title: Stereoselective induction of developmental toxicity and immunotoxicity by acetochlor in the early life stage of zebrafish.
abstract: Acetochlor (ACT) has been frequently detected in the aquatic environment and implicated in disruption of the immune system in fish, the mechanisms of which, especially at enantiomeric levels, remains unclear. In the present study, embryonic zebrafish were exposed to ACT and its enantiomers at concentrations of 0, 2, 8, 15, 30 and 60 μM from 2 h post-fertilization (hpf) to 72 hpf. We demonstrated that ACT and its enantiomers could cause time- and concentration-dependent mortality (72 h LC50ranged from 48.4 to 53.1 μM) and developmental malformations (e.g., 48 h EC50for yolk sac edema ranged from 36.7 to 54.1 μM), as well as increase transcription of the key genes involved in the innate immune system. A consistent enantioselectivity in these endpoints was observed with (-)-R-ACT showed stronger effects than (+)-S-ACT, and the transcription levels of il-1β exhibited significant enantioselectivity at concentrations as low as 8 μM. Further Western blot analysis revealed that significant elevations of Il-1β protein expression in all (-)-R-ACT treatment groups. According to the molecular docking and molecular dynamics simulations, the enantioselectivity between ACT enantiomers was attributed to the distinct binding affinity to Il-1β. Overall, our in vivo and in silico studies uniquely disclosed the enantioselective immunotoxicity of ACT and its underlying mechanisms and highlighted the need to evaluate the environmental risk of chiral chloroacetamide herbicide in aquatic organisms at enantiomeric levels.
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China; Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China. Electronic address: twq0228@163.com.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tu
authors.affiliation: Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China; Key Laboratory of Poyang Lake of Ministry of Education, Nanchang University, Nanchang 330031, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Deng
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Chunmian
authors.initials: C
authors.lastname: Lin
authors.affiliation: Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000276:immunology; D006540:Herbicides / Q000737:chemistry / Q000633:toxicity*; D053583:Interleukin-1beta / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013237:Stereoisomerism; D014052:Toluidines / Q000737:chemistry / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities / Q000196:embryology
chemical_list: D006540:Herbicides; D053583:Interleukin-1beta; D014052:Toluidines; D014874:Water Pollutants, Chemical; C043377:acetochlor
keywords: Acetochlor; Developmental toxicity; Enantioselectivity; Innate immune system; Molecular modeling