Effect of Resveratrol on Sodium Valproate-Induced Oxidative Stress in the Hippocampal Tissue of BALB/c Mouse Fetuses

Background and Objective: Sodium valproate (SV) is a commonly used antiepileptic drug; however, its therapeutic application is limited due to its potential to induce oxidative stress. Resveratrol, a natural polyphenol, possesses antioxidant properties. This study was conducted to determine the effect of resveratrol on SV-induced oxidative stress in the hippocampal tissue of BALB/c mouse fetal brains. Methods: In this experimental study, 40 pregnant female BALB/c mice were randomly assigned to 5 groups of 8, including control, SV at 40 mg/kg/bw, SV at 40 mg/kg/bw + resveratrol at 0.6 mg/kg/bw, SV at 40 mg/kg/bw + resveratrol at 0.35 mg/kg bw, and SV at 40 mg/kg/bw + resveratrol at 0.225 mg/kg/bw. SV was administered orally per day, and resveratrol was administered daily via intraperitoneal injection. From gestational day 8 to 18, pharmacological interventions were initiated and continued until the birth of the neonates. On gestational day 18, the maternal mice were anesthetized, and 8 fetuses from each group were separated. Following the anesthesia of the fetuses, the brain tissue was dissected. Subsequently, oxidative stress parameters, including the malondialdehyde (MDA) level in nmol/mg as an index of lipid peroxidation, glutathione (GSH) level alterations in µg/mg, and protein carbonyl (PC) level alterations in nmol/mg, were evaluated in the hippocampal tissue. Results: SV induced oxidative stress by increasing MDA (4.8 nmol/mg) and PC (51.4 nmol/mg protein), and also decreasing GSH (31.86 μg/mg) in the brain tissue compared to the control group (P<0.05). In a concentration-dependent manner, resveratrol reduced oxidative stress by decreasing MDA and PC to 3.02 and 37.21 nmol/mg, respectively, and also by increasing GSH to 49.76 μg/mg in the brain tissue. The most significant effect was observed at a concentration of 0.6 mg/kg/bw, which was statistically significant compared to the SV group (P<0.05). Conclusion: The combined administration of SV and resveratrol culminates in a reduction in inflammation and oxidative stress-related factors in mouse fetuses.