Handbook of Vitamin C Research

308Mustafa NazıroğluFuture DirectionsMany antiepileptic drugs are metabolized to generate reactive metabolites with thecapability of covalent binding to macromolecules as proteins or other vital biomolecules andhence elicit systemic toxicity. There are conflicting reports on interaction of antiepilepticdrugs, oxidative stress and ascorbic acid supplementation in the systemic toxicity of cells.Hence, there is a need for further studies on the interaction of new antiepileptic drugs,oxidative stress and ascorbic acid supplementation in epileptic animals and humans.Transient receptor potential (TRP) channels were first described in Drosphila, wherephotoreceptors carrying trp gene mutations exhibit a transient voltage response to continuouslight [61]. Like many other cells, neurons contain polyADP-ribose polymerase 1 (PARP-1),an enzyme that responds to DNA damage by cleaving NAD + and attaching ADP-ribose(ADPR) residues to nuclear proteins to facilitate DNA repair. Overactivation of PARP-1 cankill cells by depleting NAD + , preventing energy and is involved in opening TRPM2 cationchannels (Figure 1). Deletion of exon 11 of TRPM2 is known to cause dysregulation ofcellular calcium homeostasis in response to oxidative stress in epilepsy [66]. There is noreport on the role of TRP in epileptic patients and animals via free oxygen radicals. There isalso no report on the effect of ascorbic acid in the channels in epileptic cells. Hence, thesubjects should be clarified in future experiments.Table 1. Effects of Vitamin C doses on epileptic seizures in rat modelsVitamin C dose (mg/kg) Epilepsy induced by Effect ReferenceHigh (300)High (500)High (800)PTZAmphetaminePenicillinAnticonvulsantConvulsantNo effectYamamato et al. [49]Pierce et al. [54]Ayyildiz et al. [30]Intermediate (100-200)Intermediate (100)Intermediate (250)Intermediate (250)Intermediate (250)Intermediate (250)Intermediate (250)Low (30)Low (50)Low (50)PTZ; pentylentetrazol;PenicillinPTZPilocarpinePilocarpinePTZKainic acidPilocarpinePTZAmphetamineKainic acidAnticonvulsantConvulsantAnticonvulsantAnticonvulsantNo effectNo effectAnticonvulsantNo effectanticonvulsantNo effectAyyildiz et al. [30]Oliveira et al. [44]Xavier et al. [56]Xu and Stringer [64]Xu and Stringer [64]Xu and Stringer [64]Santos and Freitas [2]Oliveira et al. [44]Wambebe and Skomba [53]Sumanont et al. [55]References[1] Nazıroğlu, M. Molecular Mechanisms of vitamin E on intracellular signaling pathwaysin brain. In: Reactive Oxygen Species and Diseases. Ed.; Laszlo Goth, ResearchSignpost Press: Kerala, India. pp 2007,239-256.[2] Santos LFL, Freitas RLM, 2008 Pharm Biochem Behaviour 89, 1-5.