The effects of vitamin D3 and melatonin combination on pentylenetetrazole-induced seizures in mice.

Abstract

BACKGROUND Epileptic seizures are associated with the overproduction of free radicals in the brain leading to neuronal cell death. Therefore, reduction of oxidative stress may inhibit seizure-induced neuronal cell damage. Current study evaluated the effects of Vit D3 and melatonin and their combination on pentylenetetrazol (PTZ)-induced tonic clonic seizures in mice. METHODS Animals were divided into six groups. Group I was administrated with normal saline (0.5 ml, intraperitoneally (i.p.)) on the 15th day of experiment. Group II was injected with PTZ (60 mg/kg dissolved in 0.5 ml normal saline, i.p) on the 15th day. Groups III-IV were treated with diazepam (4 mg/kg/day), Vit D3 (6000 IU/kg/day), melatonin (20 mg/kg/day) and Vit D3 (6000 IU/kg/day)/melatonin (20 mg/kg/day), respectively, and were then injected with PTZ (60 mg/kg) on the 15th day of experiment. Immediately after the injection of PTZ on the 15th day, mice were observed for a 30-min period for the measurement of seizure latency and duration. For determination of oxidative stress markers, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured in mouse brains. RESULTS Treatment with Vit D3, melatonin, and Vit D3/melatonin significantly increased seizure latency and decreased seizure duration. The brain level of MDA was lower and SOD activity was greater than the PTZ group. Mice treated with Vit D3/melatonin had lower seizure duration compared to other treated groups. CONCLUSIONS Combination of Vit D3 and melatonin may reduce seizure frequency in epileptic patients; this effect may result from various mechanisms including inhibition of oxidative stress.