Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats

被引：55
作者：
Huang, Quanfang [1 ]
Huang, Renbin [2 ]
Zhang, Shijun [2 ]
Lin, Jun [2 ]
Wei, Ling [2 ]
He, Min [2 ]
Zhuo, Lang [2 ,3 ]
Lin, Xing [2 ]
机构：
[1] Guangxi Univ Chinese Med, Affiliated Hosp 1, Nanning 530023, Peoples R China
[2] Guangxi Med Univ, Nanning 530021, Peoples R China
[3] Inst Bioengn & Nanotechnol, Singapore 169483, Singapore
来源：
TOXICOLOGY LETTERS | 2013年 / 217卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Genistein; Hydrocotyle sibthorpioides; Alcohol; Liver fibrosis; NF-KAPPA-B; INDUCED LIVER-INJURY; INHIBITING OXIDATIVE STRESS; CARBON-TETRACHLORIDE; STELLATE CELLS; EXPRESSION; ACTIVATION; PREVENTS; DISEASE; ACID;
D O I：
10.1016/j.toxlet.2012.12.014
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0-9.5 g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2 mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-alpha and myeloperoxidase, via down-regulation of nuclear factor-kappa B. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of alpha-smooth muscle actin and transforming growth factor beta(1) proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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页码：102 / 110
页数：9
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