Inhibition of Valproic Acid-Induced Prenatal Developmental Abnormalities with Antioxidants in Rats

Valproic acid (VP) is a very effective therapy for the management of generalized epilepsy. However, its use during pregnancy leads to increased risk of teratogenesis and cognitive malfunctioning in postnatal growing children. Antioxidants are used commercially as a palliative therapy. This study compares the different antioxidants effects on VP-induced teratogenicity. Pregnant female rats (n = 80) were divided into eight groups (n = 10) as follows: Group I, control group; Group II, disease group valproic acid (500 mg/kg); Groups III and IV, treated with 2000 and 8000 mg/kg vitamin C, respectively; Groups V and VI, treated with selenium 100 and 200 μg/kg dose, respectively; and Groups VII and VIII, administered grape seed extract 300 and 600 mg/kg, respectively. Groups III-VIII received valproic acid (500 mg/kg) along with their respective treatments. All treatments were given via an oral route. The fetuses were double stained, and levels of superoxide dismutase (SOD), catalase (CAT), nitrite, glutathione (GSH), and malondialdehyde (MDA) were estimated. Resorption rate was significantly reduced in Vit. C treated groups at both dose levels. Maternal death rate was decreased remarkably in all treatment groups. Vit. C at a high dose (8000 mg/kg) and grape seed at a high dose (600 mg/kg) significantly reduced the incidence of delayed cervical ossification. The values of MDA were significantly reduced in all groups except the Vit. C group (2000 mg/kg). However, no significant elevation was observed in the values of SOD, CAT, and GSH. The current study concluded that vitamin C at a high dose (8000 mg/kg) and grape seed extract at a high dose (600 mg/kg) had partially protected the fetuses exposed to VP.