The protective role of HO-1 and its generated products (CO, bilirubin, and Fe) in ethanol-induced human hepatocyte damage
Autor: | Natascha C. Nüssler, Liegang Liu, Jing Zhao, Liping Hao, Antje Lehmann, Fangfang Song, Ping Yao, Peter Neuhaus, Andreas K. Nussler |
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Rok vydání: | 2009 |
Předmět: |
Physiology
Bilirubin Iron Flavonoid Protoporphyrins Deferoxamine Pharmacology Hemoglobins chemistry.chemical_compound Malondialdehyde Physiology (medical) Organometallic Compounds medicine Humans heterocyclic compounds Disulfides Ferrous Compounds Enzyme Inhibitors Liver Diseases Alcoholic Heme Transaminases chemistry.chemical_classification Carbon Monoxide Ethanol L-Lactate Dehydrogenase Hepatology Zinc protoporphyrin Gastroenterology Cytochrome P-450 CYP2E1 CYP2E1 Glutathione Allyl Compounds Cytochrome P-450 CYP2E1 Inhibitors medicine.anatomical_structure chemistry Biochemistry Hepatocyte Toxicity Hepatocytes Quercetin Heme Oxygenase-1 |
Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 296:G1318-G1323 |
ISSN: | 1522-1547 0193-1857 |
Popis: | 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. |
Databáze: | OpenAIRE |
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