Avermectin induces cardiac toxicity in early embryonic stage of zebrafish

Avermectin is a widely used insecticide, and it is mainly effective against animal parasites and insects. Given its extensive use in agriculture, a large amount of avermectin is accumulated in natural waters. Avermectin is a neurotoxin that affects the autonomous behavior of zebrafish and inhibits neurological responses in invertebrates via GABA-chloride channels. In this study, we used zebrafish as a model organism to explore the lethal teratogenic effects of different avermectin concentrations. We found that 50-μg/L avermectin could cause significant malformation abnormalities during the development of zebrafish heart, changes in heart rate, and significant reduction in hatching rate and body length. Transcriptome data revealed that 499 genes were upregulated and 877 genes were downregulated at 72 h post-fertilization (hpf), whereas 1805 genes were upregulated and 836 genes were downregulated at 120 hpf. According to gene ontology (GO) enrichment analysis, avermectin affected cardiac circulation and myocardial fiber development. KEGG analysis revealed that avermectin treatment significantly altered the activity of signal pathways associated with cardiac rhythm and vascular smooth muscle contraction. The main target of avermectin was identified as the heart, as it affected heart development and function by altering cardiac-related gene expression that led to a heart defect phenotype. Our findings indicate that developing zebrafish are sensitive to avermectin, which targets the heart.