Effects of chelating agents on tissue distribution and excretion of nickel in mice.
N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), di-hydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetra-acetic acid (CDTA), and 2,3-dimercaptosuccinic acid (DMSA) were studied for their relative efficacies in the distribution and excretion of nickel in mice exposed to nickel. Mice were injected intraperitoneally with NiCl2 (5mgNi/kg) and 30 min or 24 hr later, they were injected intraperitoneally with chelating agents (400 mumol/kg). At 30 min after treatment with nickel, these chelating agents all significantly enhanced the fecal excretion of nickel, and DMSA significantly increased the urinary excretion of the metal. At 24 hr after nickel treatment, BGD, DDTC, and DHED significantly increased the fecal excretion of nickel and BGD was the most effective on the fecal excretion of nickel. CDTA and DMSA significantly enhanced the urinary excretion of the metal. At 30 min after nickel treatment, chelating agents other than CDTA effectively depressed nickel concentration in the kidney, lung, and testes. BGD, CDTA, and DMSA significantly reduced the nickel concentration in the liver. However, DDTC and DHED caused the redistribution of nickel to the brain. At 24 hr after nickel treatment, these chelating agents were effective in mobilizing nickel from the kidney, and chelating agents other than DHED were effective in mobilizing nickel from the liver, lung, and testes. These results indicate that the injection of BGD or DMSA at both 30 min and 24 hr after treatment with nickel can remove nickel from the body without redistribution of nickel to other tissues, such as brain, more effectively than DDTC, DHED, and CDTA. Furthermore, the pattern of excretion of nickel after treatment with the chelating agents was related to the partition coefficients of the nickel-chelating agent complexes.
Xie
J
J
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Funakoshi
T
T
Shimada
H
H
Kojima
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009532:Nickel / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution / Q000187:drug effects
D002614:Chelating Agents; C022838:nickel chloride; D009532:Nickel