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Journal of Nutrition Vol. 119 No. 4 April 1989, pp. 607-611
Copyright © 1989 by American Society for Nutrition
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The Effect of Valproic Acid on 65Zn Distribution in the Pregnant Rat1,2,

Carl L. Keen, Jeffrey M. Peters and Lucille S. Hurley

Departments of Nutrition and Internal Medicine, University of California, Davis, CA 95616

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.

KEY WORDS: • zinc • valproic acid • embryonic development • Zn-drug interactions

1 Presented in part at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, Nevada, May 1988 [KEEN, C. L., AMEMIYA, K., PETERS, J., CASEY, S. & HURLEY, L. S. (1988) The effect of 6-mercaptopurine (6MP) and valproic acid (VPA) on 65Zn distribution in the pregnant rat. FASEB J. 2: A866].

2 Supported in part by the National Institutes of Health Grant No. HD-01743.

Manuscript received 15 August 1988. Revision accepted 30 November 1988.






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