Meso-2,3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice

Marie Weldon Taubeneck, Jose L. Domingo, Juan M. Llobet, Carl L Keen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Meso-2,3-dimercaptosuccinic acid (DMSA) is a chelating agent used to treat heavy metal intoxication. DMSA has been reported to be teratogenic in the mouse, and it has been suggested that this teratogenicity may be secondary to DMSA-induced alterations in Zn metabolism. In the present study, 0, 400 or 800 mg DMSA/kg body weight were administered on gestation days 6-15 to pregnant Swiss mice by gavage (PO) or subcutaneous injection (SC). Mice were fed a diet containing 14 μg Cu, 10 μg Cu, 120 μg Fe, 1175 μg Mg and 6.8 mg Ca/g diet. A sub-grioup of mice inthe 800 mg DSMA/kg Sc group was fed a diet containing 250 μg Zn/g. DMSA administration did not result in overt maternal toxicity. There was no effect of the drug on fetal or placental weight, or on crown-rump length. However, some fetuses from DMSA-treated dams were characterized by skeletal abnormalities including supernumerary ribs, unossified anterior phalanges and malformed sternebrae. Drug exposure was not associated with consistent changes in tissue Zn, Fe, Ca or Mg levels. Supplemental Zn had no marked effects on the fetus. Fetal liver Cu concentrations exhibited dose-dependent decreases with increasing DSMA dose. This finding suggests that the developmental toxicity of DMSA may be mediated through disturbed maternal/fetal copper metabolism.

Original languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalToxicology
Volume72
Issue number1
DOIs
StatePublished - 1992

Fingerprint

Succimer
Metabolism
Copper
Mothers
Nutrition
Diet
Toxicity
Fetus
Crown-Rump Length
Ribs
Subcutaneous Injections
Chelating Agents
Heavy Metals
Pharmaceutical Preparations
Liver
Dams
Body Weight
Tissue
Weights and Measures
Pregnancy

Keywords

  • Copper
  • Meso-2,3-dimercaptosuccinic acid (DMSA)
  • Oral administration
  • Pregnant mice
  • Subcutaneous administration
  • Zinc

ASJC Scopus subject areas

  • Toxicology

Cite this

Meso-2,3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice. / Taubeneck, Marie Weldon; Domingo, Jose L.; Llobet, Juan M.; Keen, Carl L.

In: Toxicology, Vol. 72, No. 1, 1992, p. 27-40.

Research output: Contribution to journalArticle

Taubeneck, Marie Weldon ; Domingo, Jose L. ; Llobet, Juan M. ; Keen, Carl L. / Meso-2,3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice. In: Toxicology. 1992 ; Vol. 72, No. 1. pp. 27-40.
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