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 language | English (US) |
|---|---|
| Pages (from-to) | 27-40 |
| Number of pages | 14 |
| Journal | Toxicology |
| Volume | 72 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1992 |
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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 journal › Article
}
TY - JOUR
T1 - Meso-2,3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice
AU - Taubeneck, Marie Weldon
AU - Domingo, Jose L.
AU - Llobet, Juan M.
AU - Keen, Carl L
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Copper
KW - Meso-2,3-dimercaptosuccinic acid (DMSA)
KW - Oral administration
KW - Pregnant mice
KW - Subcutaneous administration
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=0026510834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026510834&partnerID=8YFLogxK
U2 - 10.1016/0300-483X(92)90083-Q
DO - 10.1016/0300-483X(92)90083-Q
M3 - Article
C2 - 1311466
AN - SCOPUS:0026510834
VL - 72
SP - 27
EP - 40
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 1
ER -