The effect of valproic acid on 65Zn distribution in the pregnant rat.
The effect of valproic acid on the distribution of gavaged 65Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake.
Keen
C L
CL
Department of Nutrition, University of California, Davis 95616.
Peters
J M
JM
Hurley
L S
LS
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008970:Molecular Weight; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology* / Q000633:toxicity; D015032:Zinc / Q000172:deficiency / Q000493:pharmacokinetics*; D015037:Zinc Radioisotopes
D002352:Carrier Proteins; D015037:Zinc Radioisotopes; C017800:zinc-binding protein; D014635:Valproic Acid; D015032:Zinc