Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid

Tamura, Toru

doi:10.1093/toxsci/47.2.170

Cited by 18 publications

(13 citation statements)

References 29 publications

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“…In a previous study, development of thyroid adenomas was observed in B6C3F1 mice fed a diet containing 1.5 and 3%KA for 20 months (Fujimoto et al, 1998). Proliferative lesions of thyroid follicular cells were also increased in rats fed a diet containing 2 and 4%KA for 12 weeks after DHPN initiation, with marked elevation in serum TSH with decreased serum T3 and T4 apparent from weeks 1 to 12 Tamura et al, 1999b). Moreover, inhibition of iodide uptake causing serum thyroid hormone depression and diffuse follicular cell hypertrophy in the thyroid was observed in rats given 0.03%KA for 4 weeks without DHPN initiation (Tamura et al, 1999a).…”

Section: Introductionmentioning

confidence: 76%

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

et al. 2001

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In order to evaluate the threshold dose of thyroid tumor-promoting effects of KA, male F344 rats were initiated with N-bis(2-hydroxypropyl) nitrosamine (DHPN; 2000 mg/kg body wt., single s.c. injection) and, starting 1 week later, received pulverized basal diet containing 0%, 0.002%, 0.008%, 0.03%, 0.125%, 0.5% or 2%KA for 20 weeks. Five rats each in the 0%, 0.125%, 0.5% and 2%KA groups were sacrificed at week 12, and 10 rats each in all groups at week 20. As an additional experiment, three groups without DHPN initiation received basal diet, a diet containing 0.5% or 2%KA for 20 weeks. The serum T4 levels were significantly decreased in the DHPN-initiated groups given 0.125%KA or more at week 12. No significant decreases in serum T3 levels were observed in the groups treated with DHPN + KA and a significant increase was evident in the 2%KA-alone group at week 20. Some rats in the DHPN + 2%KA group at weeks 12 and 20 and the 2%KA-alone group at week 20 showed pronounced elevation of serum TSH. Thyroid weights were significantly increased in the DHPN-initiated groups receiving 0.5% and 2%KA at weeks 12 and 20 and in the 2%KA-alone group at week 20. Histopathologically, the incidences of focal thyroid follicular cell hyperplasias in the DHPN-initiated groups treated with 0.125%, 0.5% and 2%KA at week 20 were 5/10, 10/10 and 8/8 rats, respectively. At week 20, adenomas were observed in 7/10 rats in the DHPN + 0.5%KA group and 8/8 rats in the DHPN + 2%KA group, and carcinomas were observed in 6/8 rats in the DHPN + 2%KA group. In the groups without DHPN initiation, only focal follicular cell hyperplasia was observed in 1/9 rats in the 2%KA-alone group. These results suggest that the no-observed-adverse effect for the thyroid tumor-promoting effect of KA is 0.03% (15.5 mg/kg/day) under the present experimental conditions, and that KA possesses weak tumorigenic activity in rats due to continuous serum TSH stimulation by a non-genotoxic mechanism.

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Section: Introductionmentioning

confidence: 76%

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

et al. 2001

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“…As for the effect of KA on the thyroid gland, it was reported that the dietary administration of KA significantly decreased the levels of serum T3 and T4, while significantly increasing the serum TSH level and thyroid weights, and inhibiting iodine uptake and iodine organification in several studies (Hirose et al, 2001;Tamura et al, 1999;Fujimoto et al, 1999). Recently, we have also reported thyroid weight gain and a morphological change, i.e., follicular epithelial hypertrophy, observed in the thyroid of rats orally administered KA for 4 weeks (Higa et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Effects of Kojic Acid on Thyroidal Functions in Rats by Single-Dose Administration and in Cultured Rat Thyroid Cells (Frtl-5 Cells)

Higa

Ohkubo

Kitajima³

et al. 2002

J. Toxicol. Sci.

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-The effects of kojic acid (KA) on thyroidal function were studied by single-dose administration in rats and in cultured rat thyroid cells . In rats receiving a single dose of 1,000 mg/kg KA orally, the 125 I uptake from blood into the thyroid gland was significantly lower than that of the control group from 30 min to 24 hr after administration. The 125 I organification activity of the KA groups was significantly lower than control from 30 min to 6 hr after administration. However, the 125 I organification activity at 24 hr or 48 hr after administration recovered enough to be nearly comparable with the control group. In the study in FRTL-5 cells, KA inhibited iodine organification dose-dependently, but did not inhibit iodine uptake. These results suggest that the observed lower iodine uptake activity in the single-dose administration study in rats was due to the inhibition of iodine organification caused by the oral administration of KA, consequently decreasing iodine in the entire thyroid gland.Although serum T4 showed a tendency to decrease from 2 hr to 48 hr after administration of KA, serum TSH did not show any evident change associated with KA in the single-dose administration study in rats. Based on these results, it is presumed that a massive dose or long administration period might be needed to decrease serum T4 and increase serum TSH.From these results, it is presumed that KA affected thyroidal function when given at a massive dose or in a long administration period by inhibiting iodine organification in the thyroid.

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“…Organic formation of iodine was significantly decreased in the 2% KA group (Table 2). Histopathologically, decreased colloid in the follicles, and hypertrophy/diffuse hyperplasia were apparent in this group 13 . Inhibition of iodine uptake and organic iodine formation in the thyroid gland by kojic acid have also been recently reported by others 14,15 .…”

Section: Methodsmentioning

confidence: 73%

“…Kojic acid (KA), a secondary fungal metabolite produced many species of Aspergillus, Acetobacter, and Penicillium, has bacteriostatic and antioxidative potential. S i n c e i t i n h i b i t s m u s h r o o m t y r o s i n a s e a n d polyphenoloxidase, it has been used as a food additive to prevent enzymic browning of raw crabs and shrimps, and as a skin depigmenting agent in cosmetics 5 . Continuous oral treatment with kojic acid for 20 months in mice resulted in induction of thyroid adenomas in both sexes 6 .…”

Section: Introductionmentioning

confidence: 99%

Environmental Agents, Endocrine Disrupting Chemicals and Rat Thyroid Carcinogenesis

et al. 2001

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Thyroid cell proliferation caused by environmental compounds is well known to be associated promotion of carcinogenesis. For example, kojic acid, a secondary fungal metabolite, induces cell proliferation in rat thyroid follicular epithelium, and promotes thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). This was due to negative feedback through the pituitary-thyroid axis caused by inhibition of iodide uptake and iodine organification. Subcutaneous cholesterol pellets containing 17β-estradiol 3-benzoate also enhance rat thyroid carcinogenesis in ovariectomized female rats initiated with DHPN, although this was not the case with weak endocrine disrupting chemicals such as methoxychlor, atrazine and bisphenol A, which rather caused inhibition, possibly due to decrease in body weight gain. A high soybean diet enhances thyroid cell proliferation with increase in serum TSH level in synergism with a low iodine diet, presumably soybean diet primarily stimulate serum TSH release from the pituitary specifically under iodine deficiency conditions. (J Toxicol Pathol 2001; 14: 71-77)

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Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid

Cited by 18 publications

References 29 publications

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

Effects of Kojic Acid on Thyroidal Functions in Rats by Single-Dose Administration and in Cultured Rat Thyroid Cells (Frtl-5 Cells)

Environmental Agents, Endocrine Disrupting Chemicals and Rat Thyroid Carcinogenesis

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