The effect of warfarin on the development of male rat offspring cerebellum

Subject Areas : Developmental biology of plants and animals , development and differentiation in microorganisms

Mino Mahmoodi ¹ , Mona Baroodabi ² , Siyamak Shahidi ³

1 - Department of Biology, Faculty of Basic Sciences, Islamic Azad University,Hamadan Branch, Hamadan, Iran.
2 - Department of Biology, Faculty of Basic Sciences, Islamic Azad University,Hamadan Branch, Hamadan, Iran.
3 - Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Received: 2016-01-10 Accepted : 2016-02-20 Published : 2016-05-21

Keywords: Embryo, Rat, Cerebellum, Warfarin,

Abstract :

Warfarin is an oral anticoagulant agent prescribed for treating cardio-vascular disorder. It reduces the synthesis of vitamin K- dependent factors. As it can easily pass through the placenta, have unwilling effects on embryo. The aim of this study was to evaluate the effect of warfarin on the brain development of rat's offspring. In this study, 30 pregnant wistar rats were randomly divided in 5 groups, control, receiving normal saline, and receiving warfarin in doses at 0.25, 0.5, 0.65 ml/kg during days 14 – 18 of gestation by gavages. 40 days after birth, 6 male newborn were randomly selected in each groups. After anesthesia, serial cross sections of the left hemisphere of the brain were prepared and histological studies were done. The data were analyzed by using one-way ANOVA and Tukey post-test. P

References:

[1]      Assadi M, Jyuu W, Anderson K, Carran M, Bilaniuk L, Leone P. 2012. Vitamin K Antagonist Warfarin for Palliative Treatment of Metachromatic Leukodystrophy. J Cent NervSyst Dis; 26 (4): 73-79.

[2]      Bartke N, Hannun YA. 2009 .Bioactive sphingolipids: metabolism and function, J Lipid Res; 50: 91-6.

[3]      Cerminara N, Lang E, SillitoeR, Apps R.2015. Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits, Nature Reviews Neuroscience; 16: 79-93.

[4]      Denisova N, Booth S. 2005. Vitamin K and Sphingolipid Metabolism.Nutrition Reviews; 63(4): 111-121.

[5]      Ferland. 2012. Vitamin K an emerging nutrient in brain function.Biofactors and Cognitive Function; 151-157.

[6]      Furuya H, Shimizu Y, Kawamori T. 2011. Sphingolipids in cancer. Metastasis Reviews; 30(10): 567–576.

[7]      Higley M, Sabatini B. 2012. Calcium Signaling in Dendritic Spines. Cold Spring HarbPerspect Biology; 4:2077-2097.

[8]      Hirsh J, Donnell M, Eikelboom JW. 2007 . Beyond unfractionated heparin and warfarin current and future advances.Circulation; 116 (5): 552-60.

[9]      Holbrook AM, Pereira JA, Labiris R, Donald H, Douketis JD, Crowther M, 2005. Wells PS. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med; 165 (10): 1095-106.

[10]  Macina Orest T, Schardein James L.2007. Warfarin human developmental Toxicants Boca Raton, CRC Taylor & Francis; 193- 4.

[11]  Marien P, Ackermann H, Adamaszek M, et al. 2014. language and the cerebellum, Cerebellum; 13: 386-410.

[12]  Moyer TP, OKane DJ, Baudhuin LM, et al. 2009, WarfarinSensitivity Genotyping. A Review of the Literature and Summary of Patient Experience Mayo Clin Proc; 84 (12): 1079-1094.

[13]  Posse E, Sipione S. 2010. Sphingolipidsand gangliosides of the nervous system in membrane function and dysfunction, Frontiers in Membrane Biochemistry; 584 (9): 1748-1759.

[14]  Roth MJ, Synofzik M, Lindner A. 2013. The cerebellum optimizes perceptual predictions about external sensory events. Curr Biol; 23: 930-935.

[15]  Sarna JR, Hawkes R. 2003. Patterned Purkinje cell death in the cerebellum. ProgNeurobiol; 70 (6): 473-507.

[16]  Sato Y, Murata M, Chiba T, Umegaki K. 2015, A Systematic Review of the Acceptable Intake Level of Vitamin K among Warfarin Users, Shokuhin Eiseigaku Zasshi; 56 (4):157-65.

[17]  Sugiyama T, Takaki T, Sakanaka K, Sadamaru H. 2007. Warfarin-induced impairment of cortical bone material quality andcompensatory adaptation of cortical bone structure to mechanicalstimuli. Journal of Endocrinology; 194: 213-222

[18]  Sundaram Lev. 1990. Vitamin K and phosphate mediated enhancement of brain sulfotransferase activity. BiochemBiophys Res Commun; 169 (3): 927-32.

[19]   Zeidan YH, Hannun YA. 2007, Translational aspects of sphingolipid metabolism, Trends Mol Med; 13: 327-336.