Efficient analysis of toxicity and mechanisms of environmental pollutants with network toxicology and molecular docking strategy: Acetyl tributyl citrate as an example

Abstract

The study aims to promote network toxicology strategy to efficiently investigate the putative toxicity and underlying molecular mechanisms of environmental pollutants through an example of exploring brain injury induced by ATBC exposure. By utilizing ChEMBL, STITCH, GeneCards, and OMIM databases, we identified 213 potential targets associated with ATBC exposure and brain injury. Further refinements via STRING and Cytoscape software highlight 23 core targets, including AKT1, CASP3, and HSP90AA1. GO and KEGG pathway analysis conducted through DAVID and FUMA databases reveal that core targets of ATBC-induced brain toxicity are predominantly enriched in cancer signaling and neuroactive ligand receptor interaction pathways. Molecular docking was performed with Autodock, which confirmed robust binding between ATBC and core targets. Together, these findings suggest that ATBC may impact the occurrence and development of brain cancer and brain related inflammation, whereas pose risks for cognitive impairment and neurodegeneration, by modulating the apoptosis and proliferation of brain cancer cells, activating inflammatory signaling pathways, and regulating neuroplasticity. This research provides a theoretical basis for understanding the molecular mechanism of ATBC-induced brain toxicity, as well as establishing a foundation for the prevention and treatment of prostatic diseases associated with exposure to plastic products containing ATBC and certain ATBC-overwhelmed environments. Moreover, our network toxicology approach also expedites the elucidation of toxicity pathways for uncharacterized environmental chemicals.

Keywords: ATBC; Brain injury; Molecular docking; Network toxicology.