• Home
  • Search Results
  • Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity.

Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2019-09-24)
Angélica María Sabogal-Guáqueta, Fabian Hobbie, Akshaya Keerthi, Asmaa Oun, Arjan Kortholt, Erik Boddeke, Amalia Dolga
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
D-(+)-Glucose solution, 45% in H2O, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Sodium pyruvate, ReagentPlus®, ≥99%
Sigma-Aldrich
Antimycin A from Streptomyces sp.
Sigma-Aldrich
Rotenone, ≥95%
Sigma-Aldrich
Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, ≥98% (TLC), powder
Sigma-Aldrich
Oligomycin from Streptomyces diastatochromogenes, ≥90% total oligomycins basis (HPLC)
Sigma-Aldrich
L-Glutamic acid monosodium salt hydrate, ≥99% (HPLC), powder
Sigma-Aldrich
Linalool, 97%
Sigma-Aldrich
Pyridinium chlorochromate, 98%
Sigma-Aldrich
1-Bromo-3-chloropropane, for isolation of RNA
Sigma-Aldrich
Adenosine 5′-diphosphate monopotassium salt dihydrate, bacterial, ≥95%, powder
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Sigma-Aldrich
1-Bromo-3-chloropropane, 99%
Supelco
2,4-Dinitrophenol, PESTANAL®, analytical standard
Sigma-Aldrich
Sodium succinate dibasic hexahydrate, puriss. p.a., ≥98.0% (NT)
Sigma-Aldrich
Dimethyl (S)-(−)-malate, 98%