The ligand-docking approach explores the binding affinity of PFOS and PFOA for major endogenous antioxidants: A potential mechanism to fuel oxidative stress

Per- and polyfluoroalkyl substances (PFAS) are emerging environmental contaminants having worldwide distribution. These compounds impose toxic impacts on organisms by impairing redox homeostasis. However, their mode of mechanism is still vague. Hence, the present study aims to explore the potential intermolecular interactions between endogenous antioxidant enzymes and two common PFAS, viz. perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Five endogenous antioxidant enzymes, namely glutathione peroxidase-4 (GPx4), Glutathione-S-Transferase (GST), Catalase (CAT), Glutathione Reductase (GR), and Superoxide dismutase-1 (SOD1) engaged in maintaining redox homeostasis were selected for this study. The present in silico study was performed through molecular docking analysis using the AutoDock algorithm. In addition, intermolecular interactions were studied using Digital Studio Visualizer. Results indicated that PFOS and PFOA interacted with ligand-binding pockets of antioxidant enzymes with stable hydrogen bonds. Non-polar hydrophobic interactions, including the van der Waals, further strengthened such bindings. Therefore, these results suggest that both PFOS and PFOA can disrupt redox homeostasis by blocking the amino acid residues at catalytic sites of intrinsic antioxidant enzymes through multiple non-covalent interactions. Results of the present study also open the scope for scientists to confirm these intermolecular interactions through in-vivo/ex-vivo studies.