Role of oxidative stress in alcohol-induced liver injury

• Published in: Archives of toxicology Vol. 83; no. 6; pp. 519 - 548
• Main Authors: Cederbaum, Arthur I, Lu, Yongke, Wu, Defeng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-06-2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol Drinking - adverse effects; Alcohol use; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Antioxidants; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cytochrome P-450 CYP2E1 - drug effects; Cytochrome P-450 CYP2E1 - metabolism; Environmental Health; Enzyme Induction - drug effects; Ethanol; Ethanol - toxicity; Humans; Liver; Liver - drug effects; Liver - enzymology; Liver Diseases, Alcoholic - enzymology; Liver Diseases, Alcoholic - physiopathology; Medical sciences; Occupational Medicine/Industrial Medicine; Oxidative Stress - drug effects; Pharmacology/Toxicology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reactive Oxygen Species - metabolism; Review Article; Toxicology; Antioxidants; Oxidative stress; Reactive oxygen species; TNFα; CYP2E1; Alcoholic liver injury; Ethanol; Digestive system; Enzyme; Toxicity; Alcoholism; Cytochrome P450; Liver; Cytokine; Antioxidant; Alcoholic beverage; Lesion; Tumor necrosis factor α
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-009-0432-0

Reactive oxygen species (ROS) are highly reactive molecules that are naturally generated in small amounts during the body's metabolic reactions and can react with and damage complex cellular molecules such as lipids, proteins, or DNA. Acute and chronic ethanol treatments increase the production of ROS, lower cellular antioxidant levels, and enhance oxidative stress in many tissues, especially the liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury. Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury. Special emphasis is placed on CYP2E1, which is induced by alcohol and is reactive in metabolizing and activating many hepatotoxins, including ethanol, to reactive products, and in generating ROS.