フタル酸ジメチルによるヒト肝毒性およびそのメカニズムの包括的分析

Dimethyl phthalate (DMP), a commonly used plasticizer, is known for its slow degradation rate and has been implicated in potential human health toxicity. Due to its central role in metabolism and detoxification, the liver is especially susceptible to damage from environmental toxins such as DMP. Potential targets of DMP and liver injury-associated targets were systematically identified using databases including CTD, SwissTargetPrediction, TargetNet, and GeneCards. An interaction network was subsequently constructed for these targets, and core clusters were extracted for further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, molecular docking was conducted to evaluate the binding affinities between DINP and the core targets. A total of 167 potential targets and 37 core targets were identified. The GO analysis indicated a broad cellular distribution of these targets, with significant involvement in immune response regulation and transcription factor activity. KEGG pathway analysis revealed the IL-17 and HIF-1 signaling pathways to be notably enriched. Molecular docking studies demonstrated strong binding of DMP to core targets SIRT1 and RELA, with binding energies of <  - 5 kcal/mol. Our findings suggest that DMP may mediate its toxic effects through the IL-17 and HIF-1 signaling pathways and by binding to core targets such as SIRT1 and RELA. This study contributes to the understanding of the molecular mechanisms underlying DMP-induced hepatotoxicity.