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多柔比星诱导性心肌病:7-羟基黄烷酮心脏保护作用的初步研究。

Doxorubicin-Induced Cardiomyopathy: A Preliminary Study on the Cardioprotective Benefits of 7-Hydroxyflavanone.

机构信息

Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa.

Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town 7505, South Africa.

出版信息

Int J Mol Sci. 2023 Oct 20;24(20):15395. doi: 10.3390/ijms242015395.

Abstract

The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content ( ≤ 0.001) and superoxide dismutase activity ( ≤ 0.001) whilst decreasing ROS ( ≤ 0.001), malondialdehyde production ( ≤ 0.001) and the secretion of interleukin-6 ( ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha ( ≤ 0.05) and pAMPK ( ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity ( ≤ 0.001), apoptosis ( ≤ 0.001) and necrosis ( ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC.

摘要

黄酮类化合物的治疗特性据称可提供针对多柔比星(Dox)诱导的心脏毒性(DIC)的心脏保护益处。在本研究中,我们旨在研究 7-羟基黄烷酮(7H)的预防特性,7H 是一种具有抗氧化特性的黄酮类化合物,可预防 DIC。通过用 Dox 处理 H9c2 心肌细胞 6 天来建立 DIC 的体外模型。同样,还对细胞进行了 7H 共同处理,以评估其减轻 DIC 的能力。获得的数据表明,7H 作为共同处理,通过增强总谷胱甘肽含量(≤0.001)和超氧化物歧化酶活性(≤0.001),同时降低 ROS(≤0.001)、丙二醛产生(≤0.001)和白细胞介素-6 的分泌(≤0.001),减轻 Dox 诱导的氧化应激。数据还显示线粒体功能得到改善,表现为增强的生物能、线粒体膜电位以及 PGC1-alpha(≤0.05)和 pAMPK(≤0.001)的表达。7H 还能够减弱 Dox 诱导的 caspase 3/7 活性(≤0.001)、凋亡(≤0.001)和坏死(≤0.05),从而进一步突出了其心脏保护潜力。总之,我们的研究结果表明了 7H 的心脏保护益处,因此表明它可能是一种针对 DIC 的合适的心脏保护剂候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e0e/10607478/2f6101a8d7bd/ijms-24-15395-g001.jpg

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