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Background and Objective: Valproic acid is used in the epilepsy, bipolar and migraine therapy. As a histone deacetylase inhibitor, Valproic acid has been recently under investigation in cancer treatment, either alone or in combination with either chemotherapy or radiotherapy. This study was done to determine the effect of Valproic acid and radiotherapy on viability of MCF-7 breast cancer cell line. Methods: In this descriptive - analytic study, MCF-7 cell line was obtained from the Iranian Pasteur Institute. The cells were treated and incubated by different concentrations of Valproic acid (1, 2, 4, 8, 16, 32, 64 and 128 mM) either alone or in combination with various dosages (0 .5, 2, 4, 6 and 8 Gray) of radiotherapy. After cell viability assay, using the Neutral red staining, the most nearest results to LD50 were selected. Cell viability was evaluated with trypan blue staining. Results: The most nearest concentrations of LD50 was doses of 2, 8 and 16 mM of valproic acid and dosage of Gray 4 of radiation. There was a significant dose-dependent correlation between reduction of cell viability with valproic acid concentration (P<0.05). Conclusion: Valproic acid, either alone or combination with radiotherapy caused a significant decline in the cell viability of MCF-7 breast cancer cell line.

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Background and Objective: Ovarian cancer is the fifth common cancer among women and the number of new cases is increasing. Valproic acid is a histone deacetylase inhibitor effectively used to treat epilepsy and bipolar disease. Recently, this compound has attracted attention as an anti-cancer agent. Bim is one of the most important genes of mitochondrial pathway of apoptosis, and it plays an important role in the biology of cancer. Expression of this gene is greatly reduced in ovarian cancer. This study was done to evaluate the effect of valproic acid on the viability of ovarian cancer cells, apoptosis and Bim gene expression in A2780 line.
Methods: In this experimental study, the human ovarian cancer cells (A2780) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated by various concentrations valproic acid (1-30 mM) and were incubated for 24, 48 and 72 hours. After the incubation of period, cell viability was investigated using MTT. Apoptosis was analyzed by flow-cytometry method in the cells were treated by valproic acid. The Real time PCR test was used to assess the effect of this drug on the expression of Bim gene.
Results: The results of MTT assay showed that valproic acid reduced the viability of A2780 cells, and this effect was time and dose-dependent. The reduction of cell viability at 30 mM concentration and 72 hours after treatment, was maximum and statistically significant (P<0.05). Exposure to valproic acid significantly increased the percentage of apoptotic cells (P<0.05). Also, Valproic acid significantly increased the expression of Bim (P<0.05).
Conclusion: Valproic acid reduced viability in ovarian cancer cell line A2780. Valproic acid increased cell death by altering the expression of genes involved in apoptosis in ovarian cancer cell line A2780.

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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.