State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Sci Total Environ. 2023 Dec 15;904:167037. doi: 10.1016/j.scitotenv.2023.167037. Epub 2023 Sep 12.
Circadian rhythm aligns numerous biological functions in majority of animals. Aside from well-known external factors such as the light-dark cycle and temperature, circadian rhythm can also be regulated by rarely explored factors such as synthetic substances. Here, we established a circadian behavior screening approach utilizing zebrafish larvae model, which integrated high-throughput capabilities with automated batch processing. With this approach, we systematically analyzed the circadian disruptive effects of >60 synthetic substances commonly detected in aquatic environment by assessing both the circadian period length and amplitude of circadian behavior, with an exposure concentration set at 100 μg/L. Among tested substances, a series of circadian disrupting compounds (circadian disruptors) were identified. Several categories of the hit compounds can be recognized, such as phthalate (diisopentyl phthalate (DIPP), with 10.1 % and 49.6 % increases for circadian period length and amplitude, respectively), neuroactive substance (mirtazapine, with 10.6 % and 63.1 % increases, respectively), and biocides (thiamethoxam, with 100.3 % increase for amplitude). Among these compounds, DIPP increased circadian period length and amplitude with a high degree. Aside from DIPP, we further examined eleven other phthalates and demonstrated that benzyl butyl phthalate, diisobutyl phthalate and diisohexyl phthalate could also significantly increase the zebrafish circadian period length by 7.9 %, 3.7 % and 8.5 %, respectively. Collectively, the present findings substantiated the feasibility of this high throughput screening strategy for circadian disruptor's discovery and provided novel insights into understanding of the potential risks of synthetic substances.
昼夜节律使大多数动物的许多生物功能保持同步。除了众所周知的外部因素，如光-暗周期和温度，昼夜节律也可以通过很少被探索的因素来调节，如合成物质。在这里，我们建立了一种利用斑马鱼幼虫模型的昼夜节律行为筛选方法，该方法将高通量能力与自动化批量处理相结合。通过这种方法，我们系统地分析了 >60 种在水生环境中经常检测到的合成物质对昼夜节律的破坏作用，评估了昼夜节律行为的昼夜节律周期长度和幅度，暴露浓度设定为 100μg/L。在测试的物质中，发现了一系列具有昼夜节律破坏作用的化合物（昼夜节律破坏剂）。可以识别出几类命中化合物，如邻苯二甲酸酯（邻苯二甲酸二异戊酯（DIPP），分别使昼夜节律周期长度和幅度增加 10.1%和 49.6%）、神经活性物质（米氮平，分别增加 10.6%和 63.1%）和杀生物剂（噻虫嗪，幅度增加 100.3%）。在这些化合物中，DIPP 使昼夜节律周期长度和幅度增加的程度较高。除了 DIPP，我们还进一步研究了其他 11 种邻苯二甲酸酯，结果表明，邻苯二甲酸苄基丁酯、邻苯二甲酸二异丁酯和邻苯二甲酸二异辛酯也分别显著增加了斑马鱼昼夜节律周期长度 7.9%、3.7%和 8.5%。总的来说，这些发现证实了这种高通量筛选策略发现昼夜节律破坏剂的可行性，并为了解合成物质的潜在风险提供了新的见解。
