Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity
Mitochondrial dysfunction and inflammation contribute to the initiation and development of several brain pathological conditions, including Alzheimer’s disease and cerebral ischemia. Linalool is an aromatic plant-derived monoterpene alcohol with reported anti-inflammatory, and anti-oxidant properties...
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Format: | Article |
Language: | English |
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Elsevier
2019-10-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332219323625 |
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doaj-5827b3ed09394ccebcc28f0e9c9a1871 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Angélica María Sabogal-Guáqueta Fabian Hobbie Akshaya Keerthi Asmaa Oun Arjan Kortholt Erik Boddeke Amalia Dolga |
spellingShingle |
Angélica María Sabogal-Guáqueta Fabian Hobbie Akshaya Keerthi Asmaa Oun Arjan Kortholt Erik Boddeke Amalia Dolga Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity Biomedicine & Pharmacotherapy Oxidative stress Linalool OHSC Mitochondria Neuroprotection |
author_facet |
Angélica María Sabogal-Guáqueta Fabian Hobbie Akshaya Keerthi Asmaa Oun Arjan Kortholt Erik Boddeke Amalia Dolga |
author_sort |
Angélica María Sabogal-Guáqueta |
title |
Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity |
title_short |
Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity |
title_full |
Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity |
title_fullStr |
Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity |
title_full_unstemmed |
Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity |
title_sort |
linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and nmda toxicity |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-10-01 |
description |
Mitochondrial dysfunction and inflammation contribute to the initiation and development of several brain pathological conditions, including Alzheimer’s disease and cerebral ischemia. Linalool is an aromatic plant-derived monoterpene alcohol with reported anti-inflammatory, and anti-oxidant properties. We investigated the role of linalool on glutamate-induced mitochondrial oxidative stress in immortalized neuronal HT-22 cells. Glutamate induced oxidative stress in neuronal cells, as detected by real-time cell impedance measurements, MTT assay, and analysis of Annexin V/PI. Administration of linalool 100 μM reduced cell death mediated by glutamate. Staining of glutamate-stimulated mitochondria by MitoTracker revealed improved morphology in the presence of linalool. Furthermore, we demonstrated a potential neuroprotective effect of linalool in conditions of oxidative stress by a reduction of mitochondrial ROS and mitochondrial calcium levels, and by preserving mitochondrial membrane potential. Experiments using both high-resolution respirometry and Seahorse Extracellular flux analyzer showed that linalool was able to promote an increase in uncoupled respiration that could contribute to its neuroprotective capacity. Linalool protection was validated using organotypic hippocampal slices as ex vivo model with NMDA as a stimulus to induce excitotoxity cell damage. These results demonstrate that linalool is protective in an in vitro model of glutamate-induced oxidative stress and in an ex-vivo model for excitotoxity, proposing linalool as a potential therapeutic agent against neurodegenerative brain diseases where oxidative stress contributes to the pathology of the disease. |
topic |
Oxidative stress Linalool OHSC Mitochondria Neuroprotection |
url |
http://www.sciencedirect.com/science/article/pii/S0753332219323625 |
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AT angelicamariasabogalguaqueta linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT fabianhobbie linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT akshayakeerthi linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT asmaaoun linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT arjankortholt linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT erikboddeke linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity AT amaliadolga linaloolattenuatesoxidativestressandmitochondrialdysfunctionmediatedbyglutamateandnmdatoxicity |
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1721432862517886976 |
spelling |
doaj-5827b3ed09394ccebcc28f0e9c9a18712021-05-21T04:17:45ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-10-01118Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicityAngélica María Sabogal-Guáqueta0Fabian Hobbie1Akshaya Keerthi2Asmaa Oun3Arjan Kortholt4Erik Boddeke5Amalia Dolga6Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the Netherlands; Biomedical Sciences of Cells & Systems, Molecular Neurobiology, Faculty of Medical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Neuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area- School of Medicine, SIU, University of Antioquia, Medellín, Colombia; Corresponding authors at: Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, Groningen, the Netherlands.Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the Netherlands; Department of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology, University of Groningen, Groningen, the NetherlandsDepartment of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology, University of Groningen, Groningen, the NetherlandsNeuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area- School of Medicine, SIU, University of Antioquia, Medellín, ColombiaDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the NetherlandsMitochondrial dysfunction and inflammation contribute to the initiation and development of several brain pathological conditions, including Alzheimer’s disease and cerebral ischemia. Linalool is an aromatic plant-derived monoterpene alcohol with reported anti-inflammatory, and anti-oxidant properties. We investigated the role of linalool on glutamate-induced mitochondrial oxidative stress in immortalized neuronal HT-22 cells. Glutamate induced oxidative stress in neuronal cells, as detected by real-time cell impedance measurements, MTT assay, and analysis of Annexin V/PI. Administration of linalool 100 μM reduced cell death mediated by glutamate. Staining of glutamate-stimulated mitochondria by MitoTracker revealed improved morphology in the presence of linalool. Furthermore, we demonstrated a potential neuroprotective effect of linalool in conditions of oxidative stress by a reduction of mitochondrial ROS and mitochondrial calcium levels, and by preserving mitochondrial membrane potential. Experiments using both high-resolution respirometry and Seahorse Extracellular flux analyzer showed that linalool was able to promote an increase in uncoupled respiration that could contribute to its neuroprotective capacity. Linalool protection was validated using organotypic hippocampal slices as ex vivo model with NMDA as a stimulus to induce excitotoxity cell damage. These results demonstrate that linalool is protective in an in vitro model of glutamate-induced oxidative stress and in an ex-vivo model for excitotoxity, proposing linalool as a potential therapeutic agent against neurodegenerative brain diseases where oxidative stress contributes to the pathology of the disease.http://www.sciencedirect.com/science/article/pii/S0753332219323625Oxidative stressLinaloolOHSCMitochondriaNeuroprotection |