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Drug Metabolism and Disposition Fast Forward
First published on August 18, 2005; DOI: 10.1124/dmd.105.006189

0090-9556/05/3311-1661-1665$20.00
DMD 33:1661-1665, 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

Yoshihisa Kato, Koichi Haraguchi, Tomoaki Yamazaki, Ryohei Kimura, Nobuyuki Koga, Shizuo Yamada, and Masakuni Degawa

School of Pharmaceutical Sciences and COE Program in the 21st Century, University of Shizuoka, Shizuoka, Japan (Y.K., T.Y., R.K., S.Y., M.D.); Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan (K.H.); and Faculty of Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan (N.K.)

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.

Address correspondence to: Dr. Yoshihisa Kato, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan. E-mail: kato{at}ys7.u-shizuoka-ken.ac.jp






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