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.
Authors: Vinijkumthorn Ruethaiwan, Prapaiwan Nawarus, Chotikaprakal Thanapon, Prompiram Phirom, Phaonakrop Narumon, Roytrakul Sittiruk, Tesena Parichart
Journal: Equine veterinary journal
Summary
# Phenylbutazone-induced gastric injury and the bile acid connection Phenylbutazone remains a commonly used NSAID in equine practice, yet its potential to trigger gastrointestinal ulceration warrants better early detection methods. Ruethaiwan and colleagues employed proteomic analysis using liquid chromatography–tandem mass spectrometry to compare protein expression in serum and faecal samples from seven horses receiving a clinical dose of phenylbutazone (4.4 mg/kg twice daily for 7 days) against seven placebo controls, subsequently validating their findings through enzyme-linked immunosorbent assay. The research identified 226 differentially expressed serum proteins and 181 faecal proteins, with a particularly striking elevation in fatty acid-binding protein 6 (FABP6)—serum concentrations increased from 1.15 ng/mL at baseline to 1.80 ng/mL by day 8 in treated horses, significantly higher than placebo controls. The proteomic integration revealed that phenylbutazone-induced mucosal damage appears mechanistically linked to dysregulation of the bile acid pathway, specifically through increased expression of SLC10A1 and FABP6, suggesting that aberrant bile acid homeostasis may compound gastric injury. For practitioners, these findings present a potential serum biomarker for early detection of phenylbutazone gastroenteropathy, which could facilitate more timely cessation of treatment and implementation of preventative gastroprotection protocols, though further validation across larger populations and longer treatment durations remains necessary.
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Practical Takeaways
- •Serum FABP6 may serve as an early biomarker for PBZ-induced gastrointestinal injury, allowing detection within 8 days of treatment initiation for better clinical decision-making
- •Clinical doses of phenylbutazone (4.4 mg/kg twice daily) demonstrate measurable gastric mucosal damage; consider shorter treatment durations and monitor closely for GI signs
- •Bile acid pathway involvement in PBZ toxicity suggests potential for targeted nutritional or pharmaceutical interventions to mitigate gastrointestinal complications
Key Findings
- •Proteomic analysis identified 226 significantly altered serum proteins and 181 faecal proteins in PBZ-treated horses compared to controls (p<0.05)
- •FABP6 (fatty acid-binding protein 6) significantly increased in serum of PBZ-treated horses from 1.15±0.33 ng/mL on Day 0 to 1.80±0.37 ng/mL on Day 8 (p=0.01)
- •On Day 8, serum FABP6 was significantly higher in treatment group (1.80±0.37 ng/mL) versus control group (1.20±0.48 ng/mL; p=0.02)
- •PBZ-induced gastric mucosal damage appears linked to dysregulation of bile acid homeostasis pathway involving SLC10A1 and FABP6