N,N-disubstituted dithiocarbamates as cadmium antagonists: N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine.
The newly synthesized dithiocarbamate analog, N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine (MeOBDCG) reduced whole-body cadmium levels 66% in cadmium-laden mice when given as 3 injections at 1.0 mmol/kg. Renal and hepatic Cd concentrations were reduced 78 and 85%, respectively. After 6 injections, the whole-body cadmium burden was reduced 71%, while renal and hepatic levels were lowered 84% and 91%, respectively. Mobilized cadmium was excreted almost exclusively by the fecal route. There was no evident toxicity consequent to treatment as judged by mouse body weights and by gross appearance of organs upon dissection. On a molar dose basis, MeOBDCG was more effective than N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) in removing cadmium from both renal and hepatic deposits. An in-vitro assessment of the interaction of MeOBDCG, BDCG and N-methyl-N-dithiocarboxy-D-glucamine with murine cadmium-metallothionein (Cd-MT) revealed a direct relationship between the extent of cadmium depletion from Cd-MT and the relative in-vivo efficacies of the 3 analogs.
Gale
G R
GR
Research Service, VA Medical Center, Charleston, SC 29403.
Atkins
L M
LM
Smith
A B
AB
Singh
P K
PK
Jones
M M
MM
D000818:Animals; D002104:Cadmium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002106:Cadmium Radioisotopes; D008297:Male; D051379:Mice; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000494:pharmacology*; D014018:Tissue Distribution
D002106:Cadmium Radioisotopes; D013859:Thiocarbamates; D002104:Cadmium; C060427:N-(4-methoxybenzyl)glucamine dithiocarbamate; D013012:Sorbitol; C048763:N-benzylglucamine dithiocarbamate