Evaluation of CREB gene expression to investigate resveratrol’s protective effect against sodium valproate-induced oxidative stress in mouse neural tissue

Sodium valproate (SV) is a widely used antiepileptic drug; however, its therapeutic application may be limited by its potential to induce oxidative stress. The present study evaluated the protective effect of resveratrol (REV) on CREB gene expression and malondialdehyde (MDA) levels in mouse neural tissue following prenatal exposure to sodium valproate. Fifteen Balb-C mice were kept in five groups of three per cage (two females and one male) and monitored daily for estrous cycles. After confirming pregnancy, the mice were divided into the following five groups: control, SV (400 mg/kg), SV (400 mg/kg) + REV (600 mg/kg), SV (400 mg/kg) + REV (350 mg/kg), and SV (400 mg/kg) + REV (225 mg/kg). Drug interventions began on days eight to eighteen of pregnancy and continued until delivery. Two to three days before birth, eight fetuses from each group were surgically removed under anesthesia. Thebrain tissue was collected and CREB gene expression was measured using real-time PCR. Lipid peroxidation was assessed using the thiobarbituric acid reactive substances (TBARS) method to measure malondialdehyde (MDA) levels. Sodium valproate significantly reduced CREB gene expression in brain tissue (p < 0.001) and increased MDA levels (p < 0.001). In contrast, resveratrol significantly upregulated CREB expression (p < 0.001) and reduced MDA concentrations, with the most pronounced gene expression effect observed at 350 mg/kg and the strongest reduction in lipid peroxidation at 600 mg/kg. The findings showed that resveratrol can effectively counteract sodium valproate-induced CREB gene downregulation and oxidative stress.