Modulation of Oxidative Stress by Alcohol
It is well established that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in causing acute and chronic alcohol toxicity. Biochemical signs of oxidative damage can be detected in experimental animals exposed to ethanol as well as in alcoholic patients. Ethanol-induced oxidative stress is the consequence of the combined effect of an increased production of ROS by the mitochondria and the alcohol-inducible cytochrome P-4502E1 (CYP2E1) and the impairment of antioxidant defenses. Furthermore, by promoting the activation of Kuppfer cells, ethanol causes the release of cytokines, ROS, and RNS. The mechanisms by which oxidative damage contribute to alcohol toxicity include direct hepatocellular damage, induction of apoptosis, and the stimulation of collagen deposition by hepatic stellate cells. In addition, lipid peroxidation products and, particularly acetaldehyde-malondialdehyde adducts, along with immune reactions triggered by oxidative stress, might also contribute to perpetuate hepatic inflammation. The implication of oxidative stress in alcohol liver damage gives a rationale to the clinical application of therapies aimed to prevent or reduce ethanol-induced oxidative damage by antioxidant compounds.