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Scientific reports2024; 14(1); 27684; doi: 10.1038/s41598-024-75734-1

Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics.

Abstract: Ethyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h and 11 metabolites at 8 h, highlighting its time-dependent impact on metabolic pathways such as phenylalanine and arginine biosynthesis. Moreover, EP significantly lowered the expression of inflammatory markers interleukin (IL)-6 and heme oxygenase (HO)-1, indicating its potential as an anti-inflammatory agent. Blood chemistry analysis revealed notable reductions in glucose and triglyceride levels. These findings demonstrate that EP is a substance with potential effects on pathways associated with inflammation, oxidative stress, and metabolic processes.
© 2024. The Author(s).
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Publication Date: 2024-11-12 PubMed ID: 39532936PubMed Central: PMC11557697DOI: 10.1038/s41598-024-75734-1Google 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 research article explores the effects of a potentially therapeutic compound, Ethyl Pyruvate (EP), on the blood metabolites and immune cells in horses. The study suggests that EP has time-dependent impacts on metabolic pathways and might exhibit anti-inflammatory properties.

Research Methods

  • This study used advanced liquid chromatography-mass spectrometry (LC-MS) based metabolomics, which is a technique used to identify and quantify cellular metabolites. This method helps in deconstructing the complex network of metabolic reactions and pathways.
  • Along with this, the researchers applied a quantitative polymerase chain reaction (qPCR), a method used for measuring the quantity of specific DNA sequences or genes in a sample.
  • Furthermore, a detailed blood chemistry analysis was performed to understand more granular impacts of EP on horses’ blood.

Key Findings

  • The researchers found a significant change in 28 metabolites at 1 hour and 11 metabolites at 8 hours after EP administration, highlighting that the impact of EP is time-dependent. This primarily affected metabolic pathways associated with the biosynthesis of phenylalanine and arginine, which are essential amino acids for mammals.
  • The study also revealed that EP significantly lowered the expression of inflammatory markers such as Interleukin 6 (IL-6) and Heme Oxygenase 1 (HO-1). These are mediating molecules in the body’s response to inflammation, suggesting that EP could act as an anti-inflammatory agent.
  • The blood chemistry analysis showed a noticeable reduction in glucose and triglyceride levels after the application of EP, implying potential effects on metabolic processes.

Implications of the Study

  • The findings provide new insights into the potential therapeutic properties of Ethyl Pyruvate (EP), particularly its anti-inflammatory and antioxidant effects.
  • It also stresses the impact of EP on specific metabolic pathways, which can be valuable knowledge for studying diseases linked with metabolic dysfunctions.
  • The successful application of integrated methods (LC-MS, qPCR, and blood chemistry analysis) used in this study also demonstrates their potential utility in future research into disease mechanisms and therapeutic agents.

Cite This Article

APA
Kwak YB, Seo SA, Kim M, Yoon J. (2024). Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics. Sci Rep, 14(1), 27684. https://doi.org/10.1038/s41598-024-75734-1

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 14
Issue: 1
Pages: 27684
PII: 27684

Researcher Affiliations

Kwak, Young Beom
  • Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea.
Seo, Soo Ah
  • Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Busan, Republic of Korea.
  • Future Earth Research Institute, PNU JYS Science Academy, Pusan National University, Busan, 46241, Republic of Korea.
Kim, Myunghoo
  • Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Busan, Republic of Korea. kimmhmm3@gmail.com.
  • Future Earth Research Institute, PNU JYS Science Academy, Pusan National University, Busan, 46241, Republic of Korea. kimmhmm3@gmail.com.
Yoon, Jungho
  • Korea Racing Authority, Gwacheon, Republic of Korea. junghoy11@gmail.com.

MeSH Terms

  • Pyruvates / metabolism
  • Animals
  • Metabolomics / methods
  • Horses
  • Metabolic Networks and Pathways / drug effects
  • Anti-Inflammatory Agents / pharmacology
  • Chromatography, Liquid / methods
  • Oxidative Stress / drug effects
  • Metabolome / drug effects
  • Male
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism

Conflict of Interest Statement

The authors declare no competing interests.

References

This article includes 49 references
  1. Yang R, Zhu S, Tonnessen TI. Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries.. J. Inflamm. (Lond) 13, 37 (2016).
    pmc: PMC5135784pubmed: 27980458doi: 10.1186/s12950-016-0144-1google scholar: lookup
  2. Cruz RJ Jr, Harada T, Sasatomi E, Fink MP. Effects of ethyl pyruvate and other alpha-keto carboxylic acid derivatives in a rat model of multivisceral ischemia and reperfusion.. J. Surg. Res. 165, 151–157 (2011).
    pubmed: 19959189doi: 10.1016/j.jss.2009.07.008google scholar: lookup
  3. Koprivica I, Djedovic N, Stojanovic I, Miljkovic D. Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. Inflamm. Res. 71, 169–182 (2022).
    pmc: PMC8742706pubmed: 34999919doi: 10.1007/s00011-021-01529-zgoogle scholar: lookup
  4. Cruz RJ Jr, Harada T, Sasatomi E, Fink MP. Effects of ethyl pyruvate and other α-keto carboxylic acid derivatives in a rat model of multivisceral ischemia and reperfusion.. J. Surg. Res. 165, 151–157 (2011).
    pubmed: 19959189
  5. Sharifi-Rad M et al. Oxidative stress, and antioxidants: Back and forth in the pathophysiology of Chronic diseases.. Front. Physiol. 11, 694 (2020).
    pmc: PMC7347016pubmed: 32714204doi: 10.3389/fphys.2020.00694google scholar: lookup
  6. Newsholme P, Cruzat VF, Keane KN, Carlessi R, de Bittencourt PI Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes.. Biochem. J. 473, 4527–4550 (2016).
    pubmed: 27941030doi: 10.1042/bcj20160503cgoogle scholar: lookup
  7. Shin JH, Kim SW, Jin Y, Kim ID, Lee JK. Ethyl pyruvate-mediated Nrf2 activation and hemeoxygenase 1 induction in astrocytes confer protective effects via autocrine and paracrine mechanisms.. Neurochem Int. 61, 89–99 (2012).
    pubmed: 22521774doi: 10.1016/j.neuint.2012.04.005google scholar: lookup
  8. Jang HJ et al. Ethyl pyruvate induces heme oxygenase-1 through p38 mitogen-activated protein kinase activation by depletion of glutathione in RAW 264.7 cells and improves survival in septic animals.. Antioxid. Redox Signal. 17, 878–889 (2012).
    pmc: PMC3392619pubmed: 22369644doi: 10.1089/ars.2011.3994google scholar: lookup
  9. Kim SW, Lee HK, Shin JH, Lee JK. Up-down regulation of HO-1 and iNOS gene expressions by ethyl pyruvate via recruiting p300 to Nrf2 and depriving it from p65.. Free Radic Biol. Med. 65, 468–476 (2013).
    pubmed: 23891677doi: 10.1016/j.freeradbiomed.2013.07.028google scholar: lookup
  10. Djedovic N et al. Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. Biomed. Pharmacother. 96, 78–85 (2017).
    pubmed: 28965011doi: 10.1016/j.biopha.2017.09.110google scholar: lookup
  11. Han Y, Englert JA, Yang R, Delude RL, Fink MP. Ethyl pyruvate inhibits nuclear factor-kappab-dependent signaling by directly targeting p65.. J. Pharmacol. Exp. Ther. 312, 1097–1105 (2005).
    pubmed: 15525791doi: 10.1124/jpet.104.079707google scholar: lookup
  12. Dong N et al. Ethyl pyruvate protects against Salmonella intestinal infection in mice through down-regulation of pro-inflammatory factors and inhibition of TLR4/MAPK pathway.. Int. Immunopharmacol. 71, 155–163 (2019).
    pubmed: 30901678doi: 10.1016/j.intimp.2019.03.019google scholar: lookup
  13. Djedovic N et al. Ethyl pyruvate induces tolerogenic dendritic cells.. Front. Immunol. 10, 157 (2019).
    pmc: PMC6374627pubmed: 30792716doi: 10.3389/fimmu.2019.00157google scholar: lookup
  14. Jacobs CC et al. Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses.. Equine Vet. J. 45, 333–339 (2013).
    pubmed: 22943507doi: 10.1111/j.2042-3306.2012.00634.xgoogle scholar: lookup
  15. Schroeder EL et al. Preliminary safety and biological efficacy studies of ethyl pyruvate in normal mature horses.. Equine Vet. J. 43, 341–347 (2011).
    pubmed: 21492212doi: 10.1111/j.2042-3306.2010.00214.xgoogle scholar: lookup
  16. Johnson LM et al. Multicenter placebo-controlled randomized study of ethyl pyruvate in horses following surgical treatment for >/= 360 degrees large Colon volvulus.. Front. Vet. Sci. 7, 204 (2020).
    pmc: PMC7187886pubmed: 32373640doi: 10.3389/fvets.2020.00204google scholar: lookup
  17. Kennedy AD et al. Metabolomics in the clinic: A review of the shared and unique features of untargeted metabolomics for clinical research and clinical testing.. J. Mass. Spectrom. 53, 1143–1154 (2018).
    pubmed: 30242936doi: 10.1002/jms.4292google scholar: lookup
  18. Yin P, Xu G. Current state-of-the-art of nontargeted metabolomics based on liquid chromatography-mass spectrometry with special emphasis in clinical applications.. J. Chromatogr. A. 1374, 1–13 (2014).
    pubmed: 25444251doi: 10.1016/j.chroma.2014.11.050google scholar: lookup
  19. Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA. Untargeted metabolomics strategies-challenges and emerging directions.. J. Am. Soc. Mass. Spectrom. 27, 1897–1905 (2016).
    pmc: PMC5110944pubmed: 27624161doi: 10.1007/s13361-016-1469-ygoogle scholar: lookup
  20. Pang Z et al. Using MetaboAnalyst 5.0 for LC-HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data.. Nat. Protoc. 17, 1735–1761 (2022).
    pubmed: 35715522doi: 10.1038/s41596-022-00710-wgoogle scholar: lookup
  21. Kim SW, Lee HK, Shin JH, Lee JK. Up-down regulation of HO-1 and iNOS gene expressions by ethyl pyruvate via recruiting p300 to Nrf2 and depriving it from p65.. Free Radic. Biol. Med. 65, 468–476 (2013).
    pubmed: 23891677
  22. Djedovic N et al. Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. Biomed. Pharmacother. 96, 78–85 (2017).
    pubmed: 28965011doi: 10.1016/j.biopha.2017.09.110google scholar: lookup
  23. Alsharhan H, Ficicioglu C. Disorders of phenylalanine and tyrosine metabolism.. Transl. Sci. Rare Dis. 5, 3–58 (2020).
    doi: 10.3233/trd-200049google scholar: lookup
  24. Han, Q., Phillips, R. S. & Li, J. Vol. 6 22 (Frontiers Media SA, 2019).
    pmc: PMC6468166pubmed: 31024928
  25. Grace RF, Glader B. Red blood cell enzyme disorders.. Pediatr. Clin. North Am. 65, 579–595 (2018).
    pubmed: 29803284doi: 10.1016/j.pcl.2018.02.005google scholar: lookup
  26. Birkenmeier G et al. Ethyl pyruvate combats human leukemia cells but spares normal blood cells.. PLoS One. 11, e0161571 (2016).
    pmc: PMC5006986pubmed: 27579985
  27. Worku N et al. Ethyl pyruvate emerges as a safe and fast acting agent against Trypanosoma Brucei by targeting pyruvate kinase activity.. PLOS ONE. 10, e0137353 (2015).
    pmc: PMC4560413pubmed: 26340747doi: 10.1371/journal.pone.0137353google scholar: lookup
  28. Pittard J, Yang J. Biosynthesis of the aromatic amino acids.. EcoSal Plus. 3 (2008).
    pubmed: 26443741doi: 10.1128/ecosalplus.1123.1126.1121.1128google scholar: lookup
  29. Kung CW, Lee YM, Cheng PY, Peng YJ, Yen MH. Ethyl pyruvate reduces acute lung injury via regulation of iNOS and HO-1 expression in endotoxemic rats.. J. Surg. Res. 167, e323–e331 (2011).
    pubmed: 21324485
  30. Fink M. Ethyl pyruvate: A novel anti-inflammatory agent.. J. Intern. Med. 261, 349–362 (2007).
    pubmed: 17391109
  31. Lee YC et al. L-arginine and L-citrulline supplementation have different programming effect on regulatory T-cells function of infantile rats.. Front. Immunol. 9, 2911 (2018).
    pmc: PMC6295647pubmed: 30619275
  32. Wijnands KA, Castermans TM, Hommen MP, Meesters DM, Poeze M. Arginine and citrulline and the immune response in sepsis.. Nutrients. 7, 1426–1463 (2015).
    pmc: PMC4377861pubmed: 25699985
  33. Popovic PJ, Zeh III, Ochoa JB. Arginine and immunity.. J. Nutr. 137, 1681S–1686S (2007).
    pubmed: 17513447
  34. Lange SM et al. l-Citrulline metabolism in mice augments CD4 + T cell proliferation and cytokine production in Vitro, and Accumulation in the mycobacteria-infected lung.. Front. Immunol. 8, 10.3389/fimmu.2017.01561 (2017).
    pmc: PMC5696333pubmed: 29201027
  35. Lee YC et al. L-Arginine and L-Citrulline supplementation have different Programming Effect on Regulatory T-Cells function of infantile rats.. Front. Immunol. 9, 10.3389/fimmu.2018.02911 (2018).
    pmc: PMC6295647pubmed: 30619275
  36. Tang Y et al. Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.. Front. Immunol. 14, 10.3389/fimmu.2023.1114129 (2023).
    pmc: PMC10291621pubmed: 37377971
  37. Wypych TP et al. Microbial metabolism of l-tyrosine protects against allergic airway inflammation.. Nat. Immunol. 22, 279–286 (2021).
    pubmed: 33495652doi: 10.1038/s41590-020-00856-3google scholar: lookup
  38. Kang MS et al. Dehydroabietic acid, a phytochemical, acts as ligand for PPARs in macrophages and adipocytes to regulate inflammation.. Biochem. Biophys. Res. Commun. 369, 333–338 (2008).
    pubmed: 18267111doi: 10.1016/j.bbrc.2008.02.002google scholar: lookup
  39. Kim E et al. Dehydroabietic acid suppresses inflammatory response via suppression of Src-, Syk-, and TAK1-mediated pathways.. Int. J. Mol. Sci. 20, 1593 (2019).
    pmc: PMC6480320pubmed: 30934981
  40. Yu DH, Noh DH, Song RH, Park J. Ethyl pyruvate downregulates tumor necrosis factor alpha and interleukin (IL)-6 and upregulates IL-10 in lipopolysaccharide-stimulated canine peripheral blood mononuclear cells.. J. Vet. Med. Sci. 72, 1379–1381 (2010).
    pubmed: 20495301
  41. Hollenbach M et al. Ethyl pyruvate and ethyl lactate down-regulate the production of pro-inflammatory cytokines and modulate expression of immune receptors.. Biochem. Pharmacol. 76, 631–644 (2008).
    pubmed: 18625205
  42. Seo MS, Kim HJ, Kim H, Park SW. Ethyl pyruvate directly attenuates active secretion of HMGB1 in proximal tubular cells via induction of heme oxygenase-1.. J. Clin. Med. 8, 629 (2019).
    pmc: PMC6572201pubmed: 31072024
  43. Hauser B et al. Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.. Crit. Care Med. 33, 2034–2042 (2005).
    pubmed: 16148477
  44. Olek RA et al. The effect of ethyl pyruvate supplementation on rat fatty liver induced by a high-fat diet.. J. Nutr. Sci. Vitaminol (Tokyo). 59, 232–237 (2013).
    pubmed: 23883694doi: 10.3177/jnsv.59.232google scholar: lookup
  45. Kiechle FL, Jarett L. Phospholipids and the regulation of pyruvate dehydrogenase from rat adipocyte mitochondria.. Mol. Cell. Biochem. 56, 99–105 (1983).
    pubmed: 6646116doi: 10.1007/bf00227209google scholar: lookup
  46. Akkoc H et al. Protective effect of ethyl pyruvate on liver injury in streptozotocin-induced diabetic rats.. Acta Gastroenterol. Belg. 75, 336–341 (2012).
    pubmed: 23082705
  47. Ju KD et al. Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy.. Am. J. Physiology-Renal Physiol. 302, F606–F613 (2012).
    pubmed: 22129969
  48. Koprivica I, Vujičić M, Gajić D, Saksida T, Stojanović I. Ethyl Pyruvate Stimulates Regulatory T Cells and ameliorates type 1 Diabetes Development in mice.. Front. Immunol. 9, 10.3389/fimmu.2018.03130 (2019).
    pmc: PMC6335294pubmed: 30687329
  49. Zhang M et al. Hepatoprotective effects of ethyl pyruvate against CCl4-induced hepatic fibrosis via inhibition of TLR4/NF-kappaB signaling and up-regulation of MMPs/TIMPs ratio.. Clin. Res. Hepatol. Gastroenterol. 42, 72–81 (2018).
    pubmed: 28601590doi: 10.1016/j.clinre.2017.04.008google scholar: lookup

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