The rate of the in vivo dithiocarbamate-induced mobilization of hepatic and renal cadmium deposits.
The dithiocarbamate-induced removal of aged cadmium from intracellular sites in the kidneys and liver of mice has been followed as a function of time. The processes are quite rapid with the entire course of the cadmium-removal process being completed in 60-90 min. An examination of the rates at which a dithiocarbamate removes cadmium from hepatic and renal deposits in vivo and from metallothionein in vitro, suggests strongly that the processes are similar. A common mechanism is proposed for both processes which involves the direct attack by the dithiocarbamate on cadmium ion incorporated into metallothionein. Such a mechanism is consistent with the similarities in rates and the degree of overall mobilization of cadmium by the same dithiocarbamate both in vitro and in vivo. The administration of 1 mmol/kg of sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeOBDCG) to cadmium-loaded mice leads to a reduction of in vivo renal and hepatic cadmium levels of 45% and 30%, respectively, over a period of only 1 h. Previously the incubation of metallothionein in vitro in the presence of 1 mmol/l of MeOBDCG was found to lead to the reduction of the cadmium content of metallothionein of approximately 60% over a period of 1 h. The administration of higher doses of this compound (2 mmol/kg and 4 mmol/kg) to cadmium-loaded mice led to an even more rapid and more extensive removal of cadmium from both the liver and the kidney. The major factors which limit the ability of dithiocarbamates to mobilize cadmium from in vivo sites appear to be molecular structural features which hinder or prevent the access of the dithiocarbamates to the intracellular sites at which the majority of aged cadmium deposits are held.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, TN 37235.
Gale
G R
GR
Singh
P K
PK
Smith
A B
AB
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002105:Cadmium Poisoning / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013012:Sorbitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D013859:Thiocarbamates; D002104:Cadmium; C060427:N-(4-methoxybenzyl)glucamine dithiocarbamate; D013012:Sorbitol