Uchiyama Yosuke, Yamazaki Daiju, Kobayashi Naoki, Kanda Yasunari, Sugita-Konishi Yoshiko
Department of Physical and Chemical Sciences, Kanagawa Prefectural Institute of Public Health.
Division of Pharmacology, National Institute of Health Sciences.
Shokuhin Eiseigaku Zasshi. 2022;63(6):210-217. doi: 10.3358/shokueishi.63.210.
Citreoviridin (CTV) is a mycotoxin produced by various fungi, including Penicillium citreonigrum. One of the toxicities reportedly associated with CTV is neurotoxicity. CTV is also suspected to be associated with acute cardiac beriberi (also known as "Shoshin-kakke") and Keshan disease, which can have adverse effects on the heart, so the in vivo and in vitro toxicity of CTV on the heart or cardiomyocytes in experimental animal models have been reported. However, the toxicity of CTV for the human heart, especially its electrophysiological effect, remains poorly understood. Therefore, to investigate the electrophysiological effect of CTV on the human cardiomyocytes, we conducted a multi-electrode array (MEA) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The MEA revealed that 30 μmol/L of CTV stopped the beating of hiPSC-CMs, and the field potential duration and first peak amplitude were shortened at 10 μmol/L. Before the hiPSC-CMs stopped beating, the length of the inter-spike interval varied two- to four-fold. These results demonstrated that CTV induced an electrophysiological disturbance on human cardiomyocytes. This is first paper to elucidate the electrophysiological effect of CTV on human heart directly and may aid in analyzing the risk associated with CTV to ensure food safety.
黄绿青霉素（CTV）是由包括桔青霉在内的多种真菌产生的一种霉菌毒素。据报道，与CTV相关的毒性之一是神经毒性。CTV还被怀疑与急性心脏脚气病（也称为“冲心性脚气病”）和克山病有关，这两种疾病会对心脏产生不利影响，因此已有关于CTV在实验动物模型中对心脏或心肌细胞的体内和体外毒性的报道。然而，CTV对人类心脏的毒性，尤其是其电生理效应，仍知之甚少。因此，为了研究CTV对人类心肌细胞的电生理效应，我们使用人类诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）进行了多电极阵列（MEA）实验。MEA结果显示，30μmol/L的CTV使hiPSC-CMs停止跳动，在10μmol/L时场电位持续时间和第一个峰值幅度缩短。在hiPSC-CMs停止跳动之前，峰间期长度变化了两到四倍。这些结果表明，CTV对人类心肌细胞产生了电生理干扰。这是第一篇直接阐明CTV对人类心脏电生理效应的论文，可能有助于分析与CTV相关的风险以确保食品安全。
