title: Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.
abstract: Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation.
authors.affiliation: Department of Bioanalysis and Drug Analysis, Medical University of Warsaw, Banacha 1 St., 02-097 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dominiak
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wilkaniec
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Jęśko
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.
authors.forename: Grzegorz A
authors.initials: GA
authors.lastname: Czapski
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lenkiewicz
authors.affiliation: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101 St., 02-089 Warsaw, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Kurek
authors.affiliation: Department of Bioanalysis and Drug Analysis, Medical University of Warsaw, Banacha 1 St., 02-097 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wroczyński
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland. Electronic address: agataadamczyk72@gmail.com.
authors.forename: Agata
authors.initials: A
authors.lastname: Adamczyk
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000378:metabolism*; D018036:Selenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018036:Selenium Compounds; C105370:selol; D012643:Selenium
keywords: Lipopolysaccharide; Neurodegenerative disease; Neuroinflammation; Organic selenium compound; Selenoenzyme; Selol