Effects of folate supplementation on cleft palate induced by lamotrigine or cyclophosphamide: An experimental study in mice

This study aims to elucidate the preventive role of folate supplementation on induction of cleft palate in mice by drugs of two separate categories i.e. lamotrigine (newer antiepileptic and antipsychotic) and cyclophosphamide (anticancer and immunosuppressive). 10 pregnant swiss white mice (C) received normal saline intraperitoneally on day 10 of gestation. Two groups of 10 pregnant mice (T1) and (T2) each received lamotrigine or cycloposphamide respectively 10 mg/kg body weight (bw) intraperitoneally on day 10 of gestation. Folate was supplemented 0.8 μg/kg bw intraperitoneally along with lamotrigine or cyclophosphamide to two more groups of 10 pregnant mice (T3) and (T4) each respectively on the same day 10, of gestation. Fetuses were collected by Caesarian Section on day 18 of gestation. Fetuses collected from all the groups were examined macroscopically with stereomicroscope for palatal malformations. Coronal sections of fetal head were taken for histological study of palatine defects. Cleft palates were detected in 42 out of 70 (60.00%) fetuses of lamotrigine treated group (T1) and 49 out of 61 (80.33%) fetuses of cyclophosphamide treated group (T2). Folate supplementation resulted in different response; 15 out of 72 (20.83%) fetuses in T3 group and 51 out of 64 (79.69%) fetuses in T4 group had cleft palate. The difference was highly significant (p<0.001) when folic acid was administered with lamotrigine (T3) and was not significant (p>0.05) when it was administered with cyclophosphamide (T4) as compared to only lamotrigine (T1) or cyclophosphamide (T2) treated groups respectively. The preventive efficacies of folate supplementation for cleft palate vary considerably and in the same subject under identical conditions, depend primarily on the mechanism of action of the inducing agent.