The Oxidative Stress in Epilepsy-Focus on Melatonin

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Oxidative stress, an imbalance of oxidants, causes cellular damage and is linked to seizure activity and lipid peroxidation.
• Antiseizure medications typically reduce oxidative stress, but levetiracetam's effect remains unclear.
• Various exogenous antioxidants, including curcumin, demonstrate anticonvulsant properties in preclinical models and some clinical studies for epilepsy.

Purpose of the Study:

• To investigate the dual role of melatonin, an antioxidant, in seizure activity.
• To explore the potential of antioxidants, including melatonin, as adjunctive therapies for epilepsy.

Main Methods:

• Review of experimental and clinical studies on oxidative stress, seizure activity, and antioxidant interventions.
• Analysis of data on the effects of exogenous and endogenous melatonin on seizure thresholds and activity.
• Examination of potential mechanisms, including GABA-mediated inhibition and dopaminergic transmission.

Main Results:

• Exogenous antioxidants, such as vitamin E, resveratrol, hesperidin, curcumin, and melatonin, have shown anticonvulsant effects in animal models.
• Clinical data suggest curcumin's efficacy as an adjuvant for pediatric intractable epilepsy.
• Melatonin attenuates seizure activity in rodents, with clinical support, but endogenous melatonin may promote seizures by reducing brain dopaminergic transmission.

Conclusions:

• Antioxidants, including melatonin, may serve as beneficial adjuvants in epilepsy therapy.
• Melatonin's potential use extends to epilepsy patients with comorbid sleep disorders.
• The proconvulsive effect of endogenous melatonin warrants further investigation, particularly regarding its impact on dopaminergic pathways.