Ethanol-induced oxidative stress in the liver.
Oxygen stress is well recognized to be a key step in the pathogenesis of ethanol-associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen-reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol-inducible cytochrome P-450 in the microsomes, as well as the molybdo-flavoenzymes xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a prooxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Although many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes, the detailed mechanism of ethanol-induced oxidative stress on mitochondria remains to be clarified further. Studies of our laboratory using a confocal laser scanning microscopic system strongly suggest that active oxidants produced during ethanol metabolism modulate mitochondrial energy synthesis in isolated and cultured hepatocytes. In addition, our investigations implicate endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocyte mitochondria exposed to ethanol. The fluorographic investigations using the confocal laser scanning microscopy may be useful to extend our knowledge and provide a new view about ethanol-associated oxidative stress and metabolic changes in hepatocytes.
Kurose
I
I
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Higuchi
H
H
Kato
S
S
Miura
S
S
Ishii
H
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D008830:Microbodies / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D000431:Ethanol; D002374:Catalase; D005979:Glutathione Peroxidase