Alcohol, Oxidative Stress, and Free Radical Damage

By Defeng Wu, A. Cederbaum. Alcohol Research and Health, 2003

1,242 citations recorded by the source corpus.

Reactive oxygen species (ROS) are small, highly reactive, oxygen-containing 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 fats, proteins, or DNA. Alcohol promotes the generation of ROS and/or interferes with the body’s normal defense mechanisms against these compounds through numerous processes, particularly in the liver. For example, alcohol breakdown in the liver results in the formation of molecules whose further metabolism in the cell leads to ROS production. Alcohol also stimulates the activity of enzymes called cytochrome P450s, which contribute to ROS production. Further, alcohol can alter the levels of certain metals in the body, thereby facilitating ROS production. Finally, alcohol reduces the levels of agents that can eliminate ROS (i.e., antioxidants). The resulting state of the cell, known as oxidative stress, can lead to cell injury. ROS production and oxidative stress in liver cells play a central role in the development of alcoholic liver disease.

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Citations in the corpus

• Molecular mechanisms of alcohol-mediated carcinogenesis (2007, background): “Several enzyme systems are capable of producing ROS, including the cytochrome P450 2E1 ( CYP2E1 )-dependent microsomal mono-oxygenase system , the mitochondrial respiratory chain and the cytosolic enzymes xanthine oxidase and aldehyde oxidas”
• Overview: How Is Alcohol Metabolized by the Body? (2006, background): “…consumption can increase ROS production and lead to oxidative stress though a variety of pathways, includ ing, but not limited to, the following (Wu and Cederbaum 2003): • Changes in the cells’ redox state (i.e., in the ratio of NADH to NAD+) as a result of ethanol metabolism by ADH and ALDH,…”
• Oxidative stress and male infertility--a clinical perspective. (2008, background): “Excessive alcohol consumption causes an increase in systemic oxidative stress as ethanol stimulates the production of ROS, while many alcohol abusers have diets deficient in protective antioxidants (Wu and Cederbaum, 2003; Koch et al., 2004).”
• Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction (2006, background): “CYP2E1 may generate reactive oxygen intermediates, such as superoxide radicals [172], which play a key role in liver injury because of the interaction with cellular proteins or DNA [173].”
• Alcohol-induced oxidative stress. (2007, background): “Reactive oxygen species (ROS) are small, highly reactive, oxygen-containing molecules that can react with and damage complex cellular molecules, particularly in the liver (Wu and Cederbaum, 2003).”
• Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants (2024, background): “Unbound iron is known to catalyze the decomposition of hydrogen peroxide (Fenton reaction) with the concomitant formation of damaging hydroxyl radicals (Wu and Cederbaum 2003).”