Abstract

Valproate (VPA)  has been shown to induce neural tube defect in human and mice. In this study, we investigated the ability of butanolic extract from leaves of Chrysanthemum fantanesii, vitamin E and C to modulate VPA-induced toxicity and oxidation damage in maternal and fetal tissues in mice. Plant extract, VPA and vitamins were administered orally to pregnant mice from the 6 to 17th day of gestation. Animals received plant extract (200 mg/kg per day), vitamin E (100 mg/kg per day) and vitamin C (8.3 mg/kg per day) with an oral administration of VPA (400 mg /kg per day) under the same conditions. On day 18 of gestation pregnant mice were sacrificed, fetuses, placenta and maternal tissues were removed, homogenized and used for the determination of lipid peroxidation rates (LPO) using thiobarbituric acid reactive substance (TBARS) method. Embryotoxicity wasassessed by counting the number of implants, live and dead fetuses, and resumptions. Thefetuses were observed for malformation including neural tube defect (Exencephaly), open eyes and skeletal malformation. The results show clearly that there is a positive correlation between the increase in LPO and congenital malformation. Plant extract, vitamin E and C caused partial decrease of embryo toxicity and congenital malformation induced by VPA in mice.

Key words: Valproic acid, congenital malformation, embryotoxicity, oxidative stress, lipid peroxidation, Chrysanthemum fantanesii, vitamin E and C.