Analyzing the potential targets and mechanisms of chronic kidney disease induced by common synthetic Endocrine Disrupting Compounds (EDCs) in Chinese surface water environment using network toxicology and molecular docking techniques

Abstract

Long-term exposure to NP and OP, as common synthetic endocrine-disrupting chemicals (EDCs) in surface water environments in China, is closely associated with the development of chronic kidney disease (CKD). However, their potential targets and toxicological mechanisms for inducing CKD remain unknown. This study utilizes network toxicology and molecular docking techniques to explore the potential toxic targets and molecular mechanisms of CKD induction by NP and OP. We identify 49 core targets of NP and OP action in CKD using the Comparative Toxicogenomics Database (CTD) and GeneCards databases. Using the STRING database and Cytoscape software, we identify five hub genes: MAPK3, TNF, BCL2, ESR1, and FOS. We construct a nomogram model based on the CKD dataset GSE66494, utilizing these five hub genes. Calibration and ROC curves demonstrate that the model has good diagnostic value for CKD, and the DCA curve indicates that the model has high clinical utility. Single-gene GSEA enrichment analysis identifies five hub genes that influence the development of CKD through multiple biological pathways, revealing that several immune-regulatory signaling pathways are activated. The CIBERSORT algorithm identifies eight types of immune cell infiltration levels that change significantly during CKD development, and correlation analyses suggest that the five hub genes are strongly associated with multiple immune cell infiltrations. The molecular docking results suggested that ESR1, MAPK3, and TNF had the lowest binding energies and high binding affinities with NP and OP. The results of molecular dynamics simulations similarly confirmed the stability of the interactions between ESR1, MAPK3 and TNF proteins with NP and OP. The results of this study provide a theoretical basis for understanding the potential toxicity targets and mechanisms of NP- and OP-induced CKD and promote the application of network toxicology and molecular docking techniques in the study of environmental pollutants.

Keywords: Chronic kidney disease; Molecular docking; Network toxicology; Nonylphenol; Octylphenol.