A possible mechanism for 2,2 ',4,4 ',5,5 '-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

作者：Kato Yoshihisa^*; Onishi Mao; Haraguchi Koichi; Ikushiro Shinichi; Ohta Chiho; Koga Nobuyuki; Endo Tetsuya; Yamada Shizuo; Degawa Masakuni

来源：Toxicology and Applied Pharmacology, 2011, 254(1): 48-55.

DOI：10.1016/j.taap.2011.04.020

• 2,2 ',4,4 ',5,5 '-Hexachlorobiphenyl
• UDP-glucuronosyltransferase
• Thyroxine
• Mice

Serum total thyroxine (T(4)) level was markedly decreased, without significant increases in the levels of hepatic T(4)-UDP-glucuronosyltransferase (T(4)-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100 mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [(125)I]T(4) to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [(125)I]T(4) and [(125)I]T(4)-glucuronide at 90-120 min after injection of [(125)I]T(4) slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [(125)I]T(4), liver-selective increases in the [(125)I[T(4) accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [(125)I]T(4) in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [(125)I]T(4) dosed, respectively. The present findings indicated that the C8153-mediated decreases in the level of serum total T(4) in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T(4) in the liver.

• 出版日期2011-7-1