Integration of network toxicology and bioinformatics identifies key targets and pathways in 1,3-butadiene-induced nephrotoxicity

1,3-Butadiene (1,3-BD) is a gaseous environmental pollutant classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). While its carcinogenic effects are well-known, the molecular mechanisms underlying its nephrotoxicity remain unclear. This study utilizes network toxicology and bioinformatics to explore the targets and mechanisms of 1,3-BD-induced nephrotoxicity. Key targets such as BCL2, CASP3, MMP9, SIRT1, and TNF were identified as central mediators of renal toxicity. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses highlighted processes related to oxidative stress, signaling, and apoptosis. Molecular docking, molecular dynamics simulations, and CETSA further confirmed the interactions between 1,3-BD and these targets. Additionally, using the TCGA database, we found that these targets have diagnostic and prognostic significance in renal cancer. Our findings suggest that BCL2, CASP3, MMP9, SIRT1, and TNF may play crucial roles in both nephrotoxicity and renal cancer progression, offering new insights into the molecular mechanisms of 1,3-BD-induced renal injury and potential intervention targets.