title: Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence.
abstract: Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in the United States and Europe. The spectrum of ALD ranges from fatty liver to alcoholic hepatitis and cirrhosis, which may eventually lead to hepatocellular carcinoma. In developed countries as well as developing nations, ALD is a major cause of end-stage liver disease that requires liver transplantation. The most effective therapy for ALD is alcohol abstinence; however, for individuals with severe ALD and those in whom alcohol abstinence is not achievable, targeted therapies are absolutely necessary. In this context, advances of our understanding of the pathophysiology of ALD over the past two decades have contributed to the development of therapeutic modalities (e.g., pentoxifylline and corticosteroids) for the disease although the efficacy of the available treatments remains limited. This article is intended to succinctly review the recent experimental and clinical findings of the involvement of oxidative stress and redox signaling in the pathophysiology of ALD and the development of mechanistically based antioxidant modalities targeting oxidative stress and redox signaling mechanisms. The biochemical and cellular sources of reactive oxygen and nitrogen species (ROS/RNS) and dysregulated redox signaling pathways associated with alcohol consumption are particularly discussed to provide insight into the molecular basis of hepatic cell dysfunction and destruction as well as tissue remodeling underlying ALD.
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Virginia Tech Corporate Research Center.|Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, USA.
authors.forename: Zhenquan
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Virginia Tech Corporate Research Center.|Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University.
authors.forename: Hara
authors.initials: H
authors.lastname: Misra
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Virginia Tech Corporate Research Center.|Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University.|Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, Virginia.
authors.forename: Y Robert
authors.initials: YR
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species