In vivo and in vitro efficacy of a new carbodithioate for the mobilization of cadmium.
Female Wistar rats with chronic cadmium intoxication (oral exposure to low dosages of CdCl2 in drinking water over a period of 90 d) were used to examine the in vivo ability of a newly developed chelator, sodium N-(4-methylbenzyl)-4-O-(beta-D-galactopyranosyl)-D-glucamine-N- carbodithioate (MeBLDTC), singly and in combination with sodium 4-carboxy-amidopiperidine-N-carbodithioate (INADTC) as agents to induce the biliary and urinary excretion of cadmium. The combined administration of the two dithiocarbamates, which differ greatly in molecular weight and structural features, led to a synergistic increase in the biliary excretion of cadmium and an enhanced reduction of renal cadmium levels. The use of such a coadministration produced an increase in the biliary excretion of cadmium that was more than double that expected if the compounds acted in an additive fashion. Such mixed-chelation therapy has potential utility in the treatment of human chronic cadmium intoxication. The hepatocytes isolated from chronically Cd-intoxicated rats were used as an in vitro screening model system for the new chelator. The plasma membrane integrity study with MeBLDTC at 0.48 mmol/20 ml of hepatocyte incubate using the trypan blue exclusion test and lactate dehydrogenase (LDH) leakage test revealed no differences in the cell viability with or without chelator. The cellular metabolic competence measured as the rate of urea synthesis also did not show any marked deviation from that of controls when incubated with MeBLDTC at three different concentrations. In the hepatocyte cultures, MeBLDTC induced a significant removal of cadmium from the hepatocytes at concentrations as low as 0.04 mmol/20 ml.
Bláha
K
K
Center for Industrial Hygiene and Occupational Disease, National Institute of Public Health, Prague, Czech Republic.
Nerudová
J
J
Jehlicová
H
H
Cikrt
M
M
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism*; D016923:Cell Death; D002614:Chelating Agents / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D013859:Thiocarbamates / Q000494:pharmacology*; D014018:Tissue Distribution
D002614:Chelating Agents; D004187:Disaccharides; C091507:N-(4-methylbenzyl)-4-O-galactopyranosyl-glucamine-N-carbodithioate; D010880:Piperidines; D013859:Thiocarbamates; D002104:Cadmium; C040979:4-carboxamidopiperidine-N-dithiocarboxylate