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: Shulin Zhuang, Zhisheng Zhang, Wenjing Zhang, Lingling Bao, Chao Xu, Hu Zhang
• Journal: Aquatic toxicology (Amsterdam, Netherlands) (Aquat Toxicol) Vol. 159 Pg. 119-26 (Feb 2015) ISSN: 1879-1514 [Electronic] Netherlands
• PMID: 25540855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-1beta
• Organothiophosphates
• Pesticides
• Water Pollutants, Chemical
• pyraclofos

Topics

• 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)