Mobilization of cadmium in mice by combined treatment with N-benzyl-N-dithiocarboxy-D-glucamine and diesters of meso-2, 3-dimercaptosuccinic acid.
Mice which had received a non-lethal injection of cadmium (Cd) as CdCl2 nine days prior to therapy were treated with N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) alone or in combination with either di(iso-butyl)dimercaptosuccinate (DiBDMS) or di(iso-amyl)-dimercaptosuccinate (DiADMS). Seven injections of BDCG (1.0 mmole/kg), DiBDMS (0.4 mmole/kg), and DiADMS (0.4 mmol/kg) reduced whole body Cd burdens 50%, 54% and 37%, respectively; coadministration of BDCG + DiBDMS and BDCG + DiADMS produced respective reductions of 65% and 61%. Seven injections of BDCG lowered renal Cd concentrations an average of 82%, but reduced hepatic Cd concentrations only 53%. The DMSA diesters were more effective in lowering hepatic Cd than in reducing the levels of Cd in the kidneys. The respective hepatic and renal Cd reductions were 50% and 20% after treatment with DiADMS, and were 73% and 30% after treatment with DiBDMS. Coadministration of BDCG with DiADMS reduced hepatic and renal Cd concentrations 74% and 82%, respectively, while BDCG co-administered with DiBDMS yielded respective reductions of 80% and 82%. It is suggested that combined use of these newer Cd complexing agents in studies of experimental Cd poisoning may now permit resolution of the issue of reversibility of Cd-induced nephrotoxicity.
Gale
G R
GR
Veterans Administration 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 / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013012:Sorbitol / Q000031:analogs & derivatives*; D004113:Succimer / Q000031:analogs & derivatives / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*
D002614:Chelating Agents; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D002104:Cadmium; C060082:di-(isobutyl)dimercaptosuccinate; C060083:di-(isoamyl)dimercaptosuccinate; D013012:Sorbitol; D004113:Succimer; C048763:N-benzylglucamine dithiocarbamate