EVALUATION OF THE EFFECT OF CARBAMAZEPINE AND PHENYTOIN ON THE SKELETAL OSSIFICATION OF ALBINO RAT FETUSES
Gamal Hosny Mohamed, Hanan Nabih Gadallah
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University
Background: Congenital malformations are anatomical or structural anomalies which are taken place during embryogenesis. Several medicines and certain chemicals may cause malformations or permanent defects which may lead to death through passing fetal circulation, which is called teratogenesis. Carbamazepine and phenytoin are recently used in the treatment of epileptic cases for long period. Phenytoin is considered as an appropriate alternative to carbamazepine for the treatment of partial seizures in patients unable to tolerate carbamazepine. Possible side effects especially on organ functions are expected. Antiepileptic drugs are administered to pregnant women who possess the risk of epilepsy periods. There are controversial reports about the effects of these drugs on congenital anomalies, so any structural or functional malformation must be recorded to monitor usage of these drugs.
Aim of the Work: The purpose of the present work was to study skeletal ossification in albino rat fetus under the influence of maternal carbamazepine and phenytoin treatment to assess their teratogenic effect.
Material and Methods: In this work forty pregnant albino rats were used. The pregnant albino rats were divided into four groups; Group I (control group): consisted of 10 pregnant rats and were given no medications. Group II (Carbamazepine group): consisted of 10 pregnant rats and were given 1.8 ml of carbamazepine (tegretol suspension) for 10 days starting from the sixth day of determination of pregnancy via gastric tube. This dose is equivalent to human daily maintenance therapeutic dose (2000 mg/day). The drug was brought in suspension form 5 ml/100 mg from Novartis pharmaceutical, UK Ltd. Group III (Phenytoin group): consisted of 10 pregnant rats and were given 25 mg/kg/day phenytoin intraperitoneal for 10 days starting from the sixth day of determination of pregnancy. Group IV (Combined group): consisted of 10 pregnant rats and were given 1.8 ml of carbamazepine via gastric tube plus 25 mg/kg/day phenytoin intraperitoneal for 10 days starting from the sixth day of determination of pregnancy.
Results: The results revealed that phenytoin administration had mild effects on ossification of fetal bones, while carbamazepine administration had marked effects on ossification of fetal bones. The combination of carbamazepine and phenytoin increased the delaying of ossification in the combined group as compared to all other groups. A significant delay in ossification was especially noticed in sternum, cervical and sacral vertebrae, pubis and metacarpal bones of the fetuses of the combined group as compared to carbamazepine group which indicated that carbamazepine had a synergistic role to phenytoin in the combined group.
Conclusion: The combination of maternal carbamazepine and phenytoin during pregnancy, markedly delayed ossification in rat fetuses. This suggests that carbamazepine acts as a positive coteratogen to phenytoin in delaying ossification.