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Research ArticleArticle

THE DECREASE IN LEVEL OF SERUM THYROXINE BY 2,2′,4,5,5′-PENTACHLOROBIPHENYL IN RATS AND MICE: NO CORRELATION WITH FORMATION OF METHYLSULFONYL METABOLITES

Yoshihisa Kato, Koichi Haraguchi, Tomoaki Yamazaki, Ryohei Kimura, Nobuyuki Koga, Shizuo Yamada and Masakuni Degawa
Drug Metabolism and Disposition November 2005, 33 (11) 1661-1665; DOI: https://doi.org/10.1124/dmd.105.006189
Yoshihisa Kato
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Koichi Haraguchi
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Tomoaki Yamazaki
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Ryohei Kimura
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Nobuyuki Koga
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Shizuo Yamada
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Masakuni Degawa
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Abstract

A relationship between formation of methylsulfonyl (MeSO2) metabolites of 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4) level was examined in the rats and mice after a single i.p. injection of PentaCB (342 μmol/kg body weight). In either rats or mice, levels of the 3- and 4-MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent fashion up to 8 days after PentaCB-treatment. However, there was a marked difference between rats and mice in the amount of the metabolites formed, and the cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB treatment in the liver was 4 to 15 times higher in mice than in rats. On the other hand, a 40 to 60% decrease in level of serum total T4 occurred in both rats and mice at 1 day after PentaCB treatment, and the decrease was retained up to 8 days after PentaCB treatment. Thus, there was a marked difference between rats and mice in the formation of MeSO2 metabolites from PentaCB but not a significant difference between rats and mice in PentaCB-induced decrease in the level of serum total T4, indicating that PentaCB-induced decrease in the level of serum total T4 is not necessarily dependent on the MeSO2 metabolites formed.

Footnotes

  • This work was supported in part by a Grant-in-Aid for Scientific Research (C) (no. 15510058, Y.K.; no. 16590101, K.H.; no. 17590104, M.D.) from Japan Society for the Promotion of Science, by a Health Sciences Research Grant for Research on Environmental Health (H11-Seikatsu-024, M.D.) from the Ministry of Health and Welfare of Japan, and by a Health and Labour Sciences Research Grants for Risk Analysis Research on Food and Pharmaceuticals (H13-Seikatsu-013, Y.K.) from Ministry of Health, Labour and Welfare of Japan.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.105.006189.

  • ABBREVIATIONS: PCB, polychlorinated biphenyl; MeSO2, methylsulfonyl; PentaCB, 2,2′,4,5,5′-pentachlorobiphenyl; T4, thyroxine; TSH, thyroid-stimulating hormone; UDP-GT, UDP-glucuronosyltransferase; AUC, area under the curve.

    • Received June 22, 2005.
    • Accepted August 18, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 33 (11)
Drug Metabolism and Disposition
Vol. 33, Issue 11
1 Nov 2005
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THE DECREASE IN LEVEL OF SERUM THYROXINE BY 2,2′,4,5,5′-PENTACHLOROBIPHENYL IN RATS AND MICE: NO CORRELATION WITH FORMATION OF METHYLSULFONYL METABOLITES
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Research ArticleArticle

THE DECREASE IN LEVEL OF SERUM THYROXINE BY 2,2′,4,5,5′-PENTACHLOROBIPHENYL IN RATS AND MICE: NO CORRELATION WITH FORMATION OF METHYLSULFONYL METABOLITES

Yoshihisa Kato, Koichi Haraguchi, Tomoaki Yamazaki, Ryohei Kimura, Nobuyuki Koga, Shizuo Yamada and Masakuni Degawa
Drug Metabolism and Disposition November 1, 2005, 33 (11) 1661-1665; DOI: https://doi.org/10.1124/dmd.105.006189

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Research ArticleArticle

THE DECREASE IN LEVEL OF SERUM THYROXINE BY 2,2′,4,5,5′-PENTACHLOROBIPHENYL IN RATS AND MICE: NO CORRELATION WITH FORMATION OF METHYLSULFONYL METABOLITES

Yoshihisa Kato, Koichi Haraguchi, Tomoaki Yamazaki, Ryohei Kimura, Nobuyuki Koga, Shizuo Yamada and Masakuni Degawa
Drug Metabolism and Disposition November 1, 2005, 33 (11) 1661-1665; DOI: https://doi.org/10.1124/dmd.105.006189
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