Decoding the role of phthalate plasticizers (DBP, DOP, and DEHP) in idiopathic pulmonary fibrosis: an integrated network toxicology and machine learning approach.

The molecular mechanism of idiopathic pulmonary fibrosis (IPF) caused by phthalate (PAE) is not well understood, presenting notable clinical and toxicological challenges. This research seeks to advance drug toxicology and formulate targeted prevention and treatment strategies by examining the impact of three PAEs (DBP, DOP, DEHP) on IPF. Using databases such as PubChem, Encyclopedia of Traditional Chinese Medicine 2.0 (ETCM2.0), PharmMapper, and GEO, we identified 15 potential targets related to exposure to the three PAEs and IPF. Further refinement through the STRING database and Cytoscape (version 3.10.3) software highlighted 10 core targets. Functional enrichment through the Enrichr platform emphasized that the Toll-like receptor signaling pathway and the IL-17 signaling pathway are key mediators in plasticizer-induced IPF. Through machine learning, three core targets were ultimately selected. Molecular docking confirmed strong binding between the three PAEs and the core targets. Overall, this research offers significant insights into the molecular mechanisms underlying plasticizer-induced IPF and underscores the value of network toxicology in evaluating the toxicity of emerging environmental pollutants. It enhances our understanding of the health risks associated with PAEs and presents novel strategies to mitigate their impact on fibrotic diseases.