Preliminary safety and biological efficacy studies of ethyl pyruvate in normal mature horses.
Abstract: Endotoxaemia causes substantial morbidity and mortality in horses with colic and sepsis. Ethyl pyruvate is a novel anti-inflammatory medication that improved survival in preclinical models of severe sepsis endotoxaemia and intestinal ischaemia and reperfusion in rodents, swine, sheep and dogs and may be a useful medication in horses. Objective: Ethyl pyruvate has no adverse effects in normal horses and is biologically active based on suppression of proinflammatory gene expression in endotoxin stimulated whole blood, in vitro. Methods: Physical and neurological examinations, behaviour scores, electrocardiograms and clinicopathological tests were performed on 5 normal healthy horses receiving 4 different doses of ethyl pyruvate. Doses included 0, 50, 100 and 150 mg/kg bwt administered in a randomised crossover design with a 2 week washout period between doses. Biological efficacy was assessed by stimulating whole blood with endotoxin from the horses that received ethyl pyruvate prior to and 1 and 6 h after drug infusion. Gene expression for TNFα, IL-1β and IL-6 was assessed. Results: There were no effects of drug or dose (0, 50, 100 or 150 mg/kg bwt) on any of the physical or neurological examination, behaviour factors, electrocardiogram or clinical pathological results collected from any of the horses. All parameters measured remained within the normal reference range. There was a significant reduction in TNFα, IL-1β and IL-6 gene expression in endotoxin stimulated whole blood from horses 6 h after receiving 150 mg/kg bwt ethyl pyruvate. There were no detectable effects on gene expression of any of the other doses of ethyl pyruvate tested. Conclusions: We were unable to detect any detrimental effects of ethyl pyruvate administration in normal horses. Ethyl pyruvate significantly decreased proinflammatory gene expression in endotoxin stimulated blood 6 h after drug administration. Conclusions: Ethyl pyruvate may be a safe, effective medication in endotoxaemic horses.
© 2011 EVJ Ltd.
Publication Date: 2011-01-19 PubMed ID: 21492212DOI: 10.1111/j.2042-3306.2010.00214.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses a study on the safety and efficacy of a novel anti-inflammatory medication, ethyl pyruvate, in treating horses suffering from endotoxaemia. The study indicates that this medication has no adverse effects on horses and further proves its biological activity through the reduction of proinflammatory gene expression in endotoxin-stimulated horse blood.
Objective and Methodology
- The main objective of the research was to establish the safety and biological activity of ethyl pyruvate in horses, with a key focus on its anti-inflammatory properties. The research hypothesized that this medication does not have an adverse effect on horses and can suppress proinflammatory gene expressions.
- The methodology involved physical and neurological examinations, behavior scores, electrocardiograms, and clinicopathological tests on five healthy horses. The horses received four different doses of ethyl pyruvate, administered randomly with a two-week recovery period between doses.
- Biological activity of ethyl pyruvate was assessed by stimulating the horse’s whole blood with endotoxin at different time intervals after administration of the drug. The gene expression for proinflammatory markers – TNFα, IL-1β, and IL-6, was studied.
Results and Findings
- The study found no observable impact of the drug or its dose (whether 0, 50, 100, or 150 mg/kg bwt) on any of the physical or neurological examinations, behavior, electrocardiogram, or clinical-pathological results of any horse. Everything remained within the normal reference range, thereby confirming the safety of ethyl pyruvate.
- In terms of evaluating the biological activity of ethyl pyruvate, the study records a significant reduction in the expression of TNFα, IL-1β, and IL-6 genes in endotoxin-stimulated whole blood from the horses 6 hours after receiving 150 mg/kg bwt ethyl pyruvate. This highlights the drug’s anti-inflammatory efficacy.
- While no detectable effects on gene expression were observed with the other tested doses of the drug, the significant observation made with the 150 mg/kg bwt dose indicates potential efficacy at higher dosage levels.
Conclusions
- The study concluded that ethyl pyruvate administration does not have any detrimental effects on horses, making it a safe medication option. Its ability to reduce proinflammatory gene expressions in endotoxin-stimulated horse blood also presented its potential effectiveness.
- The discovery might make ethyl pyruvate a viable anti-inflammatory medication for treating endotoxaemia in horses while opening doors for further research on its efficacy at varying dosage levels.
Cite This Article
APA
Schroeder EL, Holcombe SJ, Cook VL, James MD, Gandy JC, Hauptman JG, Sordillo LM.
(2011).
Preliminary safety and biological efficacy studies of ethyl pyruvate in normal mature horses.
Equine Vet J, 43(3), 341-347.
https://doi.org/10.1111/j.2042-3306.2010.00214.x Publication
Researcher Affiliations
- Department of Large Animal Clinical Studies, College of Veterinary Medicine, Michigan State University, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / adverse effects
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Endotoxemia / drug therapy
- Endotoxemia / veterinary
- Female
- Gene Expression
- Heart Rate / drug effects
- Horse Diseases / blood
- Horse Diseases / chemically induced
- Horses / blood
- Lipopolysaccharides / toxicity
- Male
- Pyruvates / adverse effects
- Pyruvates / therapeutic use
Citations
This article has been cited 7 times.- Koprivica I, Djedovic N, Stojanović I, Miljković Đ. Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. Inflamm Res 2022 Feb;71(2):169-182.
- Johnson LM, Holcombe SJ, Shearer TR, Watson V, Gandy J, Southwood LL, Lynch TM, Schroeder EL, Fogle CA, Sordillo LM. Multicenter Placebo-Controlled Randomized Study of Ethyl Pyruvate in Horses Following Surgical Treatment for ≥ 360° Large Colon Volvulus.. Front Vet Sci 2020;7:204.
- Taylor S. A review of equine sepsis.. Equine Vet Educ 2015 Feb;27(2):99-109.
- Liu YY, Chen NH, Chang CH, Lin SW, Kao KC, Hu HC, Chang GJ, Li LF. Ethyl pyruvate attenuates ventilation-induced diaphragm dysfunction through high-mobility group box-1 in a murine endotoxaemia model.. J Cell Mol Med 2019 Aug;23(8):5679-5691.
- Chakhtoura M, Chain RW, Sato PY, Qiu CC, Lee MH, Meissler JJ, Eisenstein TK, Koch WJ, Caricchio R, Gallucci S. Ethyl Pyruvate Modulates Murine Dendritic Cell Activation and Survival Through Their Immunometabolism.. Front Immunol 2019;10:30.
- Nagatome M, Kondo Y, Kadowaki D, Saishyo Y, Irikura M, Irie T, Ishitsuka Y. Ethyl pyruvate attenuates acetaminophen-induced liver injury and prevents cellular injury induced by N-acetyl-p-benzoquinone imine.. Heliyon 2018 Feb;4(2):e00521.
- Worku N, Stich A, Daugschies A, Wenzel I, Kurz R, Thieme R, Kurz S, Birkenmeier G. Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity.. PLoS One 2015;10(9):e0137353.
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