An efficient analysis of the toxicity and mechanisms of butyryl acetylcitrate-induced erectile dysfunction based on network toxicology and molecular docking strategies

The aim of this study is to investigate the potential molecular mechanisms underlying the induction of erectile dysfunction toxicity by Acetyl Tributyl Citrate through the application of network toxicology and molecular docking techniques. Potential targets associated with ATBC were identified using the ChEMBL and SwissTargetPrediction databases, while potential targets related to ED were explored through Genecards, OMIM, and TTD databases. A cross-gene target network diagram for ATBC-ED was constructed using Cytoscape 3.7.2 software, and relevant targets were imported into the STRING database to establish a protein-protein interaction network. Comprehensive analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways for these intersecting genes were performed utilizing DAVID database and microbioinformatics software. Among these pathways, we selected five core genes—EP300, EZH2, HDAC1, HDAC2, and SMARCA4—for molecular docking studies with Autodock. Ultimately, we identified 59 potential targets associated with ATBC exposure and ED. Subsequent optimization using STRING and Cytoscape software highlighted the top 20 core targets including EP300, EZH2, HDAC1, HDAC2, and SMARCA4. The core targets induced by ATBC in relation to ED are primarily enriched in processes involving chromatin remodeling; negative regulation of RNA polymerase II transcription; nuclear-cytoplasmic transport; chromatin binding; as well as thyroid hormone signaling pathway interactions. Molecular docking confirmed a high binding affinity between ATBC and these core targets. In summary, these findings suggest that ATBC may induce erectile dysfunction by modulating chromatin remodeling processes along with negative regulation of RNA polymerase II transcription as well as thyroid hormone signaling pathways.