title: Heme oxygenase-1 mediates the protective role of quercetin against ethanol-induced rat hepatocytes oxidative damage.
abstract: Quercetin, one of the most widely distributed flavonoids in plants, possesses strong free radical scavenging ability and potent hepatoprotective effects. However, the protective effect and mechanism of quercetin on ethanol-induced oxidative damage in hepatocytes remain unclear. In this study, primary rat hepatocytes were incubated with ethanol and quercetin in the presence or absence of ZnPP 9, an antagonist of HO-1 induction. The ethanol-induced hepatotoxicity was found to be greatly diminished by pre-treatment of quercetin and this hepatoprotective effect could be partly blocked by ZnPP 9. This study also showed that quercetin significantly stimulated HO-1 expression at both mRNA and protein levels, then subsequently induced HO-1 activity. To further study the signaling pathways underlying quercetin-induced HO-1 up-regulation, HO-1 expression and activity in cytosolic microsomal fractions and Nrf2 expression in nuclear fractions were analyzed following quercetin or/and MAPK inhibitor(s) as well as PI3K inhibitor incubation for primary rat hepatocytes. These results indicated that ERK was required to induce HO-1 expression in rat hepatocytes. In summary, these data suggested that quercetin attenuates ethanol-induced oxidative stress through a pathway which involves ERK activation and HO-1 upregulation.
authors: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
authors: Shuang
authors: S
authors: Liu
authors: Wei
authors: W
authors: Hou
authors: Ping
authors: P
authors: Yao
authors: Na
authors: N
authors: Li
authors: Biyun
authors: B
authors: Zhang
authors: Liping
authors: L
authors: Hao
authors: Andreas K
authors: AK
authors: Nüssler
authors: Liegang
authors: L
authors: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D000431:Ethanol; D008315:Malondialdehyde; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D005978:Glutathione