Biliary excretion of cadmium in rat. III. Effects of chelating agents and change in intracellular thiol content on biliary transport and tissue distribution of cadmium

Abstract

The effects of changes in S-containing intracellular ligands on biliary excretion of Cd were studied in rats. Injection of Zn or Cu salts 24 h before i.v. injection of 109CdCl2 (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with Cys (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered 1/2 h after Cd injection (before the synthesis of metallothionein), the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine and dithioerythritol) increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. When these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.