A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

作者：Kato Yoshihisa^*; Suzuki Hiroshi; Haraguchi Koichi; Ikushiro Shinichi; Ito Yoshihiko; Uchida Shinya; Yamada Shizuo; Degawa Masakuni

来源：Toxicology and Applied Pharmacology, 2010, 249(3): 238-246.

DOI：10.1016/j.taap.2010.09.024

• Phenobarbital
• UDP glucuronosyltransferase
• Thyroxine
• Rodent

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T(4)) and triodothyronine were examined in male mice hamsters rats and guinea pigs One day after the final administration of PB (80 mg/kg intrapentoneal once daily for 4 days) significant decreases in the levels of the serum total T(4) and free T(4) occurred in mice hamsters and rats while a significant decrease in the level of serum triodothyronine was observed in hamsters and rats among the animals examined In addition a significant decrease in the level of serum thyroid stimulating hormone was observed in only hamsters among the rodents examined Significant increases in the level and activity of hepatic T(4) UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice hamsters and rats while the increase in the amount of Mary [(125)I]T(4)-glucuromde after an intravenous injection of [(125)I]T(4) to the PB-pretreated animals occurred only in rats In mice rats and hamsters but not guinea pigs PB pretreatment promoted the clearance of [(125)I]T(4) from the serum led to a significant increase in the steady state distribution volumes of [(125)I]T(4) and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [(125)I]T(4) The present findings indicate that the PB-mediated d

• 出版日期2010-12-15