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 (T 4 ) and hepatic T 4 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 4 levels were significantly decreased in both WT and TTR‐null mice. The KC500 pretreatment also promoted serum [ 125 I]T 4 clearance in both strains of mice administrated with [ 125 I]T 4 , and the promotion of serum [ 125 I]T 4 clearance in WT mice occurred without inhibition of the [ 125 I]T 4 ‐TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady‐state distribution volume of [ 125 I]T 4 , hepatic accumulation level of [ 125 I]T 4 , 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 4 level occurs in a TTR‐unrelated manner and further suggest that KC500‐promoted T 4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T 4 transportation from serum to liver.