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Journal of veterinary internal medicine2018; 32(5); 1740-1747; doi: 10.1111/jvim.15241

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

Abstract: 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. Objective: Because α-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. Methods: 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). Methods: 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 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 [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 [α-TOH]. Conclusions: In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.
© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2018-08-22 PubMed ID: 30133798PubMed Central: PMC6189351DOI: 10.1111/jvim.15241Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored the potential of lipid peroxidation biomarkers for diagnosing equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM), a neurodegenerative disorder in horses associated with a deficiency in α-tocopherol (α-TOH). The researchers hypothesized that certain by-products of lipid peroxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses, and could serve as biomarkers for the disease.

Objectives and Methodology of the Study

  • The study aimed to identify potential biomarkers of oxidative stress to help diagnose eNAD/EDM in horses. The focus was on F-isoprostanes (F IsoP), F-neuroprostanes (F NP), and oxysterols, which are by-products of lipid peroxidation.
  • The researchers conducted different studies using healthy and eNAD/EDM affected Quarter horse foals aged 1 to 4 years. Investigations included quantifying concentrations of these potential biomarkers in serum, CSF, and spinal cord tissue.
  • The concentrations of the potential biomarkers [F IsoP], [F NP], and [oxysterols] were measured using gas chromatography-negative ion chemical ionization mass spectrometry and high performance liquid chromatography mass spectrometry respectively. These were compared with respective α-TOH concentrations.

Study Results and Interpretation

  • The study results suggested that spinal cord tissue in eNAD/EDM horses had increased levels of cholesterol oxidation markers [7-ketocholesterol], [7-hydroxycholesterol], and [7-keto-27-hydrocholesterol], while [24-ketocholesterol] was lower.
  • No significant difference between eNAD/EDM affected and unaffected horses was found for F IsoP and F NP levels in CSF, serum oxysterols, and CSF oxysterols. This indicates these biomarkers may not be useful for diagnosing eNAD/EDM.
  • No correlation was observed between the concentrations of F IsoP, F NP, or oxysterols and that of α-TOH, the deficiency of which is associated with eNAD/EDM. Therefore, α-TOH concentration may not be an accurate indicator of the ketone and cholesterol peroxidation resulting from its deficiency.

Conclusion and Further Applications

  • The study concluded that certain markers of cholesterol oxidation in the spinal cord tissue were significantly increased in horses with eNAD/EDM. This suggests potential for using these markers as diagnostic tools for eNAD/EDM.
  • Importantly, the lack of correlation between α-TOH concentration and the potential biomarkers suggests that the oxidative stress in eNAD/EDM may be more complex than just α-TOH deficiency. Further research may be required to fully understand the connection between α-TOH deficiency, oxidative stress, and eNAD/EDM pathology.

Cite This Article

APA
Finno CJ, Estell KE, Winfield L, Katzman S, Bordbari MH, Burns EN, Miller AD, Puschner B, Tran CK, Xu L. (2018). Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy. J Vet Intern Med, 32(5), 1740-1747. https://doi.org/10.1111/jvim.15241

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 32
Issue: 5
Pages: 1740-1747

Researcher Affiliations

Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California.
Estell, Krista E
  • William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, California.
Winfield, Laramie
  • William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, California.
Katzman, Scott
  • William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, California.
Bordbari, Matthew H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California.
Burns, Erin N
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California.
Miller, Andrew D
  • Department of Biomedical Sciences, Section of Anatomic Pathology, Cornell University College of Veterinary Medicine, Ithaca, New York.
Puschner, Birgit
  • Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, California.
Tran, Cecilia K
  • Department of Medicinal Chemistry, University of Washington, Seattle, Washington.
Xu, Libin
  • Department of Medicinal Chemistry, University of Washington, Seattle, Washington.

MeSH Terms

  • Aging
  • Animals
  • Biomarkers
  • Female
  • Genetic Predisposition to Disease
  • Horse Diseases / blood
  • Horses
  • Isoprostanes / blood
  • Lipid Metabolism
  • Lipid Peroxidation
  • Lipids / chemistry
  • Male
  • Neuroaxonal Dystrophies / blood
  • Neuroaxonal Dystrophies / genetics
  • Neuroaxonal Dystrophies / veterinary

Grant Funding

  • K01 OD015134 / NIH HHS
  • L40 TR001136 / NCATS NIH HHS
  • R00 HD073270 / NICHD NIH HHS
  • R01 HD092659 / NICHD NIH HHS

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Citations

This article has been cited 8 times.
  1. Palmisano M, Kulp J, Bender S, Stefanovski D, Robinson M, Johnson A. Measurement of 8-hydroxy-2'-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia. J Vet Intern Med 2024 Mar-Apr;38(2):1207-1213.
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