Toxicological Sciences, Vol 47, 170-175, Copyright © 1999 by Society of Toxicology
T Tamura, K Mitsumori, H Onodera, N Fujimoto, K Yasuhara, K Takegawa and M Takahashi
In order to elucidate the mechanisms of reduction of serum thyroid hormones
caused by continuous administration of kojic acid (KA) and its thyroid
tumor-promotion effects, male F344 rats were given pulverized basal diet
containing 0.008%, 0.03%, 0.125%, 0.5%, or 2% KA for 4 weeks. As an
untreated control group, additional rats were given basal diet alone for
the same period. The thyroid 125I uptake was significantly decreased in the
groups receiving 0.03% or more. In addition, significant reduction of
organic formation of iodine and serum T3 and T4 levels were observed in the
2% KA group along with pronounced elevation of serum (TSH). Both absolute
and relative thyroid weights were significantly increased in the groups
receiving 0.5% of KA or more. Histopathologically, decreased colloid in the
thyroid follicles and follicular cell hypertrophy in the thyroid were
apparent at high incidences in the groups given 0.03% or more. In addition,
thyroid capsular fibrosis was evident in all rats of the 2% KA group. In
quantitative morphometrical analysis, the ratio of the area of follicular
epithelial cells to the area of colloids was significantly increased in the
groups given 0.03% KA or more. The results suggest that KA alteration of
thyroid-related hormone levels in the 2% KA group are due to inhibition of
iodide uptake and iodine organification in the thyroid, with
tumor-promoting effects on development of thyroid proliferative lesions,
probably secondary to prolonged serum TSH stimulation resulting from
negative feedback through the pituitary- thyroid axis.
ARTICLES
Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
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