Abstract

Objective: Topiramate is an antiepileptic drug (AED) used for the treatment of partial seizure in adult and children epileptic patients. It passed through the placenta causing a birth defect. However, little literature focused on placental alteration due to the administration of topiramate during pregnancy. So, applying different predictive parameters; placental weight, histopathological (Haematoxylin and Eosin), histochemical (periodic acid Schiff’s) and immunohistochemistry (Caspase-3).Methods: Topiramate was orally administrated to the pregnant rats with dose 100 mg/kg rats from 5th to 19th day of gestation. The dam’s undergone hysterectomy and the placentae were weighted and stained by Haematoxylin and Eosin, periodic acid Schiff’s and Caspase-3. Results: The study indicated that there is statistically significant (P<0.05) increase in the treated placental weight (0.4717±0.03788) compared with control group (0.5208±0.02930). Also, the light microscopic examination of the placental specimens using Haematoxylin and Eosin staining revealed that an alteration in both basal and labyrinth zone. Apoptotic feature in spongiotrophoblast and trophoblasts is detected. Positive Periodic acid Schiff’s reaction for polysaccharides in the topiramate-treated group. Caspase-3 is showing apoptotic cells in the trophoblast layer.Conclusion: Long-term daily use of topiramate during pregnancy can lead to obvious pathological histotoxic effects in layers of placenta tissues which may be implicated in cognitive affection. Various effects of topiramate necessitate further investigations.

Highlights

  • Topiramate chemical structure is 2,3:4,5-Bis-O-(1-methyl-ethylidene)beta-D-fructopyranose sulfamate, its molecular formula is C12H21NO8S, its molecular weight is 339.36204g/mol

  • The light microscopic examination of the placental specimens using Haematoxylin and Eosin staining revealed that an alteration in both basal and labyrinth zone

  • Long-term daily use of topiramate during pregnancy can lead to obvious pathological histotoxic effects in layers of placenta tissues which may be implicated in cognitive affection

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Summary

Introduction

Topiramate chemical structure is 2,3:4,5-Bis-O-(1-methyl-ethylidene)beta-D-fructopyranose sulfamate, its molecular formula is C12H21NO8S, its molecular weight is 339.36204g/mol. In 1996, it was approved by Food and Drug administration (FDA) for the treatment of partial seizure in adult epileptic patients. This drug is used in children with refractory partial seizures with or without secondary generalised tonic-clonic seizures. This drug reduces of voltage Na+gates in central nervous system (CNS). It acts as carbonic anhydrase inhibitor, increases postsynaptic GABA receptor and reduces activation of the kainate subtypes of glutamate receptors [2]. It was confirmed that topiramate has antidepressant activity in mice [4]

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