Effect of Quercetin on Sodium Valproate Induced Neural Tube Defects and Skeletal Teratogenicity in Rat Embryos

Authors

  • Mahmood Khaksary Mahabady1 1- Dept. of Anatomy and Embryology, School of Veterinary Medicine, Shahid Chamran University, Ahvaz, Iran.
  • Mohammad Reza Gholami2 2- Dept. of Anatomy, School of Medicine, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
  • Hossein Najafzadeh Varzi3 3- Dept. of Pharmacology and Toxicology, School of Veterinary Medicine, Shahid Chamran University, Ahvaz, Iran.
  • Abolfazl Zendehdel4 4- Dept. of Internal Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
  • Zahra Lotfalian5 5- School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.

DOI:

https://doi.org/10.22100/jkh.v10i3.711

Keywords:

Sodium valproate, Quercetin, Teratogenicity, Rats’ Embryo

Abstract

Introduction: Sodium valproate is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy. Teratogenic effects of sodium valproate were seen in some studies. There are many reports that the teratogenic effects of sodium valproate can be decreased by application of antioxidant drugs and stimulation of maternal immune system. It seems that quercetin has an antioxidant effect. The aim of this study was to determaine protective effects of sodium valproate induced teratogenicity in fetuses of rat by quercetin.

Methods: This study was performed on 36 pregnant rats randomly assigned to 6 groups (6 rats in each group). The first group (control group) received normal saline intraperitonealy and the other groups (test groups) received sodium valproate (300 mg/kg), quercetin (75 mg/kg), quercetin (200 mg/kg), sodium valproate plus quercetin (75 mg/kg) and sodium valproate plus quercetin (200 mg/kg) intraperitonealy, respectively. Fetuses were carried out in 20th day of gestation, then weight and length of fetuses was determined; they were stained by Alizarin red- Alcian blue method and investigated by stereomicroscope for teratogenic effects.

Results: Percentage of cleft palate, spina bifida and exencephaly was 17.70%, 20% and 20%, respectively, in group which received only sodium valproate, while it was decreased to 13.95%, 11.62% and 13.95% by quercetin (75 mg/kg) and so to 11.11%, 11.11% and 11.11%, respectively, in the group which received qeurcetin (200 mg/kg).

Conclusion: quercetin can decrease incidence of teratogenicity induced by sodium valproate.

References

Wu Gang, Nan C, Rollo JC, Huang X, Tian J. Sodium valproate-induced congenital cardiac abnormalities in mice are associated with the inhibition of histone deacetylase. Journal of Biomedical Science 2010;17:16

Cylan AN, Duru S, Ceylon, S. Valproic acid sodium-induced spina bifida occulta in the rat. Neurosurg Rev 2001;24:31-4.

Defoort EN, Kim PM, Winn LM. Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: a potential mechanism for valproic acid-induced neural tube defects. Molpharmacol 2006;69:1304-10.

Gupta M, Gupta YG, Agarwal S, Aneja S, Kohli k. A randomized, double-blind, placebo controlled trial of melatonin add- on thrapy in epileptic children on valproate monotherapy: effect on glutathione peroxidase and glutathione reductase enzymes. British Jounal of Clinical Pharmacology 2004;58:542-7.

Tung EW, Winn LM. Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects. Mol Pharmacol 2011;80:979-87.

Etemad L, Moshiri M, Moallem SA. Epilepsy drugs and effects on fetal development: Potential mechanisms. J Res Med Sci 2012;17:876-81.

Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: The rotterdam study. The American Journal of Clinical Nutrition 2002;75:880-6.

Nguyen TT, Tran E, Nguyen TH, Do PT, Huynh TH, Huynh H. The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis 2004;25:647-59.

Decharneux T, Dubois F, Beauloye C, Wattiaux-DeConinck S, Waniaux R. Effect of various flavonoids on lysosomes subjected to an oxidative stress. BiochemicalPharmacolog 1992;44:1243-8.

Rice-Evans A, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived Polyphenolic flavonoids. Free Radic Ress 1995;22:375-83.

Prater MR, Zimmerman KL, Lee Ward D, Holladay SD. Reduced birth defects caused by maternal immune stimulation in methylnitrosourea-exposed mice: Association with placental improvement. Birth Defects Research 2004;70:862-9.

Saxen L. Mechanisms of teratogenesis. Journal of Embroyology and Experimental Morphology 1976;36:1-12.

Holladay SD, Sharova LV, Smith BJ, Gogal Jr RM, Ward DL, Blaylock BL. Nonspecific stimulation of the maternal immune system. Effects on teratogen-induced fetal malformations. Teratology 2000;62:413-9.

Winn LM, Wells PG. Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity. Free Radical Biology and Medicine 1999;26:266-74.

Abbott BD, Probst MR, Perdew GH, Buckalew AR. AH receptor, ARNT, glucocorticoid receptor, EGF receptor, EGF, TGF alpha, TGF beta 1, TGF beta 2, and TGF beta 3 expression in human embryonic palate, and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Teratology 1998;58:30-43.

Liang C, Oest ME, Jones JC, Prater MR. Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation. Birth Defects Research (Part B) 2009;86:362-9.

Gohari Behbahani N, KhaksaryMahabady M, Ranjbar R, Najafzadehvarzi H, Mohammadian B. The effects of quercetin and retinoic acid on skeletal system of rat embryos in prenatal period. Zahedan Journal of Research in Medical Sciences 2014; 16:29-34.[Persian].

Dwivedi N, Flora SJS. Dose dependent efficacy of quercetin in preventing arsenic induced oxidative stress in rat blood and liver. Journal of Cell and Tissue Research 2011;11:2506-611.

Liu S, Hou W, Yao P, Zhang B, Sun S, Nussler AK, et al. Quercetin protects against ethanol-induced oxidative damage in rat primary hepatocytes. Toxicology in Vitro 2010;24:516-22.

Sistani Karampour N, Arzi A, Najafzadeh Varzi H, Mohammadian B, Rezaei M. Quercetin preventive effects on theophylline-induced anomalies in rat embryo. Jundishapur J Nat Pharm Prod 2014;9:e17834.[Persian].

Menegola E, Broccia ML, Direnzo F, Giavini E. Comparative study of sodium valproate-induceed skeletal malformations using single or double staining methods. Reproduction Toxicology 2002;16:815-23.

Paulson RB, Sucheston ME, Hayes TG, Paulson GW. Teratogenic effect of valproate in the CD-1 mouse fetus. Arch Neurol 1985;42:980-3.

Hrubec T, Yan Salafia C.M, Holladay S.D. Valproic acid-induced fetal malformations are reduced by maternal immune stimulation with granulocyte-macrophage colony-stimulating factor or interferon-gamma. Anat Rec A DiscovMol Cell Evol Biol 2006;288:1303-9.

Vorhees CV. Teratogenicity and developmental toxicital toxicity of alproic acid in rats. Teratology 1987;35:195-202.

Padmanabhan R, Shafiullah M. Amelioration of sodium valproate-induced neural tube defects in mouse fetuses by maternal folic acid supplemention during gestation. Congenit Anom (Kyoto) 2003;43:29-40.

Menegola E, Broccia ML, Prati M, Giavini E. Stage-dependent skeletal malformations induce by valproic acid in rat. Int J Biology 1998;42:99-102.

Khaksary Mahabady M, Najafzadeh Varzi H, Ranjbar R, Rahgozar O. Prophylactic effects of melatonin on sodium valproate-induced neural tube defects and skeletal malformations in rat embryos. American Journal of Applied Sciences 2011;8:413-9.

Ehlers K, Stürje H, Merker HJ, Nau H. Valproic acid-induced spina bifida: A mouse model. Teratology 1992;45:145-54.

Faiella A, Wernig M, Consalez GG, Hostic U, Hofmann C, Hustert E, et al. Amouse model for valproat teratogenicity: Parental effects, homeotic transformations, and altered HOX expression. Human Molecular Genetic 2000;9:227-36.

Kawai Y, Arinze A. Valproic acid–induced gene expression through production of reactive oxygen species. Cancer Res 2006;66:6563-9.

Published

2015-06-27

Issue

Section

Original Article(s)

How to Cite

Effect of Quercetin on Sodium Valproate Induced Neural Tube Defects and Skeletal Teratogenicity in Rat Embryos. (2015). Knowledge and Health in Basic Medical Sciences, 10(3), Page:35-43. https://doi.org/10.22100/jkh.v10i3.711

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