BILIARY-EXCRETION OF EXOGENOUS CADMIUM, AND ENDOGENOUS COPPER AND ZINC IN THE EISAI HYPERBILIRUBINURIC (EHB) RAT WITH A NEAR ABSENCE OF BILIARY GLUTATHIONE

Mutant Eisai hyperbilirubinuric (EHB) rats derived from an inbred stra in of Sprague-Dawley (SD) rats are characterized by a near absence of biliary excretion of glutathione (GSH) due to inherently impaired ATP- driven organic anion transport. Cd (0.1 mg/kg bw from CdCl2) was injec ted intravenously into EHB fats and control SD rats, Output of biliary excretion of Cd was followed over 15-min intervals up to 60 min. Cd w as excreted rapidly and reached the maximum level (73.2 ng/15 min) in the period from 15 to 30 min in SD rats. Its excretion in EHB rats, ho wever was one-fortieth (only 1.8 ng/15 min) of that in SD rats, Biliar y concentrations of two endogenous metals, Cu and Zn were also measure d. The output of Cu in EHB rat bile (50 ng/15 min before Cd injection) was about one-fifth of that in SD rat bile (270 ng/15 min). The outpu t was not influenced by the Cd injection in the two groups. There was a slight difference of Zn output between the two groups, The biliary e xcretion of GSH was 500 to 700 mu g/15 min and only 1 to 2 mu g/15 min in SD and EHB rats, respectively, Sixty min after Cd injection, the C d concentrations in the serum, liver and kidney were slightly higher i n EHB rats than in SD rats. There was no difference in the hepatic met allothionein (MT-I and-II) concentration between SD (34 mu g/g liver) and EHB (33 mu g/g liver) rats, The renal Cu concentration was about f our times higher in the EHB rat than in the SD rat, These results sugg est that reduced biliary excretion of Cd is mainly, but that of Cu is only partly, based in reduced canalicular transport of GSH due to lack of an ATP-driven organic anion transport system, not MT induction in EHB rats. It seems likely that biliary excretion of Cd is regulated ma inly by the canalicular anion transport in rats.