POSSIBLE TERATOGENIC EFFECTS OF ANTIEPILEPTICS IN ALBINO RATS: COMPARATIVE STUDY BETWEEN OLD AND NEW GENERATIONS: PART II

Abstract

All antiepileptic drugs (AEDs) are either known or suspected of being teratogenic. The possible teratogenic mechanism is likely to be multiple even for the same drug. Treatment of females with epilepsy in the childbearing period raises questions due to interactions between epilepsy, antiepileptic drugs (AEDs) and different forms of reproductive life. The use of AEDs in these females is a balance between seizure control and adverse effects of these drugs, which are both potentially harmful to the developing fetus, neurological development, growth and subsequent pediatric progress, which presents unique challenges to both the clinicians and their patients. Recently, number of commercially available AEDs has steadily increased. This work is a randomized single blind control trial that aims to study the possible teratogenic effects of AEDs by comparing carbamazepine (old generation) with lamotrigine (new generation) in order to detect the drug that can be used safely by epileptic pregnant females. Pregnant female albino rats (120 in number) were used. They were randomly classified into six groups (2 control and 4 treated groups) each contained 20 pregnant rats. Animals were killed on the 20th day of gestation, dissected and fetuses were exposed and randomly classified into two subgroups: The first (1/3 of fetuses) were eviscerated and preserved in 95% ethyl alcohol for skeletal staining, using Alizarin red stain. Examination included: bones of axial skeleton (skull, vertebral column, sternum and ribs) and appendicular skeleton (clavicle, scapula, forelimbs and hind limbs). The second (2/3) were fixed in Bouin’ s solution for visceral examination. Examination of the axial skeleton: craniofacial bones showed highly significant reduction in complete ossification centers (OCs) of all treated groups in comparison with the control with no significant difference between lamotrigine and carbamazepine in therapeutic doses. Other parts of axial skeleton were not affected in therapeutic treated groups. Appendicular skeleton, except metacarpal OCs, showed no difference from control in therapeutic doses. There was a highly significant reduction in complete metacarpal OCs of both doses of carbamazepine and ¼ LD50 of lamotrigine, in comparison with the control, but there was a highly significant increase in both doses of lamotrigine in comparison with corresponding doses of carbamazepine. Similarly, there was a highly significant reduction in complete metatarsal OCs in both ¼ LD50 doses in comparison with the control. No significant difference was recorded in complete metatarsal OCs of therapeutic dose of lamotrigine and a highly significant increase in ¼ LD50 dose in comparison with corresponding doses of carbamazepine.Visceral findings: no abnormalities were detected among fetuses in therapeutic doses of treated groups. Fetuses of ¼ LD50 treated groups showed internal abnormalities in heads cross sections, while other levels showed no difference from control. Conclusion: lamotrigine in therapeutic dose can be used safely by epileptic pregnant females.