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Equine veterinary journal2012; 45(3); 333-339; doi: 10.1111/j.2042-3306.2012.00634.x

Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses.

Abstract: Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are limited for these horses. Ethyl pyruvate (EP), an anti-inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses. Objective: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (LPS) in horses. Methods: Horses received 30 ng/kg bwt LPS in saline to induce signs of endotoxaemia. Next, horses received lactated Ringer's solution (LRS), (n = 6), 150 mg/kg bwt EP in LRS, (n = 6), or 1.1 mg/kg bwt flunixin meglumine (FM), (n = 6). Controls received saline followed by LRS (n = 6). Physical examinations, behaviour pain scores and blood for clinical pathological testing and gene expression were obtained at predetermined intervals for 24 h. Results: Lipopolysaccharide infusion produced clinical and clinicopathological signs of endotoxaemia and increased expression of tumour necrosis factor alpha (TNFα), interleukin 6 (IL-6) and IL-8 (P<0.001) compared with controls. Leucopenia and neutropenia occurred in all horses that received LPS. Horses treated with EP and FM had significantly (P<0.0001) reduced pain scores compared with horses receiving LPS followed by LRS. Flunixin meglumine was significantly more effective at ameliorating fever compared with EP. Both EP and FM significantly diminished TNFα expression. Ethyl pyruvate significantly decreased, but FM significantly increased, IL-6 expression. Neither EP nor FM altered IL-8 expression. Conclusions: Ethyl pyruvate administered following LPS diminished the clinical effects of endotoxaemia and decreased proinflammatory gene expression in horses. Ethyl pyruvate suppressed expression of proinflammatory cytokines better than FM. However, FM was a superior anti-pyretic compared with EP. Ethyl pyruvate may have therapeutic applications in endotoxaemic horses.
© 2012 EVJ Ltd.
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Publication Date: 2012-09-03 PubMed ID: 22943507DOI: 10.1111/j.2042-3306.2012.00634.xGoogle Scholar: Lookup
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  • Non-U.S. Gov't

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.

The research paper focused on verifying the therapeutic efficacy of Ethyl Pyruvate (EP), a known anti-inflammatory agent, in diminishing the impact of endotoxaemia—a common condition in horses suffering from colic caused by the activation of inflammatory cascade. The study found that EP successfully reduced the clinical signs of endotoxaemia and decreased the expression of proinflammatory genes in horses.

Objectives and Methodology

  • The study aimed to understand the influence of Ethyl Pyruvate (EP) on outward signs of endotoxaemia, along with its impact on the expression of proinflammatory cytokines after the horse was subjected to the lipopolysaccharide (LPS).
  • To reproduce signs of endotoxaemia, horses were administered 30 ng/kg bwt LPS in saline.
  • The horses were then treated with lactated Ringer’s solution (LRS), 150 mg/kg bwt EP in LRS, or 1.1 mg/kg bwt flunixin meglumine (FM), a commonly used nonsteroidal anti-inflammatory drug in horses.
  • Physical examinations, behavior pain scores, and blood for clinical pathology testing and gene expression analyses were conducted at predetermined intervals for 24 hours.

Results and Conclusions

  • LPS infusion successfully induced clinical signs of endotoxaemia in horses and led to increased expression of proinflammatory cytokines, such as tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and IL-8.
  • All horses that received LPS exhibited leucopenia and neutropenia, a decrease in white blood cells, specifically in number of neutrophils.
  • Horses treated with EP and FM presented significantly reduced pain scores compared to those receiving only LPS followed by LRS.
  • Comparing FM and EP, FM functioned more efficiently in reducing fever.
  • However, both EP and FM significantly decreased TNFα expression. Significant differences were noticed in IL-6 expression where EP reduced its expression and FM increased it.
  • Neither EP nor FM influenced the expression of IL-8.
  • The research concluded that EP, when administered post LPS, reduced the clinical implications of endotoxaemia and lowered the expression of proinflammatory genes in horses. Despite FM’s superior antipyretic abilities, EP suppressed expression of proinflammatory cytokines more effectively.
  • The findings suggested EP’s potential application in treating endotoxaemic horses.

Cite This Article

APA
Jacobs CC, Holcombe SJ, Cook VL, Gandy JC, Hauptman JG, Sordillo LM. (2012). Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses. Equine Vet J, 45(3), 333-339. https://doi.org/10.1111/j.2042-3306.2012.00634.x

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 45
Issue: 3
Pages: 333-339

Researcher Affiliations

Jacobs, C C
  • Departments of Large, College of Veterinary Medicine, Michigan State University, East Lansing, USA.
Holcombe, S J
    Cook, V L
      Gandy, J C
        Hauptman, J G
          Sordillo, L M

            MeSH Terms

            • Actins / genetics
            • Actins / metabolism
            • Animals
            • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
            • Body Temperature / drug effects
            • Clonixin / analogs & derivatives
            • Clonixin / therapeutic use
            • Female
            • Gene Expression Regulation / drug effects
            • Horse Diseases / chemically induced
            • Horse Diseases / drug therapy
            • Horses
            • Inflammation / chemically induced
            • Inflammation / drug therapy
            • Inflammation / veterinary
            • Interleukin-6 / genetics
            • Interleukin-6 / metabolism
            • Interleukin-8 / genetics
            • Interleukin-8 / metabolism
            • Lipopolysaccharides / toxicity
            • Male
            • Pyruvates / therapeutic use
            • Tumor Necrosis Factor-alpha / genetics
            • Tumor Necrosis Factor-alpha / metabolism

            Citations

            This article has been cited 14 times.
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