The Effects on Rat Thyroid Function of an Hepatic Microsomal Enzyme Inducer

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Abstract
1 Following daily administration to male albino rats for 2 weeks, β-naphthoflavone (25 and 60 mg kg-1, i.p.) and phenobarbitone (100 mg kg-1, p.o.) produced their characteristic patterns of induction of P450-related enzyme activities. β-naphthoflavone also induced p-nitrophenol glucuronidation by 160% over controls, while phenobarbitone produced only a 45% induction of this conjugation activity.2 β-Naphthoflavone produced significant reductions in plasma thyroxine (T4) concentrations on days 4 and 16 and also decreased tri-iodothyronine (T3) on day 4. Thyroid-stimulating hormone (TSH) was significantly increased on day 16 by the higher dose of β-naphthoflavone. Thyroid weight was significantly increased at both dose levels on day 16 and liver weight was significantly increased on both days 4 and 16. No histopathological changes were seen in the liver or pituitary, but 30% of the animals showed minimal to mild follicular epithelial hypertrophy of the thyroid gland.3 Phenobarbitone had no effect on T4concentrations, but significantly decreased T3on day 4. TSH increased by 60% on day 16, but was not statistically significant compared with controls. Thyroid weight was significantly increased on day 16 and liver weight was significantly increased on days 4 and 16. Mild to moderate thyroid follicular epithelial hypertrophy and moderate hepatocyte hypertrophy occurred in all animals. No histopathological changes were seen in the pituitary.4 The early changes in T4and/or T3were probably due to increased hepatic clearance by induction of thyroxine glucuronidation with both compounds. Thyroid hypertrophy would be expected to follow as a result of activation of the hypothalamic-pituitary-thyroid axis. Data for the two compounds suggest some variation in the precise mechanism of action, which has not yet been fully elucidated.