Hepatic Transport and Bile Secretion: Physiology and Pathophysiology

Abstract

Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture, on the levels of serum thyroid hormones such as total thyroxine (T₄) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. Four days after a single intraperitoneal injection of KC500, significant decreases in the levels of the serum total T₄ and free T₄ occurred in all the animals examined, whereas a significant decrease in the level of serum triiodothyronine was observed only in guinea pigs among the animals examined. In addition, no significant change in the level of serum thyroid-stimulating hormone was observed in any of the rodents examined. A significant increase in the activity of hepatic T₄-UDP-glucuronosyltransferase after the KC500 administration occurred only in guinea pigs, whereas the increase in the amount of biliary [¹²⁵I]T₄ glucuronide after an intravenous injection of [¹²⁵I]T₄ to the KC500-pretreated animals occurred only in rats. On the other hand, in all the rodents examined, KC500-pretreatment promoted the clearance of [¹²⁵I]T₄ from the serum and led to a significant increase in the steady-state distribution volumes of [¹²⁵I]T₄. Likewise, its pretreatment raised the concentration ratio (<i>K</i>_p value) of the liver to serum and the liver distribution of [¹²⁵I]T₄ in all the rodents tested. The present findings indicate that for the first time the KC500-mediated decrease in the serum T₄ level in mice, hamsters, rats and guinea pigs occurs mainly through an increase in the accumulation level of T₄ in the liver.