Teratogenic Effect of Carbamazepine Administration in Pregnant Rats

Background: Carbamazepine "CBZ" (Tegretol) is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It has been assigned to pregnancy category D by the U.S Food and Drug Administration (FDA). CBZ can cause fetal harm when administered to pregnant women. Epidemiological data suggested that there may be an association between the use of CBZ during pregnancy and congenital malformations, specifically spina bifida and developmental disorders. The possible malformation-specific risks with CBZ use during pregnancy need to be considered, so the present work was conducted to evaluate the genotoxicity of two doses of CBZ (3.6 mg and 10.8 mg/ 100g body weight/ day) in pregnant female rats and their fetuses. Chromosomal aberration in bone marrow cells and histopathological examination of liver and kidney of pregnant rats were also determined. Materials and Methods: Fourty five pregnant Sprague Dawley rats were randomly divided into the groups. The first was administered oral doses of distilled water and served as control. The other two groups were administered oral doses of CBZ suspended in distilled water equivalent to 3.6 mg and 10.8 mg/100g body weight/day respectively for 15 day from the 6th day to the 20th day of gestation. Females were sacrificed on the 20th day of gestation. Results: Administration of CBZ 3.6 mg and 10.8 mg /100g body weight to pregnant rats from the 6th till the 20thday of gestation. Decreased fetal body weight, crown-rump length, increased resorbed and dead fetuses were observed compared to the control ones. Moreover, CBZ-high dose group(10.8mg/100g) causedmalformations that could be described as severe growth retardation. At the same time, bone marrow metaphases of CBZ-treated pregnant rats revealed structural chromosomal aberrations. Whereas, histopathological examination of liver and kidney of pregnant rats treated with both doses of CBZshowed cellular alterations.Conclusion:It has been found that usage of antiepileptic CBZ during gestational period may create risk, associated with maternal toxicity, hepato- and nephrotoxicity and chromosomal aberrations in pregnant rats, with intrauterine growth retardation which was manifested by low body weight, length reduction and malformations. These alterations were dose dependent. The benefits of taking CBZ must be weighed against the potential risks to boththe developing fetus and the mother.