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白藜芦醇和维生素E对乙醇诱导的小鼠氧化损伤的保护作用:生化和免疫学基础

Protective effect of resveratrol and vitamin E against ethanol-induced oxidative damage in mice: biochemical and immunological basis.

作者信息

Das Subir Kumar, Mukherjee Sukhes, Gupta Geetanjali, Rao D N, Vasudevan D M

机构信息

Department of Biochemistry, Agartala Govt Medical College, Kunjaban P.O., Agartala 799006, Tripura, India.

出版信息

Indian J Biochem Biophys. 2010 Feb;47(1):32-7.

Abstract

The metabolism of ethanol gives rise to the generation of excess amounts of reactive oxygen species and is also associated with immune dysfunction. We examined the efficacy of resveratrol and vitamin E on the immunomodulatory activity and vascular function in mice with liver abnormalities induced by chronic ethanol consumption by measuring the protein, liver-specific transaminase enzymes, antioxidant enzymes and non-enzymes such as reduced glutathione (GSH) content, thiobarbituric acid reactive substance (TBARS) level, nitrite level, and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and cytokines such as interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)-alpha, gamma interferon (IFN-gamma), vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-beta1 in mice blood. Ethanol (1.6 g/kg body wt/day) exposure for 12 wks significantly increased TBARS and nitrite levels and GST activity, and significantly decreased GSH content and the activities of SOD, CAT, GR and GPx in whole blood hemolyzate of 8-10 wks-old male BALB/c mice (weighing 20-30 g). Ethanol exposure also elevated the activities of transaminase enzymes (AST and ALT), IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1, while decreasing the albumin concentration and IL-4 activity in the serum. Both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) treatment significantly reduced AST, ALT, GST, IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1 activities and levels of TBARS and nitrite, and elevated albumin content, GSH level and activities of SOD, CAT, GR and GPx, compared to ethanol-treated group. Thus, results from the study demonstrated that both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) can effectively ameliorate ethanol (1.6 g kg(-1) day(-1))-induced oxidative challenges, immunomodulatory activity and angiogenesis processes.

摘要

乙醇的代谢会导致大量活性氧的产生,并且还与免疫功能障碍有关。我们通过测量蛋白质、肝脏特异性转氨酶、抗氧化酶和非酶类物质(如还原型谷胱甘肽(GSH)含量、硫代巴比妥酸反应性物质(TBARS)水平、亚硝酸盐水平)以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPx)和谷胱甘肽-S-转移酶(GST)的活性,以及小鼠血液中白细胞介素(IL)-2、IL-4、IL-10、肿瘤坏死因子(TNF)-α、γ干扰素(IFN)-γ、血管内皮生长因子(VEGF)-A和转化生长因子(TGF)-β1等细胞因子,来研究白藜芦醇和维生素E对慢性乙醇摄入诱导的肝脏异常小鼠免疫调节活性和血管功能的影响。对8-10周龄雄性BALB/c小鼠(体重20-30克)连续12周每天暴露于乙醇(1.6克/千克体重/天),显著增加了TBARS和亚硝酸盐水平以及GST活性,并显著降低了全血溶血产物中GSH含量以及SOD、CAT、GR和GPx的活性。乙醇暴露还提高了转氨酶(AST和ALT)、IL-10、TNF-α、IFN-γ、VEGF-A和TGF-β1的活性,同时降低了血清中白蛋白浓度和IL-4活性。与乙醇处理组相比,白藜芦醇(5毫克/千克体重/天)和维生素E(80毫克/千克体重/天)处理均显著降低了AST、ALT、GST、IL-10、TNF-α、IFN-γ、VEGF-A和TGF-β1的活性以及TBARS和亚硝酸盐水平,并提高了白蛋白含量、GSH水平以及SOD、CAT、GR和GPx的活性。因此,该研究结果表明,白藜芦醇(5毫克/千克体重/天)和维生素E(80毫克/千克体重/天)均可有效改善乙醇(1.6克/千克体重/天)诱导的氧化应激、免疫调节活性和血管生成过程。

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