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DOE OSTI · 21529108

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

Kato, Yoshihisa·Suzuki, Hiroshi·Haraguchi, Koichi·Ikushiro, Shinichi·Ito, Yoshihiko·Uchida, Shinya·Yamada, Shizuo·Degawa, Masakuni
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Abstract

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine 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{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 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 [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.

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60 APPLIED LIFE SCIENCESAMINO ACIDSANESTHETICSANIMALSANTICONVULSANTSAZINESBARBITURATESBETA DECAY RADIOISOTOPESBODYCARBOXYLIC ACIDSCENTRAL NERVOUS SYSTEM AGENTSCENTRAL NERVOUS SYSTEM DEPRESSANTSCHROMATOGRAPHYDAYS LIVING RADIOISOTOPESDIGESTIVE SYSTEMDRUGSELECTRON CAPTURE RADIOISOTOPESGLANDSGUINEA PIGSHAMSTERSHETEROCYCLIC COMPOUNDSHIGH-PERFORMANCE LIQUID CHROMATOGRAPHYHORMONESHYPNOTICS AND SEDATIVESINTERMEDIATE MASS NUCLEIINTERNAL CONVERSION RADIOISOTOPESIODINE 125IODINE ISOTOPESISOTOPESLIQUID COLUMN CHROMATOGRAPHYLIVERMALESMAMMALSMICENUCLEIODD-EVEN NUCLEIORGANIC ACIDSORGANIC COMPOUNDSORGANIC HALOGEN COMPOUNDSORGANIC IODINE COMPOUNDSORGANIC NITROGEN COMPOUNDSORGANIC OXYGEN COMPOUNDSORGANSPEPTIDE HORMONESPHENOBARBITALPITUITARY HORMONESPROTEINSPYRIMIDINESRADIOISOTOPESRATSRODENTSSEPARATION PROCESSESTHYROID HORMONESTHYROXINETRIIODOTHYRONINETSHVERTEBRATES

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Kato, Yoshihisa, Suzuki, Hiroshi, Haraguchi, Koichi, Ikushiro, Shinichi, Ito, Yoshihiko, Uchida, Shinya, Yamada, Shizuo, Degawa, Masakuni. 2010-12-15. A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents. https://doi.org/10.1016/j.taap.2010.09.024

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