Dithiocarbamate-induced redistribution and increased brain uptake of lead in rats.
The effects of dithiocarbamates on brain uptake and tissue distribution of 203Pb were studied in rats injected intravenously with 100 microCi of 203Pb (28.6 nmol/kg b.wt.) as lead acetate. The dithiocarbamates--sodium diethyldithiocarbamate (DEDTC), tetraethylthiuram disulphide (disulfiram), sodium dimethyldithiocarbamate (DMDTC) and tetramethylthiuram disulphide (thiram)--were administered perorally in doses of 2 mmol/kg. Half of the dose was given 2h before and half immediately after the injection of 203Pb. The concentration of 203Pb in tissues, plasma and erythrocytes, and in urine and feces was determined by gamma counting. Four hours after injection of 203Pb, the dithiocarbamate-treated rats had a significantly higher concentration of lead in brain, liver and lung and a significantly lower concentration of lead in kidney, femur and erythrocytes compared to controls. At 72 h the brain concentration of lead in rats administered thiram, DMDTC, disulfiram or DEDTC was 100, 15, 10, and 4 times higher respectively, than in controls. At 72 h these rats also had higher levels of lead in liver, lung and kidney than did controls. The kidneys of dithiocarbamate-treated rats had a higher concentration of lead at 72 h than at 4 h, and during this time the lead concentration in femur had increased in the treated groups as well as in the controls. Excretion was mainly via feces. In controls about 15% of the dose was excreted in feces at 72 h. Fecal excretion at 72 h in DEDTC and DMDTC-treated rats was about 25% and in thiram and disulfiram-treated rats about 7% of the dose. The total urinary excretion of lead at 72 h was about 9% of the dose in controls, 5% in the DEDTC and DMDTC-treated groups and about 1% in the thiram and disulfiram-treated groups. The results indicate that a lipid-soluble complex between lead and the dithiocarbamates is formed in vivo and that these complexes have a high capacity to penetrate the blood-brain barrier and be retained in brain due to binding to lipid rich brain constituents. The toxicity of the complexes is not known, but it is possible that there is intracellular release of inorganic lead after metabolism/decomposition of the complex.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004125:Dimethyldithiocarbamate / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D007700:Kinetics; D007854:Lead / Q000378:metabolism*; D008297:Male; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology*; D013893:Thiram / Q000494:pharmacology; D014018:Tissue Distribution
D004125:Dimethyldithiocarbamate; D013859:Thiocarbamates; D013893:Thiram; D007854:Lead; D004050:Ditiocarb; D004221:Disulfiram