Curcumin maintains cardiac and mitochondrial function in chronic kidney disease
Curcumin maintains cardiac and mitochondrial function in chronic kidney disease
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DOI：
10.1016/j.freeradbiomed.2013.03.017
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发表时间：
2013-08-01
影响因子：
7.4
通讯作者：
Zazueta, Cecilia
中科院分区：
文献类型：
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作者：
Correa, Francisco;Buelna-Chontal, Mabel;Zazueta, Cecilia
姜黄素是从姜黄中提取的一种具有抗氧化活性的天然色素，广泛应用于传统医药中，因其无毒、多效性，目前正被研究用于多种疾病的化学预防。在慢性肾衰竭中，导致心血管疾病的致病机制与氧化应激增加有关，这一过程不可避免地与线粒体功能障碍有关。因此，在这项研究中，我们的目的是调查，如果姜黄素预处理发挥心脏保护作用，在大鼠模型的肾大部切除术（5/6 Nx）及其对线粒体稳态的影响。在肾切除前7天和手术后60天（5/6 Nx +curc），对Wistar大鼠口服姜黄素（120 mg/kg）。肾切除术后几天检测到肾功能不全，而心脏功能的变化一直观察到方案结束。我们的研究结果表明，姜黄素治疗保护对病理重塑，减少缺血事件，并保留尿毒症大鼠的心脏功能。脑保护与活性氧产生减少、氧化应激标志物减少、抗氧化反应增加和活性金属蛋白酶-2减少有关。我们还观察到姜黄素的心脏保护作用与维持线粒体功能有关。在5/6 Nx + curc中，（408.5 +/- 68.7 nmol/min/mg蛋白质）（104.4 +/- 52.3 nmol/min/mg蛋白，P < 0.05），姜黄素处理大鼠的线粒体显示出增强的氧化磷酸化能力，（分别为3.6 +/- 1 vs 1.1 +/- 0.9和3.1 +/- 0.7 vs 1.2 +/- 0.8，P < 0.05）。参与心脏保护的机制包括直接的抗氧化作用和可能与蛋白激酶C激活的下游信号传导相关的间接策略。(C)2013 Elsevier Inc. All rights reserved.
Curcumin, a natural pigment with antioxidant activity obtained from turmeric and largely used in traditional medicine, is currently being studied in the chemoprevention of several diseases for its pleiotropic effects and nontoxicity. In chronic renal failure, the pathogenic mechanisms leading to cardiovascular disorders have been associated with increased oxidative stress, a process inevitably linked with mitochondrial dysfunction. Thus, in this study we aimed at investigating if curcumin pretreatment exerts cardioprotective effects in a rat model of subtotal nephrectomy (5/6Nx) and its impact on mitochondrial homeostasis. Curcumin was orally administered (120 mg/kg) to Wistar rats 7 days before nephrectomy and after surgery for 60 days (5/6Nx+curc). Renal dysfunction was detected a few days after nephrectomy, whereas changes in cardiac function were observed until the end of the protocol. Our results indicate that curcumin treatment protects against pathological remodeling, diminishes ischemic events, and preserves cardiac function in uremic rats. Cardioprotection was related to diminished reactive oxygen species production, decreased oxidative stress markers, increased antioxidant response, and diminution of active metalloproteinase-2. We also observed that curcumin's cardioprotective effects were related to maintaining mitochondrial function. Aconitase activity was significantly higher in the 5/6Nx + curc (408.5 +/- 68.7 nmol/min/mg protein) than in the 5/6Nx group (104.4 +/- 52.3 nmol/min/mg protein, P < 0.05), and mitochondria from curcumin-treated rats showed enhanced oxidative phosphorylation capacities with both NADH-linked substrates and succinate plus rotenone (3.6 +/- 1 vs 1.1 +/- 0.9 and 3.1 +/- 0.7 vs 1.2 +/- 0.8, respectively, P < 0.05). The mechanisms involved in cardioprotection included both direct antioxidant effects and indirect strategies that could be related to protein kinase C-activated downstream signaling. (C) 2013 Elsevier Inc. All rights reserved.