Der einflu� von chelatbildnern auf verteilung und Toxicit�t von cadmium

Niemeier, Brandi S.

doi:10.1007/bf00369020

Cited by 26 publications

(5 citation statements)

References 5 publications

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“…However, several of the rabbits succumbed later from kidney damage. In a follow-up of these studies, Tepperman (8) showed that BAL increased the uptake of cadmium in the kidneys, an observation confirmed by Niemeier (9). Also, EDTA has been shown to decrease the acute lethality from a single injection of cadmium (10-13).…”

Section: Chelating Agents and Cadmium Toxicitymentioning

confidence: 87%

Chelating agents and cadmium toxicity: problems and prospects.

Nordberg¹

1984

Environ Health Perspect

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Symptoms and signs in humans after excessive exposure to cadmium usually involve the gastrointestinal tract after single oral intake, the lung after acute inhalation, and the kidney after long-term exposure. These organs are usually considered to be the "critical" organs, i.e., the organs most sensitive at a certain type of exposure. The type of Cd-related damage that is most common in humans is probably the renal toxicity after long-term exposure. Most animal experiments, including the most recently published ones, have involved study of gross toxicity and tissue distribution after in ection of cadmium in acute experiments. The observations in the older literature that the influence of chelating agents on Cd distribution and excretion is confined to the early period after acute Cd exposure has been confirmed and extended, and the relationship to the time course of metallothionein synthesis has been demonstrated. Although the injection experiments concerning cadmium distribution, particularly those employing repeated exposure, may furnish information that can form a basis for speculation about long-term toxicity to the kidney, there is a lack of direct studies in animals of possible beneficial effects of chelating agents on renal toxicity of cadmium after prolonged exposure. Among the few studies reported, either an increased renal toxicity or a lack of influence on renal toxicity has been observed. The problems in finding a treatment scheme that can be beneficial for the renal toxicity resulting from long-term cadmium exposure thus remain; however, the prospects of finding such schemes in the future seem favorable in view of some of the recent observations.

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Section: Chelating Agents and Cadmium Toxicitymentioning

confidence: 87%

Chelating agents and cadmium toxicity: problems and prospects.

Nordberg¹

1984

Environ Health Perspect

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“…Following ingestion, cadmium moves rapidly to intracellular sites (21) where typical water-soluble chelating agents (even those with very high values for their stability constants with cadmium) are unable to remove it (22-26). Thus, an approach based solely on structural variations designed to optimize the stability constant of the complex of the cadmium ion with the chelating agent was shown not to be a fruitful approach in early studies (22)(23)(24)(25). The only type of chelating group, other than dithiocarbamate that has been shown capable of mobilizing intracellular cadmium, is the vicinal dithiol group, which has been examined in some detail by Cherian and his co-workers (27,28).…”

Section: Introductionmentioning

confidence: 99%

Structural factors in the in vivo chelate mobilization of aged cadmium deposits.

Singh

Jones

1990

Environ Health Perspect

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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 pi constants for the parts of the molecular structures other than the dithiocarbamate grouping (sigma pi) 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 of these factors in designing chelating agents to enhance the excretion of other toxic metals from their intracellular sites is discussed.

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“…While the typical approach to developing more efficacious therapeutic chelating agents for toxic metals is via a systematic study of the factors that affect the stability constants of the metal complexes that are formed (16)(17)(18)(19), this approach has not been taken in the present study because of the solubility problems that arise in determining the stability constants of dithiocarbamatecadmium complexes (20 (22)(23)(24)(25)(26). Thus, an approach based solely on structural variations designed to optimize the stability constant of the complex of the cadmium ion with the chelating agent was shown not to be a fruitful approach in early studies (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, an approach based solely on structural variations designed to optimize the stability constant of the complex of the cadmium ion with the chelating agent was shown not to be a fruitful approach in early studies (22)(23)(24)(25). The only type of chelating group, other than dithiocarbamate that has been shown capable of mobilizing intracellular cadmium, is the vicinal dithiol group, which has been examined in some detail by Cherian and his co-workers (27,28).…”

Section: Introductionmentioning

confidence: 99%

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

Singh¹,

Jones²,

Jones³

1990

Environmental Health Perspectives

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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.

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Der einflu� von chelatbildnern auf verteilung und Toxicit�t von cadmium

Cited by 26 publications

References 5 publications

Chelating agents and cadmium toxicity: problems and prospects.

Chelating agents and cadmium toxicity: problems and prospects.

Structural factors in the in vivo chelate mobilization of aged cadmium deposits.

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

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