[The role of oxidative stress in alcoholic liver injury].
BACKGROUND
Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. ROLE OF CYTOCHROME P4502E1 IN ETHANOL-INDUCED OXIDATIVE STRESS: Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. ROLE OF MITOCHONDRIA IN ALCOHOL-INDUCED OXIDATIVE STRESS. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanol-fed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. ROLE OF KUPFFER CELLS IN ALCOHOL-INDUCED LIVER INJURY: Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. ROLE OF NEUTROPHILS IN ALCOHOL-INDUCED LIVER INJURY: Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. ROLE OF NITRIC OXIDE IN ALCOHOL-INDUCED OXIDATIVE STRESS: High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. ROLE OF ANTIOXIDANTS IN ETHANOL-INDUCED OXIDATIVE STRESS: Chronic ethanol consumption is associated with reduced liver glutathione and alpha-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity.


CONCLUSIONS
Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.
Radosavljević
Tatjana
T
Medicinski fakultet, Beograd Institut za patolosku fiziologiju. tanjamm@med.bg.ac.yu
Mladenović
Dusan
D
Vucević
Danijela
D
D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress
D009569:Nitric Oxide; D019392:Cytochrome P-450 CYP2E1