PMID: 20650137Oct 1, 1995Paper

Lack of attenuation of valproic acid-induced embryotoxicity by compounds involved in one-carbon transfer reactions

Toxicology in Vitro : an International Journal Published in Association with BIBRA
D K HansenT F Grafton

Abstract

Previous reports have indicated that valproic acid (VPA) is a developmental toxicant in vitro as well as in vivo, producing primarily neural tube defects. The mechanism for the drug's embryotoxic effects is unknown; however, work from our laboratory over the last few years has indicated that addition of various folate derivatives did not significantly decrease the incidence of VPA-induced neural tube defects. It is possible that some compound involved in one-carbon transfer reactions other than folate could protect against VPA embryotoxicity. We have examined the ability of l- or d-serine, sodium formate and l-methionine to decrease VPA-induced embryotoxicity. CD strain rat embryos were cultured for 48 hr beginning on day 9 of gestation. Each compound was examined for embryotoxicity, and a non-embryotoxic concentration was added to the culture medium 3 hr before the addition of 150 mug VPA/ml. Neither l-serine (300 mug/ml), d-serine (300 mug/ml), sodium formate (600 mug/ml) or l-methionine (1.12 mg/ml) were able to decrease VPA-induced developmental toxicity in vitro. The morphological scores of the embryos were not increased, nor was the frequency of embryos with open neural tubes decreased by treatment with any of these compo...Continue Reading

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Citations

Jan 14, 2012·Systems Biology in Reproductive Medicine·Hyung-yul LeeDeborah K Hansen
Apr 1, 2005·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Nicholas D E Greene, Andrew J Copp

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