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

Journal Article · Tue Dec 14 23:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.09.024· OSTI ID:21529108

Kato, Yoshihisa ^[1]; Suzuki, Hiroshi ^[2]; Haraguchi, Koichi ^[3]; Ikushiro, Shinichi ^[4]; Ito, Yoshihiko; Uchida, Shinya; Yamada, Shizuo; Degawa, Masakuni ^[2]

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1. Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa 769-2193 (Japan)
2. School of Pharmaceutical Sciences and Global Center of Excellence Program, University of Shizuoka, Shizuoka 422-8526 (Japan)
3. Daiichi College of Pharmaceutical Sciences, Fukuoka 815-8511 (Japan)
4. Faculty of Engineering, Toyama Prefectural University, Toyama 939-0398 (Japan)

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.

• OSTI ID: 21529108
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 249; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AZINES
BARBITURATES
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
GUINEA PIGS
HAMSTERS
HETEROCYCLIC COMPOUNDS
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
HORMONES
HYPNOTICS AND SEDATIVES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MALES
MAMMALS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHENOBARBITAL
PITUITARY HORMONES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RATS
RODENTS
SEPARATION PROCESSES
THYROID HORMONES
THYROXINE
TRIIODOTHYRONINE
TSH
VERTEBRATES