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Journal of veterinary pharmacology and therapeutics2017; 41(2); 239-245; doi: 10.1111/jvp.12464

Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations.

Abstract: In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups. Before treatment and 3 and 7 days after initiation of treatment, gastroscopy was performed and glandular gastric biopsies were collected and frozen at -80°C. Glandular disease was assessed on a scale of 0-4. Prostaglandin E concentrations in biopsies were measured using a commercially available enzyme-linked immunosorbent assay. All phenylbutazone-treated horses developed grade ≥2 glandular disease. Prostaglandin concentrations increased over time (p = .0017), but there was no effect of treatment (p = .49). These findings indicate that despite induction of glandular disease grade ≥2, phenylbutazone did not decrease basal glandular gastric prostaglandin E concentration.
Publication Date: 2017-11-16 PubMed ID: 29148168DOI: 10.1111/jvp.12464Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial

Summary

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The study explores how phenylbutazone, a high-dose drug in horses, leads to gastric diseases. It demonstrates that contrary to popular belief, the usage of this drug does not decrease the concentration of prostaglandin E in horses’ stomachs.

Study Design

  • The study involved 12 horses that were randomly split into two groups: one to receive phenylbutazone treatment and the other act as a control group treated with a placebo.
  • The treatment group received a dosage of 4.4 mg/kg of phenylbutazone every 12 hours for 7 days, while the placebo group received molasses in the same time intervals without the drug.
  • Gastroscopy was conducted, and gastric biopsies were collected from the horses before the treatment began, and again 3 and 7 days after the initiation of the treatment, with all samples stored at -80°C.

Measurement and Analysis

  • The level of glandular disease in the horses was graded on a scale of 0 to 4.
  • Prostaglandin E concentrations in the biopsied tissues were determined using the enzyme-linked immunosorbent assay, a standard laboratory procedure for detecting specific proteins.
  • All the horses that received phenylbutazone treatment developed glandular disease of grade 2 or higher.

Findings

  • The study found that the concentration of prostaglandin E increased over time, but this increase was not affected by the treatment.
  • This result counters the prevalent assumption that phenylbutazone-associated ulceration in horses is due to a decrease in gastric prostaglandins. The research instead shows that phenylbutazone did not lower the base glandular gastric concentration of prostaglandin E, debunking the popular belief.

Implications

  • The study’s findings suggest that the mechanisms underpinning the gastric disease induced by phenylbutazone in horses are still not entirely understood. Therefore, additional research is required to comprehend the precise relationship between phenylbutazone and the associated gastric conditions.
  • This new information can impact how equine gastroenterology is approached, potentially leading to different preventative measures or treatments.

Cite This Article

APA
Pedersen SK, Cribb AE, Read EK, French D, Banse HE. (2017). Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations. J Vet Pharmacol Ther, 41(2), 239-245. https://doi.org/10.1111/jvp.12464

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 41
Issue: 2
Pages: 239-245

Researcher Affiliations

Pedersen, S K
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
  • TD Equine Veterinary Group, Calgary, AB, Canada.
Cribb, A E
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Read, E K
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
French, D
  • TD Equine Veterinary Group, Calgary, AB, Canada.
Banse, H E
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Dinoprostone / analysis
  • Enzyme-Linked Immunosorbent Assay / veterinary
  • Gastric Mucosa / chemistry
  • Gastric Mucosa / pathology
  • Gastroscopy / veterinary
  • Horse Diseases / chemically induced
  • Horse Diseases / pathology
  • Horses
  • Phenylbutazone / adverse effects
  • Stomach Diseases / chemically induced
  • Stomach Diseases / metabolism
  • Stomach Diseases / pathology
  • Stomach Diseases / veterinary

Citations

This article has been cited 8 times.
  1. Vokes J, Lovett A, Sykes B. Equine Gastric Ulcer Syndrome: An Update on Current Knowledge.. Animals (Basel) 2023 Apr 5;13(7).
    doi: 10.3390/ani13071261pubmed: 37048517google scholar: lookup
  2. Taguchi T, Morales Yniguez FJ, Takawira C, Andrews FM, Lopez MJ. Agmatine Administration Effects on Equine Gastric Ulceration and Lameness.. J Clin Med 2022 Dec 8;11(24).
    doi: 10.3390/jcm11247283pubmed: 36555900google scholar: lookup
  3. Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses.. Animals (Basel) 2022 Oct 26;12(21).
    doi: 10.3390/ani12212939pubmed: 36359062google scholar: lookup
  4. Paul LJ, Ericsson AC, Andrews FM, Keowen ML, Morales Yniguez F, Garza F Jr, Banse HE. Gastric microbiome in horses with and without equine glandular gastric disease.. J Vet Intern Med 2021 Sep;35(5):2458-2464.
    doi: 10.1111/jvim.16241pubmed: 34351018google scholar: lookup
  5. Whitfield-Cargile CM, Coleman MC, Cohen ND, Chamoun-Emanuelli AM, DeSolis CN, Tetrault T, Sowinski R, Bradbery A, Much M. Effects of phenylbutazone alone or in combination with a nutritional therapeutic on gastric ulcers, intestinal permeability, and fecal microbiota in horses.. J Vet Intern Med 2021 Mar;35(2):1121-1130.
    doi: 10.1111/jvim.16093pubmed: 33656183google scholar: lookup
  6. Banse HE, Andrews FM. Equine glandular gastric disease: prevalence, impact and management strategies.. Vet Med (Auckl) 2019;10:69-76.
    doi: 10.2147/VMRR.S174427pubmed: 31406687google scholar: lookup
  7. Tesena P, Yingchutrakul Y, Roytrakul S, Wongtawan T, Angkanaporn K. Serum protein expression in Equine Glandular Gastric Disease (EGGD) induced by phenylbutazone.. J Vet Med Sci 2019 Mar 20;81(3):418-424.
    doi: 10.1292/jvms.18-0679pubmed: 30674748google scholar: lookup
  8. Banse HE, MacLeod H, Crosby C, Windeyer MC. Prevalence of and risk factors for equine glandular and squamous gastric disease in polo horses.. Can Vet J 2018 Aug;59(8):880-884.
    pubmed: 30104780