Chao Yu Kai, Liau Ian
Department of Applied Chemistry, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
Biomed Opt Express. 2021 Oct 28;12(11):7162-7172. doi: 10.1364/BOE.438836. eCollection 2021 Nov 1.
Doxorubicin (DOX) is a potent chemotherapeutic agent known to induce cardiotoxicity. Here we applied one-dimensional scanning multiphoton imaging to investigate the derangement of cardiac dynamics induced by DOX on a zebrafish model. DOX changed the cell morphology and significantly prolonged calcium transient and sarcomere contraction, leading to an arrhythmia-like contractile disorder. The restoration phase of calcium transient dominated the overall prolongation, indicating that DOX perturbed primarily the protein functions responsible for recycling cytosolic calcium ions. This novel finding supplements the existing mechanism of DOX cardiotoxicity. We anticipate that this approach should help mechanistic studies of drug-induced cardiotoxicity or heart diseases.
阿霉素（DOX）是一种已知会诱发心脏毒性的强效化疗药物。在此，我们应用一维扫描多光子成像技术，以斑马鱼模型研究DOX诱导的心脏动力学紊乱。DOX改变了细胞形态，并显著延长了钙瞬变和肌节收缩时间，导致类似心律失常的收缩紊乱。钙瞬变的恢复阶段主导了整体延长，表明DOX主要扰乱了负责回收胞质钙离子的蛋白质功能。这一新发现补充了现有的DOX心脏毒性机制。我们预计，这种方法将有助于药物诱导的心脏毒性或心脏病的机制研究。
