Studies on thyroid function in rats subjected to repeated oral administration with kojic acid.
To elucidate the effects of kojic acid on thyroid function, the compound was given orally to male rats for 4 weeks at 0, 4, 15, 62.5, 250 and 1,000 mg/kg. In 1,000 mg/kg treatment of kojic acid, the rats showed a slight decrease in motility, inhibition of body weight gain, and a decrease in food consumption. An increase in thyroid weight and a morphological change, i.e., hypertrophy of epithelial cells of the thyroid gland follicles, were observed after 1 week of administration. In addition, the uptake of radioactive iodine from blood into the thyroid gland was enhanced and the TCA-precipitable radioactive iodine in the thyroid gland increased in those rats. However, the rates of the iodination in the thyroid gland did not change during the experiment period. Although serum T4 concentration was low in the rats treated with 1,000 mg/kg kojic acid, it was not observed in any changes in TSH concentration. None of these changes were found in the other groups. These observations suggest that massive administration of kojic acid may decrease blood T4 concentration and that thyroid function may be enhanced compensatorily. On the other hand, the absorption of kojic acid was rapid as manifested by the Tmax of blood concentrations of radioactivity, which was as short as 1.0 +/- 0.0 hr, and the t1/2 was 4.8 +/- 0.3 hr. Blood concentrations of radioactivity disappeared nearly completely at 24 hr after administration. This result indicates that the toxic effect observed on the thyroid gland treated with only the largest dosage of kojic acid may depend on a fast decrease following a transient increase of concentration of the compound in the blood.
Higa
Y
Y
Sansho Seiyaku Co., Ltd., Fukuoka, Japan.
Ohkubo
A
A
Kitajima
S
S
Hatori
A
A
Kariya
K
K
D000818:Animals; D007455:Iodine / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D011753:Pyrones / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors
D009183:Mycotoxins; D011753:Pyrones; D013963:Thyroid Hormones; C011890:kojic acid; D007455:Iodine