Evaluation of fetal protective effect of Resveratrol against teratogenic effect of sodium valproate in mice through evaluation of inflammation, apoptosis and oxidative stress pathways

Background: There are some studies that sodium valproate is associated with some major and minor malformations and its placental transfer influences oxidative stress processes. Resveratrol is a drug with few side effects and high antioxidant and cell protection properties,. Objectives: This study aimed to evaluate the protective effects of Resveratrol as a natural compound with antioxidant properties on oxidative stress and teratogenic effect induced by transfer of transplacental sodium valperoate in mice Methods: The female mice (25-30 gm, 3 weeks years old) were divided into 5 groups (6 mice per group). Of control, Sodium Valperoate (400 mg/kg/day by gavage from day 8 to 18 of pregnancy.) and Resveratrol (225,350,600 mg/kg/day by IP+SodiumValperoate 400mg/kg/day). All groups were received as a single injection. Administration for 10 consecutive days of pregnancy period were done. After baby mice were born, all neonatal mice were killed with beheading. Then, the liver,heart, brain, and kidney tissues were excited. Then samples were used for assessment of oxidative stress markers including lipid peroxidation (LPO), glutathione (GSH), and protein carbonyl (PrC) content .and inflammatory markers as IL6,NfKB,Sirt1 by realtime PCR and their tissues for histopathology studies Results: This study showed that SodiumValperoate caused a significant decrease in GSH concentration. Also were observed a significant increase in lipid peroxidation (LPO) and protein carbonyl contents. However, Resveratrol treatment significantly inhibited oxidative stress markers, decreased IL6, NfKB, and Sirt1 in heart, kidney and liver and brain of neonatal mice significantly which affected by sodium valproate.(P<0.05).Also histopathology studies show protective effect of Resveratrol in theses tissues Conclusions: Our findings showed that resveratrol has a protective effect against oxidative stress and inflammatory process induced by placental transfer of sodium valproate in mice