Resveratrol protects primary rat hepatocytes against oxidative stress damage: Activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes
Resveratrol protects primary rat hepatocytes against oxidative stress damage: Activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes
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DOI：
10.1016/j.ejphar.2008.06.067
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发表时间：
2008-09-04
影响因子：
5
通讯作者：
Victor Vega, Felix
中科院分区：
文献类型：
--
作者：
Andres Rubiolo, Juan;Mithieux, Gilles;Victor Vega, Felix
氧化应激被认为是肝脏病理发展的重要因素。内源性产生的活性氧或作为外源代谢的结果被酶和非酶细胞系统消除。除了内源性防御外，饮食中抗氧化剂的消耗对防止氧化损伤引起的疾病的发展具有重要作用。白藜芦醇是一种天然化合物，是人类饮食的一部分。这种分子已被证明具有许多生物学特性，包括抗氧化活性。我们决定测试白藜芦醇是否可以保护培养的原代肝细胞免受氧化应激损伤，如果是这样，则确定该化合物是否影响细胞解毒系统及其通过调节抗氧化和if期解毒酶表达的Nrf2转录因子的调节。通过测定释放到培养基中的乳酸脱氢酶的活性来检测细胞坏死死亡。抗氧化酶和第11相酶的活性用先前描述的方法测定。用共聚焦显微镜研究Nrf2转录因子的激活，用western blot和定量PCR分别检测Nrf2及其编码mRNA的表达水平。白藜芦醇预处理能有效保护氧化应激培养的肝细胞，提高过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、NADPH醌氧化还原酶和谷胱甘肽s转移酶的活性。白藜芦醇增加Nrf2的水平并诱导其向细胞核转运。此外，它还增加了Nrf2编码mRNA的浓度。在这项工作中，我们表明白藜芦醇可能是一种有用的药物，可以保护肝细胞免受氧化应激引起的损伤。(C) 2008 Elsevier B.V.版权所有
Oxidative stress is recognized as an important factor in the development of liver pathologies. The reactive oxygen species endogenously generated or as a consequence of xenobiotic metabolism are eliminated by enzymatic and nonenzymatic cellular systems. Besides endogen defences, the antioxidant consumption in the diet has an important role in the protection against the development of diseases product of oxidative damage. Resveratrol is a naturally occurring compound which is part of the human diet. This molecule has been shown to have many biological properties, including antioxidant activity. We decided to test if resveratrol could protect primary hepatocytes in culture from oxidative stress damage and if so, to determine if this compound affects the cellular detoxifying systems and their regulation through the Nrf2 transcription factor that regulates the expression of antioxidant and phase If detoxifying enzymes. Cell death by necrosis was detected by measuring the activity of lactate dehydrogenase liberated to the medium. The activities of antioxidant and phase 11 enzymes were measured using previously described methods. Activation of the Nrf2 transcription factor was studied by confocal microscopy and the Nrf2 and its coding mRNA levels were determined by western blot and quantitative PCR respectively. Resveratrol pre-treatment effectively protected hepatocytes in culture exposed to oxidative stress, increasing the activities of catalase, superoxide dismutase, glutathione peroxidase, NADPH quinone oxidoreductase and glutathione-S-transferase. Resveratrol increases the level of Nrf2 and induces its translocation to the nucleus. Also, it increases the concentration of the coding mRNA for Nrf2. In this work we show that resveratrol could be a useful drug for the protection of liver cells from oxidative stress induced damage. (C) 2008 Elsevier B.V. All rights reserved.