PUBLICATION

Mepanipyrim induces cardiotoxicity of zebrafish (Danio rerio) larvae via promoting AhR-regulated COX expression pathway

Authors
Shen, C., He, J., Zhu, K., Zheng, N., Yu, Y., He, C., Yang, C., Zuo, Z.
ID
ZDB-PUB-221115-79
Date
2023
Source
Journal of environmental sciences (China)   125: 650-661 (Journal)
Registered Authors
He, Chengyong
Keywords
AhR agonist, CH223191, Cardiotoxicity, Cytochrome coxidase, Mepanipyrim, Zebrafish (Danio rerio)
MeSH Terms
  • Animals
  • Cardiotoxicity*/metabolism
  • Electron Transport Complex IV/metabolism
  • Embryo, Nonmammalian
  • Larva
  • Pesticides*/toxicity
  • Receptors, Aryl Hydrocarbon/metabolism
  • Water Pollutants, Chemical*/toxicity
  • Zebrafish/metabolism
PubMed
36375947 Full text @ J. Environ. Sci. (China).
CTD
36375947
Abstract
The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish (Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the mRNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase (COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae. Additionally, the AhR antagonist CH223191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping