Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan.
School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
J Appl Toxicol. 2019 Dec;39(12):1701-1709. doi: 10.1002/jat.3895. Epub 2019 Sep 9.
The effects of Kanechlor-500 (KC500) on the levels of serum total thyroxine (T ) and hepatic T in wild-type C57BL/6 (WT) and its transthyretin (TTR)-deficient (TTR-null) mice were comparatively examined. Four days after a single intraperitoneal injection with KC500 (100 mg/kg body weight), serum total T levels were significantly decreased in both WT and TTR-null mice. The KC500 pretreatment also promoted serum [ I]T clearance in both strains of mice administrated with [ I]T , and the promotion of serum [ I]T clearance in WT mice occurred without inhibition of the [ I]T -TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [ I]T , hepatic accumulation level of [ I]T , and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500-mediated decrease in serum T level occurs in a TTR-unrelated manner and further suggest that KC500-promoted T accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T transportation from serum to liver.
本研究比较了凯恩氯 500（KC500）对野生型 C57BL/6（WT）及其转甲状腺素蛋白（TTR）缺陷（TTR-/-）小鼠血清总甲状腺素（T ）和肝 T 水平的影响。KC500（100mg/kg 体重）单次腹腔注射 4 天后，WT 和 TTR-/-小鼠的血清总 T 水平均显著降低。KC500 预处理还促进了给予 [I]T 的两种品系小鼠的血清 [I]T 清除，而 WT 小鼠中血清 [I]T 清除的促进作用并未抑制 [I]T-TTR 复合物的形成。此外，KC500 预处理导致两种品系小鼠的肝重、[I]T 的稳态分布容积、[I]T 在肝中的蓄积水平以及肝与血清的浓度比显著增加。这些发现表明，KC500 介导的血清 T 水平降低与 TTR 无关，并且进一步表明 KC500 促进 T 在肝脏中的蓄积是通过肝肥大的发展和 T 从血清向肝脏的转运的促进来实现的。
