaccharide,AA/MDA protein and DNA adducts.The metabolic derivatives of alcohol together with other comorbidity factors,including hepatitis B and C viral infections,dysregulated iron metabolism,abuse of antibiotics,schistosomiasis,toxic drug metabolites,autoimmune disease and other non-specific factors,have been shown to underlie liver diseases.In view of the multiple etiology of liver diseases,attempts to delineate the mechanism by which each etiological factor causes liver disease has always proved cumbersome if not impossible.In the case of alcoholic liver disease(ALD),it is even more cumbersome and complicated as a result of the many toxic metabolic derivatives of alcohol with their varying liver-specific toxicities.In spite of all these hurdles,researchers and experts in hepatology have strived to expand knowledge and scientific discourse,particularly on ALD and its associated complications through the medium of scientific research,reviews and commentaries.Nonetheless,the molecularmechanisms underpinning ALD,particularly those underlying toxic effects of metabolic derivatives of alcohol on parenchymal and non-parenchymal hepatic cells leading to increased risk of alcohol-induced fibrohepatocarcinogenesis,are still incompletely elucidated.In this review,we examined published scientific findings on how alcohol and its metabolic derivatives mount cellular attack on each hepatic cell a

关 键 词：Alcoholic hepatitis Lipopolysaccharide Fibro-hepatocarcinogenesis Mitogen activated PROTEINKINASE Transforming growth factor beta Small motheragainst DECAPENTAPLEGIC 

分 类 号：R735.7[医药卫生—肿瘤]