An in silico insight on inhibitory potential of short-chain PFHxA and PFHxS against endogenous antioxidant enzymes

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic chemicals that are globally used in various commercial products like cloths, carpets, cookware, firefighting foams, cosmetics, electronic products, etc. Inappropriate disposal of these consumer products could lead to environmental contamination with PFAS. Nowadays short-chain PFAS are substituting the long chain PFAS due to their short half-life. However, multiple studies have suggested that short-chain PFAS such as Perfluorohexanoic acid (PFHxA) and Perfluorohexanesulfonic acid (PFHxS) modulate antioxidant enzyme activities, induce Reactive Oxygen Species production, and contribute to oxidative stress in organisms. Notably, experimental set-ups aiming to investigate the mode of action of these compounds on antioxidants are entirely lacking. Hence in the present study, a ligand-docking approach was adopted to investigate the potential intermolecular interactions between short-chain PFAS and major antioxidants such as Glutathione peroxidase-4, Glutathione reductase, Glutathione S-Transferase, Catalase, and Superoxide dismutase-1. Three-dimensional structures of proteins were processed and docked individually with PFHxA and PFHxS using the AutoDock vina.. Results indicated significant binding affinities between various antioxidant proteins and PFAS. Interestingly, non-covalent interactions such as H-bonds, van der Waals, CH bonds, halogen bonds, and alkyl/pi-alkyl were apparent at protein-ligand interface. Hence, these results suggest that both PFHxA and PFHxS may potentially interact with the endogenous antioxidants and this outcome can be detrimental to the redox homeostasis of living organisms.