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

Dawson, Jennifer; Raymond, Angela M; Winn, Louise M.

doi:10.1016/j.taap.2005.07.008

Cited by 69 publications

(38 citation statements)

References 35 publications

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“…Folic acid has been shown to reduce the incidence of neural tube defects caused by valproic acid (Dawson et al, 2006;Padmanabhan and Shafiullah, 2003) retinoic acid (Reynolds et al, 2003;Firat et al, 2005), ochratoxin A (Katagiri et al 2007), Fumonisin B1 (Sadler et al, 2002), ethanol (Yanaguita et al, 2008), arsenic (Gefrides et al, 2002) and hyperthermia (Shin and Shiota, 1999;Li et al, 2003). Its role in the prevention of other congenital defects has not yet been fully explored.…”

Section: Discussionmentioning

confidence: 99%

Role of folic acid in chlorpyrifos induced teratogenicity in mice

Tafweez¹

2014

Afr. J. Biotechnol.

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Folic acid is known to reduce the incidence of neural tube defects, in animal experiments however, it has not been effective in reducing the congenital anomalies caused by antiepileptics and many other chemicals. Pesticides of organophosphate group such as chlorpyrifos are widely used in agriculture and household, and are shown to be teratogenic in animal studies. This study was designed to explore the effect of folic acid on chlorpyrifos induced teratogenicity. Pregnant mice were divided into groups of 8 animals each, and were exposed to oral dose of chlorpyrifos and/or folic acid on gestation days (GD) 6 and 7 or GD 1 to 15. Fetuses were recovered on 15 th day of gestation. On morphological and morphometeric examination it was found that chlorpyrifos is teratogenic to mice fetuses in an oral dose of 100 ug/gbw when given on GD 6 and 7. It was embryo toxic and caused growth retardation and morphological anomalies of skull, body curvature, skin, limbs, eyes and ears. Folic acid in a dose of 2 ug/gbw, when given at the time of chlorpyrifos exposure (GD 6 and 7), lead to significant improvement in crown-rump (CR) length and weight of fetuses, reduction in the number of resorptions and frequency of anomalies. However the CR length and weight of fetuses given folic acid and chlorpyrifos were significantly less than the control. There was no additional benefit of giving folic acid in the same dose from GD1 to 15. Thus this study was aimed at confirming the teratogenic potential of cholorpyrifos in mice and assessing the role of folic acid in the prevention of teratogenesis induced by chlorpyrifos.

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Section: Discussionmentioning

confidence: 99%

Role of folic acid in chlorpyrifos induced teratogenicity in mice

Tafweez¹

2014

Afr. J. Biotechnol.

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“…Additionally, mice lacking the genes for folate binding proteins that transport folic acid into cells exhibit NTDs (Spiegelstein et al, 2003;Tang and Finnell, 2003). Human studies indicate that folic acid supplementation may be protective against VA-induced NTDs, but mouse models demonstrate strain specificity with some strains protected and others not (Dawson et al, 2006). It has long been known that VA can disrupt the cell cycle and that cellular proliferation is essential for normal neural tube development.…”

Section: Discussionmentioning

confidence: 99%

Valproic acid‐induced fetal malformations are reduced by maternal immune stimulation with granulocyte‐macrophage colony‐stimulating factor or interferon‐γ

Hrubec

Yan

et al. 2006

Anat. Rec.

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Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly or anencephaly, as well as spina bifida. In mice, nonspecific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes-induced NTDs. We hypothesized that nonspecific activation of the maternal immune system with interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce valproic acid (VA)-induced defects as well. Female CD-1 mice were given immune stimulant prebreeding: either IFN-g or GM-CSF. Approximately half of the control and immune-stimulated pregnant females were then exposed to 500 mg/kg VA on the morning of gestational day 8. The incidence of developmental defects was determined on gestational day 17 from at least eight litters in each of the following treatment groups: control, VA only, IFN-g only, IFN-g þ VA, GM-CSF only, and GM-CSF þ VA. The incidence of NTDs was 18% in fetuses exposed to VA alone, compared to 3.7% and 2.9% in fetuses exposed to IFN-g þ VA, or GM-CSF þ VA respectively. Ocular defects were also significantly reduced from 28.0% in VA exposed groups to 9.8% in IFN-g þ VA and 12.5% in GM-CSF þ VA groups. The mechanisms by which maternal immune stimulation prevents birth defects remain unclear, but may involve maternal or fetal production of cytokines or growth factors which protect the fetus from the dysregulatory effects of teratogens. Anat

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“…Recently, Pittschieler et al [25] reported a significant reduction of spontaneous abortion and premature delivery in women treated with VPA and carbamazepine after periconceptional folic acid supplementation. Folic acid or methionine supplementation were able to reduce the neural tube defects induced by VPA in some strain of mice [26][27][28] but not in other strains [29,30] showing that the genetic background plays an important role in susceptibility to drug-induced congenital malformations.…”

Section: Hyperacetylationmentioning

confidence: 99%

Biomarkers of teratogenesis: Suggestions from animal studies

Giavini

Menegola

2012

Reproductive Toxicology

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a b s t r a c tBiomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

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

Cited by 69 publications

References 35 publications

Role of folic acid in chlorpyrifos induced teratogenicity in mice

Role of folic acid in chlorpyrifos induced teratogenicity in mice

Valproic acid‐induced fetal malformations are reduced by maternal immune stimulation with granulocyte‐macrophage colony‐stimulating factor or interferon‐γ

Biomarkers of teratogenesis: Suggestions from animal studies

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