Enhanced mobilization of hepatic cadmium in mice upon coadministration of an N, N-disubstituted dithiocarbamate and an alkyl monoester of dimercaptosuccinate.
Oral (po) administration of mono-iso-amyl (2,3-dimercapto) succinate (Mi-ADMS), 0.5 mmol/kg for three consecutive days, to mice previously injected with cadmium (Cd) chloride reduced the whole body Cd burden 34%. Intraperitoneal (ip) administration of N-iso-amyl-N-glucaminedithiocarbamate (i-AmGDTC) by the same regimen reduced total body Cd 41%. Coadministration of the two compounds reduced the whole body Cd burden 60% (p less than 0.05). The liver Cd concentration was reduced 56% and 50%, respectively, by Mi-ADMS given po and i-AmGDTC given ip, each at 0.5 mmol/kg for three consecutive days. Coadministration of the two chelators reduced the liver Cd concentration 90% (p less than 0.05). The kidney Cd concentration was reduced 10% by Mi-ADMS alone, and 60% by i-AmGDTC alone, but there was only a 47% reduction when the two chelators were coadministered, probably as a result of redistribution of mobilized hepatic Cd to the kidneys. As 50-55% of the administered Cd is sequestered in the liver in this mouse model, it is concluded that coadministration of the two chemical classes of Cd complexing agents may offer a therapeutic advantage over administration of either agent alone.
Walker
E M
EM
John L. McClellan Memorial Department of Veterans Affairs Hospital, Little Rock, AR 72205-5484.
Smith
A B
AB
Gale
G R
GR
Jones
M M
MM
D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D019256:Cadmium Chloride; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology*
D002712:Chlorides; D013386:Succinates; D013859:Thiocarbamates; D002104:Cadmium; D019256:Cadmium Chloride