Evidence for basolateral uptake of cadmium in the kidneys of rats

In three separate sets of studies, the effects of ureteral ligation and coadministration of cadmium with cysteine or glutathione (GSH) (in either a 4:1 or 2:1 ratio of thiol to cadmium) on the renal disposition of cadmium were assessed in rats 1 h after the administration of cadmium. In all experiments, co-administration of cadmium with either cysteine or GSH caused the renal accumulation of cadmium to increase significantly (by approximately 60-70%) 1 h after injection. Moreover, in all experiments in which both ureters had been ligated in a rat prior to the administration of cadmium, the net total renal accumulation of cadmium was only about 20% less than that in control animals that had not undergone bilateral ureteral ligation when cadmium was administered as cadmium chloride. Furthermore, in animals in which only one ureter had been ligated, the net accumulation of cadmium in the kidney whose ureter had been ligated was between 25 and 30% less than that in the contralateral kidney. Coadministration of cadmium with cysteine or GSH also caused the net accumulation of cadmium to be increased in rats whose ureter(s) had been ligated. Overall, the present findings indicate that there is a significant basolateral component in the acute, in vivo, renal tubular uptake of cadmium. Moreover, the findings indicate that the basolateral uptake of cadmium is enhanced when cadmium is coadministered with cysteine or GSH.