Oxidative stress and redox signaling mechanisms of alcoholic liver disease: Updated experimental and clinical evidence
Open Access
- 5 December 2011
- journal article
- review article
- Published by Wiley in Journal of Digestive Diseases
- Vol. 13 (3), 133-142
- https://doi.org/10.1111/j.1751-2980.2011.00569.x
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.Keywords
This publication has 82 references indexed in Scilit:
- An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: Regulation of proinflammatory cytokines and hepatic steatosis in miceHepatology, 2011
- Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosisHepatology, 2011
- Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in miceFree Radical Biology & Medicine, 2010
- Ethanol-induced HO-1 and NQO1 Are Differentially Regulated by HIF-1α and Nrf2 to Attenuate Inflammatory Cytokine ExpressionOnline Journal of Public Health Informatics, 2010
- Treatment of alcoholic liver diseaseTherapeutic Advances in Gastroenterology, 2010
- Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liverToxicology and Applied Pharmacology, 2010
- The LDL modification hypothesis of atherogenesis: an updateJournal of Lipid Research, 2009
- Exogenous thioredoxin prevents ethanol-induced oxidative damage and apoptosis in mouse liverHepatology, 2009
- Resveratrol alleviates alcoholic fatty liver in miceAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2008
- Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseasesFree Radical Biology & Medicine, 2008