Effective exploration of the toxicity and molecular mechanisms of plasticisers in pulmonary fibrosis by network toxicology and molecular docking strategies: an example of butylbenzyl phthalate

Corresponding author: TENG Jingjing, tjj@ahcdc.com.cn

DOI: 10.12201/bmr.202504.00004

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  Abstract: Background: Butylbenzyl phthalate (BBP) is a widely used plasticiser that is environmentally persistent due to its remarkable resistance to degradation. Recent studies have confirmed the correlation between BBP exposure and the development of reduced lung function and pulmonary fibrosis. This persistent disease is characterised by a high mortality rate and a lack of effective treatments, making it necessary to explore the mechanisms of its toxic effects.Methods: In this study, we used network toxicology combined with molecular docking technology to screen the targets of BBP and those related to pulmonary fibrosis through PubChem, GeneCards and other databases, and analysed the intersecting genes by using a Wayne diagram. Protein-protein interaction (PPI) networks were constructed to screen the core targets, and the pathway mechanisms were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking using AutoDock was performed to verify the binding patterns of the core targets and BBPs.Results: A total of 91 potential targets of BBP-induced pulmonary fibrosis were screened, among which PTGS2, CYP3A4 and TRPV1 were the core targets (binding energies of -1.84, -1.68 and 0.56 kcal/mol, respectively). Enrichment analysis showed that BBP regulated fibrosis progression through G protein-coupled receptor signalling pathway, calcium signalling pathway and cAMP signalling pathway. Molecular docking confirmed that BBP was stably bound to the core target through hydrogen bonding and hydrophobic interaction.Conclusion: This study is the first to reveal the molecular mechanism of BBP-induced lung fibrosis through network toxicology, clarifying the key roles of PTGS2 and CYP3A4 and the signalling pathway network, and providing a theoretical basis for targeted therapy and drug development. This study provides a new methodological reference for the exploration of the mechanism of the association between environmental toxicants and diseases.

  Key words: Butyl benzyl phthalate; Pulmonary fibrosis; Network toxicology; Molecular docking

  Submit time: 2 April 2025

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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