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 [I-125]T-4 clearance in both strains of mice administrated with [I-125]T-4, and the promotion of serum [I-125]T-4 clearance in WT mice occurred without inhibition of the [I-125]T-4-TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [I-125]T-4, hepatic accumulation level of [I-125]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.