Comparative Study of Teratogenic Effects of Gabapentin Administration via Peritoneum and Gavages on Skeletal System of Mice Fetuses Using Alizarin-red S and Alcian-blue Staining Techniques

Gabapentin is a novel antiepileptic drug that is used for the treatment of partial and secondary generalized seizures. There are few and sometimes contradictory reports concerning the teratogenic effects of this drug. This study was done to compare teratogenic effects of gabapentin on skeletal system when it is used intraperitoneally and via gavages. In an experimental research, 60 mature female Balb/c mice were chosen and randomly divided into six groups: two experimental groups which received 25mg/kg (I), and 50 mg/kg (II) of gabapentin intraperitoneally from the initiation of pregnancy for the first 15 days of pregnancy. The other two experimental groups,i.e. III and IV, received the same doses at the same periods but via gavages. Two control groups,i.e. V and VI, received normal saline at the same time intraperitoneally and via gavages. Dams were dissected under deep anesthesia by eter inhalation on the 18th gestational day and embryos were harvested. The macroscopic observation was performed by a stereomicroscope. Then the embryo's weights, resorption and the number of dead and alive fetuses were determined and registered. Finally, malformed fetuses were double strained for bone and cartilage and their skeletons were examined. Data were analyzed by ANOVA and Chi-square tests using SPSS software. Differences less than 0.05 (P < 0.05) were considered significant. Both experimental groups I and II revealed similar malformations which can be categorized as three sets: 1- Decreased fetal body weight and increased fetal resorption 2-Macroscopic external malformations 3- Skeletal malformations.The mean fetal body weight in group I (0.98 0.063 g) and group II (0.91 0/06 g) was lower in comparison to the control group (1.17 0.033 g). Also, an increase in resorbed fetuses was observed in both experimental groups as compared to the fetuses in the control group. Macroscopic malformations in both experimental groups included exencephaly, limbs defects, brachygnathia, vertebral column deformity and generally malformed fetuses. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity and mandibular hypoplasia. In the experimental groups III and IV only delayed ossification was observed.No malformation was found in the control groups. This study revealed that the route of gabapentin administration may induce different teratogenic effects on mice fetuses.