Glutamate Excitotoxicity and Oxidative Stress in Epilepsy: Modulatory Role of Melatonin

Abstract

Epilepsy is thought to be associated with oxidative stress, glutamate excitotoxicity, and mitochondrial dysfunction. The enhanced synthesis and release of oxygen free radicals is linked to the low and oxidative potential of the central nervous system. Glutamate excitotoxicity also contributes significantly to the production of reactive nitrogen species that cause nitrosative stress. A decrease in adenosine triphosphate synthesis, which leads to free radical formation, is associated with mitochondrial dysfunction. The brain is very much susceptible to degeneration and oxidative stress because of its low antioxidant enzyme activity. Melatonin, a hormone secreted by the pineal gland, has remarkable antioxidant properties. Melatonin and its analogs that bind to melatonin receptors have a significant role in suppressing seizures. Melatonin scavenges oxygen free radicals such as hydroxyl radical, peroxy radical, peroxynitrite anion, and superoxide radical and stimulates synthesis of superoxide dismutase and glutathione peroxidase, which are potent antioxidant enzymes. Melatonin administration has been shown to be effective in both experimental models and patients suffering from epilepsy. In this review, we compile the literature supporting consequences of seizures and the protective role of melatonin during seizures.