Ferric citrate CYP2E1-independently promotes alcohol-induced apoptosis in HepG2 cells via oxidative/nitrative stress which is attenuated by pretreatment with baicalin.
In the case of alcoholic liver injury, an iron overload is always present. Both alcohol and iron can individually induce oxidative stress in liver. However, the combined effect of physiological concentrations of alcohol and iron on oxidative stress in hepatocytes remains unknown. Baicalin has been demonstrated to be an antioxidant or iron chelator in animal experiments. In this study, we investigated the injury to hepatocytes CYP2E1-independently induced by the combination of alcohol and iron and the protective effect of baicalin. Compared with cells treated with ethanol alone, ferric citrate enhanced the accumulation of reactive oxygen and nitrogen species, increased the occurrence of protein carbonylation/nitration and the levels of 4-hydroxy-2-nonenal, changed the distribution of iNOS, and eventually resulted in apoptosis. However, pretreatment with baicalin inhibited the oxidative stress induced by the combination of alcohol and iron, mainly by chelating iron. Our findings therefore suggest that iron could CPY2E1-independently enhance the oxidative stress induced by alcohol, which probably contributes to the pathogenesis of alcoholic liver disease. Baicalin is a promising phytomedicine for preventing alcoholic liver disease.
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China.
Yan
Y
Xu
Yunchao
Y
Feng
Hailing
H
Li
Zhonghong
Z
Gao
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D006801:Humans; D015538:Nitrosation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*
D005290:Ferric Compounds; D005419:Flavonoids; C038044:baicalin; D000431:Ethanol; C025314:ferric citrate; D019392:Cytochrome P-450 CYP2E1