Avermectin induces developmental toxicity and immunotoxicity in zebrafish larvae

Avermectin has been widely used in agriculture and animal husbandry for decades, and its associated environmental problems have raised increasing concerns regarding its safety. This study investigated the developmental and immunotoxicity of avermectin in zebrafish larvae and its underlying mechanisms. The results showed that exposure to 0.15-0.60 μg/mL avermectin for 72 h induced developmental malformations in zebrafish larvae, including decreased heart rate, spinal curvature, and edema. It also significantly reduced the numbers of immune cells such as neutrophils, T cells, and macrophages. At the molecular level, avermectin upregulated the levels of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β, IL-6), and activated the TLR4/MyD88/NF-κB inflammatory signaling pathway. Transcriptomic analysis identified 1085 differentially expressed genes, and KEGG enrichment analysis suggested that signaling pathways such as the complement and coagulation cascades, IL-17 signaling pathway, and Toll-like receptor signaling pathway may collectively mediate the immunotoxicity. In conclusion, avermectin causes multiple toxic injuries in zebrafish larvae by triggering excessive inflammatory responses and immunosuppression.