Toxicology and Applied Pharmacology 2012-09-15

Comparative study on 2,2',4,5,5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice.

Yoshihisa Kato, Sekihiro Tamaki, Koichi Haraguchi, Shin-ichi Ikushiro, Masashi Sekimoto, Chiho Ohta, Tetsuya Endo, Nobuyuki Koga, Shizuo Yamada, Masakuni Degawa

Index: Toxicol. Appl. Pharmacol. 263(3) , 323-9, (2012)

Full Text: HTML

Abstract

The relationships between the changes in the levels of serum total thyroxine (T(4)), serum T(4)-transthyretin (TTR) complex, and accumulation of T(4) in tissues by 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T(4) was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T(4) level was significantly decreased along with a decrease in serum T(4)-TTR complex, and the levels of serum total T(4) in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T(4) by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [(125)I]T(4) from the serum after [(125)I]T(4)-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [(125)I]T(4) in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [(125)I]T(4) and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T(4) level occurs mainly through increase in accumulation level of T(4) in the liver and further indicate that the increased accumulation of T(4) in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T(4)-TTR complex formation.Copyright © 2012 Elsevier Inc. All rights reserved.