A study on the interactions between perfluorosulfonic acids and P-glycoprotein

Abstract

Perfluoroalkyl substances (PFAS) have received a great deal of attention due to the ubiquitous occurrence and persistence in the environment, resistance to degradation, and biological accumulation in wildlife and humans. PFAS are being detected around the globe, raising concerns regarding the toxicity and health risks to humans. Studies have shown that environmental toxicants, including PFAS, can interact with transporter proteins involved in the absorption and distribution, as well as detoxification, of drugs, xenobiotics and other toxicants. In this study, the effects of PFAS of different carbon chain lengths, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorobutane sulfonic acid (PFBS), on the activity of P-glycoprotein (P-gp) were investigated using the Caco-2 cell line model. Additionally, it was investigated whether PFOS, PFHxS and PFBS cross the Caco-2 cell monolayer. Two known P-gp substrates, quinidine and verapamil, were used to inhibit P-gp in Caco-2 cells, to examine whether PFOS, PFHxS and PFBS might be substrates of P-gp. No interaction between the tested compounds and digoxin were observed, suggesting that these individual PFAS did not modulate the activity of P-gp. Nevertheless, it was observed that PFOS, PFHxS and PFBS crossed the Caco-2 monolayer. Inhibition of P-gp by known inhibitors caused a slight decrease in the rate of PFOS and PFHxS, but not PFBS, in the apical to basolateral direction and in the basolateral to apical direction, suggesting that active uptake and efflux might be involved in the transport of PFOS, PFHxS, but not PFBS, across the Caco-2 monolayer.