caa a22 4500 445852798 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-010-0613-x doi (NATIONALLICENCE)springer-10.1007/s00204-010-0613-x Perfluorooctane sulfonate increased hepatic expression of OAPT2 and MRP2 in rats [Elektronische Daten] [Wen-Guang Yu, Wei Liu, Li Liu, Yi-He Jin] The toxicity of perfluorooctane sulfonate (PFOS), a persistent organic compound, is of great concern. Several studies have reported that PFOS decreases circulating thyroid hormone (TH) concentrations. However, the mechanisms involved remain to be determined. Female rats were exposed to (1) vehicle; (2) PFOS (0.2, 1.0, and 3.0mg/kg); (3) propylthiouracil (PTU, 10mg/kg); or (4) PTU (10mg/kg)+PFOS (3.0mg/kg) by gavage once a day for 5 consecutive days. Parameters including contents of total T4 (TT4) and total T3 (TT3) in both serum and bile, serum concentrations of transthyretin and thyroglobulin, as well as transcripts of transporters involved in hepatic uptake and efflux of T4 were determined in control and PFOS-exposed groups. TT4 and TT3 were also analyzed in PTU and PTU+PFOS groups in order to reflect the different hormone effects between PFOS, PTU, and PFOS+PTU. Results showed that serum TT4 and TT3 decreased, while bile TT4 and TT3 remained stable following PFOS exposure. Exposure to 3.0mg/kg of PFOS significantly enhanced hepatic organic anion transporter OATP2 mRNA expression (1.43 times of control). Treatment with PFOS increased hepatic expression of multidrug resistance-associated protein MRP2, approximately 1.80 and 1.69 times of control in 1.0 and 3.0mg/kg groups, respectively. Spearman's correlation coefficients revealed that MRP2 mRNA expression correlated well with serum TT4 level (r=−0.528, P=0.012). Serum thyroglobulin and transthyretin levels remained stable. Serum TT3, bile TT4, and bile TT3 were significantly different between PFOS and PTU groups. No significant differences of TT4 and TT3 in both serum and bile were observed between PTU and PTU+PFOS (P>0.05). In conclusion, PFOS increased hepatic expression of OAPT2, which could possibly enhance hepatic uptake and metabolism of T4 in rats. PFOS-induced TT4 deficiency is mainly due to the extrathyroidal metabolism of T4, which is probably different from the classic goitrogen, PTU. Springer-Verlag, 2010 Perfluorooctane sulfonate nationallicence Wistar rat nationallicence Thyroid hormone nationallicence Organic anion transporters 1 and 2 nationallicence Multidrug resistance-associated protein 2 nationallicence Propylthiouracil nationallicence Yu Wen-Guang Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut Liu Wei Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut Liu Li Division of Hygienic Toxicology, School of Public Health, China Medical University, North 2 Road 92, 110001, Shenyang, Liaoning, China aut Jin Yi-He Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 613-621 0340-5761 85:6<613 2011 85 204 https://doi.org/10.1007/s00204-010-0613-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0613-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yu Wen-Guang Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut NATIONALLICENCE 700 1- Liu Wei Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut NATIONALLICENCE 700 1- Liu Li Division of Hygienic Toxicology, School of Public Health, China Medical University, North 2 Road 92, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Jin Yi-He Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, 116024, Dalian, People's Republic of China aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 613-621 0340-5761 85:6<613 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer