Dynamic intra-renal changes in cadmium distribution detected by LA-ICP-MS in mice administered cadmium-metallothionein.

Abstract

Administration of cadmium-metallothionein (Cd-MT) complex has been known to cause acute nephrotoxicity due to free Cd ions during the breakdown of the Cd-MT protein in renal cells. However, the fate of the renal Cd after Cd-MT administration remains elusive. We applied LA-ICP-MS to visualize Cd distribution in the kidneys of mice administered Cd-MT. In the initial several hours, Cd was detected predominantly in the renal cortex. Elevated urinary β2-microglobulin and glucose within a day and rapid induction of MT-I mRNA indicated the generation of toxic free Cd ions. Unexpectedly, however, the Cd distribution changed drastically: from the cortex to the boundary of the cortex and outer medulla until three days. From 3 to 18 h, renal Cd concentrations decreased rapidly, accompanied by a large amount of urinary Cd excretion. These results suggest that the injected Cd-MT was transiently distributed in the surface nephrons in the cortex, and the free Cd ions derived from the decomposed Cd-MT were released into the lumen of proximal tubules and then partly reabsorbed at the boundary of the cortex and outer medulla, where the S3-segment proximal tubules exist abundantly. Thus, the LA-ICP-MS revealed dynamic changes in Cd distribution, suggesting the intra-renal transport of the Cd-MT-derived free Cd ions in the kidneys.