PUBLICATION

Famoxadone-cymoxanil induced cardiotoxicity in zebrafish embryos

Authors
Huang, Y., Chen, Z., Meng, Y., Wei, Y., Xu, Z., Ma, J., Zhong, K., Cao, Z., Liao, X., Lu, H.
ID
ZDB-PUB-201002-125
Date
2020
Source
Ecotoxicology and environmental safety   205: 111339 (Journal)
Registered Authors
Lu, Huiqiang
Keywords
Calcium signaling pathway, Cardiotoxicity, Famoxadone-cymoxanil, Oxidative stress, Zebrafish
MeSH Terms
  • Acetamides/toxicity*
  • Animals
  • Apoptosis/drug effects
  • Calcium Signaling/drug effects
  • Calcium Signaling/genetics
  • Cardiotoxicity
  • Down-Regulation
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Fungicides, Industrial/toxicity*
  • Gene Expression Regulation, Developmental/drug effects
  • Heart/drug effects*
  • Heart/embryology
  • Heart Rate/drug effects
  • Kruppel-Like Transcription Factors/genetics
  • Kruppel-Like Transcription Factors/metabolism
  • Oxidative Stress/drug effects
  • Strobilurins/toxicity*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
32961491 Full text @ Ecotoxicol. Environ. Saf.
Abstract
Famoxadone-cymoxanil is a new protective and therapeutic fungicide, but little research has been done on it or its toxicity in aquatic organisms. In this study, we used zebrafish to investigate the cardiotoxicity of famoxadone-cymoxanil and the potential mechanisms involved. Zebrafish embryos were exposed to different concentrations of famoxadone-cymoxanil until 72 h post-fertilization (hpf), then changes of heart morphology in zebrafish embryos were observed. We also detected the levels of oxidative stress, myocardial-cell proliferation and apoptosis, ATPase activity, and the expression of genes related to the cardiac development and calcium-signaling pathway. After famoxadone-cymoxanil exposure, pericardial edema, cardiac linearization, and reductions in the heart rate and cardiac output positively correlated with concentration. Although myocardial-cell apoptosis was not detected, proliferation of the cells was severely reduced and ATPase activity significantly decreased, resulting in a severe deficiency in heart function. In addition, indicators of oxidative stress changed significantly after exposure of the embryos to the fungicide. To better understand the possible molecular mechanisms of cardiovascular toxicity in zebrafish, we studied the transcriptional levels of cardiac development, calcium-signaling pathways, and genes associated with myocardial contractility. The mRNA expression levels of key genes in heart development were significantly down-regulated, while the expression of genes related to the calcium-signaling pathway (ATPase [atp2a1], cardiac troponin C [tnnc1a], and calcium channel [cacna1a]) was significantly inhibited. Expression of klf2a, a major endocardial flow-responsive gene, was also significantly inhibited. Mechanistically, famoxadone-cymoxanil toxicity might be due to the downregulation of genes associated with the calcium-signaling pathway and cardiac muscle contraction. Our results found that famoxadone-cymoxanil exposure causes cardiac developmental toxicity and severe energy deficiency in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes