Perfluorooctane sulfonate increased hepatic expression of OAPT2 and MRP2 in rats
0301 basic medicine
Fluorocarbons
Dose-Response Relationship, Drug
Organic Anion Transporters
01 natural sciences
Rats
Up-Regulation
Random Allocation
Thyroxine
03 medical and health sciences
Alkanesulfonic Acids
Antithyroid Agents
Hypothyroidism
Liver
Propylthiouracil
Animals
Bile
Triiodothyronine
ATP-Binding Cassette Transporters
Environmental Pollutants
Female
RNA, Messenger
Rats, Wistar
0105 earth and related environmental sciences
DOI:
10.1007/s00204-010-0613-x
Publication Date:
2010-11-02T15:30:41Z
AUTHORS (4)
ABSTRACT
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 3.0 mg/kg); (3) propylthiouracil (PTU, 10 mg/kg); or (4) PTU (10 mg/kg) + PFOS (3.0 mg/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 3.0 mg/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 3.0 mg/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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (40)
CITATIONS (37)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....