Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy

Carrie J Finno, Krista E. Estell, Laramie Winfield, Scott A Katzman, Matthew H. Bordbari, Erin N. Burns, Andrew D. Miller, Birgit Puschner, Cecilia K. Tran, Libin Xu

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Abstract

Background: 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. Hypothesis: Because α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2-isoprostanes (F2IsoP), F4-neuroprostanes (F4NP) 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 [F2IsoP] and [F4NP] 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 α-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 [F2IsoP] and [F4NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2IsoP], [F4NP], or [oxysterols] and respective [α-TOH]. Conclusions and Clinical Importance: In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.

Original languageEnglish (US)
Pages (from-to)1740-1747
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume32
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Neuroaxonal Dystrophies
Lipid Peroxidation
Horses
biomarkers
Oxidative Stress
lipid peroxidation
oxidative stress
Biomarkers
horses
myeloencephalopathy
cerebrospinal fluid
Neuroprostanes
Cerebrospinal Fluid
F2-Isoprostanes
spinal cord
foals
Spinal Cord
Isoprostanes

Keywords

  • ataxia
  • equine
  • genetics
  • vitamin E

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy. / Finno, Carrie J; Estell, Krista E.; Winfield, Laramie; Katzman, Scott A; Bordbari, Matthew H.; Burns, Erin N.; Miller, Andrew D.; Puschner, Birgit; Tran, Cecilia K.; Xu, Libin.

In: Journal of Veterinary Internal Medicine, Vol. 32, No. 5, 01.09.2018, p. 1740-1747.

Research output: Contribution to journalArticle

Finno, Carrie J ; Estell, Krista E. ; Winfield, Laramie ; Katzman, Scott A ; Bordbari, Matthew H. ; Burns, Erin N. ; Miller, Andrew D. ; Puschner, Birgit ; Tran, Cecilia K. ; Xu, Libin. / Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy. In: Journal of Veterinary Internal Medicine. 2018 ; Vol. 32, No. 5. pp. 1740-1747.
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abstract = "Background: 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. Hypothesis: Because α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2-isoprostanes (F2IsoP), F4-neuroprostanes (F4NP) 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 [F2IsoP] and [F4NP] 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 α-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 [F2IsoP] and [F4NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2IsoP], [F4NP], or [oxysterols] and respective [α-TOH]. Conclusions and Clinical Importance: In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.",
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AU - Finno, Carrie J

AU - Estell, Krista E.

AU - Winfield, Laramie

AU - Katzman, Scott A

AU - Bordbari, Matthew H.

AU - Burns, Erin N.

AU - Miller, Andrew D.

AU - Puschner, Birgit

AU - Tran, Cecilia K.

AU - Xu, Libin

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N2 - Background: 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. Hypothesis: Because α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2-isoprostanes (F2IsoP), F4-neuroprostanes (F4NP) 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 [F2IsoP] and [F4NP] 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 α-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 [F2IsoP] and [F4NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2IsoP], [F4NP], or [oxysterols] and respective [α-TOH]. Conclusions and Clinical Importance: In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.

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