State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; State Key Laboratory for Conservation and Utilization of Bio-Resources, School of Life Sciences, Center for Life Sciences, Yunnan University, Kunming 650091, China.
J Hazard Mater. 2021 May 5;409:124999. doi: 10.1016/j.jhazmat.2020.124999. Epub 2020 Dec 30.
Organophosphorus flame retardants (OPFRs) have been implicated as neurotoxicants, but their potential neurotoxicity and mechanisms remain poorly understood. Herein, we investigated the neurotoxicity of selected OPFRs using zebrafish as a model organism. Environmentally relevant concentrations (3-1500 nM) of three classes of OPFRs (aryl-OPFRs, chlorinated-OPFRs, and alkyl-OPFRs) were tested in zebrafish larvae (2-144 h post-fertilisation) alongside the neurotoxic chemical chlorpyrifos (CPF) that inhibits acetylcholinesterase (AChE). Exposure to aryl-OPFRs and CPF inhibited AChE activities, while chlorinated- and alkyl-OPFRs did not inhibit these enzymes. Biolayer interferometry (BLI) was used to probe interactions between OPFRs and AChE. The association and dissociation response curves showed that, like CPF, all three selected aryl-OPFRs, triphenyl phosphate (TPHP), tricresyl phosphate (TCP) and cresyl diphenyl phosphate (CDP), bound directly to AChE. The affinity constant (K) for TPHP, TCP, CDP and CPF was 2.18 × 10, 5.47 × 10, 1.05 × 10 and 1.70 × 10 M, respectively. In addition, molecular docking revealed that TPHP, TCP, CDP and CPF bound to AChE with glide scores of - 7.8, - 8.3, - 8.1 and - 7.3, respectively. Furthermore, the calculated binding affinity between OPFRs and AChE correlated well with the K values measured by BLI. The present study revealed that aryl-OPFRs can act as potent AChE inhibitors, and may therefore present a significant ecological risk to aquatic organisms.
有机磷阻燃剂 (OPFRs) 已被认为具有神经毒性，但它们的潜在神经毒性和机制仍知之甚少。在此，我们使用斑马鱼作为模型生物研究了选定的 OPFR 的神经毒性。在斑马鱼幼虫（受精后 2-144 小时）中测试了 3 类 OPFRs（芳基-OPFRs、氯化-OPFRs 和烷基-OPFRs）和神经毒性化学物质毒死蜱（CPF）的环境相关浓度（3-1500 nM），CPF 抑制乙酰胆碱酯酶 (AChE)。芳基-OPFRs 和 CPF 的暴露抑制了 AChE 活性，而氯化和烷基-OPFRs 则没有抑制这些酶。生物层干涉法 (BLI) 用于探测 OPFRs 和 AChE 之间的相互作用。结合和解离响应曲线表明，与 CPF 一样，所有 3 种选定的芳基-OPFRs，三苯基磷酸酯 (TPHP)、磷酸三邻甲苯酯 (TCP) 和磷酸二苯异辛酯 (CDP)，都直接与 AChE 结合。TPHP、TCP、CDP 和 CPF 的亲和力常数 (K) 分别为 2.18×10、5.47×10、1.05×10 和 1.70×10 M。此外，分子对接表明 TPHP、TCP、CDP 和 CPF 与 AChE 的结合的滑行分数分别为-7.8、-8.3、-8.1 和-7.3。此外，OPFRs 和 AChE 之间的计算结合亲和力与 BLI 测量的 K 值很好地相关。本研究表明，芳基-OPFRs 可以作为有效的 AChE 抑制剂，因此可能对水生生物构成重大生态风险。
