Kanechlor 500‐mediated changes in serum and hepatic thyroxine levels primarily occur in a transthyretin‐unrelated manner

The effects of Kanechlor‐500 (KC500) on the levels of serum total thyroxine (T4) and hepatic T4 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 T4 levels were significantly decreased in both WT and TTR‐null mice. The KC500 pretreatment also promoted serum [125I]T4 clearance in both strains of mice administrated with [125I]T4, and the promotion of serum [125I]T4 clearance in WT mice occurred without inhibition of the [125I]T4‐TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady‐state distribution volume of [125I]T4, hepatic accumulation level of [125I]T4, and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500‐mediated decrease in serum T4 level occurs in a TTR‐unrelated manner and further suggest that KC500‐promoted T4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T4 transportation from serum to liver. In both wild‐type C57BL/6 (WT) and its transthyretin (TTR)‐null mice, treatment with Kanechlor‐500 (KC500) resulted in a significant decrease in serum total thyroxine (T4) level and led to promotion of hepatic accumulation of T4. Furthermore, no significant inhibition of [125I]T4‐TTR complex formation by KC500 was observed in WT mice. The present findings indicate that the KC500‐mediated decrease in serum T4 level primarily occurs in a TTR‐unrelated manner and further demonstrates the KC500‐mediated promotion of T4 accumulation in the liver.