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.

Cobinamide is effective for treatment of hydrogen sulfide–induced neurological sequelae in a mouse model

“…Although the mechanisms of H 2 S-induced seizures are unknown, changes in concentrations of neurotransmitters such as GABA and glutamate and neural inflammation have been associated with seizures. 38,39 We did not measure GABA and glutamate in the above study, but we observed neuroinflammation. Cob at 100 mg/kg reduced neuroinflammation, and this may have reduced seizure activity.…”

“…Seizure activity in surviving mice was significantly reduced or prevented by Cob. Although the mechanisms of H 2 S‐induced seizures are unknown, changes in concentrations of neurotransmitters such as GABA and glutamate and neural inflammation have been associated with seizures . We did not measure GABA and glutamate in the above study, but we observed neuroinflammation.…”

Intranasal Glyphosate-Based Herbicide Administration Alters the Redox Balance and the Cholinergic System in the Mouse Brain

“…Once released, GLU must be rapidly removed (Daikhin and Yudkoff, 2000), in order to avoid neurotoxicity (Leibowitz et al, 2012). GLU excitotoxicity is one of the main factors for ROS generation in the brain (Bai et al, 2016;Cattani et al, 2017;Vishnoi et al, 2016). IN exposure to GlyBH affected the GPT activity in PFC and CPu.…”

Attenuated glutamate induced ROS production by antioxidative compounds in neural cell lines

“…In those process, glutamate-induced neurodegenerative diseases and neuronal cell death is usually associated with oxidative stress. [8][9][10] The over accumulated ROS, as well as the oxidative stress, are tightly associated with inhibition of glutathione synthesis, nitrosative stress et al [11][12][13] Several antioxidants compounds has been investigated to reduce oxidative stress, and potentially served as therapeutic agent. [14][15][16][17] Polyphenols are one of the groups exhibit strong free radicals scavenging activity.…”