Meso-2,3-dimercaptosuccinic acid and sodium N-benzyl-N-dithiocarboxy-D-glucamine as antagonists for cadmium intoxication.
Orally administered meso-2,3-dimercaptosuccinic acid (DMSA) is an effective antagonist for acute oral cadmium chloride (1 mmol/kg) intoxication in mice when administered up to 8 h after cadmium ingestion. Administration of sodium N-benzyl-N-dithiocarboxy-D-glucamine (NaB) i.p. along with DMSA p.o. resulted in kidney and liver cadmium levels only marginally smaller than those obtained with DMSA alone. Both chelation treatment regimens permitted survival of 80% or more of the animals, in comparison to a survival rate of 40-50% in untreated animals. Intraperitoneally administered NaB by itself is a very effective antagonist for cadmium chloride administered intraperitoneally in either acute or chronic cadmium intoxication. A dose-response study was made of the mobilization of cadmium from the liver and kidney of cadmium-loaded mice by NaB; this showed that NaB is one of the most effective cadmium mobilizing agents developed to date. We have also confirmed the earlier report of Kojima and his co-workers of the ability of NaB to remove cadmium from animals which have been treated with cadmium over an extended period of time. NaB causes a very large increase in the biliary excretion of cadmium. Nuclear magnetic resonance (NMR) spectra of 113Cd in bile from treated animals and model solutions indicates that such cadmium is undergoing rapid ligand exchange.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Basinger
M A
MA
Topping
R J
RJ
Gale
G R
GR
Jones
S G
SG
Holscher
M A
MA
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000032:analysis; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D013012:Sorbitol / Q000031:analogs & derivatives*; D004113:Succimer / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*
D002614:Chelating Agents; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D002104:Cadmium; D013012:Sorbitol; D008668:Metallothionein; D004113:Succimer; C048763:N-benzylglucamine dithiocarbamate