Cyflumetofen disrupts the blood-brain barrier and induces neurotoxicity in zebrafish larvae

Cyflumetofen is a novel non-systemic acylacetonitrile miticide widely used in agriculture to control various harmful mites. However, its potential safety risks to the nervous system of non-target organisms require further evaluation. Cyflumetofen induces developmental toxicity in zebrafish larvae, manifested as pericardial edema, yolk sac enlargement, and reduced body length. To evaluate the impact on the nervous system, cyflumetofen was found to damage neuronal and motor neuron cells in zebrafish larvae, reduce locomotor activity, and alter brain tissue structure. Additionally, cyflumetofen induces apoptosis in zebrafish larvae and leads to oxidative stress, which may be a critical pathway contributing to neurotoxicity. Furthermore, cyflumetofen disrupts the blood-brain barrier (BBB) structure in zebrafish larvae and reduces the levels of tight junction (TJ) proteins. Molecular-level studies reveal that cyflumetofen interferes with the Wnt/β-catenin signaling pathway and upregulates the expression levels of genes associated with Parkinson's disease (PD) pathogenesis (pink1, parkin, and lrrk2).