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铊暴露干扰斑马鱼(Danio rerio)胚胎心脏发育:从表型到基因型。

Thallium exposure interfered with heart development in embryonic zebrafish (Danio rerio): From phenotype to genotype.

机构信息

Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Department of Agricultural Chemistry, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan.

出版信息

Sci Total Environ. 2023 Jun 20;878:162901. doi: 10.1016/j.scitotenv.2023.162901. Epub 2023 Mar 21.

DOI:10.1016/j.scitotenv.2023.162901
PMID:36948317
Abstract

Thallium (Tl) is a rare trace metal element but increasingly detected in wastewater produced by coal-burning, smelting, and more recently, high-tech manufacturing industries. However, the adverse effects of Tl, especially cardiotoxicity, on aquatic biota remain unclear. In this study, zebrafish model was used to elucidate the effects and mechanisms of Tl(I) cardiotoxicity in developing embryos. Exposure of embryonic zebrafish to low-dose Tl(I) (25-100 μg/L) decreased heart rate and blood flow activity, and subsequently impaired swim bladder inflation and locomotive behavior of larvae. Following high-level Tl(I) administration (200-800 μg/L), embryonic zebrafish exhibited pericardial edema, incorrect heart looping, and thinner myocardial layer. Based on RNA-sequencing, Tl(I) altered pathways responsible for protein folding and transmembrane transport, as well as negative regulation of heart rate and cardiac jelly development. The gene expression of nppa, nppb, ucp1, and ucp3, biomarkers of cardiac damage, were significantly upregulated by Tl(I). Our findings demonstrate that Tl(I) at environmentally relevant concentrations interfered with cardiac development with respect to anatomy, function, and transcriptomic alterations. The cardiotoxic mechanisms of Tl(I) provide valuable information in the assessment of Tl-related ecological risk in freshwater environment.

摘要

铊(Tl)是一种稀有微量元素,但在燃煤、冶炼和最近的高科技制造业等行业产生的废水中越来越多地被检测到。然而,铊对水生生物的不良影响,特别是心脏毒性,仍不清楚。在这项研究中,使用斑马鱼模型来阐明Tl(I)在胚胎发育过程中心脏毒性的作用和机制。暴露于低剂量 Tl(I)(25-100μg/L)的胚胎斑马鱼心率和血流活动降低,随后会损害鳔充气和幼鱼的运动行为。在高剂量 Tl(I)(200-800μg/L)处理后,胚胎斑马鱼表现出心包水肿、心脏循环错误和心肌层变薄。基于 RNA 测序,Tl(I)改变了负责蛋白质折叠和跨膜运输的途径,以及心率和心胶质发育的负调控。心脏损伤标志物 nppa、nppb、ucp1 和 ucp3 的基因表达被 Tl(I)显著上调。我们的研究结果表明,Tl(I)在环境相关浓度下干扰了心脏发育,包括解剖、功能和转录组改变。Tl(I)的心脏毒性机制为评估淡水环境中与 Tl 相关的生态风险提供了有价值的信息。

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