Reduction of lead retention by mono-3-methylbutan-1-yl meso-2,3-dimercaptosuccinate in suckling rats.
The mono-3-methylbutan-1-yl (monoisoamyl) ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) was previously found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in mobilizing cadmium and mercury deposits in young and adult mice and rats. It was also tested to mobilize lead in and adult mice. It was also tested to mobilized lead in adult mice. The purpose of this study was to evaluate the ability of Mi-ADMS to chelate lead at a very young age, in sucking rats. Lead was applied intraperitoneally at the dose of 5 mg kg-1 in the form of lead acetate to six-day-old rats. Treatment with DMSA and Mi-ADMS was administered orally at the dose of 0.25 mmol kg-1, either as early (0.5 and 24 h) or a delayed (4th and 5th day after lead application) therapy. At the end of the experiment (6th day) lead was determined by atomic absorption spectrometry in the skeleton, liver, kidney and brain of the animals. Results showed that Mi-ADMS was more efficient than DMSA after early application in reducing the skeletal, kidney and brain content of lead. After delayed application it was either (skeleton and kidneys) or better (brain) than DMSA. There was no statistically significant influence of either chelator on liver lead content. The major finding is that Mi-ADMS at low doses causes a much higher reduction in brain retention of lead in sucklings than DMSA. This is important because the brain is considered to be the target organ of lead toxicity in the youngest age group.
Blanusa
M
M
Department of the Physiology of Mineral Metabolism, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Kostial
K
K
Piasek
M
M
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D000833:Animals, Suckling; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D004113:Succimer / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D002614:Chelating Agents; D007854:Lead; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer