Dicofol induces developmental cardiotoxicity in zebrafish embryos through oxidative stress mechanisms.

Dicofol (DCF), a widely used organochlorine acaricide, has raised global concerns due to its persistence, bioaccumulation, and toxicity. Although banned in many developed countries, DCF is still used in some regions, posing ecological and health risks. Here, we investigated the developmental cardiotoxicity of DCF in zebrafish embryos and its underlying mechanisms. DCF exposure caused ventricular reduction, atrial enlargement, pericardial edema, intracardiac blood congestion, reduced heart rate, and an increased sinus venosus-bulbus arteriosus (SV-BA) distance. These defects were associated with altered expression of cardiac development genes, indicating disrupted transcriptional regulation. Transcriptomic analysis revealed that DCF disrupts mitochondrial oxidative phosphorylation, leading to reduced ATP production and excessive reactive oxygen species (ROS) generation. Impaired antioxidant defenses further destabilized cardiac developmental gene networks and promoted cardiomyocyte injury and apoptosis. Biochemical assays confirmed elevated ROS levels, lipid peroxidation, and reduced antioxidant enzyme activity, while acridine orange staining demonstrated increased cardiomyocyte apoptosis. Notably, co-treatment with astaxanthin (ASTA) effectively mitigated DCF-induced cardiac defects, restored gene expression, and reduced oxidative damage. These findings identify oxidative stress as a key mediator of DCF-induced cardiotoxicity and demonstrate the potential of natural antioxidants in alleviating pesticide toxicity. This study offers mechanistic insights into the developmental hazards of legacy organochlorine pesticides and emphasizes the need for stricter environmental regulation and safer alternatives.