Handbook of Vitamin C Research

Effects of Vitamin C on Oxidative Stress-Induced Molecular… 307antiepileptic drug therapy [58, 59], whereas topiramate, induces antioxidant role in epilepticanimals and humans [38].Alteration in antioxidant enzyme resulting in reduction in GSH-Px activity and elevatedglutathione reductases has been demonstrated in children and adults receiving valproic acidtherapy [58, 59]. Sometimes, such changes have been associated with elevated serum lipidperoxidative levels in children receiving chronic valproic acid therapy [58, 59]. Sudha et al.[60] reported that antiepileptic drug (phenobarbital) showed a significant increase in plasmaascorbic acid levels in erythrocytes of ten epileptic patients compared to their pre-treatmentcondition.Figure 1. A large number of studies seizure-induced cell damage to excitotoxic mechanisms [seereference 28]. Free radical generation can induce seizure activity by direct activation of glutaminesynthatase thereby permitting an abnormal build up of excitatory neurotransmitter glutamic acid. Theonset of oxygen induced convulsions in epileptic patients and animals is correlated with a decrease incerebral content of neurotransmitter GABA because of inhibition of enzyme glutamate decarboxylaseby the reactive oxygen species (ROS). Convulsions can results in augmented glutamate release, leadingto Ca 2+ uptake through N-methyl-D-aspartate (NMDA) and voltage- gated Ca 2+ channels (VGCC).Mitochondria were reported to accumulate Ca 2+ provided cytosolic Ca 2+ rises exceed 400 nM orprovided mitochondrial uptake dominates mitochondrial Ca 2+ extrusion [62], thereby leading todepolarization of mitochondrial membranes. On the other hand, exposure of mitochondria high freeCa 2+ was shown to increase formation of ROS [63]. Sustained depolarization of mitochondrialmembranes and enhanced ROS production. ROS activates transient potential melastatin 2 (TRPM2)channels and Ca 2+ influx increases by activation of TRPM2 via ROS [61]. The molecular pathway maybe a cause of epileptic seizures and the subject should urgently investigate.