Effects of a Six-Week Exposure to Excess Iodide on Thyroid Glands of Growing and Nongrowing Male Fischer-344 Rats

Kanno, J; Nemoto, Tetsuo; Kasuga, Tsutomu; Hayashi, Yuzo

doi:10.1177/019262339402200104

Cited by 14 publications

(3 citation statements)

References 25 publications

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“…It has also been reported that administration of excess iodide promotes thyroid tumor development in rats initiated with N -bis(2-hydroxypropyl)-nitrosamine (Kanno et al 1992). However, iodide excess alone has not been sufficient in inducing follicular cell hyperplasia and thyroid tumors in rats but more commonly causes hypothyroidism (Backer and Hollowell 2000; Kanno et al 1994). This is believed to be due partly to the escape from the Wolff-Chaikoff effect (acute inhibition of iodine organification) that is seen within days of exposure to excess iodide (Wolff and Chaikoff 1948).…”

mentioning

confidence: 99%

Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points

Glatt

Ouyang²,

Welsh³

et al. 2005

Environ Health Perspect

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Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB-and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5′-deiodinase I (5′-DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein–coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress–related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression.

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confidence: 99%

Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points

Glatt

Ouyang²,

Welsh³

et al. 2005

Environ Health Perspect

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“…Pisarev and Itoiz [15] observed that KI decreased the action of TSH and cAMP on thyroid growth and protein synthesis. On the contrary Kanno et al [16] reported that an excess of iodide induced a significant increase in thyroid weight, pituitary weight, serum TSH, and T 4 in growing rats.…”

Section: Thyroid Gland and Proliferationmentioning

confidence: 87%

Thyroid: Iodine Beyond the Thyronines

Juvenal¹,

Thomasz²,

Oglio³

et al. 2011

curr chem biol

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Although thyroid gland function is mainly under the control of pituitary TSH, other factors may also play a role in this process. Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of parameters such as thyroid proliferation and function. Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iododeltalactone (ILδ) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids can inhibit several thyroid parameters suggesting that these compounds may be the intermediates in the thyroid autoregulation process.

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“…This test measures the accumulation of 125 I in the thyroid gland (phase I), followed by measurement of thyroid: blood 125 I ratio using discharge with perchlorate (phase II). 122 –125 In phase I, compounds that inhibit 125 I uptake into the thyroid or organification of 125 I in the gland (eg, NIS and TPO inhibitors) will have lower accumulation of radiolabel in the thyroid gland, whereas compounds that alter TH levels at extrathyroidal sites (eg, by enzyme induction and enhanced T4 metabolism) generally increase the uptake of 125 I into the thyroid gland. Phase II animals are treated with perchlorate which releases unbound 125 I from the thyroid.…”

Section: Other Types Of Supporting Datamentioning

confidence: 99%

Adversity Considerations for Thyroid Follicular Cell Hypertrophy and Hyperplasia in Nonclinical Toxicity Studies: Results From the 6th ESTP International Expert Workshop

Huisinga

Bertrand²,

Chamanza

et al. 2020

Toxicol Pathol

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The European Society of Toxicologic Pathology organized an expert workshop in May 2018 to address adversity considerations related to thyroid follicular cell hypertrophy and/or hyperplasia (FCHH), which is a common finding in nonclinical toxicity studies that can have important implications for risk assessment of pharmaceuticals, food additives, and environmental chemicals. The broad goal of the workshop was to facilitate better alignment in toxicologic pathology and regulatory sciences on how to determine adversity of FCHH. Key objectives were to describe common mechanisms leading to thyroid FCHH and potential functional consequences; provide working criteria to assess adversity of FCHH in context of associated findings; and describe additional methods and experimental data that may influence adversity determinations. The workshop panel was comprised of representatives from the European Union, Japan, and the United States. Participants shared case examples illustrating issues related to adversity assessments of thyroid changes. Provided here are summary discussions, key case presentations, and panel recommendations. This information should increase consistency in the interpretation of adverse changes in the thyroid based on pathology findings in nonclinical toxicity studies, help integrate new types of biomarker data into the review process, and facilitate a more systematic approach to communicating adversity determinations in toxicology reports.

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Effects of a Six-Week Exposure to Excess Iodide on Thyroid Glands of Growing and Nongrowing Male Fischer-344 Rats

Cited by 14 publications

References 25 publications

Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points

Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points

Thyroid: Iodine Beyond the Thyronines

Adversity Considerations for Thyroid Follicular Cell Hypertrophy and Hyperplasia in Nonclinical Toxicity Studies: Results From the 6th ESTP International Expert Workshop

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