Molecular docking to investigate the inhibitory activity and the role of nitric oxide in anticonvulsant effects of vitamin D on pentylenetetrazole‑induced epileptic seizures in rats

Abstract

Despite the great breakthroughs in the field of epilepsy studies, the present drugs are ineffective in one-third of the patients, as well as without providing a definite treatment. There is accumulating evidence suggesting the role of vitamin D in epilepsy. The aim of this study was to investigate the effect of vitamin D on seizure formation, post-seizure cognitive functions, and the possible role of nitric oxide and oxidative stress in this effect, in the PTZ-induced seizure rat model. Sixty male Wistar albino rats were used in this study. The rats were randomly divided into 11 groups each containing 6 animals: Group 1: Control; Group 2: Saline+PTZ (45 mg/kg); Group 3: Vitamin D (1.5 mg/kg)+PTZ; Group 4: L-Arginine (500 mg/kg)+PTZ; Group 5: L-NAME (60 mg/kg)+PTZ; Group 6: 7-Nitroindazole (40 mg/kg); Group 7: Aminoguanidine (100 mg/kg)+PTZ; Group 8: Vitamin D+L- Arginine+PTZ; Group 9: Vitamin D+L-NAME+PTZ; Group 10: Vitamin D+7-Nitroindazole+PTZ; Group 11: Vitamin D+Aminoguanidine+PTZ. Animal behavior was evaluated with open field and passive avoidance tests. Nitric oxide (NO), total oxidative status (TOS), and total antioxidant status (TAS) levels in the cortex and hippocampus brain regions were determined by ELISA method. The treatment of vitamin D in combination with NO inhibitors has a positive effect on the PTZ-induced seizures and ameliorate post-seizure learning deficits. Moreover, the combination of vitamin D with NO inhibitors reduced oxidative stress and NO levels after seizures in the cortex and hippocampus. Also, we employed molecular docking and density functional theory analysis to investigate the inhibitory activity, reactivity, and stability of Vitamin D with other NO inhibitors. Vitamin D supplementation could be effective as a supportive treatment drug in epileptic patients, according to the findings.