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Abstract Title:

Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways.

Abstract Source:

J Hepatol. 2007 Aug;47(2):253-61. Epub 2007 Mar 7. PMID: 17433488

Abstract Author(s):

Ping Yao, Andreas Nussler, Liegang Liu, Liping Hao, Fangfang Song, Anja Schirmeier, Natascha Nussler

Article Affiliation:

Department of General-, Visceral-, and Transplantation Surgery, Humboldt University, Charité, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.

Abstract:

BACKGROUND/AIMS: Flavonoids, including quercetin, have been reported to have potent hepatoprotective effects, which may be associated with HO-1 induction. However, since the effect and signaling pathway of quercetin involved in HO-1 induction against alcoholic liver damage are still not fully understood, this is the target of the present study. METHODS: Human hepatocytes were incubated with ethanol (100 mM) and quercetin (10-200 microM), and cellular damage and HO-1 activity were measured. Nrf2 expression in cytosolic and nuclear fractions was studied following the incubation with MAPK inhibitor(s). RESULTS: Ethanol exposure resulted in a sustained glutathione depletion, malondialdehyde elevation, and evident release of cellular LDH and AST. Quercetin exerted a dose-dependent protective effect against alcoholic oxidative stress, and increased the EC50 of ethanol by approx. 40%, which is parallel to HO-1 induction with quercetin. Zinc protoporphyrin-9 abrogated the protective effect and dramatically enhanced ethanol cytotoxicity. SB203580 (p38 inhibitor) and especially PD98059 (ERK inhibitor) blocked quercetin-derived HO-1 induction and Nrf2 translocation, and subsequently inhibited the quercetin-related protection. CONCLUSIONS: HO-1 up-regulation by quercetin protected human hepatocytes from ethanol-induced oxidative stress. Among MAPK signaling pathways, p38 and ERK mediated quercetin-derived Nrf2 translocation into nuclei and subsequent induction of HO-1 activity, and the latter showed a stronger mediating effect.

Study Type : In Vitro Study

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Sayer Ji
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