The health risk of triadimefon (TF) to cardiovascular system of human is still unclear, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems) who are at a greater risk. Therefore, firstly we explored the toxic effects and possible mechanism of cardiovascular toxicity induced by TF using zebrafish model. Zebrafish at stage of 48 h post fertilization (hpf) exposed to TF for 24 h exhibited morphological malformations which were further confirmed by histopathologic examination, including pericardial edema, circulation abnormalities, serious venous thrombosis and increased distance between the sinus venosus (SV) and bulbus arteriosus (BA) regions of the heart. In addition to morphological changes, TF induced functional deficits in the heart of zebrafish, including bradycardia and a significant reduced cardiac output that became more serious at higher concentrations. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. Q-PCR (quantitative real-time polymerase chain reaction) results demonstrated that the expression level of genes related to ATPase (atp2a1l, atp1b2b, atp1a3b), calcium channel (cacna1ab, cacna1da) and cardiac troponin C (tnnc1a) were significantly decreased after TF exposure. For the first time, the present study revealed that TF exposure had observable morphological and functional negative impacts on cardiovascular system of zebrafish. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction following TF exposure. These findings generated here can provide information for better pesticide poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.

中文翻译：

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三唑酮在斑马鱼生命早期的心血管毒性及其对人类健康的潜在影响^☆

三唑酮（TF）对人体心血管系统的健康风险尚不清楚，尤其是对农药自杀人群，职业人群（农民，零售商和制药工人）和特殊人群（幼儿和婴儿，孕妇，老年人和免疫系统受损的人）的风险更大。因此，首先，我们使用斑马鱼模型探讨了TF诱导的心血管毒性的毒性作用及其可能的机制。受精（hpf）于TF暴露24 h后48h的斑马鱼表现出形态畸形，经组织病理学检查进一步证实，包括心包水肿，循环异常，严重的静脉血栓形成以及窦静脉与球囊之间的距离增加心脏的动脉区（BA）。除形态变化外，TF还引起斑马鱼心脏的功能缺陷，包括心动过缓，并且心输出量显着下降，在较高浓度下心输出量会变得更加严重。为了更好地了解斑马鱼心血管毒性的潜在分子机制，我们研究了与钙信号通路和心肌收缩有关的基因的转录水平。Q-PCR（定量实时聚合酶链反应）结果表明，与ATPase（为了更好地了解斑马鱼心血管毒性的潜在分子机制，我们研究了与钙信号通路和心肌收缩有关的基因的转录水平。Q-PCR（定量实时聚合酶链反应）结果表明，与ATPase（为了更好地了解斑马鱼心血管毒性的潜在分子机制，我们研究了与钙信号通路和心肌收缩有关的基因的转录水平。Q-PCR（实时定量聚合酶链反应）结果表明，与ATPase（TF暴露后，atp2a11，atp1b2b，atp1a3b），钙通道（cacna1ab，cacna1da）和心肌肌钙蛋白C（tnnc1a）显着降低。本研究首次显示，TF暴露对斑马鱼的心血管系统具有可观察到的形态和功能负面影响。从机理上讲，这种毒性可能是由于与TF暴露后与钙信号通路和心肌收缩相关的基因下调的压力所致。此处产生的这些发现可为更好的农药中毒治疗，职业病预防提供信息，并为风险管理措施提供理论基础。