ZFIN ID: ZDB-PUB-200610-9
Exposure to the AhR agonist cyprodinil impacts the cardiac development and function of zebrafish larvae
Tang, C., Shen, C., Zhu, K., Zhou, Y., Chuang, Y.J., He, C., Zuo, Z.
Date: 2020
Source: Ecotoxicology and environmental safety   201: 110808 (Journal)
Registered Authors: Chuang, Yung-Jen, He, Chengyong
Keywords: AhR activity prediction, Aryl hydrocarbon receptor, Cyprodinil, Development toxicity, Zebrafish (Danio rerio)
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/metabolism*
  • Cytochrome P-450 CYP1A1/genetics
  • Cytochrome P-450 CYP1A1/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Fungicides, Industrial/metabolism
  • Heart/drug effects
  • Heart/embryology
  • Hep G2 Cells
  • Humans
  • Larva/drug effects*
  • Larva/genetics
  • Larva/metabolism
  • Molecular Docking Simulation
  • Organogenesis/drug effects
  • Organogenesis/genetics
  • Protein Binding
  • Pyrimidines/toxicity*
  • Receptors, Aryl Hydrocarbon/agonists*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 32516676 Full text @ Ecotoxicol. Environ. Saf.
ABSTRACT
Cyprodinil is a broad-spectrum pyrimidine amine fungicide that has been reportedly used worldwide. However, toxicity studies of cyprodinil on aquatic organisms, specifically zebrafish (Danio rerio), are lacking. In our present study, we predicted cyprodinil binding to the aryl hydrocarbon receptor (AhR) by using molecular docking simulation. Then, we used recombinant HepG2 cells and Tg(cyp1a1-12DRE:egfp) transgenic zebrafish to further assess the AhR agonistic activity of cyprodinil. Besides, the significant upregulation of cyp1a1 further verified that statement. Moreover, we found that zebrafish exposure to cyprodinil induced developmental toxicity in the larvae, particularly during cardiac development. The expression levels of cardiac development-related genes, namely tbx5, nkx2.5, gata4, and tnnt2, were markedly altered, which might cause the adverse effects of cyprodinil on cardiac function and development. In summary, we found that cyprodinil, as an AhR agonist, induced development toxicity in zebrafish larvae, especially on cardiac. Data here can assess the potential effects on organisms in the aquatic environment and promote the regulation and safe use of cyprodinil.
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