Loratadine disrupts cardiovascular and swim bladder development in zebrafish

The widespread presence of antihistamines such as loratadine in aquatic environments poses emerging ecotoxicological concerns, yet their developmental impacts remain poorly characterized. In this study, zebrafish embryos were exposed to loratadine (35–350 μg/L) to evaluate its developmental effects. By 2–3 days post-fertilization (dpf), exposed larvae exhibited marked cardiac defects, including pericardial edema, reduced heart rate and cardiac output, and fractional area change ( p  < 0.05). By 4–6 dpf, a complete failure of swim bladder inflation was observed in the exposed group, confirmed by histological analysis showing significantly reduced bladder area ( p  < 0.0001). Behavioral assays revealed impaired locomotion, with decreased total distance and swimming speed ( p  < 0.001). Molecular analyses showed that loratadine significantly altered the expression of cardiac genes ( acta1b , atp2a2a , gata4 , hand2 , tbx5a ) and suppressed key regulators of swim bladder development ( fgf10a , smo , gli2a , fzd2 , fzd5 , wnt2bb ) ( p  < 0.05), ultimately resulting in abnormal cardiac and swim bladder development. These findings highlight the pronounced ecotoxicological impact of loratadine on aquatic vertebrates and reinforce the urgent need for improved environmental surveillance and wastewater remediation strategies to curb pharmaceutical contamination in freshwater ecosystems.