Abstract
Epoxide hydrolase (EH) and glutathione S-transferase (GST) are involved in the detoxification of epoxide, which may be attributable to the mechanism of ter-atogenicity of antiepileptic drugs (AEDs).In this study, such AEDs as phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), zonisamide (ZNS) and valproic acid (VPA) on the activities of these enzymes were investigated using rat liver microsomes.Within respective therapeutic concentrations, PHT, PB, CBZ and ZNS did not affect EH activity while VPA showed a concentration-dependent inhibitory effect on EH activity at 100μg/mlor more.Regarding the activities of GST isozymes, PHT and ZNS did not affect the activities at any concentrations studied while CBZ (10μg/ml or more) and PB (40μg/ml or more) inhibited GST 7-7 activity.VPA showed concentration-dependent inhibitory effects on activities of GST 1-1, 2-2, 4-4 ad 7-7 at 100μg/ml or more.These results may partly explain the increased incidences of malformation in offspring exposed to AED polytherapy including VPA, CBZ and PB through the accumulation of epoxide intermediates of AEDs.
