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Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

Abstract

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb,  More>>
Authors:
Dawson, Jennifer E; [1]  Raymond, Angela M; [1]  Winn, Louise M [1] 
  1. Department of Pharmacology and Toxicology and School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6 (Canada)
Publication Date:
Mar 01, 2006
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 211; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.07.008; PII: S0041-008X(05)00401-1; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; BORON CHLORIDES; DEFECTS; EMBRYOS; ENZYMES; FOLIC ACID; LEUKEMIA; LEUKEMIA VIRUSES; LYMPHOMAS; MICE; PANTOTHENIC ACID; PREGNANCY; PYRAZOLINES
OSTI ID:
20783436
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; TXAPA9; TRN: US06R1433086652
Submitting Site:
INIS
Size:
page(s) 124-132
Announcement Date:
Jan 12, 2010

Citation Formats

Dawson, Jennifer E, Raymond, Angela M, and Winn, Louise M. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.07.008.
Dawson, Jennifer E, Raymond, Angela M, & Winn, Louise M. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice. United States. doi:10.1016/j.taap.2005.07.008.
Dawson, Jennifer E, Raymond, Angela M, and Winn, Louise M. 2006. "Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice." United States. doi:10.1016/j.taap.2005.07.008. https://www.osti.gov/servlets/purl/10.1016/j.taap.2005.07.008.
@misc{etde_20783436,
title = {Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice}
author = {Dawson, Jennifer E, Raymond, Angela M, and Winn, Louise M}
abstractNote = {In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.}
doi = {10.1016/j.taap.2005.07.008}
journal = {Toxicology and Applied Pharmacology}
issue = {2}
volume = {211}
place = {United States}
year = {2006}
month = {Mar}
}