Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice.
Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD.
Shimada
H
H
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Kawagoe
M
M
Kamenosono
T
T
Kiyozumi
M
M
Funakoshi
T
T
Kojima
S
S
D000818:Animals; D001646:Bile / Q000378:metabolism; D002104:Cadmium / Q000493:pharmacokinetics* / Q000652:urine; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D005243:Feces / Q000737:chemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis; D051379:Mice; D015394:Molecular Structure; D013012:Sorbitol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
D002614:Chelating Agents; D013859:Thiocarbamates; D002104:Cadmium; C060427:N-(4-methoxybenzyl)glucamine dithiocarbamate; C068198:N-4-hydroxymethylbenzylglucamine dithiocarbamate; C068199:N-4-carboxybenzylglucamine dithiocarbamate; D013012:Sorbitol; D008668:Metallothionein; C048763:N-benzylglucamine dithiocarbamate