Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats]

Journal Article · Thu Mar 01 00:00:00 EST 1984 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8454233· OSTI ID:5762371

Klaassen, C D; Waalkes, M P; Cantilena, Jr, L R

The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

• Research Organization: Kansas Medical Center, Kansas City
• OSTI ID: 5762371
• Journal Information: Environ. Health Perspect.; (United States), Vol. 54
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CADMIUM
METABOLISM
TISSUE DISTRIBUTION
CHELATING AGENTS
BIOLOGICAL EFFECTS
METALLOTHIONEIN
BIOCHEMICAL REACTION KINETICS
BAL
COMPARATIVE EVALUATIONS
DTPA
EDTA
EXCRETION
EXPERIMENTAL DATA
MICE
NTA
PENICILLAMINE
RATS
TOXICITY
AMINO ACIDS
ANIMALS
CARBOXYLIC ACIDS
CLEARANCE
DATA
DISTRIBUTION
DITHIOLS
DRUGS
ELEMENTS
INFORMATION
KINETICS
MAMMALS
METALLOPROTEINS
METALS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
REAGENTS
RODENTS
THIOLS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)