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Published on: June 7, 2018
Famoxadone-cymoxanil induced cardiotoxicity in zebrafish embryos
Yong Huang1, Zhiyong Chen2, Yunlong Meng1
1Center for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China; College of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China.
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.
Insights
Famoxadone-cymoxanil fungicide exposure causes heart defects and energy deficiency in zebrafish embryos by disrupting cardiac development and calcium signaling pathways.
Area of Science:
- Environmental Toxicology
- Cardiovascular Toxicology
- Developmental Biology
Background:
- Famoxadone-cymoxanil is a novel fungicide with limited research on its aquatic toxicity.
- Understanding its effects on aquatic organisms, particularly cardiac function, is crucial.
Purpose of the Study:
- To investigate the cardiotoxicity of famoxadone-cymoxanil in zebrafish embryos.
- To elucidate the underlying molecular mechanisms of this toxicity.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of famoxadone-cymoxanil.
- Assessed heart morphology, heart rate, cardiac output, oxidative stress, cell proliferation, apoptosis, ATPase activity, and gene expression.
Main Results:
- Exposure led to dose-dependent pericardial edema, cardiac linearization, reduced heart rate, and cardiac output.
- Significant reduction in myocardial cell proliferation and ATPase activity, indicating energy deficiency.
- Downregulation of key genes in cardiac development and calcium signaling pathways, including klf2a.
Conclusions:
- Famoxadone-cymoxanil induces cardiac developmental toxicity and severe energy deficiency in zebrafish.
- Mechanisms involve downregulation of calcium signaling and cardiac muscle contraction-related genes.
