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Diphenyl diselenide protects neuronal cells against oxidative stress and mitochondrial dysfunction: Involvement of the glutathione-dependent antioxidant system
- Source :
- Redox Biology, Vol 20, Iss, Pp 118-129 (2019), Redox Biology, Repositório Institucional da UnB, Universidade de Brasília (UnB), instacron:UNB
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Oxidative stress and mitochondrial dysfunction are critical events in neurodegenerative diseases; therefore, molecules that increase cellular antioxidant defenses represent a future pharmacologic strategy to counteract such conditions. The aim of this study was to investigate the potential protective effect of (PhSe)2 on mouse hippocampal cell line (HT22) exposed to tert-BuOOH (in vitro model of oxidative stress), as well as to elucidate potential mechanisms underlying this protection. Our results showed that tert-BuOOH caused time- and concentration-dependent cytotoxicity, which was preceded by increased oxidants production and mitochondrial dysfunction. (PhSe)2 pre-incubation significantly prevented these cytotoxic events and the observed protective effects were paralleled by the upregulation of the cellular glutathione-dependent antioxidant system: (PhSe)2 increased GSH levels (> 60%), GPx activity (6.9-fold) and the mRNA expression of antioxidant enzymes Gpx1 (3.9-fold) and Gclc (2.3-fold). Of note, the cytoprotective effect of (PhSe)2 was significantly decreased when cells were treated with mercaptosuccinic acid, an inhibitor of GPx, indicating the involvement of GPx modulation in the observed protective effect. In summary, the present findings bring out a new action mechanism concerning the antioxidant properties of (PhSe)2. The observed upregulation of the glutathione-dependent antioxidant system represents a future pharmacologic possibility that goes beyond the well-known thiol-peroxidase activity of this compound.<br />Graphical abstract fx1<br />Highlights • (PhSe)2 protects HT22 cells against cell death induced by tert-BuOOH. • (PhSe)2 prevents the oxidative stress and mitochondrial dysfunction induced by tert-BuOOH. • (PhSe)2 increases GPx activity and GSH levels in HT22 cells. • The modulation of GPx is involved in the protective effect of (PhSe)2.
- Subjects :
- 0301 basic medicine
GPX1
Antioxidant
medicine.medical_treatment
Clinical Biochemistry
Antioxidantes
Pharmacology
medicine.disease_cause
Biochemistry
Antioxidants
Mice
chemistry.chemical_compound
0302 clinical medicine
Organoselenium Compounds
Benzene Derivatives
Cytotoxicity
lcsh:QH301-705.5
Neurons
Diphenyl diselenide
lcsh:R5-920
Glutationa peroxidase
Chemistry
Disseleneto de difenila
Mitocôndria
Oxidants
Glutathione
Mitochondria
GCLC
lcsh:Medicine (General)
Oxidation-Reduction
Research Paper
HT22 cells
Cell Survival
Protective Agents
Models, Biological
Cell Line
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
Stress oxidativo
Organic Chemistry
Tert-BuOOH
Oxidative Stress
030104 developmental biology
lcsh:Biology (General)
Glutathione peroxidase
Lipid Peroxidation
Mitochondrial dysfunction
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....f35d46470dc9a9c1f868682927295baa