Influence of chelating agents on the distribution and excretion of cadmium in rats
Journal Article
·
· Toxicol. Appl. Pharmacol.; (United States)
The effects of the chelating agents CaNa2-ethylenediaminetetraacetate (EDTA), CaNa3-diethylenetriaminepentaacetate (DTPA), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropanol (BAL), and 2,3-dimercaptopropane-1-sulfonate (DMPS) and of the lipophilic chelating agents Puchel, Puchel-bisamidocysteineethyl ester (Puch-D), and EDTA-bis-amidocysteineethyl ester (EDTA-D) on the distribution of iv injected Cd were studied in male Sprague-Dawley rats. The chelating agents were injected iv as single doses given 10 sec, 1 hr, or 3 hr after 3 mumol/kg Cd + 115mCd. When the chelating agents were injected within 10 sec after the metal, all agents reduced the total body cadmium burden by varying extents ranging from 3% of that in untreated control rats after 0.01 mmol BAL/kg to 94% following 0.1 mmol DTPA/kg. When given 1 hr after Cd injection, the efficacy of all the agents tested was markedly reduced or abolished; at this time only Puchel and Puch-D provoked significant reductions in the body burden of Cd by 21 and 32%, respectively. When treatment was delayed until 3 hr after Cd injection, only Puch-D was able to reduce the body and liver burden of the metal by 14 and 9%, respectively. Combined treatment with Puchel + DTPA, BAL + DTPA, or BAL + DMPS did not enhance Cd removal to an extent greater than that expected from the equivalent dose of the more effective agent of that pair alone. Repeated administration of DTPA, 20 X 0.1 mmol/kg, during 4 weeks by ip or po administration of the same dose in the drinking water over 4 weeks, was no no more effective than the first dose of the chelating agent alone. Gel chromatographic studies of the distribution of Cd among the proteins of the liver cytosol in treated and untreated animals indicate that neither DTPA nor Puchel was able to release Cd from the metallothionein complex.
- Research Organization:
- Kernforschungszentrum Karlsruhe, Institut fuer Genetik und fuer Toxikologie von Spaltstoffen, Federal Republic of Germany
- OSTI ID:
- 5893834
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 67:3; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
BIOLOGICAL EFFECTS
BODY BURDEN
CADMIUM
CARBOXYLIC ACIDS
CHELATING AGENTS
CLEARANCE
DISTRIBUTION
DRUGS
DTPA
EDTA
ELEMENTS
EXCRETION
INJECTION
INTAKE
INTRAVENOUS INJECTION
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
TISSUE DISTRIBUTION
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
BIOLOGICAL EFFECTS
BODY BURDEN
CADMIUM
CARBOXYLIC ACIDS
CHELATING AGENTS
CLEARANCE
DISTRIBUTION
DRUGS
DTPA
EDTA
ELEMENTS
EXCRETION
INJECTION
INTAKE
INTRAVENOUS INJECTION
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
TISSUE DISTRIBUTION