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

Abstract

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 [¹²⁵ I]T₄ clearance in both strains of mice administrated with [¹²⁵ I]T₄ , and the promotion of serum [¹²⁵ I]T₄ clearance in WT mice occurred without inhibition of the [¹²⁵ I]T₄ -TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [¹²⁵ I]T₄ , hepatic accumulation level of [¹²⁵ I]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.

Keywords: Kanechlor-500; TTR-deficient mice; UDP-glucuronosyltransferase; polychlorinated biphenyl; thyroxine; transthyretin.