Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

6PPDQ, a rubber tire-derived environmental pollutant, exhibits significant hepatotoxicity. However, its hepatotoxic mechanisms remain insufficiently studied and systematically evaluated. This study integrated network toxicology, transcriptomics, metabolomics to investigate toxicity mechanisms. ADMETlab 3.0 was used predict physicochemical properties multiorgan toxicity. The targets related 6PPDQ liver injury were obtained from public databases, protein-protein interaction (PPI) constructed identify key targets. Meanwhile, molecular docking performed assess 6PPDQ's binding affinity core proteins. Transcriptomics differential gene expression analysis on the livers of Kunming mice exposed 4 mg/kg explore transcriptomic alterations, while metabolomic profiling identified disrupted metabolic pathways. Network toxicology results reveal that primarily induces hepatotoxicity through apoptosis, inflammation, lipid disturbances. Key targets, including P53, Mapk1, Mapk14, Casp8, Traf6, Ripk1, Tnf, are identified, with strong affinities suggesting direct interactions. Transcriptomic analyses further confirms disruptions in TNF, NF-kappa B, oxidative phosphorylation, autophagy pathways, glycerolipid metabolism. Overall, this provides comprehensive mechanistic framework for 6PPDQ-induced new perspective subsequent studies mechanism

Язык: Английский