Dicofol induces neurotoxicity in zebrafish (Danio rerio)

Dicofol (DCF), a widely used organochlorine pesticide, is classified as a persistent organic pollutant (POP). However, its toxicological profile and the underlying mechanisms of action in vertebrates remain poorly understood. In this study, exposure of zebrafish (Danio rerio) to sublethal concentrations of DCF led to notable behavioral abnormalities in both larvae and adults, effects that were accompanied by increased apoptosis in brain tissues. Additionally, molecular docking analysis identified the α3-subunit containing Na⁺/K⁺-ATPase (ATP1A3A) as a potential target of DCF; this finding was corroborated by significant inhibition of Na⁺/K⁺-ATPase activity observed in brain tissue samples upon DCF treatment. Further investigation demonstrated elevated intracerebral calcium levels, enhanced oxidative stress, downregulation of chaperones involved in protein folding, increased protein ubiquitylation, and accumulation of phosphorylated microtubule-associated tau protein in the brains of DCF-treated adults. Transcriptomic profiling corroborated these findings, revealing activation of apoptotic pathways, dysregulation of calcium homeostasis, impairment of ROS clearance, and aberrant expression of genes related to neuronal function. In summary, our findings demonstrate that DCF exposure induces toxicity in zebrafish by disrupting multiple signaling cascades, culminating in neuronal apoptosis and neurotoxicity. These findings underscore the potential ecological risks and human health implications associated with DCF exposure. ENVIRONMENTAL IMPLICATION: Exposure to the persistent organic pollutant dicofol (DCF) induces neurotoxicity in zebrafish by disrupting multiple signaling cascades. Such disruption triggers calcium dysregulation, oxidative stress, protein misfolding, phosphorylated tau protein accumulation, and neuronal apoptosis, which are hallmarks of neurodegeneration. Given the evolutionary conservation of these toxicity mechanisms across vertebrates, DCF may pose potential ecological risks to other aquatic species, suggesting that DCF contamination in water sources could represent an unrecognized environmental risk factor for human neurological health. These findings warrant regulatory attention to this legacy pesticide.