title: Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells.
abstract: Selol is an organic selenitetriglyceride formulation containing selenium at +4 oxidation level that can be effectively incorporated into catalytic sites of of Se-dependent antioxidants. In the present study, the potential antioxidative and cytoprotective effects of Selol against sodium nitroprusside (SNP)-evoked oxidative/nitrosative stress were investigated in PC12 cells and the underlying mechanisms analyzed. Spectrophoto- and spectrofluorimetic methods as well as fluorescence microscopy were used in this study; mRNA expression was quantified by real-time PCR. Selol dose-dependently improved the survival and decreased the percentage of apoptosis in PC12 cells exposed to SNP. To determine the mechanism of this protective action, the effect of Selol on free radical generation and on antioxidative potential was evaluated. Selol offered significant protection against the elevation of reactive oxidative species (ROS) evoked by SNP. Moreover, this compound restored glutathione homeostasis by ameliorating the SNP-evoked disturbance of GSH/GSSG ratio. The protective effect exerted by Selol was associated with the prevention of SNP-mediated down-regulation of antioxidative enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR), and thioredoxin reductase (TrxR). Finally, GPx inhibition significantly abolished the cytoprotective effect of Selol. In conclusion, these results suggest that Selol effectively protected PC12 cells against SNP-induced oxidative damage and death by adjusting free radical levels and antioxidant system, and suppressing apoptosis. Selol could be successfully used in the treatments of diseases that involve oxidative stress and resulting apoptosis.
authors: Department of Bioanalysis and Drug Analysis, Medical University of Warsaw, 1 Banacha St., 02-097, Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Dominiak
authors: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland.
authors: Anna
authors: A
authors: Wilkaniec
authors: Department of Bioanalysis and Drug Analysis, Medical University of Warsaw, 1 Banacha St., 02-097, Warsaw, Poland.
authors: Piotr
authors: P
authors: Wroczyński
authors: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland.
authors: Henryk
authors: H
authors: Jęśko
authors: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland. agataadamczyk72@gmail.com.
authors: Agata
authors: A
authors: Adamczyk
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D015538:Nitrosation; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D018036:Selenium Compounds / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D018036:Selenium Compounds; D009599:Nitroprusside; C105370:selol; D005978:Glutathione
keywords: Antioxidative defense; Cytoprotection; Organic selenium compound; Oxidative/nitrosative stress; Selenoenzymes; Selol