Integration of network toxicology and zebrafish models to elucidate bisphenol BP-induced cardiotoxicity.

Bisphenol BP (BPBP), a structural analog of bisphenol A (BPA), is increasingly utilized in industrial applications; however, its potential hazards to the cardiovascular system remain unexplored. This study employed an integrated strategy combining network toxicology, molecular docking, and in vivo zebrafish models to systematically elucidate the cardiovascular toxicity of BPBP. Network toxicology identified several candidate hub genes and pathways potentially associated with BPBP-induced cardiotoxicity. Molecular docking further suggested favorable predicted interactions between BPBP and selected candidate hub proteins. In vivo zebrafish experiments revealed dose-dependent cardiovascular developmental abnormalities, including cardiac looping defects, pericardial edema, and impaired cardiac function. Additionally, BPBP exposure significantly suppressed angiogenesis, resulting in compromised vascular sprouting and aberrant vessel morphogenesis. Behavioral profiling further demonstrated that BPBP-exposed larvae exhibit substantial locomotor deficits and blunted sensorimotor responsiveness. BPBP exposure was associated with altered expression of key cardiogenesis-related genes. Furthermore, BPBP exposure was associated with excessive reactive oxygen species (ROS) accumulation, redox imbalance, and enhanced apoptosis-related responses. Collectively, our findings demonstrate that BPBP induces marked cardiovascular developmental toxicity under the tested exposure conditions, raising significant concerns regarding its safety as a BPA alternative and highlighting the need for further mechanistic investigation and toxicological assessment of BPBP, particularly under environmentally relevant exposure conditions.