Enhanced mobilization of hepatic cadmium in mice upon coadministration of an N, N-disubstituted dithiocarbamate and an alkyl monoester of dimercaptosuccinate

Res Commun Chem Pathol Pharmacol. 1992 Jan;75(1):121-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Cadmium / administration & dosage
  • Cadmium / pharmacokinetics*
  • Cadmium / toxicity
  • Cadmium Chloride
  • Chlorides / administration & dosage
  • Chlorides / pharmacokinetics*
  • Chlorides / toxicity
  • Injections, Intraperitoneal
  • Liver / drug effects
  • Liver / metabolism*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mice
  • Succinates / administration & dosage
  • Succinates / pharmacology*
  • Thiocarbamates / administration & dosage
  • Thiocarbamates / pharmacology*

Substances

  • Chlorides
  • Succinates
  • Thiocarbamates
  • Cadmium
  • Cadmium Chloride