由于开发了使用人诱导的多能干细胞衍生的心肌细胞(hiPSC-CM)的动物替代测试方法,因此评估普通化学物质以及新药的心脏毒性潜力的重要性正在增加。双酚A(BPA),它被用作塑料的主要材料,被称为内分泌干扰化学物质,最近报道即使急性暴露也会通过抑制CM中的离子通道引起心脏毒性。因此,强调了开发BPA替代品的必要性,和结构类似物,包括双酚AF,C,E,F,S已经开发出来了。然而,双酚类似物的心脏毒性数据尚不为人所知。在这项研究中,为了评估类似物的心脏毒性潜力,包括双酚A,我们进行了hiPSC-CM的生存试验和基于多电极阵列的双重心脏毒性评估.急性暴露于所有双酚类似物并不影响存活率,但是尖峰幅度,节拍期,除双酚S外,大多数双酚中的场电位持续时间均以剂量依赖性方式降低。双酚,除了双酚S,降低了hiPSC-CM的收缩力,并导致高剂量时搏动停滞。一起来看,可以表明,即使急性暴露,开发的双酚类似物也可能引起心脏毒性,认为基于MEA的双心脏毒性评价方法的应用可以有效地帮助安全替代品的开发。
The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives.