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.