当前和新兴的心脏毒性概念：用于监管目的的风险评估的适用性

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-01 DOI:10.1016/j.toxlet.2025.07.068

K. Tsarouhas

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引用次数: 0

摘要

心肌病是一种心肌疾病。心肌在结构上受到影响和/或功能异常，在许多情况下，在没有冠状动脉疾病、高血压、瓣膜疾病和先天性心脏病的情况下。在临床医生对特发性心肌病作出诊断之前，还应考虑毒性、病毒和免疫原因。对于某些药物，如抗癌药物，流行病学研究指出了心脏毒性的表现。与特定心血管药物（如钙通道阻滞剂、β受体阻滞剂）有关的其他影响主要与过量服用急性心力衰竭有关。工业化学品可以直接或间接地对心血管系统的各个组成部分施加毒性作用。心脏毒素（例如夹竹桃、毛地黄和百合中的植物糖苷）可以根据剂量和暴露时间改变心脏的功能或结构。毒素在心脏中的主要分子靶点是钠、钾和钙通道[2]。氧化应激在汞等工业化学品引起的心脏毒性中也起着至关重要的作用。金属，如铂，对肌细胞造成直接损伤，引起线粒体超微结构异常和血小板活化和聚集。钴相关的心肌病可能是由于能量产生和收缩机制受到干扰，但其他因素（营养、甲状腺功能减退）也经常涉及。已知纳米颗粒通过氧化应激和炎症、细胞凋亡和细胞增殖减少、心率降低以及心脏形成和发育中功能基因的下调来影响心脏。乙醇相关心脏毒性的病因是多因素的，个体易感性是重要的。毒素/化学物质相关扩张型心肌病在普通人群中的真实患病率尚不清楚。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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S08-02 Current and emerging concepts of cardiotoxicity: applicability inrisk assessment for regulatory purposes

Cardiomyopathy is a myocardial disorder. The heart muscle is structurally affected and/or functions abnormally, and in many cases, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease. Before clinicians conclude their diagnosis on idiopathic cardiomyopathy, toxic as well as viral and immune causes should also be considered.

For some medication, such as anticancer drugs, epidemiological studies point to cardiotoxic manifestations. Other implications related to specific cardiovascular drugs (e.g. calcium-channel blockers, beta-blockers) are mostly associated in overdose with acute heart failure ^[1].

Industrial chemicals can exert toxic action, directly or indirectly, on various components of the cardiovascular system. Cardiotoxins (e.g. plant glycosides from oleander, foxglove and lily) can alter the heart functionally or structurally depending on the dosage and exposure period. The main molecular targets of the toxins in the heart are sodium, potassium and calcium channels ^[2]. Oxidative stress plays also a crucial role in cardiac toxicity caused by industrial chemicals, like mercury. Metals like platinum, cause direct injury on the myocytes, and cause mitochondrial ultrastructural abnormalities and platelet activation and aggregation. Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often implicated. Nanoparticles are known to affect the heart through oxidative stress and inflammation, cellular apoptosis and decreased cell proliferation, decreased heart rate and down regulation of genes functioning in heart formation and development. The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. The true prevalence of toxins/ chemicals related-dilated cardiomyopathy in the general population is not known.

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