Morphological changes in developing rats exposed to valproic acid

ABSTRACT

Valproic Acid [VPA] is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the morphology of the fetuses of albino rats exposed to the drug during various trimesters of pregnancy. Experimental study. In this study pregnant rats were divided into four groups A,B,C and D. Group A [n=10] received VPA in a dose of 500mg/kg/day intraperitonealy [I/p] on days 3, 4 and 5 of gestation. Group B [n=10] received the drug in a dose of 500mg/kg/day I/P on days 8,9 and 10 of gestation. Group C [n=10] received VPA in a dose of 500mg/kg/day I/P on days 16, 17 and 18 of gestation. Group D [n=10] received no treatment and was kept as a control group. On day 21, the rats were euthanized by cervical dislocation. The fetuses were examined for any gross congenital malformation, Congenital malformations were noted in 20% of the fetuses exposed to VPA during second week of gestation i.e. group B. The anomalies included spina bifida [occulta and aperta], exophthalmia, digital abnormalities, cleft lip etc. The other experimental groups showed no such anomalies but high rate of underdevelopment was noted in group A, Moreover, there was significant reduction in body weight and crown rump length [CRL] of the fetuses in group B and C, VPA use during various gestational periods produces deleterious effects in developing rats. So, the use of this drug during pregnancy should be carefully decided