Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology.
Liver lipid peroxidation, nonheme iron, antioxidants, and protein oxidation were investigated in experimental alcohol-induced liver disease in the rat. Wistar male rats were intragastrically and continuously infused for 4 weeks with a high-fat diet plus an ethanol or an isocaloric amount of dextrose, maintaining a high blood alcohol level (200-300 mg%). This model induced fatty liver, spotty necrosis, and focal inflammation. This pathology was associated with an enhanced lipid peroxidation and a decrease in the major antioxidant factors. Hepatic alpha-tocopherol and glutathione concentrations were significantly decreased in ethanol-fed rats. Glutathione peroxidase (GPx) was also decreased, whereas glutathione S-transferase (GST) was unaffected. The nonheme iron level was significantly decreased. Protein oxidation was assessed through three parameters: protein thiols, protein carbonyl groups, and the activity of glutamine synthetase (GS), a centrilobular enzyme particularly susceptible to free-radical-mediated damage. Ethanol-fed rats had decreased protein thiol concentrations and reduced GS activity, together with increased protein carbonyls. A significant correlation between GS activity and the pathological score was observed. This study confirms the ethanol-related increase in lipid peroxidation and shows that ethanol impairs the hepatic antioxidant potential. Furthermore, evidence of oxidative protein damage is given, including decreased activity of a key enzyme of ammonia metabolism. These protein disturbances may contribute to the pathogenesis of the observed liver damage.
Rouach
H
H
Department of Biomedical Research on Alcoholism, Univ. René Descartes,Paris, France.
Fataccioli
V
V
Gentil
M
M
French
S W
SW
Morimoto
M
M
Nordmann
R
R
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000378:metabolism*
D014810:Vitamin E; D000431:Ethanol; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione