Dataset Information

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.

ABSTRACT:

Background

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an ?-tocopherol (?-TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available.

Hypothesis

Because ?-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F₂ -isoprostanes (F₂ IsoP), F₄ -neuroprostanes (F₄ NP) and oxysterols derived from free radical oxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses and could serve as potential biomarkers for disease.

Animals

Isoprostane Study A: 14 Quarter horse foals (10 healthy foals and 4 eNAD/EDM affected foals) at 1 and 6 months of age. Isoprostane Study B: 17 eNAD/EDM affected and 10 unaffected horses???1-4 years of age. Oxysterol study: eNAD/EDM affected (n?=?14, serum; n?=?11, CSF; n?=?10, spinal cord [SC]) and unaffected horses 1-4 years of age (n?=?12, serum; n?=?10, CSF; n?=?7, SC).

Procedures

Cerebrospinal fluid [F₂ IsoP] and [F₄ NP] were assessed using gas chromatography-negative ion chemical ionization mass spectrometry. Serum, CSF, and cervical SC [oxysterols] were quantified using high performance liquid chromatography mass spectrometry. Results were compared with respective ?-TOH concentrations.

Results

Spinal cord [7-ketocholesterol], [7-hydroxycholesterol], and [7-keto-27-hydrocholesterol] were higher in eNAD/EDM horses whereas [24-ketocholesterol] was lower. No significant difference was found in CSF [F₂ IsoP] and [F₄ NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F₂ IsoP], [F₄ NP], or [oxysterols] and respective [?-TOH].

Conclusions and clinical importance

In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.

SUBMITTER: Finno CJ

PROVIDER: S-EPMC6189351 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.

Finno Carrie J CJ Estell Krista E KE Winfield Laramie L Katzman Scott S Bordbari Matthew H MH Burns Erin N EN Miller Andrew D AD Puschner Birgit B Tran Cecilia K CK Xu Libin L

Journal of veterinary internal medicine 20180822 5

<h4>Background</h4>Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an α-tocopherol (α-TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available.<h4>Hypothesis</h4>Because α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F<sub>2</sub> -isoprostanes (F<sub>2</sub> IsoP), F<sub>4</sub> -neuroprostanes (F<sub>4</s ...[more]

PMID: 30133798

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Project description:A new mitochondria-targeted probe MitoCLox was designed as a starting compound for a series of probes sensitive to cardiolipin (CL) peroxidation. Fluorescence microscopy reported selective accumulation of MitoCLox in mitochondria of diverse living cell cultures and its oxidation under stress conditions, particularly those known to cause a selective cardiolipin oxidation. Ratiometric fluorescence measurements using flow cytometry showed a remarkable dependence of the MitoCLox dynamic range on the oxidation of the sample. Specifically, MitoCLox oxidation was induced by low doses of hydrogen peroxide or organic hydroperoxide. The mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenyl-phosphonium (SkQ1), which was shown earlier to selectively protect cardiolipin from oxidation, prevented hydrogen peroxide-induced MitoCLox oxidation in the cells. Concurrent tracing of MitoCLox oxidation and membrane potential changes in response to hydrogen peroxide addition showed that the oxidation of MitoCLox started without a delay and was complete during the first hour, whereas the membrane potential started to decay after 40 minutes of incubation. Hence, MitoCLox could be used for splitting the cell response to oxidative stress into separate steps. Application of MitoCLox revealed heterogeneity of the mitochondrial population; in living endothelial cells, a fraction of small, rounded mitochondria with an increased level of lipid peroxidation were detected near the nucleus. In addition, the MitoCLox staining revealed a specific fraction of cells with an increased level of oxidized lipids also in the culture of human myoblasts. The fraction of such cells increased in high-density cultures. These specific conditions correspond to the initiation of spontaneous myogenesis in vitro, which indicates that oxidation may precede the onset of myogenic differentiation. These data point to a possible participation of oxidized CL in cell signalling and differentiation.

Dataset Information

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.

Background

Hypothesis

Animals

Procedures

Results

Conclusions and clinical importance

Publications

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.

Similar Datasets

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