Utilization of Artificial Intelligence Coupled with a High-Throughput, High-Content Platform in the Exploration of Neurodevelopmental Toxicity of Individual and Combined PFAS.

IF 4.4 Q1 TOXICOLOGY
Seth D Currie, David Blake Benson, Zhong-Ru Xie, Jia-Sheng Wang, Lili Tang
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引用次数: 0

Abstract

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health concerns. This study selected eleven PFAS commonly found in drinking water and exposed Caenorhabditis elegans to concentrations ranging from 0.1 to 200 µM to assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that PFAS such as 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, and PFOS inhibited dopaminergic neuron activity, with fluorescence intensity reductions observed across concentrations from 0.1 to 100 µM. PFOS and PFBS also disrupted synaptic transmission, causing reduced motility and increased paralysis in aldicarb-induced assays, with the most pronounced effects at higher concentrations. These impairments in both neuron activity and synaptic function led to behavioral deficits. Notably, PFOS was one of the most toxic PFAS, affecting multiple neurodevelopmental endpoints. These results emphasize the developmental risks of PFAS exposure, highlighting the impact of both individual compounds and mixtures on neurodevelopment. This knowledge is essential for assessing PFAS-related health risks and informing mitigation strategies.

利用人工智能结合高通量、高含量平台探索单个和联合PFAS的神经发育毒性。
全氟烷基和多氟烷基物质(PFAS)是用于各种产品的合成化学品,如消防泡沫和不粘锅,因为它们耐热和耐降解。然而,这些相同的特性使它们在环境和人体中持久存在,引起了公众健康问题。本研究选择了饮用水中常见的11种PFAS,并将秀丽隐杆线虫暴露在0.1至200µM的浓度范围内,使用高通量,高含量筛选(HTS)平台结合人工智能进行图像分析,评估神经发育毒性。我们的研究结果表明,PFAS如6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA和PFOS抑制多巴胺能神经元的活性,在0.1至100µM的浓度范围内观察到荧光强度降低。全氟辛烷磺酸和全氟辛烷磺酸也会破坏突触传递,在涕灭威诱导的实验中导致运动能力下降和瘫痪增加,浓度越高影响越明显。这些神经元活动和突触功能的损伤导致了行为缺陷。值得注意的是,全氟辛烷磺酸是毒性最大的全氟辛烷磺酸之一,影响多个神经发育终点。这些结果强调了PFAS暴露的发育风险,强调了单个化合物和混合物对神经发育的影响。这些知识对于评估与pfas相关的健康风险和通报缓解战略至关重要。
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来源期刊
CiteScore
5.30
自引率
1.70%
发文量
21
审稿时长
10 weeks
期刊介绍: The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (“stranger to life”) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; pathophysiological interactions of natural and synthetic chemicals; development of biochemical indicators including new “-omics” approaches to identify biomarkers of exposure or effects for xenobiotics.
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