Roles of rat renal organic anion transporters in transporting perfluorinated carboxylates with different chain lengths.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Yi M WeaverBruno Hagenbuch

Abstract

Perfluorinated carboxylates (PFCAs) are generally stable to metabolic and environmental degradation and have been found at low concentrations in environmental and biological samples. Renal clearance of PFCAs depends on chain length, species, and, in some cases, gender within species. While perfluoroheptanoate (C7) is almost completely eliminated renally in both male and female rats, renal clearance of perfluorooctanoate (C8) and perfluorononanoate (C9) is much higher in female rats. Perfluorodecanoate (C10) mainly accumulates in the liver for both genders. Therefore, we tested whether PFCAs with different chain lengths are substrates of rat renal transporters with gender-specific expression patterns. Inhibition of uptake of model substrates was measured for the basolateral organic anion transporter (Oat)1 and Oat3 and the apical Oat2, organic anion transporting polypeptide (Oatp)1a1, and Urat1 with 10microM PFCAs with chain lengths from 2 to 18 (C2-C18) carbons. Perfluorohexanoate (C6), C7, and C8 inhibited Oat1-mediated p-aminohippurate transport, with C7 being the strongest inhibitor. C8 and C9 were the strongest inhibitors for Oat3-mediated estrone-3-sulfate transport, while Oatp1a1-mediated estradiol-17beta-glucuronide upta...Continue Reading

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