Mitochondrial dysfunction is a prevalent molecular event that can result in multiple adverse outcomes. Recently, a novel high throughput method to assess metabolic capacity in fish embryos following exposure to chemicals has been adapted for environmental toxicology. Assessments of oxygen consumption rates using the Seahorse XF(e) 24/96 Extracellular Flux Analyzer (Agilent Technologies) can be used to garner insight into toxicant effects at early stages of development. Here we synthesize the current state of the science using high throughput metabolic profiling in zebrafish embryos, and present considerations for those wishing to adopt high throughput methods for mitochondrial bioenergetics into their research. Chemicals that have been investigated in zebrafish using this metabolic platform include herbicides (e.g. paraquat, diquat), industrial compounds (e.g. benzo-[a]-pyrene, tributyltin), natural products (e.g. quercetin), and anti-bacterial chemicals (i.e. triclosan). Some of these chemicals inhibit mitochondrial endpoints in the μM-mM range, and reduce basal respiration, maximum respiration, and spare capacity. We present a theoretical framework for how one can use mitochondrial performance data in zebrafish to categorize chemicals of concern and prioritize mitochondrial toxicants. Noteworthy is that our studies demonstrate that there can be considerable variation in basal respiration of untreated zebrafish embryos due to clutch-specific effects as well as individual variability, and basal oxygen consumption rates (OCR) can vary on average between 100 and 300 pmol/min/embryo. We also compare OCR between chorionated and dechorionated embryos, as both models are employed to test chemicals. After 24 h, dechorionated embryos remain responsive to mitochondrial toxicants, although they show a blunted response to the uncoupling agent carbonylcyanide-4-trifluoromethoxyphenylhydrazone (FCCP); dechorionated embryos are therefore a viable option for investigations into mitochondrial bioenergetics. We present an adverse outcome pathway framework that incorporates endpoints related to mitochondrial bioenergetics. High throughput bioenergetics assays conducted using whole embryos are expected to support adverse outcome pathways for mitochondrial dysfunction.

线粒体功能障碍是一种普遍的分子事件，可导致多种不良后果。最近，一种新颖的高通量方法已被用于环境毒理学，该方法用于评估暴露于化学物质后鱼胚胎中的代谢能力。使用Seahorse XF（e）24/96细胞外通量分析仪（安捷伦科技公司）评估耗氧率可用于在开发的早期阶段了解毒物的影响。在这里，我们使用斑马鱼胚胎中的高通量代谢谱合成了科学的当前状态，并为那些希望采用高通量方法进行线粒体生物能学研究的人员提出了考虑。使用该代谢平台在斑马鱼中进行研究的化学物质包括除草剂（例如百草枯，敌草快），工业化合物（例如苯并[a] -py，三丁基锡），天然产物（例如槲皮素）和抗菌化学品（例如三氯生）。这些化学物质中的一些会抑制μM-mM范围内的线粒体终点，并减少基础呼吸，最大呼吸和备用容量。我们提供了一个理论框架，说明如何使用斑马鱼中的线粒体性能数据对所关注的化学物质进行分类并确定线粒体有毒物质的优先级。值得注意的是，我们的研究表明，由于离合器的特定作用以及个体差异，未处理的斑马鱼胚胎的基础呼吸可能会有相当大的变化，并且基础耗氧率（OCR）的平均变化范围为100至300 pmol / min。 /胚胎。我们还比较了绒毛膜化和去绒毛膜化的胚胎之间的OCR，因为这两种模型都用于测试化学物质。24小时后，去绒毛化的胚胎对线粒体毒物仍然有反应，尽管它们对解偶联剂羰基氰-4-三氟甲氧基苯基hydr（FCCP）的反应减弱。因此，去绒毛的胚胎是研究线粒体生物能学的可行选择。我们提出了一个不利的结果途径框架，其中包括与线粒体生物能相关的端点。使用整个胚胎进行的高通量生物能分析有望支持线粒体功能障碍的不良结局途径。因此，去绒毛的胚胎是研究线粒体生物能学的可行选择。我们提出了一个不利的结果途径框架，其中包括与线粒体生物能相关的端点。使用整个胚胎进行的高通量生物能分析有望支持线粒体功能障碍的不良结局途径。因此，去绒毛的胚胎是研究线粒体生物能学的可行选择。我们提出了一个不利的结果途径框架，其中包括与线粒体生物能相关的端点。使用整个胚胎进行的高通量生物能分析有望支持线粒体功能障碍的不良结局途径。