Effect of dimercaptosuccinate on the accumulation and distribution of cadmium in the liver and kidney of the rat.
The effect of dimercaptosuccinic acid (DMSA) on the tissue distribution, renal and hepatic subcellular localization of Cd2+, Zn2+ and Cu2+ in Cd(2+)-pretreated male rats and on the tissue distribution of Zn2+ and Cu2+ in the normal rat was studied. Cd(2+)-pretreated rats which received 3 x 1 mg Cd2+/kg body wt s.c. at 48 hr intervals followed after 7 days by DMSA (50 mg/kg body wt i.p.) daily for 17 days had total hepatic Cd2+ concentrations 25 per cent lower than Cd(2+)-pretreated controls (P < 0.01). DMSA did not influence the concentration or distribution of Cd2+ in the liver cytosol whereas in the mitochondrial-lysosomal and nuclei + cell debris fractions the Cd2+ concentration was reduced by 54 and 48 per cent respectively. Total renal and hepatic Cu2+ concentrations were increased by Cd2+ treatment and reduced by treatment of the Cd(2+)-exposed animal with DMSA. In the liver cytosol Cu2+, Zn2+ and Cd2+ accumulated in the metallothionein fraction and none was mobilized from the cytosol by DMSA. In the kidney cytosol Cu2+ accumulated in fractions in addition to metallothionein and was eliminated from each of these fractions following treatment with DMSA. It is concluded that the high affinity of metallothionein for these cations prevented their elimination from the cytosol and that the interaction of Cd2+ and Cu2+ with DMSA occurred in the particulate fraction and therefore delayed the response to DMSA treatment. It is suggested that long term treatment with DMSA, although ineffective in mobilizing Cd2+ from the kidney may provide a useful therapeutic measure to reduce the liver burden of Cd2+ and the high renal Cu2+ concentrations in the Cd(2+)-exposed animal.
Toxicology Research Unit, Medical Research Council of New Zealand, University of Otago Medical School, Dunedin, New Zealand.
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Mason
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000494:pharmacology*; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism
D002614:Chelating Agents; D002104:Cadmium; D003300:Copper; D004113:Succimer; D015032:Zinc