α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 μM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased heart rate. Notably, we found that α-asarone impaired the cardiac function of zebrafish by prolonging the mean QTc duration and causing T-wave abnormalities. The expressions of cardiac development-related key transcriptional regulators tbx5, nkx2.5, hand2, and gata5 were all changed under α-asarone exposure. Further investigation addressing the mechanism indicated that α-asarone triggered apoptosis mainly in the heart region of zebrafish. Moreover, the elevated expression of puma, cyto C, afap1, caspase 3, and caspase 9 in treated zebrafish suggested that mitochondrial apoptosis is likely to be the main reason for α-asarone induced cardiotoxicity. These findings revealed the cardiac developmental toxicity of α-asarone, expanding our knowledge about the toxic effect of α-asarone on living organisms.

中文翻译：

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α-细辛酮通过斑马鱼线粒体凋亡途径诱导心脏缺陷和 QT 延长

α-细辛酮是一种存在于多种植物中的天然苯丙烯，广泛用于调味食品和治疗疾病。以往的研究表明，α-细辛醚具有多种药理作用，但也有报道表明其具有毒性。然而，对其心血管影响知之甚少。本研究调查了α-细辛酮在斑马鱼中的发育毒性，尤其是心脏毒性。斑马鱼胚胎暴露于不同浓度的 α-细辛醚（1、3、5、10 和 30 μM）。发育毒性评估表明，α-细辛酮对死亡率和孵化率没有显着影响。相比之下，α-细辛酮处理的斑马鱼的畸形率呈浓度依赖性增加。最具代表性的心脏缺陷是心脏畸形率增加、心包水肿区、静脉窦-球动脉距离，心率减慢。值得注意的是，我们发现α-细辛酮通过延长平均 QTc 持续时间和导致 T 波异常来损害斑马鱼的心脏功能。与心脏发育相关的关键转录调节因子 tbx5、nkx2.5、hand2 和 gata5 的表达均在 α-细辛醚暴露下发生变化。针对该机制的进一步研究表明，α-细辛酮主要在斑马鱼的心脏区域引发细胞凋亡。此外，经处理的斑马鱼中 puma、cyto C、afap1、caspase 3 和 caspase 9 的表达升高表明线粒体凋亡可能是 α-细辛酮诱导心脏毒性的主要原因。这些发现揭示了 α-细辛醚的心脏发育毒性，