Comparative effects of three chelating agents on distribution and excretion of cadmium in rats*1

Kojima, Shoji; Kaminaka, Kazuyoshi; Kuramochi, Morio; Honda, Takeshi

doi:10.1016/0041-008x(86)90234-6

Cited by 68 publications

(38 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Substituted D-Glucamine Dithiocarbamates These compounds were prepared by use of the methods previously published by Kojima et al (1986) and Jones et al (1988b).…”

Section: Methodsmentioning

confidence: 99%

Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits

Singh¹,

Jones²,

Jones³

et al. 1989

Journal of Toxicology and Environmental Health

View full text Add to dashboard Cite

An examination of the efficacy of several structural types of chelating agents in the removal of cadmium from its intracellular deposits in mouse liver and kidneys reveals that of the structural types examined, only dithiocarbamates and a vicinal dithiol were able to mobilize cadmium from such intracellular sites. Esters of L-cysteine, a macrocyclic thioether, and a disulfide of a dithiocarbamate were unable to cause any appreciable decrease in either renal or hepatic cadmium levels. Charged groups such as carboxylic acid groups reduce the efficacy as well as the toxicity of the structural types that can otherwise mobilize such cadmium. It was also found that the administration of a cadmium-binding polymer ip leads to only a very slight net excretion of cadmium, while the po administration of this polymer leads to no net additional cadmium excretion. Of the compounds newly reported here, some are approximately equal in cadmium-mobilizing efficacy to the most effective of previously reported compounds.

show abstract

“…Substituted D-Glucamine Dithiocarbamates These compounds were prepared by use of the methods previously published by Kojima et al (1986) and Jones et al (1988b).…”

Section: Methodsmentioning

confidence: 99%

Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits

Singh¹,

Jones²,

Jones³

et al. 1989

Journal of Toxicology and Environmental Health

View full text Add to dashboard Cite

show abstract

“…The application of the Topliss procedure to this series of compounds, with a planned range of substitutions on the benzene ring, showed that of the 4-Cl, 4-CH30, 4-CH3, 3-CF3 derivatives and the parent compound, the 4-CH30 was significantly superior to all of the others on the basis of reductions it effected in both renal and hepatic cadmium levels (34). Studies previously published (15,33,34,(41)(42)(43) showed clearly the advantages of what may be called an amphipathic chelating agent, i.e., one containing both a polar and a nonpolar group on the nitrogen atom. The preparation and examination of the cyclohexyl derivatives (c-C6H11)NRj-(CS2Na), where R, = CH2CH2SO3Na, CH2CH2CH2SO3Na and CH2CH(OH)CH2SO3Na showed that more than one category of amphipathic carbodithioates is capable of mobilizing cadmium in an impressive fashion (15); the higher dosage required for these latter three compounds shows that the presence of a charged group (SO3) introduces too great a polarity to be adequately balanced by a cyclohexyl group for optimum efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…A very significant step was Kojima and his co-workers finding that replacement of the methyl group in HOCH2-(CHOH)4CH2N(CH3)CS2Na by a benzyl group to give HOCH2(CHOH)4CH2N(CH2C6H5)CS2Na resulted in a compound that was both significantly more effective and equally nontoxic (41). The corresponding 4-methylbenzyl and 4-isopropylbenzyl compounds were also quite effective (33).…”

Section: Resultsmentioning

confidence: 99%

Structural Factors in the In Vivo Chelate Mobilization of Aged Cadmium Deposits

Singh¹,

Jones²,

Jones³

1990

Environmental Health Perspectives

View full text Add to dashboard Cite

The role of structural factors in determining the relative efficacy of dithiocarbamates as chelating agents for the in vivo mobilization of aged cadmium deposits is examined for 23 newly synthesized compounds of this type. The critical feature in determining the efficacy of the compounds in mobilizing intracellular cadmium is the balance between hydrophobic and hydrophilic groups. This balance also governs the other properties of these compounds such as the organ specificity of action and the relative propensity to carry cadmium to the brain. The transport of cadmium to the brain by dithiocarbamate can be greatly reduced by the incorporation of appropriate hydrophilic groups that prevent the formation of lipid-soluble cadmium complexes that pass readily into the brain. If the chelating agents carry an additional ionic charge, their ability to pass through cellular membranes and react with intracellular deposits of cadmium is significantly reduced, with other structural factors being equal. The structural features that optimize mobilization of cadmium from the kidney do not appear to be identical with those that optimize its mobilization from the liver. The correlation of cadmiummobilizing properties of these chelating agents with the sum of the Hansch n constants for the parts of the molecular structures other than the dithiocarbamate grouping (lIn) is reasonably good for the removal of renal cadmium by derivatives of D-glucamine and D-xylamine. Another aspect of the molecular structure that appears to play a role is the presence of uncharged polar groups having the ability to form hydrogen bonds. The relevance ofthese factors in designing chelating agents to enhance the excretion of other toxic metals from their intracellular sites is discussed.

show abstract

“…Ltd (Osaka). BGD was synthesized according to the procedure reported in our previous paper (Kojima et al 1986a). All other chemicals were of reagent grade.…”

Section: Methodsmentioning

confidence: 99%

“…Repeated injection of dihydroxyethyldithiocarbamate (Gale et al 1983 c), N-methyl-D-glucamine dithiocarbamate (Shinobu et al 1984;Gale et al 1984b), and N-cyclohexyl-N-sulfonatoalkyl dithiocarbamates (Gale et al 1987) in mice following Cd exposure resulted in substantial reduction in both the liver and kidney concentrations of Cd without redistribution of Cd to brain, testes, and heart. In addition, the new dithiocarbamate derivatives, N-benzyl-D-glucamine dithiocarbamate (BGD) (Kojima et al 1986a(Kojima et al , b, 1987a, N-p-methylbenzyl-D-glucamine dithiocarbamate (Kojima et al 1987b), and N-p-isopropylbenzyl-o-glucamine dithiocarbamate (Kojima et al 1987b), were more effective in decreasing the Cd concentrations in the liver and kid- Fig. l.…”

Section: Introductionmentioning

confidence: 95%

Effect of N-benzyl-d-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats

et al. 1990

View full text Add to dashboard Cite

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 mumol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 mumol Cd as Cd-MT/kg) and thereafter they received three injections of BGD (400 mumol/kg) daily for 3 days. Urinary protein concentration and aspartate aminotransferase (AST) activity significantly increased 1 day after Cd-MT treatment and decreased to control levels at 9 days after the treatment. Urinary excretion of glucose and amino acids rose gradually reaching maximum levels 5 days after Cd-MT treatment and returned to the control levels at 9 days. BGD injection significantly reduced the increases in the urinary excretion of protein, AST, glucose and amino acid, which were produced by Cd-MT treatment. Significant increases in urine volume were observed after Cd-MT treatment. BGD injection inhibited the increase in urine volume caused by Cd-MT treatment. A long time interval (12 and 24 h) between the administrations of Cd-MT and BGD resulted in a decreased protective effect of BGD against Cd-MT-induced renal damage. Following Cd-MT injection, the major route of excretion of cadmium (Cd) was via the urine and the kidney was the major site of accumulation of Cd. BGD injection remarkably increased the urinary excretion of Cd, resulting in a significant reduction in the kidney Cd concentration. The results of this study indicate that BGD injection is effective in decreasing the Cd concentration in the kidney, resulting in the protective effect on Cd-MT-induced renal damage.

show abstract

Comparative effects of three chelating agents on distribution and excretion of cadmium in rats*1

Cited by 68 publications

References 16 publications

Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits

Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits

Structural Factors in the In Vivo Chelate Mobilization of Aged Cadmium Deposits

Effect of N-benzyl-d-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats

Contact Info

Product

Resources

About