Structure-effect relationship in the mobilization of cadmium in mice by several dithiocarbamates

The structural characteristics of several dithiocarbamates (DTCs) [N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD)] that induce in vivo mobilization of cadmium (Cd) were examined in mice. The renal and hepatic contents of Cd were lower in the treatments with Cd-DTC combinations than in that with Cd alone. Probenecid pretreatment decreased the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, but it increased the renal content of Cd and decreased the urinary excretion of the metal in Cd-HBGD and Cd-CBGD treated mice. Furthermore, although ureter-ligation did not affect the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, it increased the renal content of Cd in Cd-HBGD and Cd-CBGD treated mice. These findings suggest that Cd-MBGD and Cd-BGD complexes are taken up into the tubular cells by an organic anion transport system through the basolateral membrane, whereas Cd-HBGD and Cd-CBGD complexes are secreted to the tubular lumen by an organic anion transport system through the brush border membrane. The results of probenecid pretreatment also led us to assume that the hepatic transport of these four Cd-DTC complexes is regulated, at least in part, by a probenecid-sensitive organic anion transport system.