Uptake of perfluorooctanoate in freshly isolated hepatocytes from male and female rats

Abstract

Liver is a primary target organ for perfluorooctanoate (PFO, the deprotonated form of perfluorooctanoic acid, PFOA) distribution in both male and female rats. We studied the uptake of PFO in freshly isolated hepatocytes from male and female rats. We identified a non-saturable cell partitioning process for PFO using on-ice incubations. At 37 °C, hepatic uptake of PFO was composed of the non-saturable partition as well as a saturable, active uptake process. The K m and V max values for the active uptake process were 88.0 ± 9.1 μM and 5.61 ± 0.88 nmol/(min 10 6 cells), respectively, for male rat hepatocytes, and 76.1 ± 12.0 μM and 3.59 ± 0.29 nmol/(min 10 6 cells), respectively, for female rat hepatocytes. The values of PFO clearance by active uptake were 64.8 ± 15.7 and 47.6 ± 4.7 μL/(min 10 6 cells) for male and female rat hepatocytes, respectively. The active uptake of PFO in rat hepatocytes was inhibited by sulfobromophthalein, a known substrate of organic anion transporting polypeptides, with apparent inhibition constants of 85.9 ± 25.1 and 29.3 ± 19.2 μM in male and female rat hepatocytes, respectively. When serum albumin was added to the incubations, PFO hepatic uptake rates were reduced, but were proportional to the unbound fractions of PFO.