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多柔比星诱导性心肌病的分子机制——最新研究进展。

Molecular mechanism of doxorubicin-induced cardiomyopathy - An update.

机构信息

Department of Biomedical Sciences, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.

Department of Biomedical Sciences, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.

出版信息

Eur J Pharmacol. 2018 Jan 5;818:241-253. doi: 10.1016/j.ejphar.2017.10.043. Epub 2017 Oct 23.

Abstract

Doxorubicin is utilized for anti-neoplastic treatment for several decades. The utility of this drug is limited due to its side effects. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. There are various signalling mechanisms involved in doxorubicin cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due to oxidative stress. Cardiac mitochondrial damage is supposed after few hours following the revelation of doxorubicin. This has led important new uses for the mechanism of doxorubicin-induced cardiotoxicity and novel avenues of investigation to determine better pharmacotherapies and interventions for the impediment of cardiotoxicity. The idea of this review is to bring up to date the recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium dysregulation, endoplasmic reticulum stress, impairment of progenitor cells, activation of immune, ubiquitous system and some other parameters.

摘要

多柔比星已被临床应用于抗肿瘤治疗数十年。但其存在明显的副作用,限制了其广泛应用。多柔比星的毒性源于心肌,随后也会损伤其他器官。多柔比星的作用机制是与 DNA 嵌合,抑制拓扑异构酶 2。多柔比星的致心肌毒性涉及多种信号机制。首先,多柔比星诱导的心肌毒性是由于氧化应激。在多柔比星暴露数小时后,心肌线粒体损伤。这为多柔比星诱导的心肌毒性的作用机制提供了重要的新用途,并为确定更好的药物治疗和干预措施以阻止心肌毒性开辟了新的研究途径。本文的目的是更新多柔比星心肌病的作用机制的最新研究发现,如钙调节异常、内质网应激、祖细胞损伤、免疫激活、普遍系统和其他一些参数。

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