Exploring potential targets and mechanisms of PCB52-induced cardiotoxicity: Integration of network toxicology and zebrafish experimental evidence

作者：Linhao Zong, Xiaoyang Lu, Yuxin Yang, Jing Zhao, Ziqi Tang, Dake Cao, Linxia Sun, Miao Guan, Shixia Xu · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.118531 · 被引用次数：5 · 研究领域：Computational Drug Discovery Methods、Mitochondrial Function and Pathology、Cardiac electrophysiology and arrhythmias

2,2',5,5'-Tetrachlorobiphenyl (PCB52) exhibits high environmental mobility and bioaccumulation potential. Studies have associated elevated levels of serum PCB52 with an increased risk of cardiac diseases, yet the underlying mechanisms of its cardiotoxicity remain inadequately investigated. In this study, potential PCB52 targets and cardiotoxicity-related targets were retrieved from multiple online databases, and 150 potential targets of PCB52-induced cardiotoxicity were obtained. Protein-protein interaction (PPI) network was constructed for the potential targets. Twelve hub genes (STAT1, FN1, TP53, CCL2, ACE, PARP1, NFKB1, MTOR, HDAC2, RELA, ATM, and APP) were identified from the network using 7 algorithms from cytoHubba plugin in Cytoscape. Molecular docking was employed to validate the interactions between PCB52 and hub targets. Enrichment analysis focusing on the hub genes indicated oxidative stress, apoptosis, nuclear factor kappa-B (NF-κB) activation, and inflammatory pathways were primary processes involved. Following exposure to three concentrations of PCB52 (10, 200, and 1000 μg/L), zebrafish exhibited pericardial edema (PE), with the highest incidence of 16.4 % observed at the highest concentration. Additionally, zebrafish experiments revealed a dose-dependent increase in sinus venosus (SV)-bulbus arteriosus (BA) distance and superoxide dismutase (SOD) activity, along with a decrease in heart rate. Furthermore, dose-dependent transcriptomic analyses emphasized the si...