A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies

Takashi Yamada, Ryuichi Hasegawa, Satoshi Nishikawa, Yuki Sakuratani, Jun Yamada, Tatsuhiro Yamashita, Koichi Yoshinari, Yasushi Yamazoe, Eiichi Kamata, Atsushi Ono, Akihiko Hirose, Makoto Hayashi

Research output: Contribution to journalLetter

3 Citations (Scopus)

Abstract

Hypothyroidism induced by xenobiotic treatment was analyzed for possible underlying mechanism(s) on the basis of different responses of the thyroid gland and the liver, using a newly-created database of repeated-dose toxicity of 500 chemicals. Two mechanisms are proposed: direct inhibition of thyroid hormone biosynthesis in the thyroid gland, and stimulated degradation of thyroid hormone by induction of hepatic drug-metabolizing enzymes. In the database there were 10 chemicals inducing hypertrophy/ hyperplasia of follicular cells in the thyroid gland and having data on thyroid glands. On the basis of the chemical structure and information available in the literature, we judged three chemicals to be typical thioamide derivatives that act directly on the thyroid gland, and the others as non-thioamide derivatives that were unlikely to have any direct action on the thyroid gland. All these chemicals were classified into two groups using the ratios of relative weight increase rate of thyroid gland versus that of the liver. These values were at least 1.7, but 3.2 or more in the most of the cases for thioamide derivatives, and 1.2 or less for non-thioamide derivatives. This background analysis suggests the feasibility of parametersupported speculation on the possible underlying mechanism when new repeated-dose toxicity data on hypothyroidism becomes available.

Original languageEnglish
Pages (from-to)291-299
Number of pages9
JournalJournal of Toxicological Sciences
Volume38
Issue number2
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Hypothyroidism
Toxicity
Thyroid Gland
Thioamides
Derivatives
Thyroid Hormones
Liver
Biosynthesis
Xenobiotics
Databases
Degradation
Hypertrophy
Enzymes
Hyperplasia
Pharmaceutical Preparations
Weights and Measures

Keywords

  • Follicular cells
  • Hepatomegaly
  • Hyperplasia
  • Hypertrophy
  • Hypothyroidism mechanism
  • Relative organ weights

ASJC Scopus subject areas

  • Toxicology

Cite this

A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies. / Yamada, Takashi; Hasegawa, Ryuichi; Nishikawa, Satoshi; Sakuratani, Yuki; Yamada, Jun; Yamashita, Tatsuhiro; Yoshinari, Koichi; Yamazoe, Yasushi; Kamata, Eiichi; Ono, Atsushi; Hirose, Akihiko; Hayashi, Makoto.

In: Journal of Toxicological Sciences, Vol. 38, No. 2, 2013, p. 291-299.

Research output: Contribution to journalLetter

Yamada, T, Hasegawa, R, Nishikawa, S, Sakuratani, Y, Yamada, J, Yamashita, T, Yoshinari, K, Yamazoe, Y, Kamata, E, Ono, A, Hirose, A & Hayashi, M 2013, 'A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies', Journal of Toxicological Sciences, vol. 38, no. 2, pp. 291-299. https://doi.org/10.2131/jts.38.291
Yamada, Takashi ; Hasegawa, Ryuichi ; Nishikawa, Satoshi ; Sakuratani, Yuki ; Yamada, Jun ; Yamashita, Tatsuhiro ; Yoshinari, Koichi ; Yamazoe, Yasushi ; Kamata, Eiichi ; Ono, Atsushi ; Hirose, Akihiko ; Hayashi, Makoto. / A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies. In: Journal of Toxicological Sciences. 2013 ; Vol. 38, No. 2. pp. 291-299.
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