Role of oxidative stress in alcohol-induced liver injury.
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.
Cederbaum
Arthur I
AI
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA. Arthur.cederbaum@mssm.edu
Lu
Yongke
Y
Wu
Defeng
D
D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1