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富含多酚的苹果(Malus domestica L.)皮提取物通过其抗氧化活性减弱三氧化二砷诱导的 H9c2 细胞心脏毒性。

Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

机构信息

Agroprocessing and Natural Products Division, Council for Scientific and Industrial Research - National Institute for Interdisciplinary Science and Technology (CSIR - NIIST), Thiruvananthapuram, Kerala 695019, India.

出版信息

Food Funct. 2014 Mar;5(3):502-11. doi: 10.1039/c3fo60470e.

DOI:10.1039/c3fo60470e
PMID:24441683
Abstract

Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

摘要

有证据表明,苹果皮含有广泛的具有抗氧化活性的多酚,其摄入与改善健康益处有关。三氧化二砷 (ATO) 是治疗急性早幼粒细胞白血病 (APL) 的非常有效药物,但它会导致通过改变各种心脏离子通道和增加细胞内钙水平和活性氧 (ROS) 引起的心脏毒性。本研究的目的是研究苹果皮甲醇提取物 (APME) 和苹果皮水提物 (APAE) 对 H9c2 心肌细胞系中 ATO (5 μM) 诱导毒性的影响。我们用 ATO 和苹果皮提取物评估了细胞内固有抗氧化酶的细胞状态、ROS 水平、线粒体超氧化物、谷胱甘肽和细胞内钙。在进行基于细胞系的研究之前,我们通过 1,1-二苯基-2-苦基肼 (DPPH)、总还原能力 (TRP)、超氧阴离子和羟基自由基清除活性,以及定量总酚和类黄酮含量,评估了苹果皮提取物的抗氧化潜力。两种提取物在无细胞化学测定中均显示出相当大的抗氧化活性。此外,APME 和 APAE 均可防止 ATO 在 H9c2 细胞中引起的抗氧化状态改变。在 ATO 作用下,乳酸脱氢酶、超氧化物歧化酶、过氧化氢酶、谷胱甘肽、谷胱甘肽过氧化物酶、硫氧还蛋白还原酶、黄嘌呤氧化酶、钙超载和 caspase-3 活性的活性发生了显著差异。总的结果表明,多酚丰富的苹果皮提取物通过其抗氧化活性对 ATO 诱导的心脏毒性具有保护作用。

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