The adverse effects of paromomycin on early cardiovascular development in zebrafish (Danio rerio)

Paromomycin, a broad-spectrum aminoglycoside antibiotic, is widely used in both clinical and agricultural fields. However, its environmental impact and potential developmental toxicity have raised growing concerns. This study systematically evaluates the adverse effects of paromomycin on early cardiovascular development in zebrafish embryos from multiple biological perspectives. Zebrafish embryos were exposed to environmental concentrations of paromomycin (0, 0.3, 3, 30, and 300 μg/mL) for 5 days. Comprehensive assessments were then performed through morphological observations, cardiovascular phenotype analysis, behavioral evaluations, and integrated analysis. The results revealed that exposure to paromomycin induced dose dependent developmental damage, including decreased survival rates, delayed hatching, and increased malformation rates. Detailed cardiovascular assessments confirmed significant abnormalities in both cardiac function and vascular development. Molecular level investigations further elucidated the underlying mechanisms, showing that paromomycin exposure elevated reactive oxygen species levels, triggering oxidative stress, inducing apoptosis in the pericardial region, and disrupting the expression of key cardiovascular developmental genes. Integrating network toxicology, molecular docking, and transcriptomic analyses, this study identified six key signaling pathways involved in paromomycin induced cardiovascular toxicity. These findings provide a comprehensive mechanistic framework for understanding the developmental cardiovascular toxicity of paromomycin at environmentally relevant concentrations and offer valuable insights for the safe application and risk management of this widely used antibiotic.