title: Effects of selenium and topiramate on cytosolic Ca(2+) influx and oxidative stress in neuronal PC12 cells.
abstract: It has been widely suggested that selenium (Se) deficiency play an important role in the pathophysiology of epilepsy. It has been reported that Se provides protection against the neuronal damage in patients and animals with epilepsy by restoring the antioxidant defense mechanism. The neuroprotective effects of topiramate (TPM) have been reported in several studies but the putative mechanism of action remains elusive. We investigated effects of Se and TPM in neuronal PC12 cell by evaluating Ca(2+) mobilization, lipid peroxidation and antioxidant levels. PC12 cells were divided into eight groups namely control, TPM, Se, H(2)O(2), TPM + H(2)O(2), Se + H(2)O(2), Se + TPM and Se + TPM + H(2)O(2). The toxic doses and times of H(2)O(2), TPM and Se were determined by cell viability assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM H(2)O(2) for 10 h before analysis. The cells in all groups except control, TPM and Se were exposed to H(2)O(2) for 15 min before analysis. Cytosolic Ca(2+) release and lipid peroxidation levels were higher in H(2)O(2) group than in control, Se and TPM combination groups although their levels were decreased by incubation of Se and TPM combination. However, there is no difference on Ca(2+) release in TPM group. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in H(2)O(2) group than in control, Se and TPM groups although their values were higher in the cells incubated with Se and TPM groups than in H(2)O(2) groups. In conclusion, these results indicate that Se induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) influx and antioxidant levels. TPM modulated also lipid peroxidation and glutathione and vitamin C concentrations in the cell system.
authors.affiliation: Department of Neurology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey.
authors.forename: Seden
authors.initials: S
authors.lastname: Demirci
authors.forename: Süleyman
authors.initials: S
authors.lastname: Kutluhan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Naziroğlu
authors.forename: Abdülhadi Cihangir
authors.initials: AC
authors.lastname: Uğuz
authors.forename: Vedat Ali
authors.initials: VA
authors.lastname: Yürekli
authors.forename: Kadir
authors.initials: K
authors.lastname: Demirci
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000633:toxicity; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D012643:Selenium / Q000494:pharmacology* / Q000633:toxicity; D000077236:Topiramate
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D016877:Oxidants; D000077236:Topiramate; D005632:Fructose; D006861:Hydrogen Peroxide; D005978:Glutathione; D012643:Selenium; D001205:Ascorbic Acid; D002118:Calcium