The effects of valproic acid, vitamin E and folic acid on ribs of rat fetuses in the prenatal period

Baran, Özlem; Nergız, Yusuf; Tuncer, Mehmet Cudi

doi:10.1016/j.aanat.2005.11.010

Cited by 14 publications

(12 citation statements)

References 36 publications

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“…Although the molecular mechanism of VPA teratogenicity is unknown, evidence suggests that VPA‐induced HDAC inhibition may play a role in deregulating the expression of genes involved in transcription, translation, and cell signaling causing developmental toxicity (Jergil et al, 2009). In addition, the generation of ROS leading to VPA‐induced oxidative stress has also been implicated in VPA teratogenicity (Tabatabaei et al, 1999; Baran et al, 2005). VPA‐induced ROS have the potential to target nuclear DNA causing oxidative DNA damage and ultimately DNA DSBs (Tabatabaei et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In an in vitro model, microsomal‐dependent generation of hydrogen peroxide from VPA was shown to readily cross cell membranes, react with iron to produce highly reactive hydroxyl free radicals, and lead to cytotoxicity, which was prevented by treatment with the antioxidant catalase (Tabatabaei et al, 1999). Similarly, during development, pre‐treatment of mice with the free radical scavenger vitamin E has also been shown to decrease VPA‐induced neural tube defects (NTDs) and attenuate rib malformations (Baran et al, 2005), implicating VPA‐induced ROS in the involvement of birth defects.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of valproic acid‐initiated homologous recombination

Sha

Winn

2010

Birth Defects Research Pt B

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of valproic acid‐initiated homologous recombination

Sha

Winn

2010

Birth Defects Research Pt B

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“…Another in invivo study done in rats further supported it by attenuating VPA-induced skeletal malformations by pretreatment of vitamin E. 52 In human patients VPA therapy increased the oxidative stress by lower antioxidant activities, 53,54 in various cell line. 33 Recently published study on administration Valproic acid (VPA) at a dose of 300 mg per kg body wt significantly decreased the levels of GSH, SOD and catalase and increased the levels of ROS, TBARS, mRNA expression and the levels of the CYP2C9 enzyme which is involved in the formation of the toxic metabolite (E)-2,4-diene-VPA.…”

Section: Anti-teratogenic Agents Against Vpa Induced Teratogenesismentioning

confidence: 92%

Anti-teratogenic potential and curtailing toxicity of valproic acid

Kumar¹

2018

MOJT

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Oxidative stress responsible for causing damage in the building material of cellular macromolecules such as DNA, lipids, and proteins, along with changing redox-sensitive signaling pathways MOJ Toxicol. 2018;4(4):289-293. 289 AbstractValproic acid (VPA) is widely used as an anticonvulsant and mood-stabilizing drug. It is highly prescribed drug, particularly for epilepsy. However, besides beneficial VPA have a number of side effects due to affecting several signaling pathways through different mechanisms. VPA act as a potent teraogen causing birth defects via interfering with folate metabolism or oxidative stress generation, and histone deacetylase inhibition. However, this article aims to give an overview of the these adverse consequences of VPA are significantly curtailed by the various substances like Vitamin E, Ascorbic Acid, Folic acid, Pantothenic acid, S-adenosyl methionine (SAM) and Curcumin etc which can be focus on its therapeutic use in future against it because of no such other alternative.

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“…On the other hand, vitamin B6 + vitamin B12 significantly reduced VPA-induced exencephaly (23%), spina bifida occulta (80%), palate and rib malformations, kidney abnormalities, and fetal weight retardation. A combination of the three vitamins was effective in reducing VPA-induced exencephaly (23-30%), spina bifida occulta (60%), and palate and rib malformations (Elmazar et al, 1992;Baran et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Valproic Acid on Sciatic Nerve of Fetal Rats and Protective Effects of Folic Acid and Vitamin E

et al. 2009

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SUMMARY:We aimed to investigate the potential harmful effects of maternal valproic acid (VPA) on fetal sciatic nerve, and the protective effects of vitamin E (Vit E) and folic acid (FA) on fetal rats. Valproic acid (400mg/kg), folic acid (400mg/kg) and vitamin E (250 mg/kg) were administered to rats on each of gestation days 8-10. All fetuses were collected on gestation day 20. With thin sections of biopsies, sciatic nerve of fetuses were stained with uranyl acetat and were examined under transmission electron microscope. The fetuses (n:36) were divided into five groups: control, vpa, vpa+fa, vpa+vit e and vpa+fa+vit e groups. In each group; drug procedure, surgical procedure and histological methods were performed. Later, weights and lengths of fetuses in each group were compared and analyzed by One-Way Anova test. Administration of single doses of valproic acid (400 mg/kg) resulted in weight and length loss between control and vpa group. However, length and weight differences between the other groups were not significant. The histopathological findings of control group was normal. In vpa group, it showed extensive degenerative changes especially in myelin coat. In addition, most prominent finding in this group was condensation of collagen fibers in extensively demyelinated samples, while moderately effected areas were relatively normal. Both vpa+fa and vpa+ vit e groups exhibited similar ultrastructural changes, reflecting minimal to moderate degenerative changes. In vpa+fa+vit e group had almost the normal structure. Administration of single doses of valproic acid (400 mg/kg) resulted in a deteriorative effect on sciatic nerve at ultrastructural level. Administration of FA and Vit E had a protective effect to prevent the degenerative changes to a certain degree. Combination of FA and Vit E together following VPA administration had a more potent protective effect. The objective of the present study is to analyze histopathologic changes which may occur in a high risk experimental model after the administration of valproic acid. In addition, protective roles of the administration of folic acid and vitamin E are assessed.

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The effects of valproic acid, vitamin E and folic acid on ribs of rat fetuses in the prenatal period

Cited by 14 publications

References 36 publications

Characterization of valproic acid‐initiated homologous recombination

Characterization of valproic acid‐initiated homologous recombination

Anti-teratogenic potential and curtailing toxicity of valproic acid

The Effects of Valproic Acid on Sciatic Nerve of Fetal Rats and Protective Effects of Folic Acid and Vitamin E

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