Abstract
Methyl parathion and its degradation product p-nitrophenol have become important environmental problems due to their high toxicity and persistence. In this study, the toxicological mechanism of methyl parathion and p-nitrophenol exposure increasing the risk of depression was studied through network toxicology and molecular docking methods. Based on the comprehensive analysis of PharmMapper, STITCH, SwissTargetPrediction, Similarity ensemble approach (SEA) and GeneCards databases, 35 potential targets related to methyl parathion and p-nitrophenol exposure were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the key pathways of methyl parathion and p-nitrophenol affecting depression, included insulin-like growth factor receptor signaling pathway, serotonergic synapse. Combined with protein-protein interaction (PPI) network analysis and KEGG analysis, 14 core targets of depression related to methyl parathion and p-nitrophenol were screened out. Further, the targets MAP2K1 and APP with the highest binding scores with methyl parathion and p-nitrophenol, respectively, were screened by DeepPurpose, and the common target HRAS for molecular docking was determined. The molecular docking analysis further verified that methyl parathion and p-nitrophenol may have good binding activity with HRAS. This study provides valuable insights for understanding the molecular mechanism of environmental pollutants methyl parathion and p-nitrophenol affecting depression, and provides a theoretical basis for understanding the health risks of methyl parathion and p-nitrophenol.