Effects of Anti Epileptic Drugs Phenytoin and Phenobarbital on Ossification Indices of Mouse Femur And Tibia And The Anti Teratogenic Effects of Folic Acid on the Reduction of Their Effects

Patients suffering from epilepsy have to take antiepileptic drugs forever. It has been suggested that epilepsy itself and antiepileptic drugs are teratogenic. All aspects of the abnormalities that are induced by these drugs are unclear. Therefore, the objectives of this study were to determine the effects of two routine antiepileptic drugs on ossification. Besides, there was an attempt to decrease their teratogenic effects by using folic acid.

81 female mice (BALB/c) were selected and divided into six groups. Pregnant mice were fed with phenytoin (45mg/kg), Phenobarbital (30mg/kg), phenytoin and folic acid (15􀈝g), Phenobarbital and folic acid, folic acid and water. The embryos were removed and stained with Alizarin red S/ Alcian blue. Total length of tibia and femur, length of ossified parts of tibia and femur and ossification index were calculated. The data was analysed statistically by ANOVA, LSD and Duncan test.

Ossification index in the group treated with Phenobarbital was decreased significantly in femur. Phenytoin had no effects on ossification index. Ossification index in tibia was affected by both antiepileptic drugs. Taking folic acid improved the indices. The impact of these drugs on the tibia was more than femur.

It seems that phenytoin decreases the total length of the ossified part of the femur and therefore, has no effect on the ossification index. But phenobarbital affects the length of ossified tissue but not the total length of the femur, so it could change the ossification rate. The drugs affect the tibia and femur differently. It may be because of the different times of appearance and ossification of upper and lower limbs in the fetus