Time course of gold-induced accumulation of copper and zinc and the effects of dimercaptosuccinate and cadmium on gold metabolism in rat kidney

Abstract

After the s.c. administration of sodium aurothiomalate (SATM, 10 mg Au/kg) to male rats, the gold content of the kidney increased to a maximum after 4 days and thereafter declined slowly. The total copper content of the kidney increased at least until 11 days after SATM treatment but was not simply a function of the renal gold content. Gold and copper accumulated in the metallothionein-like, low molecular weight protein fraction and the initial uptake of gold by this fraction appeared to be related to the accumulation of copper. The Zn 2+ content of the kidney was initially unchanged but later increased with the additional Zn 2+ bound predominantly to the non-soluble components. The accumulation of low molecular weight protein-bound copper was not related either to the Zn 2+ content of this fraction or to the total Zn 2+ content of the kidney. Daily administration of dimercaptosuccinic acid (DMSA, 50 mg/kg, i.p.) for 2 weeks to SATM-pretreated rats resulted in a 50% reduction in the concentration of gold in the non-soluble fraction and in both the high and low molecular weight protein components of the soluble fraction. Copper, which accumulated in the non-soluble components and in the soluble low molecular weight protein, was lost only from the non-soluble components. Uptake of gold by the kidneys was increased when rats were pretreated with Cd 2+. The accumulation of gold in the low molecular weight protein fraction was also increased, but most of the additional gold in the kidneys was accumulated by the non-soluble components. SATM had no effect on the renal concentration or subcellular distribution of Cd 2+. It was concluded that the soluble low molecular weight metal binding protein does not have prominent regulatory or protective functions in the renal metabolism of gold.