Department of Biochemistry, University of Madras , Guindy Campus, Chennai, Tamilnadu 600 025, India.
Department of Computer Science and Engineering, Government College of Engineering , Salem, Tamilnadu 627 007, India.
J Proteome Res. 2017 Sep 1;16(9):3190-3199. doi: 10.1021/acs.jproteome.7b00176. Epub 2017 Aug 21.
Functional perturbation of mitochondria is associated with fulminant hepatic failure (FHF). d-Galactosamine/lipopolysaccharide (d-GalN/LPS)-induced FHF is a renowned model to evaluate the efficacy of hepatoprotective agents. Lycopene is an antioxidant and phytonutrient from the carotenoid family. The health benefits of lycopene are prominent against cancer and cardiovascular, lung, liver, and skin problems. Recent studies have demonstrated the hepatoprotective, antidyslipidemic, and antioxidant roles of lycopene. The current study was designed to appraise the ability of lycopene to prevent mitochondrial dysfunction during the d-GalN/LPS-induced FHF. The administration of d-GalN/LPS (300 mg and 30 μg/kg body weight, respectively) to the experimental rats induced several disturbances in mitochondrial function. The lipid peroxide and hydrogen peroxide levels were increased (p < 0.05). The activities of mitochondrial antioxidants, tricarboxylic acid (TCA) cycle, and electron transport chain enzymes and the cellular adenosine triphosphate (ATP) content were decreased (p < 0.05). Lycopene (10 mg/kg body weight for 6 days) pretreatment attenuated lipid peroxidation and prohibited the excessive synthesis of hydrogen peroxide. The d-GalN/LPS-induced impairment in ATP production and increased enzyme activities were effectively prevented by the lycopene administration. The lycopene-mediated mitochondrial protection was mainly ascribed to the strong antioxidant potential of this phytonutrient. Molecular modeling results obtained show evidence that lycopene inhibits several lipoxygenases and provides rationale for the observed prevention of lipid peroxidation in the mitochondrial membrane. The carotenoid lycopene combatted oxidative stress, scavenged free radicals, prevented ROS generation, and inhibited the toxic effects of d-GalN/LPS during FHF.
线粒体功能障碍与暴发性肝衰竭（FHF）有关。D-半乳糖胺/脂多糖（d-GalN/LPS）诱导的 FHF 是评估肝保护剂疗效的著名模型。番茄红素是类胡萝卜素家族中的一种抗氧化剂和植物营养素。番茄红素对癌症、心血管、肺、肝和皮肤问题的健康益处显著。最近的研究表明了番茄红素的保肝、抗血脂异常和抗氧化作用。本研究旨在评估番茄红素在预防 D-GalN/LPS 诱导的 FHF 期间线粒体功能障碍的能力。给实验大鼠施用 D-GalN/LPS（分别为 300mg 和 30μg/kg 体重）会引起线粒体功能的几种紊乱。脂质过氧化物和过氧化氢水平升高（p<0.05）。线粒体抗氧化剂、三羧酸（TCA）循环和电子传递链酶的活性以及细胞腺苷三磷酸（ATP）含量降低（p<0.05）。番茄红素（6 天 10mg/kg 体重）预处理可减轻脂质过氧化作用并防止过氧化氢的过度合成。番茄红素的给药有效防止了 D-GalN/LPS 诱导的 ATP 产生受损和酶活性增加。番茄红素介导的线粒体保护主要归因于这种植物营养素的强大抗氧化潜力。获得的分子建模结果表明，番茄红素抑制几种脂氧合酶，并为观察到的对线粒体膜脂质过氧化的预防提供了依据。类胡萝卜素番茄红素抵抗了氧化应激，清除了自由基，防止了 ROS 的产生，并抑制了 FHF 期间 D-GalN/LPS 的毒性作用。
