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Equine veterinary journal2025; doi: 10.1111/evj.14538

The proteomic differences and expression of fatty acid-binding protein 6 (FABP6) associated with gastrointestinal injury in horses with oral administration of a clinical dose of phenylbutazone.

Abstract: Phenylbutazone (PBZ) can potentially induce gastrointestinal ulceration, and early detection of PBZ-induced gastroenteropathy will be useful for the diagnosis, treatment, and prevention of PBZ toxicity. Objective: To identify putative proteins associated with equine gastric ulcer syndrome after clinical dose (4.4 mg/kg) administration of PBZ by proteomic study. Methods: In vivo experiments. Methods: Proteomic analysis using LC-MS/MS compared protein expression in serum and faeces of seven PBZ-treated horses with seven placebo-treated controls, and a novel putative biomarker was validated via enzyme-linked immunosorbent assay. Results: Differentially expressed proteins (DEPs) analysis on 5298 serum annotated proteins and 3538 faecal annotated proteins using the DESeq2 were performed between the control and treatment of EGUS groups. The results showed a list of 226 and 181 significant proteins in serum and faecal samples, respectively with a p adjust value <0.05. The proteomic serum and faeces samples were integrated into STITCH to illustrate PBZ interaction with bile acid homeostasis. FABP6 was significantly increased in PBZ-treated horses. The serum FABP6 concentration in the treatment group on Day 8 (1.80 ± 0.37 ng/mL) was higher than on Day 0 (1.15 ± 0.33 ng/mL, p = 0.01, 95% CI [-1.07, -0.25]). On Day 8, the serum FABP6 concentration in the treatment group was also higher than the control group (1.20 ± 0.48 ng/mL; p = 0.02, 95% CI [-1.10, -0.11]). Conclusions: Validation of all expressed proteins is a main limitation. Conclusions: Administration of PBZ at a clinical dose of 4.4 mg/kg twice daily for 7 days may cause gastric mucosal damage. PBZ treatment increased the expression of SLC10A1 and FABP6, suggesting that early gastric mucosal injury may be linked to the bile acid pathway. Bile acids could potentially exacerbate PBZ-induced EGUS.
Publication Date: 2025-05-22 PubMed ID: 40405508DOI: 10.1111/evj.14538Google Scholar: Lookup
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  • Journal Article

Summary

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The research investigates the impact of clinical doses of phenylbutazone, a common equine medication, on gastrointestinal health of horses, and identifies potential biomarkers that could be used for early detection of adverse effects.

Objective

The study aims to identify proteins that could be associated with equine gastric ulcer syndrome (EGUS) following an administration of clinically recommended dose of phenylbutazone (PBZ), a nonsteroidal anti-inflammatory drug (NSAID) often used in horses.

Methods

  • The researchers administered PBZ to seven horses, and a placebo to a control group of seven other horses. Afterward, they analyzed and compared the protein expression in the serum and faeces of both groups using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS).
  • For validation of a novel potential biomarker, they used an enzyme-linked immunosorbent assay (ELISA), a commonly used laboratory test to measure the concentration of substances such as proteins and antibodies in biological samples.

Results

  • The team identified 226 proteins in the serum and 181 significant proteins in the faecal samples that had differential expression in the treated horses compared to the control group.
  • The fatty acid-binding protein 6 (FABP6) was found to be significantly increased in horses treated with PBZ.
  • On the 8th day of administration, the FABP6 concentration was higher than on day 0 and also higher than the control group.

Conclusions

  • The study concluded that PBZ treatment at a clinical dose could cause gastric mucosal damage.
  • The increase in expression of SLC10A1 and FABP6 suggests the potential role of bile acid pathway in early gastric mucosal injury caused by PBZ.
  • Bile acids, necessary for digestion and absorption of fats, could exacerbate PBZ-induced EGUS. As such, monitoring the levels of FABP6 and SLC10A1 in horses could potentially serve as an early warning sign of PBZ-induced gastric injury.
  • However, one major limitation pointed out by the authors is the lack of validation of all expressed proteins in this study.

Cite This Article

APA
Vinijkumthorn R, Prapaiwan N, Chotikaprakal T, Prompiram P, Phaonakrop N, Roytrakul S, Tesena P. (2025). The proteomic differences and expression of fatty acid-binding protein 6 (FABP6) associated with gastrointestinal injury in horses with oral administration of a clinical dose of phenylbutazone. Equine Vet J. https://doi.org/10.1111/evj.14538

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Vinijkumthorn, Ruethaiwan
  • Department of Clinical Science and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Prapaiwan, Nawarus
  • Department of Clinical Science and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Chotikaprakal, Thanapon
  • Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Prompiram, Phirom
  • The Monitoring and Surveillance Center for Zoonotic Diseases in Wildlife and Exotic Animals, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Phaonakrop, Narumon
  • Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Roytrakul, Sittiruk
  • Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Tesena, Parichart
  • Department of Clinical Science and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.

Grant Funding

  • FF-131/2567 / Mahidol University

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