PUBLICATION
Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)
- Authors
- Zhuang, S., Zhang, Z., Zhang, W., Bao, L., Xu, C., Zhang, H.
- ID
- ZDB-PUB-141230-17
- Date
- 2015
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 159C: 119-126 (Journal)
- Registered Authors
- Keywords
- Aquatic toxicity, Enantioselectivity, Modeling, Pyraclofos, Zebrafish
- MeSH Terms
-
- Animals
- Interleukin-1beta/genetics
- Molecular Dynamics Simulation
- Organothiophosphates/toxicity*
- Pesticides/toxicity
- Protein Binding/drug effects
- Signal Transduction/drug effects
- Stereoisomerism
- Up-Regulation/drug effects*
- Water Pollutants, Chemical/toxicity*
- Zebrafish/embryology*
- PubMed
- 25540855 Full text @ Aquat. Toxicol.
Citation
Zhuang, S., Zhang, Z., Zhang, W., Bao, L., Xu, C., Zhang, H. (2015) Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio). Aquatic toxicology (Amsterdam, Netherlands). 159C:119-126.
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 3.99mg/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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping