Heme oxygenase-1 mediates the protective role of quercetin against ethanol-induced rat hepatocytes oxidative damage

被引：51
作者：
Liu, Shuang [1 ,2 ,3 ]
Hou, Wei [4 ]
Yao, Ping [1 ,2 ]
Li, Na [1 ,2 ,3 ]
Zhang, Biyun [1 ,2 ,3 ]
Hao, Liping [1 ,2 ]
Nuessler, Andreas K. [5 ]
Liu, Liegang [1 ,2 ]
机构：
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Food Hyg & Nutr, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, MOE Key Lab Environm & Hlth, Wuhan 430030, Peoples R China
[3] Hubei Ctr Dis Control & Prevent, Wuhan 430079, Peoples R China
[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Gastroenterol, Wuhan 430030, Peoples R China
[5] Tech Univ Munich, Dept Traumatol, D-81675 Munich, Germany
来源：
TOXICOLOGY IN VITRO | 2012年 / 26卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Heme oxygenase-1; Quercetin; Ethanol; Oxidative damage; Nuclear factor erythroid 2 related factor 2; Extracellular signal-regulated kinase; GENE-EXPRESSION; ANTIOXIDANT ACTIVITY; KINASE PATHWAYS; CARBON-MONOXIDE; HEPG2; CELLS; DNA-DAMAGE; STRESS; LIVER; INDUCTION; FLAVONOIDS;
D O I：
10.1016/j.tiv.2011.10.013
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：74 / 80
页数：7
相关论文
共 50 条
[11]   A SIMPLE METHOD FOR DETERMINATION OF SERUM CATALASE ACTIVITY AND REVISION OF REFERENCE RANGE [J].
GOTH, L .
CLINICA CHIMICA ACTA, 1991, 196 (2-3) :143-151
[12]   Gene regulation of heme oxygenase-1 as a therapeutic target [J].
Immenschuh, S ;
Ramadori, G .
BIOCHEMICAL PHARMACOLOGY, 2000, 60 (08) :1121-1128
[13]   The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions [J].
Kahraman, A ;
Erkasap, N ;
Köken, T ;
Serteser, M ;
Aktepe, F ;
Erkasap, S .
TOXICOLOGY, 2003, 183 (1-3) :133-142
[14]   Transcriptional regulation of heme oxygenase-1 gene expression by MAP kinases of the JNK and p38 pathways in primary cultures of rat Hepatocytes [J].
Kietzmann, T ;
Samoylenko, A ;
Immenschuh, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (20) :17927-17936
[15]   GENERATION OF SUPEROXIDE RADICAL DURING AUTOXIDATION OF HYDROXYLAMINE AND AN ASSAY FOR SUPEROXIDE-DISMUTASE [J].
KONO, Y .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1978, 186 (01) :189-195
[16]   Mechanism of heme oxygenase-1 gene induction by quercetin in rat aortic smooth muscle cells [J].
Lin, HC ;
Cheng, TH ;
Chen, YC ;
Juan, SH .
PHARMACOLOGY, 2004, 71 (02) :107-112
[17]  
Liu LG, 2004, BIOMED ENVIRON SCI, V17, P315
[18]   Quercetin protects against ethanol-induced oxidative damage in rat primary hepatocytes [J].
Liu, Shuang ;
Hou, Wei ;
Yao, Ping ;
Zhang, Biyun ;
Sun, Shanshan ;
Nuessler, Andreas K. ;
Liu, Liegang .
TOXICOLOGY IN VITRO, 2010, 24 (02) :516-522
[19]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[20]  
Mancuso C, 2004, ANTIOXID REDOX SIGN, V6, P878, DOI 10.1089/1523086041798097
12345