The tissue distribution of gold, copper and zinc in animals treated with Au (III); species differences in the binding of these metals in the kidney.

Whole body retention of Au and the distribution of Au, Cu and Zn have been measured in female rats, rabbits, guinea-pigs, hamsters and mice after either a single injection or multiple doses of Au(III). At 24 h after a single intraperitoneal injection whole body retention of Au was about 65% of the dose in the rabbit and 50% of the dose in other species. After five doses, retention (as a percentage of the total dose) ranged from 36% in mice to 49% in rats. Concentrations of Au in the kidneys were lowest in mice and highest in rats but, in all species, were greater than in other organs. In rats and guinea-pigs, but not in hamsters, rabbits and mice, treatment with Au(III) increased the Cu content of the kidneys and of the soluble fraction isolated therefrom. The latter from the rat and guinea-pig kidney contained both Au and Cu in association with a low molecular weight metalloprotein (metallothionein), which also contained Zn and was separated by ion exchange chromatography into three subspecies. Binding of Au by these metalloproteins appeared to be related to the renal accumulation of Cu. Apart from the mouse, in which renal accumulation of Au was low, slight damage resulted in the kidneys of all species after treatment with Au. It appears, therefore, that nephrotoxicity cannot be explained simply by the renal concentration of Au and the form in which it is accumulated within the tubular cells.