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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/G1318    most recent 00555.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yao, P. Articles by Nussler, A. PubMed PubMed Citation Articles by Yao, P. Articles by Nussler, A.

LIVER AND BILIARY TRACT

The protective role of HO-1 and its generated products (CO, bilirubin, and Fe) in ethanol-induced human hepatocyte damage

¹Universitätsmedizin Berlin, Charité, Campus Virchow, Department of General, Visceral, and Transplantation Surgery, Berlin, Germany; ²Tongji Medical College, Huazhong University of Science and Technology, School of Public Health, Department of Nutrition and Food Hygiene, Wuhan, People's Republic of China; ³Technical University Munich, Department of Traumatology, Munich, Germany

Submitted 28 November 2007 ; accepted in final form 23 March 2009

It has been reported that naturally occurring quercetin exerts hepatoprotective effects through heme oxygenase-1 (HO-1) induction. However, the precise mechanism of how ethanol-associated liver damage is counteracted by quercetin-enhanced HO-1 metabolism still remains unclear. To further decipher the protective role of quercetin on ethanol-induced liver damage, we treated human hepatocytes with quercetin and various (end) products of the HO-1 pathway. Our data clearly showed that quercetin treatment attenuated ethanol-induced damage, whereas hemoglobin and zinc protoporphyrin 9 (ZnPP) abolished such effects. Iron-II aggravated ethanol toxicity and was only partially reduced by quercetin. In contrast, carbon monoxide (CO) dose dependently inhibited ethanol-induced cytochrome P450 2E1 (CYP 2E1) activity and hepatotoxicity but had no influence on CYP 2E1 protein expression. Similarly, hemoglobin dramatically stimulated CYP 2E1 activity but not the protein expression in quercetin- and ethanol-cotreated hepatocytes. ZnPP significantly promoted CYP 2E1 protein expression in the presence and absence of CO treatment but inhibited ethanol-induced CYP 2E1 activation following CO incubation in quercetin- and ethanol-cotreated hepatocytes. These results suggested that quercetin virtually attenuated ethanol-derived oxidative damage via HO-1 induction. Heme degradation and CO release may mediate the protective effects through inhibiting ethanol-induced CYP 2E1 synthesis and enzymatic activity, respectively.

quercetin; CYP 2E1; heme oxygenase-1; carbon monoxide