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

Abstract

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.

Effects of Vitamin E on the Epithelial-Mesenchymal Transition in Testicular Development Exposed to Valproic Acid

“…This is consistent with previous studies, where it has been shown that the general effects of VPA could be reversed with the previous administration of antioxidants such as VE (Hsieh et al, 2014;Zhang et al, 2010), being a powerful factor to prevent the oxidation of lipids in the cell membrane. In addition, EV is capable of reducing the deleterious effects of VPA in other tissues, such as in the sciatic nerve and in the development of the nervous system with a prophylactic administration during pregnancy (Aluclu et al, 2009;Conei et al 2016). Specifically, at the testicular level, Ourique et al conducted a study in Wistar rats to evaluate the protective effect of vitamin E on functional abnormalities related to VPA-induced oxidative stress in the male reproductive system, where VE restored the antioxidant potential and prevented oxidative damage in the testes and epididymis, restoring sperm motility and testicular histological conformation, suggesting that EV may be a useful compound to minimize reproductive deterioration in patients requiring treatment with VPA (Ourique et al, 2016).…”

Protective role of vitamin E in testicular development of mice exposed to valproic acid

“…Studies in animal models have shown that the general effects of VPA could be reversed with the previous administration of antioxidants such as vitamin C or E (Hsieh et al., 2014; Zhang et al., 2010), the latter being a powerful factor to prevent the oxidation of the lipids of the cell membrane since it neutralises the destabilising action of oxygen‐free radicals on said structure. Along with this, it has been observed that the joint administration of folic acid and VE reduces the deleterious effects of VPA at the level of the sciatic nerve (Aluclu et al., 2009) and has a protective role at the level of the neural tube and spinal cord of foetuses treated with VPA (Conei et al., 2016). At the testicular level, Ourique et al.…”

“…Studies in animal models have shown that the general effects of VPA could be reversed with the previous administration of antioxidants such as vitamin C or E (Hsieh et al, 2014;Zhang et al, 2010), the latter being a powerful factor to prevent the oxidation of the lipids of the cell membrane since it neutralises the destabilising action of oxygen-free radicals on said structure. Along with this, it has been observed that the joint administration of folic acid and VE reduces the deleterious effects of VPA at the level of the sciatic nerve (Aluclu et al, 2009) and has a protective role at the level of the neural tube and spinal cord of foetuses treated with VPA (Conei et al, 2016). At the testicular level, Ourique et al (2016) conducted a study in Wistar rats to evaluate the protective effect of VE on functional abnormalities related to oxidative stress induced by VPA in the male reproductive system, where VE restored the antioxidant potential and prevented oxidative damage in the testes and epididymis, restoring sperm motility, suggesting that VE may be a useful compound to minimise reproductive impairment in patients requiring treatment with VPA (Ourique et al, 2016).…”

Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

“…12 Proses organogenesis otak tikus terjadi berdasar perhitungan hari, sedangkan pada manusia perhitungan adalah dari minggu ke bulan. Meskipun demikian, perkembangan otak tikus dan manusia memiliki kemiripan.…”