Differential protective effects of quercetin, resveratrol, rutin and epigallocatechin gallate against mitochondrial dysfunction induced by indomethacin in Caco-2 cells
Differential protective effects of quercetin, resveratrol, rutin and epigallocatechin gallate against mitochondrial dysfunction induced by indomethacin in Caco-2 cells
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DOI：
10.1016/j.cbi.2011.12.007
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发表时间：
2012-02-05
影响因子：
5.1
通讯作者：
Gotteland, Martin
中科院分区：
文献类型：
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作者：
Carrasco-Pozo, Catalina;Luisa Mizgier, Maria;Gotteland, Martin
膳食多酚对健康的有益作用不仅是由于它们的抗氧化特性，而且还由于它们的抗菌、抗炎和/或抗肿瘤活性。最近有人提出，保护线粒体！这些化合物的功能（在几种疾病如阿尔茨海默病、帕金森病、肥胖症和糖尿病中改变）可能在解释多酚对健康的有益作用方面很重要。本研究旨在评价膳食多酚槲皮素、芦丁、白藜芦醇和表没食子儿茶素没食子酸酯对吲哚美辛（indomethacin，INDO）诱导的肠上皮Caco-2细胞线粒体功能改变的保护作用，并探讨INDO产生氧化应激损伤作用的机制。INDO浓度依赖性地降低Caco-2细胞中孵育20分钟后的细胞ATP水平和线粒体膜电位。INDO还抑制线粒体复合物I的活性并引起NADH的积累;导致线粒体O-2（中心点-）的过度产生，因为它被丙酮酸盐阻止。槲皮素（0.01 mg/ml）、白藜芦醇（0.1 mg/ml）和芦丁（1 mg/ml）保护Caco-2细胞免受INDO诱导的线粒体功能障碍，而表没食子儿茶素没食子酸酯没有观察到保护作用。槲皮素在防止线粒体功能障碍方面是最有效的;这可能是由于其进入细胞并在线粒体中积累的能力。此外，其与鱼藤酮的结构相似性可能有利于其与复合物I的泛醌位点结合，保护其免受抑制剂如INDO或鱼藤酮的影响。这些发现表明，膳食多酚对线粒体可能具有新的保护作用，补充其抗氧化特性。这种新的作用可能会扩大PP在涉及线粒体功能障碍的疾病中的预防和/或治疗用途，并与细胞或组织水平上的氧化应激增加有关。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The beneficial effects of dietary polyphenols on health are due not only to their antioxidant properties but also to their antibacterial, anti-inflammatory and/or anti-tumoral activities. It has recently been proposed that protection of mitochondria! function (which is altered in several diseases such as Alzheimer, Parkinson, obesity and diabetes) by these compounds, may be important in explaining the beneficial effects of polyphenols on health. The aim of this study was to evaluate the protective effects of dietary polyphenols quercetin, rutin, resveratrol and epigallocatechin gallate against the alterations of mitochondrial function induced by indomethacin (INDO) in intestinal epithelial Caco-2 cells, and to address the mechanism involved in such damaging effect by INDO, which generates oxidative stress. INDO concentration dependently decreases cellular ATP levels and mitochondrial membrane potential in Caco-2 cells after 20 min of incubation. INDO also inhibits the activity of mitochondrial complex I and causes accumulation of NADH; leading to overproduction of mitochondrial O-2(center dot-), since it is prevented by pyruvate. Quercetin (0.01 mg/ml), resveratrol (0.1 mg/ml) and rutin (1 mg/ml) protected Caco-2 cells against INDO-induced mitochondrial dysfunction, while no protection was observed with epigallocatechin gallate. Quercetin was the most efficient in protecting against mitochondrial dysfunction; this could be due to its ability to enter cells and accumulate in mitochondria. Additionally its structural similarity with rotenone could favor its binding to the ubiquinone site of complex I, protecting it from inhibitors such as INDO or rotenone. These findings suggest a possible new protective role for dietary polyphenols for mitochondria, complementary of their antioxidant property. This new role might expand the preventive and/or therapeutic use of PPs in conditions involving mitochondrial dysfunction and associated with increased oxidative stress at the cellular or tissue levels. (C) 2011 Elsevier Ireland Ltd. All rights reserved.