The Prophylactic Effects of Folic Acid and Vitamin E against Valproic Acid During Fetal Thymus Development: an Ultrastructural Study

To evaluate histopathologic differences in the thymus of Wistar Albino rat fetuses prenatally exposed to valproic acid (VPA), folic acid (FA) and vitamin E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) and Vit -E (250 mg/kg) were administered to rats on each of gestation days 8, 9 and 10. The fetuses (n:24) were divided into four groups: control, VPA, VPA+Vit-E and VPA+FA groups. On the 20th day of gestation, all pregnant rats were sacrificed and the fetuses were extracted. Thin sections from thymus of live fetuses were stained with uranyl acetate-lead citrate and were examined under transmission electron microscope. The histopathological findings of control group was normal. In VPA group, it showed extensive degenerative changes by VPA were on all tissue compartments when compared to controls. In VPA-FA group, vacuoles, mitochondrial cristalysis and swelling were decreased in cytoplasm. In VPA-Vit-E group, lipid storage and vacuolization were observed. Mitochondrial cristalysis decreased. Our aim in the present study is to analyze histopathological changes which may occur in a high risk experimental model after giving of VPA. In addition, protective roles of the administration of FA and Vit-E are assessed.(AU) Se realizo este estudio para evaluar las diferencias histopatologicas en el timo de fetos de ratas Wistar Albinas expuestas prenatalmente a acido valproico (VPA), acido folico (AF) y vitamina E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) y vitamina E (250mg/kg) administradas a ratas en los dias 8, 9 y 10 de gestacion. Los fetos (n=24) fueron divididos en cuatro grupos: control, APV, APV + vitamina E y VPA + FA. En el dia 20 de gestacion, todas las ratas prenadas fueron sacrificadas y los fetos fueron extraidos. Se obtuvieron secciones delgadas del timo de los fetos y se tineron con citrato de uranilo - acetato de plomo, siendo examinados al microscopio electronico de transmision. Los hallazgos histopatologicos del grupo control fueron normales. En el grupo VPA, se observaron cambios degenerativos en todos los compartimentos de tejido en comparacion con los controles. En el grupo VPA+FA, las vacuolas, cristalisis mitocondrial e inflamacion se redujeron en el citoplasma. En grupo VPA + Vitamina E, se observo el almacenamiento de lipidos y vacuolizacion. La cristalisis mitocondrial disminuyo. El estudio permitio analizar los cambios histopatologicos que pueden ocurrir en un modelo experimental de alto riesgo despues de la administracion de VPA, ademas, las funciones de proteccion por la administracion de AF y vitamina E.(AU)