The effect of phenobarbital on the metabolism and excretion of thyroxine in rats
The effect of phenobarbital on thyroid function and the metabolism and biliary excretion of thyroxine in rats was determined. Phenobarbital, administered for 2 weeks at a dose of 100 mg/kg/day, resulted in an increase in hepatic and thyroid gland weights, decreased circulating levels of T4, T3 and rT3, and increased TSH levels in male and female rats. After 3 months of treatment liver and thyroid weights were still increased; however, hormone values were not as markedly affected indicating that the rats had partially compensated for the effect on thyroid function. In thyroidectomized rats the plasma clearance of thyroxine was increased with phenobarbital. In bile duct cannulated phenobarbital-treated male rats the hepatic uptake at 4 hr was markedly increased. Bile flow was increased and the 4-hr cumulative biliary excretion of administered radioactivity was increased by 42%. Most of the increase in the excretion (76%) was accounted for by an increase in the excretion of thyroxine-glucuronide in phenobarbital-treated rats. Hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats expressed as picomoles per milligram of protein was increased by 40%; enzyme activity per gram of liver was increased by about twofold which, coupled with increased hepatic weight, resulted in about a threefold increase in total hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats as compared to that of controls. Qualitatively similar effects on metabolism, excretion, and enzyme induction were noted in female rats; however, the magnitude of increase was less than that observed in male rats. It is concluded that the effect of phenobarbital on thyroid function in rats is primarily a result of its effects on the hepatic disposition of thyroid hormone.
- Research Organization:
- Hoffmann-LaRoche, Inc., Nutley, NJ (USA)
- OSTI ID:
- 5933706
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 99:2; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
Similar Records
A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents
Effect of acute administration of cadmium on the disposition of copper, zinc, and iron in the rat
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AZINES
BARBITURATES
BILE
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYMES
EXCRETION
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYPNOTICS AND SEDATIVES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIVER
MAMMALS
MATERIALS
MEDICINE
METABOLISM
MICROSOMES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDE HORMONES
PHENOBARBITAL
PYRIMIDINES
RATS
RIBOSOMES
RODENTS
SURGERY
THYROID
THYROID HORMONES
THYROIDECTOMY
THYROXINE
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES