Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, PR China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, PR China.
Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, PR China.
Aquat Toxicol. 2015 Feb;159:119-26. doi: 10.1016/j.aquatox.2014.12.006. Epub 2014 Dec 12.
Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially affects IL-1β-dependent proinflammatory signal transduction. Our in vitro and in silico studies provided a better insight into the molecular basis for aquatic toxicity and thus improved the risk assessment for pyraclofos and other chiral organophosphorus pesticides.
唑草酮是一种相对较新的有机磷农药，具有潜在的生态毒性，但它的水生毒性，特别是对映体选择性水生毒性，在很大程度上仍不清楚。本研究以斑马鱼（Danio rerio）为卓越的脊椎动物水生模式生物，评估了唑草酮对发育毒性和免疫毒性的对映体选择性差异。在 96 h 暴露后，唑草酮对映体表现出急性毒性，（R）-唑草酮和（S）-唑草酮的半数致死浓度分别为 2.23 和 3.99 mg/L。暴露于唑草酮会导致胚胎发育过程中的时间和浓度依赖性畸形，如心包水肿、卵黄囊水肿、弯曲的身体和孵化，在较高浓度下畸形的比例明显更高。低浓度唑草酮暴露引起的斑马鱼胚胎浓度依赖性免疫毒性导致免疫相关白细胞介素 1β（IL-1β）基因的 mRNA 水平显著上调。（R）-唑草酮对急性毒性、发育毒性和免疫毒性均明显高于（S）-唑草酮。分子动力学模拟表明，在原子水平上，（R）-唑草酮比（S）-唑草酮更能与 IL-1β 蛋白结合。这种对映体选择性结合主要归因于唑草酮对映体的不同结合模式及其与 IL-1β 的静电相互作用，这可能影响依赖于 IL-1β 的促炎信号转导。本研究的体外和计算研究为水生毒性的分子基础提供了更好的了解，从而提高了对唑草酮和其他手性有机磷农药的风险评估。
