Effective analysis of thyroid toxicity and mechanisms of acetyltributyl citrate using network toxicology, molecular docking and machine learning strategies.

The growing prevalence of environmental pollutants has raised concerns about their potential role in thyroid dysfunction and related disorders. Previous research suggests that various chemicals, including plasticizers like acetyl tributyl citrate (ATBC), may adversely affect thyroid health, yet the precise mechanisms remain poorly understood. The objective of this study was to elucidate the complex effects of acetyl tributyl citrate (ATBC) on the thyroid gland and to clarify the potential molecular mechanisms by which environmental pollutants influence the disease process. Through an exhaustive exploration of databases such as ChEMBL, STITCH, and GEO, we identified a comprehensive list of 19 potential targets closely associated with ATBC and the thyroid gland. After rigorous screening using the STRING platform and Cytoscape software, we narrowed this list to 15 candidate targets, ultimately identifying five core targets: CBX5, HADHB, TRIM33, TP53, and CUL4A, utilizing three well-established machine learning methods. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses conducted in the DAVID database revealed that the primary pathways through which ATBC affects the thyroid gland involve key signaling cascades, including the FoxO signaling pathway and metabolic pathways such as fatty acid metabolism. Furthermore, molecular docking simulations using Molecular Operating Environment software confirmed strong binding interactions between ATBC and these core targets, enhancing our understanding of their interactions. Overall, our findings provide a theoretical framework for comprehending the intricate molecular mechanisms underlying ATBC's effects on thyroid damage and pave the way for the development of preventive and therapeutic strategies against thyroid disorders caused by exposure to ATBC-containing plastics or overexposure to ATBC.