The Anticonvulsant Activity of Thiamine, Vitamin D3, and Melatonin Combination on Pentylenetetrazole-induced Seizures in Mice

Objective: Epilepsy is a neurological disorder associated with the elevation of oxidative stress levels and alteration in vitamins and endogenous antioxidant levels. The current study was designed to evaluate the effects of Vit D3, thiamine, melatonin, and their combination on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in mice along with measuring the alteration in oxidative stress markers. Methods: Male mice were randomly divided into seven groups; group I received normal saline (0.5 ml, i.p.) on the 15^th day, group II received PTZ (60 mg/kg, i.p) on the 15^th day, groups III-VI received diazepam (4 mg/kg), Vit D3 (6000 IU/kg, p.o.), thiamine (200 mg/kg, p.o.), and melatonin (20 mg/kg, p.o.), respectively, before PTZ (60 mg/kg, i.p.) injection on the 15th day, and group VII received the combination of Vit D3, thiamine, and melatonin, before PTZ injection on the 15^th day. After PTZ injection, the seizure latency and duration were measured. The malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were evaluated in mice brains. Results: In the treatment group, the seizure latency was greater and the seizure duration was lower than in the PTZ group. These agents decreased the MDA level and increased SOD activity compared to the PTZ group. The combination of these agents was more effective than each alone to increase seizure latency and reduce seizure duration. Conclusion: The combination of Vit D3, thiamine, and melatonin could improve PTZ-induced seizures more effectively than each one alone; this may be mediated by inhibiting oxidative stress and regulating various mechanisms involved in seizures.