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实验性大鼠肝纤维化中的氧化和硝化应激:牛磺酸的保护作用。

Oxidative and nitrosative stress in experimental rat liver fibrosis: Protective effect of taurine.

机构信息

Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608002, Chidambaram, Tamil Nadu, India.

出版信息

Environ Toxicol Pharmacol. 2010 Mar;29(2):104-10. doi: 10.1016/j.etap.2009.11.005. Epub 2009 Nov 24.

DOI:10.1016/j.etap.2009.11.005
PMID:21787590
Abstract

Taurine (TAU) has protective effects on experimental liver fibrosis. The present study investigates whether benefits of TAU are mediated through attenuation of oxidative and nitrosative stresses. Liver fibrosis was induced in male Wistar rats by simultaneous administration of iron (0.5%, w/w) and ethanol (6g/kg/day) for 60 days consecutively. Significant increases in thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, protein carbonyl content and loss of non-protein, protein and total thiols were observed in the liver of iron plus alcohol-fed rats. Nitrosative stress was marked by increased levels of S-nitrosothiols and decreased nitrite content. Accumulation of nitrated and oxidatively modified proteins in liver was further evidenced by immunohistochemical localization with specific antibodies for 4-hydroxynonenol (4-HNE), 3-nitrotyrosine (3-NT) and dinitrophenol (DNP). Decrease in mitochondrial ion-transport enzymes and disturbances in calcium and iron levels were also observed in these rats. TAU administration (2% (w/v) in drinking water) significantly reduced the levels of lipid hydroperoxides, TBARS, protein carbonyl with concomitant elevation in thiol levels. The presence of 4-HNE, 3-NT and DNP-protein adducts was minimal. TAU also improved mitochondrial enzyme activities and regulated iron and calcium levels. These results show that the restorative effect of taurine in fibrosis involves amelioration of protein and lipid damage by decreasing oxidative and nitrosative stresses.

摘要

牛磺酸(TAU)对实验性肝纤维化具有保护作用。本研究旨在探讨 TAU 的益处是否通过减轻氧化应激和硝化应激来介导。雄性 Wistar 大鼠连续 60 天同时给予铁(0.5%,w/w)和乙醇(6g/kg/天),诱导肝纤维化。在铁加酒精喂养的大鼠肝脏中,观察到硫代巴比妥酸反应物质(TBARS)、脂质过氧化物、蛋白羰基含量和非蛋白、蛋白和总巯基的丧失显著增加。硝化应激的标志是 S-亚硝基硫醇水平升高和亚硝酸盐含量降低。通过用特异性抗体 4-羟基壬烯醇(4-HNE)、3-硝基酪氨酸(3-NT)和二硝基苯酚(DNP)对肝脏进行免疫组织化学定位,进一步证明了氧化和硝化修饰蛋白的积累。这些大鼠还观察到线粒体离子转运酶的减少以及钙和铁水平的紊乱。TAU 给药(2%(w/v)在饮用水中)显著降低了脂质过氧化物、TBARS、蛋白羰基的水平,同时提高了巯基水平。4-HNE、3-NT 和 DNP-蛋白加合物的存在最小。TAU 还改善了线粒体酶活性并调节了铁和钙水平。这些结果表明,牛磺酸在纤维化中的恢复作用涉及通过减少氧化应激和硝化应激来改善蛋白和脂质损伤。

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