Stereoselective induction of developmental toxicity and immunotoxicity by acetochlor in the early life stage of zebrafish. (December 2016)

• Record Type: Journal Article
• Authors: Xu, Chao; Tu, Wenqing; Deng, Mi; Jin, Yuanxiang; Lu, Bin; Zhang, Chaonan; Lin, Chunmian; Wu, Yongming; Liu, Weiping
• Is Part Of: Chemosphere. Volume 164(2016)
• Page Start: 618
• Page End: 626
• Publication Date: 2016-12
• Subjects: Acetochlor -- Enantioselectivity -- Developmental toxicity -- Innate immune system -- Molecular modeling; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2016.09.004
• Languages: English
• ISSNs: 0045-6535

Abstract

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 μ M 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 LC50 ranged from 48.4 to 53.1 μ M) and developmental malformations ( e.g ., 48 h EC50 for yolk sac edema ranged from 36.7 to 54.1 μ M), 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 μ M. 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. Graphical abstract: Highlights: Stereoselective induction of developmental toxicity and immunotoxicity by ACT in zebrafish embryos was investigated. (-)- R -ACT showed stronger effects than (+)- S -ACT in zebrafish developmental toxicity endpoints. ACT exposure significantly increased the levels of Il-1b protein expression in all (-)- R -ACT treatment groups. Both in vivo and in silico studies uniquely disclosed the enantioselective immunotoxicity of ACT in fish.