Henan International Joint Laboratory of Aquatic Toxicology and Health Protection, College of Life Science, Henan Normal University, Xinxiang, 453007, China.
Henan International Joint Laboratory of Aquatic Toxicology and Health Protection, College of Life Science, Henan Normal University, Xinxiang, 453007, China.
Chemosphere. 2023 Sep;334:138944. doi: 10.1016/j.chemosphere.2023.138944. Epub 2023 May 19.
Resorcinol bis(diphenyl phosphate) (RDP), an emerging organophosphorus flame retardant and alternative to triphenyl phosphate (TPHP), is a widespread environmental pollutant. The neurotoxicity of RDP has attracted much attention, as RDP exhibits a similar structure to TPHP, a neurotoxin. In this study, the neurotoxicity of RDP was investigated by using a zebrafish (Danio rerio) model. Zebrafish embryos were exposed to RDP (0, 0.3, 3, 90, 300 and 900 nM) from 2 to 144 h postfertilization. After this exposure, the decreased heart rates and body lengths and the increased malformation rates were observed. RDP exposure significantly reduced the locomotor behavior under light-dark transition stimulation and the flash stimulus response of larvae. Molecular docking results showed that RDP could bind to the active site of zebrafish AChE and that RDP and AChE exhibit potent binding affinity. RDP exposure also significantly inhibited AChE activity in larvae. The content of neurotransmitters (γ-aminobutyric, glutamate, acetylcholine, choline and epinephrine) was altered after RDP exposure. Key genes (α1-tubulin, mbp, syn2a, gfap, shhα, manf, neurogenin, gap-43 and ache) as well as proteins (α1-tubulin and syn2a) related to the development of the central nervous system (CNS) were downregulated. Taken together, our results showed that RDP can affect different parameters related to CNS development, eventually leading to neurotoxicity. This study indicated that more attention should be paid to the toxicity and environmental risk of emerging organophosphorus flame retardants.
间苯二酚双（二苯基磷酸酯）（RDP）是一种新兴的有机磷阻燃剂，也是磷酸三苯酯（TPHP）的替代品，它是一种广泛存在的环境污染物。RDP 的神经毒性引起了广泛关注，因为它的结构与神经毒素 TPHP 相似。在这项研究中，使用斑马鱼（Danio rerio）模型研究了 RDP 的神经毒性。斑马鱼胚胎从受精后 2 到 144 小时暴露于 RDP（0、0.3、3、90、300 和 900 nM）中。暴露后，观察到心率和体长降低以及畸形率增加。RDP 暴露显著降低了光暗转换刺激下幼鱼的运动行为和闪光刺激反应。分子对接结果表明，RDP 可以与斑马鱼 AChE 的活性位点结合，并且 RDP 和 AChE 具有很强的结合亲和力。RDP 暴露还显著抑制了幼鱼 AChE 的活性。暴露于 RDP 后，神经递质（γ-氨基丁酸、谷氨酸、乙酰胆碱、胆碱和肾上腺素）的含量发生改变。与中枢神经系统（CNS）发育相关的关键基因（α1-微管蛋白、mbp、syn2a、gfap、shhα、manf、neurogenin、gap-43 和 ache）以及蛋白质（α1-微管蛋白和 syn2a）的表达下调。总之，我们的研究结果表明，RDP 可以影响与中枢神经系统发育相关的不同参数，最终导致神经毒性。本研究表明，应更加关注新兴有机磷阻燃剂的毒性和环境风险。
