Handbook of Vitamin C Research

Effects of Vitamin C on Oxidative Stress-Induced Molecular… 305in membrane phospholipids metabolism result in liberation of free fatty acids, particularlyfree arachidonic acid, diacylglycerols, eicosanoids, lipid peroxides and free radicals in brain.These lipid metabolites along with abnormal ion homeostasis and lack of energy regenerationmay contribute to neuronal injury [29]. Many previous studies have demonstrated thatoxidative stress might be involved in the pathophysiology of epilepsy in penicillin [30], ferricchloride [31], kainite [32], pilocarpine [2] and PTZ-induced epilepsy [33-37]. In fact, severalrecent studies have demonstrated an increase in diverse biochemical hallmarks of ROSformation, such as thiobarbituric acid reactive substances (TBARS), malondialdehyde(MDA) [2,38,39], protein carbonyl [40] and NO [41]. There are also conflicting reports onoxidative stress and epilepsy. For example, Verrotti et al. [42] recently reported that weobserved no difference in oxidative stress between epileptic patients and healthy controlsubjects.Frantseva et al. [36] presented evidence that lipid peroxidation increases during seizuresin the kindling model of epilepsy, suggesting that free radical increase during seizures occurindependent of iron salts or exocitotoxins. Ayyildiz et al. [30] reported that the most effectivedose of ascorbic acid (100 mg/kg) prevented increase in level of lipid peroxidation in thepenicillin-induced epilepsy in rats. Shin et al. [43] reported that treatment with ascorbic acid,at doses of 50 and 100 mg/kg, significantly attenuated trimethyltin-induced seizures as wellas the initial oxidative stress. The effects of ascorbate are complex, and other mechanisms,unrelated to its reactive species scavenger ability, are claimed to explain the neuroprotectiveactions of this vitamin [44]. Oliveira et al. [44] reported that 30 mg/kg ascorbate preventedtotal protein carbonylation, but did not prevented PTZ-induced convulsions. Similardissociation was observed when the effect of 100 mg/kg ascorbate on PTZ-inducedconvulsions and protein carbonylation was investigated, since this dose of ascorbatepotentiated PTZ-induced convulsions, but did not further increase total protein carbonylation[44].Wang et al. [45] provided evidence to support involvement of free radical intermediatesin iron-ascorbic acid reactions. Moreover, it was reported that ascorbate acts as prooxidant inthe presence of iron and shows excellent scavenging properties in the absence of iron [46].They also suggested that no further benefit could be achieved by increasing the intake ofascorbate, while the prooxidant action will increase, and the net effect is to shift to thedeleterious side [46]. Some authors reported that they did not observe protective effect ofvitamin C at high doses in the presence of high iron in epileptic rats [30].Treatment of Epilepsy with Vitamin C in Experimental Animal ModelsThere are different models of induction of epilepsy in experimental animals. The striatumhas been choosing as the target for the injection of PTZ because of the strong GABAergictonus that exists in this structure that makes it particularly sensitive to the effects of PTZ andother GABAergic antagonists [47]. Accordingly, the striatum is activated during seizuresinduced by different agents, such as methylmalonic acid, DL-homocysteic acid, 4-aminopyridine and PTZ [Reviewed in 48].It has been suggested that ascorbate hasneuroprotective properties in some experimental model of seizure activity induced by various