PUBLICATION
Stereoselective induction of developmental toxicity and immunotoxicity by acetochlor in the early life stage of zebrafish
- Authors
- Xu, C., Tu, W., Deng, M., Jin, Y., Lu, B., Zhang, C., Lin, C., Wu, Y., Liu, W.
- ID
- ZDB-PUB-160917-1
- Date
- 2016
- Source
- Chemosphere 164: 618-626 (Journal)
- Registered Authors
- Keywords
- Acetochlor, Developmental toxicity, Enantioselectivity, Innate immune system, Molecular modeling
- MeSH Terms
-
- Animals
- Blotting, Western
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/immunology
- Herbicides/chemistry
- Herbicides/toxicity*
- Interleukin-1beta/metabolism
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- Protein Binding
- Stereoisomerism
- Toluidines/chemistry
- Toluidines/toxicity*
- Water Pollutants, Chemical/chemistry
- Water Pollutants, Chemical/toxicity*
- Zebrafish*/abnormalities
- Zebrafish*/embryology
- PubMed
- 27635644 Full text @ Chemosphere
Citation
Xu, C., Tu, W., Deng, M., Jin, Y., Lu, B., Zhang, C., Lin, C., Wu, Y., Liu, W. (2016) Stereoselective induction of developmental toxicity and immunotoxicity by acetochlor in the early life stage of zebrafish. Chemosphere. 164:618-626.
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 LC50 ranged from 48.4 to 53.1 μM) and developmental malformations (e.g., 48 h EC50 for 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping