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抗低血压药物诱发的心脏毒性:一项体外研究。

Anti-hypotensive drug induced cardiotoxicity: an in vitro study.

作者信息

Jain Aditi, Rani Vibha

机构信息

Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, Uttar Pradesh, 210307, India.

出版信息

In Vitro Cell Dev Biol Anim. 2018 Feb;54(2):92-98. doi: 10.1007/s11626-017-0222-6. Epub 2018 Jan 10.

Abstract

Cardiotoxic side effects of broad range of drugs have emerged as an important cause of developing cardiovascular complications, as patients recover from one disease but develop another. Both cardiovascular and non-cardiovascular drugs may lead to the toxicity in the heart. Many drugs were initially not screened for cardiotoxicity, which is now an essential concern for drug discovery. Levophed is used for treating hypotension in critical care patients. Being a neurotransmitter, its concentration increases significantly in stress conditions and administration of this drug to patients' results in developing acute as well as persistent cardiac complications. Therefore, understanding its concentration-mediated effects and identifying the toxic concentration will serve as a platform to develop interventions to prevent adverse drug effects. In the present study, concentration and time-dependent effects of Levophed in H9C2 cardiomyoblasts were studied in detail by various cytotoxicity assays. Norepinephrine as a Levophed substitute was used and apoptotic cellular death was characterized by Annexin V and TUNEL DNA fragmentation assays. Morphological alterations, growth inhibition, and cellular death were also studied in detail. We observed that Levophed induces concentration-mediated deleterious effects in cardiomyoblasts. In-depth analysis of these effects will help in designing strategies in near future to combat and reduce this drug-induced cardiac toxicity.

摘要

多种药物的心脏毒性副作用已成为引发心血管并发症的一个重要原因,因为患者从一种疾病中康复后却又患上了另一种疾病。心血管药物和非心血管药物都可能导致心脏毒性。许多药物最初并未进行心脏毒性筛查,而如今这已成为药物研发中的一个重要关注点。去甲肾上腺素用于治疗重症监护患者的低血压。作为一种神经递质,其浓度在应激状态下会显著升高,给患者使用这种药物会导致急性以及持续性心脏并发症。因此,了解其浓度介导的效应并确定毒性浓度将为开发预防药物不良反应的干预措施提供一个平台。在本研究中,通过各种细胞毒性试验详细研究了去甲肾上腺素在H9C2心肌母细胞中的浓度和时间依赖性效应。使用去甲肾上腺素作为替代品,并通过膜联蛋白V和TUNEL DNA片段化试验对凋亡性细胞死亡进行了表征。还详细研究了形态学改变、生长抑制和细胞死亡情况。我们观察到去甲肾上腺素在心肌母细胞中诱导浓度介导的有害效应。对这些效应的深入分析将有助于在不久的将来设计出对抗和降低这种药物诱导的心脏毒性的策略。

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