Effect of Prior Exposure to Green Tea Extract on Fetal Hydantoin Syndrome in CD-1 Mice

Abstract

Phenytoin (PHT) is an efficacious anticonvulsant agent that is commonly used in the treatment of seizures due to epilepsy. However, the use of phenytoin during pregnancy is associated with a group of birth defects, including cleft palate and reduced size known as Fetal Hydantoin Syndrome (FHS). Phenytoin may cause adverse effects through the production of reactive oxygen species (ROS). Green tea extract (GTE) contains epigallocatechin-3-gallate (EGCG), which may be able to attenuate the effects of ROS by free radical scavenging activity. The purpose of this study was to investigate the potential of exposure to GTE to attenuate teratogenic effects induced by phenytoin. Mated CD-1 female mice were orally dosed with only 400 mg/kg GTE, 400 mg/kg GTE + 85 mg/kg PHT, 200 mg/kg GTE + 85 mg/kg PHT, or only 85 mg/kg PHT. The control group received distilled water and pH-adjusted water. Phenytoin sodium salt (in pH-adjusted distilled water) was administered on gestation day (GD) 12 and 13 and the control group was dosed with pH-adjusted water on GD 12 and 13. GTE or distilled water was administered from GD 8-16. Fetuses were removed on day 17 of gestation, weighed, measured, and examined for malformations. The incidence of cleft palate was apparently reduced in fetuses exposed to 200 mg/kg/d GTE compared to fetuses exposed to PHT alone; however, the difference was not statistically significant. Fetal weight, maternal weight gain, and the incidence of fetal resorption did not differ significantly among treatment groups. Prior and concurrent exposure to GTE may reduce the incidence of cleft palate in fetuses exposed to PHT, but a higher GTE dose or a different dosing regimen may be required.