Effect of dietary antioxidants on excretion of perfluorooctanoic acid (PFOA) via regulating uptake transporters expression and intestinal permeability in mice

Ruirui Zhang; Xin Li; Zhaoxin Su; Fangyuan Ning; Yuxue Gao

doi:10.1016/j.ecoenv.2023.115224

Effect of dietary antioxidants on excretion of perfluorooctanoic acid (PFOA) via regulating uptake transporters expression and intestinal permeability in mice

Ecotoxicol Environ Saf. 2023 Jul 4:262:115224. doi: 10.1016/j.ecoenv.2023.115224. Online ahead of print.

Authors

Ruirui Zhang¹, Xin Li², Zhaoxin Su², Fangyuan Ning², Yuxue Gao²

Affiliations

¹ Jinan Environmental Research Academy, Jinan 250100, China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China. Electronic address: zhangruirui@ucas.ac.cn.
² Jinan Environmental Research Academy, Jinan 250100, China.

PMID: 37413964
DOI: 10.1016/j.ecoenv.2023.115224

Abstract

Dietary antioxidants, including 2,6-di-tert-butyl-hydroxytoluene (BHT), α-tocopherol (αT) and tea polyphenol (TP), have been widely used in food. However, no data about the effect of food antioxidants on PFOA excretion were available. In this study, excretion of PFOA toward mice (four mice in each group) under the influence of co-ingested food antioxidants (i.e., BHT, αT, and TP) were investigated, and mechanism involved in excretion of PFOA, including RNA expression of uptake and efflux transporters in kidneys and liver involved in PFOA transport and intestinal permeability were also investigated. Chronic exposure to BHT (1.56 mg/kg) increased urinary PFOA excretion from 1795 ± 340 ng/mL (control) to 3340 ± 29.9 ng/mL (BHT treatment). TP treatment (12.5 mg/kg) decreased urinary excretion of PFOA, i.e., with a decrease percentage of 70% compared to the control. Organic anion transporting polypeptides (Oatps) act as uptake transporter mediate renal elimination or reabsorption of PFOA in the kidney. The decrease in urinary excretion of PFOA under TP treatment was associated with significantly (p < 0.05) enhanced expression of Oatp1a1 in the kidney (1.78 ± 0.58 vs 1.00 ± 0.18 in control), which facilitated renal reabsorption of PFOA and in turn decreased urinary excretion of PFOA. αT treatment (12.5 mg/kg) increased fecal PFOA excretion with a value of 228 ± 95.8 ng/g vs control (96.8 ± 22.7 ng/g). Mechanistic investigation revealed that αT treatment reduced intestinal permeability, resulting in increased fecal PFOA excretion.

Keywords: Antioxidants; Excretion; Intestinal permeability; Organic anion transporting polypeptides; Perfluorooctanoic acid.