Skip Navigation

Publication Detail

Title: Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.

Authors: Guedes, A; Galuppo, L; Hood, D; Hwang, S H; Morisseau, C; Hammock, B D

Published In Equine Vet J, (2017 May)

Abstract: BACKGROUND: The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. OBJECTIVES: To determine soluble epoxide hydrolase (sEH) activity in the digital laminae, sEH inhibitor potency in vitro, and efficacy of a sEH inhibitor as an adjunct analgesic therapy in chronic laminitic horses. STUDY DESIGN: In vitro experiments and clinical case series. METHODS: sEH activity was measured in digital laminae from euthanised healthy and laminitic horses (n = 5-6/group). Potency of 7 synthetic sEH inhibitors was determined in vitro using equine liver cytosol. One of them (t-TUCB; 0.1 mg/kg bwt i.v. every 24 h) was selected based on potency and stability, and used as adjunct therapy in 10 horses with severe chronic laminitis (Obel grades 2, one horse; 3-4, nine horses). Daily assessments of forelimb lifts, pain scores, physiologic and laboratory examinations were performed before (baseline) and during t-TUCB treatment. Data are presented as mean ± s.d. and 95% confidence intervals (CI). RESULTS: sEH activity in the digital laminae from laminitic horses (0.9±0.6 nmol/min/mg; 95% CI 0.16-1.55 nmol/min/mg) was significantly greater (P = 0.01) than in healthy horses (0.17±0.09 nmol/min/mg; CI 0.07-0.26 nmol/min/mg). t-TUCB as an adjunct analgesic up to 10 days (4.3±3 days) in laminitic horses was associated with significant reduction in forelimb lifts (36±22%; 95% CI 9-64%) and in pain scores (18±23%; 95% CI 2-35%) compared with baseline (P = 0.04). One horse developed gas colic and another corneal vascularisation in a blind eye during treatment. No other significant changes were observed. MAIN LIMITATIONS: Absence of control group and evaluator blinding in case series. CONCLUSIONS: sEH activity is significantly higher in the digital laminae of actively laminitic compared with healthy horses, and use of a potent inhibitor of equine sEH as adjunct analgesic therapy appears to decrease signs of pathologic pain in laminitic horses.

PubMed ID: 27338788 Exiting the NIEHS site

MeSH Terms: Animals; Benzoates/chemistry; Benzoates/pharmacology; Benzoates/therapeutic use*; Chronic Disease; Epoxide Hydrolases/antagonists & inhibitors; Epoxide Hydrolases/genetics; Epoxide Hydrolases/metabolism*; Female; Foot Diseases/drug therapy; Foot Diseases/enzymology; Foot Diseases/veterinary*; Hoof and Claw/pathology*; Horse Diseases/enzymology*; Horse Diseases/metabolism; Horse Diseases/pathology; Horses; Inflammation/drug therapy; Inflammation/enzymology; Inflammation/veterinary*; Liver/enzymology; Male; Molecular Structure; Phenylurea Compounds/chemistry; Phenylurea Compounds/pharmacology; Phenylurea Compounds/therapeutic use*

Back
to Top