A Study on the Anticonvulsant Activity of the Simultaneous Administration of Melatonin, Agmatine, and Vitamin D3 on Pentylenetetrazole-Induced Seizures in Mice

Abstract

Background: Epilepsy is a neurological disorder characterized by a decreased level of vitamins and endogenous antioxidants and an enhanced level of oxidative stress. Objective: We designed this study to define the effects of combining melatonin, vitamin D3 (Vit D3), and agmatine on seizures caused by pentylenetetrazole (PTZ) in male NMRI mice. Methods: The experimental groups were as follows: the first group was administered normal saline (0.5 ml, i.p.) on the last day of the trial, and the second group was administered intraperitoneal PTZ (60 mg/kg) on that day. Pre-treatment with diazepam (4 mg/kg), vitamin D3 (6000 IU/kg, p.o.), agmatine (40 mg/kg, p.o.), and melatonin (20 mg/kg, p.o) was given to the next four groups before injecting PTZ (60 mg/kg, i.p.). The last group received a compound therapy of vitamin D3, melatonin, and agmatine before PTZ injection. Afterward, the latency, duration, and oxidative stress indications were evaluated in the brains of mice. Results: Treatments enhanced the latency of seizure and reduced seizure duration in comparison with the PTZ group; the compound group increased seizure latency more than Vit D3, agmatine, and melatonin groups and decreased the duration more than pre-treatment with Vit D3. We observed enhancement in superoxide dismutase (SOD) and catalase (CAT) activity in the treatment groups, while in the combination group, elevating CAT activity was comparable with Vit D3 and agmatine groups. The malondialdehyde level decreased in diazepam, agmatine, melatonin, and combination groups. Conclusion: The compound treatment was more efficient than each one alone in improving PTZinduced seizure, which may result from suppressing oxidative stress.