Concurrent administration of D-penicillamine and zinc has no advantages over the use of either single agent on copper excretion in the rat

Abstract

The present study was conducted to examine in rats whether the combined use of D-penicillamine (DPA) and a zinc salt, or the administration of a DPA/Zn complex could have some advantages over the use of either single agent on the excretion of copper. In a first experiment, three groups of adult male Sprague Dawley rats were given by gavage one of the following treatments for 5 days: 0.5 mmol/kg/day of DPA, 0.046 mmol/kg/day of zinc acetate dihydrate, and 0.5 mmol/kg/day of DPA plus 0.046 mmol/kg/day of zinc acetate dihydrate. A fourth group of rats (control group) received deionized water during the same period. An increase in the urinary excretion of copper was observed following DPA treatment, which continued for at least 5 days after the administration of this compound was stopped. The amount of copper present in the feces, including that in the diet, was approximately 60 times greater than that normally present in control urines. During the period of zinc acetate administration, the amount of copper in the feces was slightly, but significantly greater than that during control, D-penicillamine, or D-penicillamine plus zinc acetate administration. No differences between the treated groups and the control group were found in brain, liver, kidney and spleen concentrations of rats 5 days after the end of the treatment period. In a second experiment, a similar comparison between D-penicillamine and sodium bis(3-mercapto-D-valinato)zinc hexahydrate (Na2[Zn(DPA)2] x 6H2O), both given by gavage, also showed no significant differences in the urinary excretion of copper in rats.