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Equine veterinary journal2016; 49(3); 345-351; doi: 10.1111/evj.12603

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

Abstract: The roles of soluble epoxide hydrolase and lipid mediators in inflammatory and neuropathic pain could be relevant in laminitis pain management. Objective: 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. Methods: 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. Conclusions: 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.
© 2016 EVJ Ltd.
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Publication Date: 2016-08-16 PubMed ID: 27338788PubMed Central: PMC5580818DOI: 10.1111/evj.12603Google Scholar: Lookup
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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.

This research is about the role of soluble epoxide hydrolase (sEH) and lipid mediators in managing pain associated with chronic severe laminitis in horses. The study found that sEH activity was significantly higher in the laminae tissue of horses with laminitis compared to healthy horses, and the use of a potent sEH inhibitor as part of the drug therapy helped to reduce signs of pain in the affected horses.

Objective and Methods

  • The main aim of the research was to determine the activity of sEH in the digital laminae (the sensitive and innermost part of the horse’s foot), assess the potency of sEH inhibitors, and evaluate the efficacy of an sEH inhibitor called t-TUCB as supplementary pain relief for horses suffering from chronic laminitis.
  • Experiments for sEH activity were conducted on digital laminae tissue sourced from both healthy and laminitic horses that were euthanised
  • The effectiveness of seven synthetic sEH inhibitors was determined in vitro (outside the living organism) using equine liver cytosol (intracellular fluid).
  • The most potent and stable of these inhibitors, t-TUCB, was given as a supplementary treatment to 10 horses with severe chronic laminitis. Measurements of pain levels, forelimb lifts, and physiological and laboratory examinations were carried out before and during treatment.

Results

  • Findings show that sEH activity in the digital laminae of horses with laminitis was considerably higher than in healthy horses.
  • Using t-TUCB as an additional pain relief for up to 10 days in afflicted horses resulted in a significant reduction in forelimb lifts and pain scores.
  • One horse had gas colic (a severe form of stomachache), and another developed corneal vascularisation (abnormal blood vessels growing into the clear window at the front of the eye) in a blind eye during the treatment. There were no other significant changes observed.

Conclusions

  • The study concluded that sEH activity is higher in the digital laminae of horses afflicted with laminitis compared to healthy horses.
  • Moreover, using a potent equine sEH inhibitor in combination with other pain treatments appears to decrease signs of pathological pain in horses suffering from laminitis.

Please note that there were some limitations to this study, including the absence of a control group and evaluator blinding in certain case series.

Cite This Article

APA
Guedes A, Galuppo L, Hood D, Hwang SH, Morisseau C, Hammock BD. (2016). Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis. Equine Vet J, 49(3), 345-351. https://doi.org/10.1111/evj.12603

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 49
Issue: 3
Pages: 345-351

Researcher Affiliations

Guedes, A
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, USA.
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA.
Galuppo, L
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA.
Hood, D
  • The Hoof Diagnostic and Rehabilitation Clinic, Bryan, Texas, USA.
Hwang, S H
  • Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.
Morisseau, C
  • Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.
Hammock, B D
  • Department Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, USA.

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

Grant Funding

  • P42 ES004699 / NIEHS NIH HHS
  • R01 ES002710 / NIEHS NIH HHS

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