Minimal role of metallothionein in decreased chelator efficacy for cadmium

Michael P. Waalkes, John B. Watkins, Curtis D. Klaassen

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Chelator efficacy in Cd poisoning drops precipitously if therapy is not commenced almost immediately after exposure. Metallothionein (MT), a low-molecular-weight metal-binding protein with high affinity for Cd, may be important for this phenomenon. To more fully assess this role of MT in the acute drop in chelator efficacy following Cd poisoning, rats were injected iv with radioisotopic Cd (1 mg/kg as CdCl2; 50 μCi/kg) followed by diethylenetriaminepentaacetic acid (DTPA; 90 mg/kg ip) at various times (0, 15, 30, 60, and 120 min) after Cd. The percentage to the Cd dose remaining in major organs 24 hr following Cd was determined. 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 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 treatment (1.25 mg/kg, 1 hr before Cd) failed to prolong the chelators effectiveness. Furthermore, newborn rats have high levels of hepatic MT which had no effect on the time course of chelator effectiveness since DTPA still decreased Cd organ contents if given immediately following Cd but had no effect if given 2 hr after Cd. Therefore, it appears that MT does not have an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The quick onset of chelator ineffectiveness may be due to the rapid uptake of Cd into tissues which makes it relatively unavailable of chelation.

Original languageEnglish (US)
Pages (from-to)392-398
Number of pages7
JournalToxicology and Applied Pharmacology
Volume68
Issue number3
DOIs
StatePublished - 1983
Externally publishedYes

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Metallothionein
Chelating Agents
Cadmium
Pentetic Acid
Poisoning
Chelation
Rats
Chelation Therapy
Cadmium Chloride
Liver
Dactinomycin
Carrier Proteins
Molecular Weight
Metals
Molecular weight
Tissue
Kidney
Acids
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Minimal role of metallothionein in decreased chelator efficacy for cadmium. / Waalkes, Michael P.; Watkins, John B.; Klaassen, Curtis D.

In: Toxicology and Applied Pharmacology, Vol. 68, No. 3, 1983, p. 392-398.

Research output: Contribution to journalArticle

Waalkes, Michael P. ; Watkins, John B. ; Klaassen, Curtis D. / Minimal role of metallothionein in decreased chelator efficacy for cadmium. In: Toxicology and Applied Pharmacology. 1983 ; Vol. 68, No. 3. pp. 392-398.
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