Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra- and pentachlorinated biphenyls in male Sprague-Dawley rats

被引:30
作者
Kato, Y
Haraguchi, K
Shibahara, T
Yumoto, S
Masuda, Y
Kimura, R
机构
[1] Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka 4228526, Japan
[2] Daiichi Coll Pharmaceut Sci, Minami Ku, Fukuoka 8158511, Japan
关键词
methylsulfonoyl (MeSO2) metabolites; polychlorinated biphenyls (PCBs); total thyroxine (T4); thyroid stimulating hormone (TSH); rats;
D O I
10.1093/toxsci/48.1.51
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Male Sprague-Dawley rats received four consecutive intraperitoneal (ip) doses of five kinds of methylsulfonyl (MeSO2) metabolites of tetra- and pentachlorinated biphenyls (tetra- and pentaCBs) to determine their effects on thyroid hormone levels. The five MeSO2 metabolites, which were the major MeSO2-PCBs detected in human milk, liver and adipose tissue were 3-MeSO2-2,2',4',5-tetraCB (3-MeSO2-CB49), 3-MeSO2-2,3',4',5-tetraCB (3MeSO(2)-CB70), 3-MeSO2-2,2',3',4',5-pentaCB (3-MeSO2-CB87), 3-MeSO2-2,2',4',5,5'-pentaCB (3-MeSO2-CB101), and 4-MeSO2-2,2',4',5,5'-pentaCB (4-MeSO2-CB101). All five tested MeSO2 metabolites (20 mu mol/kg once daily for 4 days) reduced serum total thyroxine levels 16-40% on days 2, 3, 4, and 7 (after the last dosage). The total triiodothyronine level was reduced 37% by treatment with 3-MeSO2-CB49 at day 7, but was increased 35% and 38% by 3-MeSO2-CB70 and 4-MeSO2-CB101 at days 3 and 4, respectively. The reductions in thyroid hormone levels led to an increase in thyroid stimulating hormone (TSH) levels by 3-MeSO2-CB49, 3-MeSO2-CB87 and 3-MeSO2-CB101. A 30% increase in thyroid weight was produced by 3-MeSO2-CB101 treatment. Thus, it is likely that all five tested MeSO2 metabolites could influence thyroid hormone metabolism. The results show that the tested 3- and 4-MeSO2 metabolites of tetra- and pentaCBs reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.
引用
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页码:51 / 54
页数:4
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