Simple Summary
Perfluorooctane sulfonate (PFOS) and polystyrene (PS) microplastics pose significant threats to environmental health due to their persistence and bioaccumulation. Co-exposure to these substances may induce synergistic multi-organ toxicity through complex mechanisms, necessitating advanced toxicological methods for risk assessment. This study employed network toxicology techniques through the following steps: Multi-organ toxicity study: Demonstrating that the co-exposure of PFOS and PS can cause varying degrees of liver, kidney, and intestinal damage through reduced antioxidant capacity. Target identification: Extracting potential functional targets of PFOS and PS from the CTD and GeneCards databases, followed by Venn analysis to identify overlapping targets. Protein interaction network analysis: Identifying hub genes (e.g., TNF, TP53, etc.) using STRING databse (https://cn.string-db.org/) and Cytoscape (Version 3.9.1) software. Molecular docking: Verifying the binding energy and interaction sites of PFOS/PS with liver damage-associated proteins (e.g., TNF, IL6, IL1B) through AutoDock Vina (Version 1.1.2) and PyMOL (Version 3.1). Conclusion: Network toxicology reveals novel pathways (e.g., inflammatory–cell death crosstalk) in PFOS/PS co-exposure, providing predictive tools for risk stratification.
Abstract
Perfluorooctane sulfonate (PFOS) has been widely utilized in products such as cotton textiles, hydraulic oils, coatings, pharmaceuticals, cosmetics, etc. Now it is widely distributed in various environmental media, wildlife, and human bodies. Polystyrene (PS) as a kind of plastics, their products under the physical, chemical, and biological decomposition in the environment are widely distributed in the air, soil, oceans, surface water, and sediments. However, PS and PFOS often coexist in the environment, making the study of their combined exposure mechanisms more aligned with actual conditions. This research integrates network toxicology and molecular biology techniques to predict the toxicity and common differentially expressed gene enrichment pathways of PFOS and PS. This study investigates the toxic effects of combined exposure to PFOS and PS on the mouse growth and development, immune functions, and other aspects. Additionally, it delves into the expression differences in various genes in mice after stimulation by PFOS and PS, the pathological changes in multiple organs, and the toxic effects on organs such as the liver, kidneys, and intestines. The results reveal that combined exposure to PFOS and PS does not significantly damage the kidney but leads to morphological damage in the liver and intestinal tissues, reduced antioxidant capacity, and the occurrence of inflammation. Based on the network toxicology findings, it is hypothesized that during combined exposure to PFOS and PS, the exacerbation of inflammatory responses further mediates the reduction in antioxidant capacity and the intensification of oxidative stress, ultimately resulting in tissue damage. This study provides innovative theoretical and research directions for the detection and prevention of combined exposure to PFOS and PS, offering a new paradigm for toxicological research, with significant theoretical and practical implications.