Study on the mechanism of thyroid toxicity induced by perfluorooctanesulfonic acid(PFOS)and perfluorooctanoic acid(PFOA)based on the integration of toxicological databases and adverse outcome pathway(AOP)analysis
Thyroid disorders are a common endocrine system disease,potentially influenced by perfluorinated and polyfluorinated substances(PFAS).This study employs the Adverse Outcome Pathway(AOP)framework to explore the potential mechanisms by which perfluorooctanesulfonic acid(PFOS)and perfluorooctanoic acid(PFOA)affect thyroid function.By integrating data from the Comparative Toxicogenomics Database(CTD),GeneCards,DisGeNET,MalaCards,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG),a network model linking PFOS/PFOA,genes,phenotypes,and thyroid disease was established.Identifying tumor necrosis factor-alpha(TNF-α)as the Molecular Initiating Event(MIE),this research demonstrates how PFOS and PFOA can elevate TNF-α levels,thereby disrupting thyroid hormone metabolic pathways,and inducing inflammation,oxidative stress,and alterations in lipid and glucose metabolism—key events(KEs)that lead to the adverse outcome of thyroid dysfunction.These findings The discovery of this AOP network provides a basis for understanding how PFASs contribute to human health by inducing inflammatory responses,oxidative stress,and affecting thyroid hormone,lipid,and glucose metabolism,which are of significant relevance for public health policy formulation.
万方数据
维普
