Handbook of Vitamin C Research

306Mustafa Nazıroğluagents, such as iron [49] and PTZ [44]. In fact ascorbate administration attenuates kainiteelicitedlipid peroxidaiton and neuronal loss in the rat hippocampus [50] and decreases thenumber and duration of methylmalonic acid-induced convulsive episodes [51]. Accordingly,an effective anticonvulsant dose of GM1 ganglioside, besides increasing catalase activity[52], increases cerebral ascorbate content [52], further suggesting a protective role forascorbate in the inhibition of methylmalonic acid-induced convulsions. Accordingly,Yamamato et al. [49] demonstrated that an ascorbate synthetic derivate prevents theoccurrence of ferric-ion-induced epileptic discharges in a rat model of post-traumaticepilepsy. Further evidence for an anticonvulsant role for ascorbate comes from a study thatreported ascorbate, at high doses (300 mg/kg) protected against PTZ-induced convulsion,further suggesting an anticonvulsant and neuroprotective role for ascorbic acid [44]. Theyreported that ascorbate at a dose that no effect on PTZ-induced convulsions or inhibition ofNa + , K + -ATPase activity (30 mg/kg) attenuated the increase in striatal protein carbonylcontent induced by PTZ. Conversely, they showed that systemic ascorbate administration(300 mg/kg) significantly prevented PTZ-induced effects, namely convulsion and increase intotal striatal protein carbonylation (it is an oxidative stress marker) and Na + , K + -ATPaseactivity inhibition. The fact that ascorbate, at the low doses (50-200 mg/kg), has beenreported to enhance amphetamine-induced behavior activation [53] and conditioned placepreference [54], and that ascorbate at a high dose (500 mg/kg), had either no, or anoppositing effect, on these behaviors [54] constitutes further evidence for a biphasic effect ofascorbate on central nervous system functions. Recent study of Ayyildiz et al. [30] reportedthat ascorbic acid, high dose (800 mg/kg), did not significantly change either the frequency oramplitude of penicillin- induced epileptic activity in rat. However, -tocopherol at high dose(500 mg/kg) had maximal anticonvulsant effect in the penicillin-induced epileptiform activityin other study of Ayyildiz et al. [55]. Ascorbic acid has been reported to significantly increasethe latency to first seizure, reduce seizure severity, and improve survival in the pilocarpinemodel at a dose of 250 mg/kg given 30 minutes before pilocarpine [56], but is reported to beineffective in the kainic acid model at 50 mg/kg [57]. In a recent study of Xu and Stringer[6] ascorbic acid was dissolved in physiological saline and administrated intraperitoneally ata dose of 250 mg/kg 10 minutes before the convulsants (pilocarpine, kainic acid and PTZ)and they were observed that ascorbic acid had significant anticonvulsant activity againstpilocarpine although vitamin C did not significant effects against PTZ- or kainic acid-inducedseizures. Recently, Santos et al. [2] reported that vitamin C pretreatment decreasedhippocampal lipid peroxidation and brain seizures in pilocarpine-induced epileptic rats.Vitamin C, Oxidative Stress and Antiepileptic DrugsThere are conflicting reports on antiepileptic drugs, oxidative stress and ascorbic acid inhumans and animals. Generally previous papers are reporting oxidant role of antiepilepticdrugs, whereas recent papers are reporting antioxidant role of antiepileptic drugs. In addition,the reports are also conflicting type of antiepileptic drugs. For example, valproic acid iscommonly used in the treatment of epilepsy and it induced oxidative stress although new