title: Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio).
abstract: 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.
authors.affiliation: 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. Electronic address: shulin@zju.edu.cn.
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lingling
authors.initials: L
authors.lastname: Bao
authors.affiliation: Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, PR China. Electronic address: chaoxu@zjut.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 210021, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D053583:Interleukin-1beta / Q000235:genetics; D056004:Molecular Dynamics Simulation; D063086:Organothiophosphates / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D015854:Up-Regulation / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D053583:Interleukin-1beta; D063086:Organothiophosphates; D010575:Pesticides; D014874:Water Pollutants, Chemical; C069547:pyraclofos
keywords: Aquatic toxicity; Enantioselectivity; Modeling; Pyraclofos; Zebrafish