Topiramate induced histopathological changes in placenta of rats

Abstract

Effect of topiramate, an antiepileptic drug, on the development of conceptus and its safety during pregnancy has been investigated in experimental rats. Rats were treated with topiramate dissolved in tap water in the doses of 40, 100 and 200 mg/kg body weight from day 9 to 12 of gestation through oral route. Fetuses along with placenta were collected for examination on day 21 of gestation after sacrificing the pregnant rats with deep ether anaesthesia. The placenta showed neither significant reduction in weight as compared to the controls nor any overt anomaly. However, on microscopic examination all treated groups showed similar structural changes which increased in severity with increase in the dose of the drug. The deciduas basalis showed thickening, heamorrhage and increased fibrinoid deposit. Disproportionately increased frequency of vacuolated giant cells was observed in the basal zone whereas frequently broken trichorial membrane, homogenous labyrinthine septa and increased fetal mesenchyme were observed in the placental barrier. The results suggested that topiramate induced dose dependent deleterious changes in the structure of placenta, therefore it should be used with caution during pregnancy.