The Effect of Valproic Acid on DNA Damage and Apoptosis After Pentylenetetrazole-induced Epileptic Seizure Generated in the Hippocampus and Cortex in Rats

Abstract

the treatment of epilepsy. Recent studies have shown that VPA may have some negative effects on nerve cells, but this issue has not been clarified yet. The aim of this study was to investigate the effect of VPA on DNA damage and apoptosis after pentylenetetrazole (PTZ) induced epileptic seizure generated in the hippocampus and cortex in rats. In the study, 18 males 230-250 grams of rats were used. Rats are divided into three groups as control (physiological serum 1 ml kg-1 + physiological serum 1 ml kg-1; n=6), PTZ (physiological serum 1 ml kg-1 + PTZ; n=6) and VPA (150 mg kg-1 VPA+PTZ; n=6). Seizure was induced by administering 45 mg kg-1 pentylenetetrazole intraperitoneally twenty minutes after the administration at the indicated doses to the PTZ group and VPA group. The brain tissues of all rats were removed, and cortex and hippocampus areas were separated 24 hours after seizure. 8-hydroxy-2'-deoxyguanosine (8-OhDG), which is a DNA damage marker, and caspase-3, which is a marker of apoptosis, were measured in the cortex and hippocampus tissues by the enzyme-linked immunosorbent assay (ELISA) method. One-way ANOVA variance analysis was used for statistical evaluation. In the PTZ group, the 8-OhDG level increased in both cortex and hippocampus compared to the control group (p<0.05). Therefore, VPA enhanced the 8-OhDG level after seizure compared to the PTZ group in the cortex and hippocampus (p<0.05). In addition, the level of caspase-3 in the cortex significantly raised compared to the control in the PTZ group (p<0.05). Moreover, VPA significantly improved the level of caspase-3 in the cortex compared to the PTZ group (p<0.05). In conclusion, VPA increased DNA damage and apoptosis after seizures in rats.