FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Lipid peroxidation biomarkers for evaluating oxidative stres...
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.
Get Full Text
Publication Date: 2018-08-22 PubMed ID: 30133798PubMed Central: PMC6189351DOI: 10.1111/jvim.15241Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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

References

This article includes 26 references
  1. Mayhew IG, Brown CM, Stowe HD. Equine degenerative myeloencephalopathy: A vitamin E deficiency that may be familial.. JVet Intern Med 1987;1:45–50.
    pubmed: 3506620
  2. Aleman M, Finno CJ, Higgins RJ. Evaluation of epidemiological, clinical, and pathological features of neuroaxonal dystrophy in Quarter Horses.. JAm Vet Med Assoc 2011;239:823–833.
    pubmed: 21916766
  3. Mayhew IG, deLahunta A, Whitlock RH. Spinal cord disease in the horse.. Cornell Vet 1978;68 Suppl 6:1–207.
    pubmed: 618720
  4. Muller DP, Goss‐Sampson MA. Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency.. Crit Rev Neurobiol 1990;5:239–263.
    pubmed: 2204484
  5. Finno CJ, Estell KE, Katzman S. Blood and cerebrospinal fluid alpha‐tocopherol and selenium concentrations in neonatal foals with neuroaxonal dystrophy.. JVet Intern Med 2015;29:1667–1675.
    pmc: PMC4831564pubmed: 26391904
  6. Niki E. Role of vitamin E as a lipid‐soluble peroxyl radical scavenger: in vitro and in vivo evidence.. Free Radic Biol Med 2014;66:3–12.
    pubmed: 23557727
  7. Choi J, Leonard SW, Kasper K. Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics.. JLipid Res 2015;56:1182–1190.
    pmc: PMC4442875pubmed: 25855633
  8. McDougall M, Choi J, Truong L. Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets.. Free Rad Mol Biol 2017;110:250–260.
    pmc: PMC5548191pubmed: 28645790
  9. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis.. Chem Rev 2011;111:5944–5972.
    pubmed: 21861450
  10. Yoshida Y, Umeno A, Shichiri M. Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo.. JClin Biochem Nutr 2013;52:9–16.
    pmc: PMC3541426pubmed: 23341691
  11. Forman HJ, Fukuto JM, Miller T. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4‐hydroxynonenal.. Arch Biochem Biophys 2008;477:183–195.
    pmc: PMC2590784pubmed: 18602883
  12. Zmijewski JW, Landar A, Watanabe N. Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium.. Biochem Soc Trans 2005;33:1385–1389.
    pmc: PMC1413972pubmed: 16246125
  13. Finno CJ, Bordbari MH, Valberg SJ. Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes.. Free Rad Mol Biol 2016;101:261–271.
    pmc: PMC5154892pubmed: 27751910
  14. Janowski BA, Grogan MJ, Jones SA. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta.. Proc Natl Acad Sci USA 1999;96:266–271.
    pmc: PMC15128pubmed: 9874807
  15. Janowski BA, Willy PJ, Devi TR. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha.. Nature 1996;383:728–731.
    pubmed: 8878485
  16. Guillemot‐Legris O, Mutemberezi V, Muccioli GG. Oxysterols in metabolic syndrome: From bystander molecules to bioactive lipids.. Trends Mol Med 2016;22:594–614.
    pubmed: 27286741
  17. Milne GL, Sanchez SC, Musiek ES. Quantification of F2‐isoprostanes as a biomarker of oxidative stress.. Nat Protoc 2007;2:221–226.
    pubmed: 17401357
  18. Xu L, Korade Z, Rosado DA Jr. An oxysterol biomarker for 7‐dehydrocholesterol oxidation in cell/mouse models for Smith‐Lemli‐Opitz syndrome.. JLipid Res 2011;52:1222–1233.
    pmc: PMC3090243pubmed: 21402677
  19. Roneus BO, Hakkarainen RV, Lindholm CA. Vitamin E requirements of adult Standardbred horses evaluated by tissue depletion and repletion.. Equine Vet J 1986;18:50–58.
    pubmed: 3948831
  20. Olkkonen VM, Beaslas O, Nissila E. Oxysterols and their cellular effectors.. Biomolecules 2012;2:76–103.
    pmc: PMC4030866pubmed: 24970128
  21. Finno CJ, Bordbari MH, Gianino G. An innate immune response and altered nuclear receptor activation defines the spinal cord transcriptome during alpha‐tocopherol deficiency.. Free Rad Mol Biol 2018;120:289–302.
    pmc: PMC5940542pubmed: 29526809
  22. Goyal S, Xiao Y, Porter NA. Oxidation of 7‐dehydrocholesterol and desmosterol by human cytochrome P450 46A1.. JLipid Res 2014;55:1933–1943.
    pmc: PMC4617353pubmed: 25017465
  23. Jessup W, Gelissen IC, Gaus K. Roles of ATP binding cassette transporters A1 and G1, scavenger receptor BI and membrane lipid domains in cholesterol export from macrophages.. Curr Opin Lipidol 2006;17:247–257.
    pubmed: 16680029
  24. Brown AJ, Jessup W. Oxysterols: Sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis.. Mol Aspects Med 2009;30:111–122.
    pubmed: 19248801
  25. Janero DR. Malondialdehyde and thiobarbituric acid‐reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury.. Free Rad Mol Biol 1990;9:515–540.
    pubmed: 2079232
  26. Lunn DP, Mayhew IG. The neurologic evaluation of horses.. Equine Vet Educ 1989;1:94–101.

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.
    doi: 10.1111/jvim.16988pubmed: 38205913google scholar: lookup
  2. Ma Y, Peng S, Donnelly CG, Ghosh S, Miller AD, Woolard K, Finno CJ. Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy. J Vet Intern Med 2024 Jan-Feb;38(1):417-423.
    doi: 10.1111/jvim.16924pubmed: 37937700google scholar: lookup
  3. Williams Louie E, Nieto J, Wensley F, Morgan JM, Finno CJ, Berryhill EH. Efficacy of the oral supplement, Equine Omega Complete, for the prevention of gastric ulcers and alpha-tocopherol supplementation in horses. J Vet Intern Med 2023 Nov-Dec;37(6):2529-2534.
    doi: 10.1111/jvim.16877pubmed: 37775973google scholar: lookup
  4. Hales EN, Habib H, Favro G, Katzman S, Sakai RR, Marquardt S, Bordbari MH, Ming-Whitfield B, Peterson J, Dahlgren AR, Rivas V, Ramirez CA, Peng S, Donnelly CG, Dizmang BS, Kallenberg A, Grahn R, Miller AD, Woolard K, Moeller B, Puschner B, Finno CJ. Increased α-tocopherol metabolism in horses with equine neuroaxonal dystrophy. J Vet Intern Med 2021 Sep;35(5):2473-2485.
    doi: 10.1111/jvim.16233pubmed: 34331715google scholar: lookup
  5. Pautova A, Burnakova N, Revelsky A. Metabolic Profiling and Quantitative Analysis of Cerebrospinal Fluid Using Gas Chromatography-Mass Spectrometry: Current Methods and Future Perspectives. Molecules 2021 Jun 11;26(12).
    doi: 10.3390/molecules26123597pubmed: 34208377google scholar: lookup
  6. Tudorachi NB, Totu EE, Fifere A, Ardeleanu V, Mocanu V, Mircea C, Isildak I, Smilkov K, Cărăuşu EM. The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis. Antioxidants (Basel) 2021 Jun 21;10(6).
    doi: 10.3390/antiox10060985pubmed: 34205576google scholar: lookup
  7. Dhama K, Latheef SK, Dadar M, Samad HA, Munjal A, Khandia R, Karthik K, Tiwari R, Yatoo MI, Bhatt P, Chakraborty S, Singh KP, Iqbal HMN, Chaicumpa W, Joshi SK. Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values. Front Mol Biosci 2019;6:91.
    doi: 10.3389/fmolb.2019.00091pubmed: 31750312google scholar: lookup
  8. Burns EN, Finno CJ. Equine degenerative myeloencephalopathy: prevalence, impact, and management. Vet Med (Auckl) 2018;9:63-67.
    doi: 10.2147/VMRR.S148542pubmed: 30234005google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.