Journal article
Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO
Phytomedicine (Stuttgart), Vol.20(8-9), pp.699-704
06/15/2013
DOI: 10.1016/j.phymed.2013.03.010
PMID: 23583009
Abstract
Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect. However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear. To explore the potential mechanism, herein, ethanol (4.0g/kg.bw.) was administrated to rats for 90 days. Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.). Quercetin (100μM) induced HO-1 and depleted heme pool when incubated to human hepatocytes. Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation. CO scavenging blocked the suppression of quercetin only on CYP2E1 activity. CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger. Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction. Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively.
Details
- Title: Subtitle
- Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO
- Creators
- Yuhan Tang - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaHongtao Tian - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, ChinaYanru Shi - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaChao Gao - Huazhong University of Science and TechnologyMingyou Xing - Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, ChinaWei Yang - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaWei Bao - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaDi Wang - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaLiegang Liu - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ChinaPing Yao - Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
- Resource Type
- Journal article
- Publication Details
- Phytomedicine (Stuttgart), Vol.20(8-9), pp.699-704
- DOI
- 10.1016/j.phymed.2013.03.010
- PMID
- 23583009
- NLM abbreviation
- Phytomedicine
- ISSN
- 0944-7113
- eISSN
- 1618-095X
- Publisher
- Elsevier GmbH
- Language
- English
- Date published
- 06/15/2013
- Academic Unit
- Epidemiology
- Record Identifier
- 9983995133002771
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