FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary pharmacology and therapeutics2017; 41(2); 230-238; doi: 10.1111/jvp.12463

Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.

Abstract: This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independently assigned pain scores (at rest, walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS. Responses to touching the joint skin to assess tactile allodynia, plasma, and synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and lameness scores were calculated and compared between control and treatments. Data were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test. p < .05 was considered significant. Data are mean ± SEM. Compared to control, pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t-TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments, plasma terminal half-lives were 13 ± 3, 13 ± 0.5, and 24 ± 5 hr, and clearances were 68 ± 15, 48 ± 5, and 14 ± 1 ml hr  kg . The 1 mg/kg t-TUCB reached the SF at high concentrations. There were no important anti-inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide analgesia in horses with inflammatory joint pain.
© 2017 John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2017-10-25 PubMed ID: 29067696PubMed Central: PMC5920688DOI: 10.1111/jvp.12463Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Randomized Controlled Trial

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 paper presents findings of a study which investigated the pain-relieving and inflammation-reducing effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB in horses experimentally inflicted with joint inflammation. The therapeutic compound was found to be significant at a certain dosage level, with limited anti-inflammatory capabilities.

Research Overview

The research aimed to:

  • Understand the pharmacokinetics, antinociceptive (pain-killing), and anti-inflammatory effects of the sEH inhibitor t-TUCB in horses.
  • Explore the efficacy of the treatment on horses with Lipopolysaccharide (LPS)-induced radiocarpal synovitis, which is an induced form of joint inflammation.

Methodology

The process used in the research included:

  • Administering LPS to create joint inflammation in seven adult healthy mares.
  • Injecting t-TUCB intravenously at varying doses, with a control group receiving no t-TUCB.
  • Using a randomized crossover design, meaning each horse, after a minimum three weeks of washout period, received each treatment; this prevents the potential bias that could have arisen from a horse’s specific reaction to a specific drug dose.
  • Assessing pain levels, lameness, and hypersensitivity to touch (tactile allodynia) up to 48 hours post treatment.
  • Measuring t-TUCB concentrations in the plasma and synovial fluid (the fluid that lubricates joints) pre and post treatment.
  • Collecting blood and synovial fluid for clinical laboratory evaluations within the same 48-hour window.

Results

From the research, the team found:

  • The 1mg/kg dosage of t-TUCB significantly reduced pain, lameness, and tactile allodynia compared to the control group and the groups with lower dosages. This indicates that specific dosage was necessary for therapeutic effects.
  • Plasma terminal half-lives varied according to dosage, which can tell us how quickly the body processes and eliminates t-TUCB.
  • The 1 mg/kg t-TUCB was found in the synovial fluid at high concentrations, further affirming the necessity of this dosage.
  • On the downside, the compound did not present any significant anti-inflammatory effects, indicating it worked more towards alleviating pain rather than reducing the inflammation itself in this setup.

Conclusion

In conclusion, the study has shown that sEH inhibition with t-TUCB can serve as a significant analgesic for horses with inflammatory joint pain. The relief was predominantly directed at the symptoms of pain rather than the inflammation itself, suggesting the compound’s primary role in pain mitigation.

Cite This Article

APA
Guedes AGP, Aristizabal F, Sole A, Adedeji A, Brosnan R, Knych H, Yang J, Hwang SH, Morisseau C, Hammock BD. (2017). Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis. J Vet Pharmacol Ther, 41(2), 230-238. https://doi.org/10.1111/jvp.12463

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 41
Issue: 2
Pages: 230-238

Researcher Affiliations

Guedes, A G P
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
Aristizabal, F
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Sole, A
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Adedeji, A
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Brosnan, R
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Knych, H
  • K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Yang, J
  • Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA.
Hwang, S-H
  • Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA.
Morisseau, C
  • Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA.
Hammock, B D
  • Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA.

MeSH Terms

  • Analgesics / pharmacokinetics
  • Analgesics / pharmacology
  • Animals
  • Benzoates / pharmacokinetics
  • Benzoates / pharmacology
  • Carpus, Animal
  • Cross-Over Studies
  • Epoxide Hydrolases / antagonists & inhibitors
  • Female
  • Horse Diseases / drug therapy
  • Horses
  • Joint Diseases / drug therapy
  • Joint Diseases / veterinary
  • Lameness, Animal / drug therapy
  • Lameness, Animal / etiology
  • Phenylurea Compounds / pharmacokinetics
  • Phenylurea Compounds / pharmacology
  • Synovitis / drug therapy
  • Synovitis / veterinary

Grant Funding

  • P42 ES004699 / NIEHS NIH HHS
  • R01 ES002710 / NIEHS NIH HHS
  • R37 ES002710 / NIEHS NIH HHS

References

This article includes 40 references
  1. Brenneis C, Sisignano M, Coste O, Altenrath K, Fischer MJ, Angioni C, Fleming I, Brandes RP, Reeh PW, Woolf CJ, Geisslinger G, Scholich K. Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation.. Mol Pain 2011 Oct 4;7:78.
    pmc: PMC3195722pubmed: 21970373doi: 10.1186/1744-8069-7-78google scholar: lookup
  2. Burkett BN, Thomason JM, Hurdle HM, Wills RW, Fontenot RL. Effects of Firocoxib, Flunixin Meglumine, and Phenylbutazone on Platelet Function and Thromboxane Synthesis in Healthy Horses.. Vet Surg 2016 Nov;45(8):1087-1094.
    pubmed: 27731498doi: 10.1111/vsu.12567google scholar: lookup
  3. Chacos N, Capdevila J, Falck JR, Manna S, Martin-Wixtrom C, Gill SS, Hammock BD, Estabrook RW. The reaction of arachidonic acid epoxides (epoxyeicosatrienoic acids) with a cytosolic epoxide hydrolase.. Arch Biochem Biophys 1983 Jun;223(2):639-48.
    pubmed: 6859878doi: 10.1016/0003-9861(83)90628-8google scholar: lookup
  4. de Grauw JC, van de Lest CH, Brama PA, Rambags BP, van Weeren PR. In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis.. Equine Vet J 2009 Sep;41(7):693-9.
    pubmed: 19927589doi: 10.2746/042516409x436286google scholar: lookup
  5. England GC, Clarke KW, Goossens L. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse.. J Vet Pharmacol Ther 1992 Jun;15(2):194-201.
    pubmed: 1359161doi: 10.1111/j.1365-2885.1992.tb01007.xgoogle scholar: lookup
  6. Goswami SK, Wan D, Yang J, Trindade da Silva CA, Morisseau C, Kodani SD, Yang GY, Inceoglu B, Hammock BD. Anti-Ulcer Efficacy of Soluble Epoxide Hydrolase Inhibitor TPPU on Diclofenac-Induced Intestinal Ulcers.. J Pharmacol Exp Ther 2016 Jun;357(3):529-36.
    pmc: PMC4885505pubmed: 26989141doi: 10.1124/jpet.116.232108google scholar: lookup
  7. Guedes A. Pain Management in Horses.. Vet Clin North Am Equine Pract 2017 Apr;33(1):181-211.
    pubmed: 28325179doi: 10.1016/j.cveq.2016.11.006google scholar: lookup
  8. Guedes A, Galuppo L, Hood D, Hwang SH, Morisseau C, Hammock BD. Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.. Equine Vet J 2017 May;49(3):345-351.
    pmc: PMC5580818pubmed: 27338788doi: 10.1111/evj.12603google scholar: lookup
  9. Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis.. Vet Anaesth Analg 2013 Jul;40(4):440-8.
    pmc: PMC3956586pubmed: 23463912doi: 10.1111/vaa.12030google scholar: lookup
  10. Inceoglu B, Jinks SL, Schmelzer KR, Waite T, Kim IH, Hammock BD. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain.. Life Sci 2006 Nov 10;79(24):2311-9.
    pmc: PMC1904345pubmed: 16962614doi: 10.1016/j.lfs.2006.07.031google scholar: lookup
  11. Inceoglu B, Jinks SL, Ulu A, Hegedus CM, Georgi K, Schmelzer KR, Wagner K, Jones PD, Morisseau C, Hammock BD. Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways.. Proc Natl Acad Sci U S A 2008 Dec 2;105(48):18901-6.
    pmc: PMC2596245pubmed: 19028872doi: 10.1073/pnas.0809765105google scholar: lookup
  12. Inceoglu B, Schmelzer KR, Morisseau C, Jinks SL, Hammock BD. Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs).. Prostaglandins Other Lipid Mediat 2007 Jan;82(1-4):42-9.
    pmc: PMC1904338pubmed: 17164131doi: 10.1016/j.prostaglandins.2006.05.004google scholar: lookup
  13. Inceoglu B, Wagner KM, Yang J, Bettaieb A, Schebb NH, Hwang SH, Morisseau C, Haj FG, Hammock BD. Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.. Proc Natl Acad Sci U S A 2012 Jul 10;109(28):11390-5.
    pmc: PMC3396532pubmed: 22733772doi: 10.1073/pnas.1208708109google scholar: lookup
  14. Johnson CB, Taylor PM, Young SS, Brearley JC. Postoperative analgesia using phenylbutazone, flunixin or carprofen in horses.. Vet Rec 1993 Oct 2;133(14):336-8.
    pubmed: 8236675doi: 10.1136/vr.133.14.336google scholar: lookup
  15. Jones PD, Tsai HJ, Do ZN, Morisseau C, Hammock BD. Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase.. Bioorg Med Chem Lett 2006 Oct 1;16(19):5212-6.
    pmc: PMC1904344pubmed: 16870439doi: 10.1016/j.bmcl.2006.07.009google scholar: lookup
  16. Lees P, Higgins AJ. Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse.. Equine Vet J 1985 Mar;17(2):83-96.
    pubmed: 3987667doi: 10.1111/j.2042-3306.1985.tb02056.xgoogle scholar: lookup
  17. Lindegaard C, Gleerup KB, Thomsen MH, Martinussen T, Jacobsen S, Andersen PH. Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis.. Am J Vet Res 2010 Jan;71(1):69-75.
    pubmed: 20043783doi: 10.2460/ajvr.71.1.69google scholar: lookup
  18. Lindegaard C, Thomsen MH, Larsen S, Andersen PH. Analgesic efficacy of intra-articular morphine in experimentally induced radiocarpal synovitis in horses.. Vet Anaesth Analg 2010 Mar;37(2):171-85.
    pubmed: 20230568doi: 10.1111/j.1467-2995.2009.00521.xgoogle scholar: lookup
  19. Liu JY, Yang J, Inceoglu B, Qiu H, Ulu A, Hwang SH, Chiamvimonvat N, Hammock BD. Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model.. Biochem Pharmacol 2010 Mar 15;79(6):880-7.
    pmc: PMC3285377pubmed: 19896470doi: 10.1016/j.bcp.2009.10.025google scholar: lookup
  20. Morisseau C, Inceoglu B, Schmelzer K, Tsai HJ, Jinks SL, Hegedus CM, Hammock BD. Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids.. J Lipid Res 2010 Dec;51(12):3481-90.
    pmc: PMC2975720pubmed: 20664072doi: 10.1194/jlr.M006007google scholar: lookup
  21. Morisseau C, Newman JW, Tsai HJ, Baecker PA, Hammock BD. Peptidyl-urea based inhibitors of soluble epoxide hydrolases.. Bioorg Med Chem Lett 2006 Oct 15;16(20):5439-44.
    pmc: PMC1892215pubmed: 16908134doi: 10.1016/j.bmcl.2006.07.073google scholar: lookup
  22. Owens JG, Kamerling SG, Stanton SR, Keowen ML, Prescott-Mathews JS. Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.. Am J Vet Res 1996 Jun;57(6):866-74.
    pubmed: 8725815
  23. Palmer JL, Bertone AL. Experimentally-induced synovitis as a model for acute synovitis in the horse.. Equine Vet J 1994 Nov;26(6):492-5.
    pubmed: 7889925doi: 10.1111/j.2042-3306.1994.tb04056.xgoogle scholar: lookup
  24. Patwardhan AM, Akopian AN, Ruparel NB, Diogenes A, Weintraub ST, Uhlson C, Murphy RC, Hargreaves KM. Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents.. J Clin Invest 2010 May;120(5):1617-26.
    pmc: PMC2860941pubmed: 20424317doi: 10.1172/JCI41678google scholar: lookup
  25. Raekallio M, Taylor PM, Bennett RC. Preliminary investigations of pain and analgesia assessment in horses administered phenylbutazone or placebo after arthroscopic surgery.. Vet Surg 1997 Mar-Apr;26(2):150-5.
    pubmed: 9068166doi: 10.1111/j.1532-950x.1997.tb01478.xgoogle scholar: lookup
  26. Rose TE, Morisseau C, Liu JY, Inceoglu B, Jones PD, Sanborn JR, Hammock BD. 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain.. J Med Chem 2010 Oct 14;53(19):7067-75.
    pmc: PMC3285450pubmed: 20812725doi: 10.1021/jm100691cgoogle scholar: lookup
  27. Santos LC, de Moraes AN, Saito ME. Effects of intraarticular ropivacaine and morphine on lipopolysaccharide-induced synovitis in horses.. Vet Anaesth Analg 2009 May;36(3):280-6.
    pubmed: 19397780doi: 10.1111/j.1467-2995.2009.00452.xgoogle scholar: lookup
  28. Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, Hammock BD. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors.. Proc Natl Acad Sci U S A 2006 Sep 12;103(37):13646-51.
    pmc: PMC1564210pubmed: 16950874doi: 10.1073/pnas.0605908103google scholar: lookup
  29. Smith G, Bertone AL, Kaeding C, Simmons EJ, Apostoles S. Anti-inflammatory effects of topically applied dimethyl sulfoxide gel on endotoxin-induced synovitis in horses.. Am J Vet Res 1998 Sep;59(9):1149-52.
    pubmed: 9736394
  30. Spector AA, Kim HY. Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism.. Biochim Biophys Acta 2015 Apr;1851(4):356-65.
    pmc: PMC4314516pubmed: 25093613doi: 10.1016/j.bbalip.2014.07.020google scholar: lookup
  31. Todhunter PG, Kincaid SA, Todhunter RJ, Kammermann JR, Johnstone B, Baird AN, Hanson RR, Wright JM, Lin HC, Purohit RC. Immunohistochemical analysis of an equine model of synovitis-induced arthritis.. Am J Vet Res 1996 Jul;57(7):1080-93.
    pubmed: 8807026
  32. Toutain PL, Autefage A, Legrand C, Alvinerie M. Plasma concentrations and therapeutic efficacy of phenylbutazone and flunixin meglumine in the horse: pharmacokinetic/pharmacodynamic modelling.. J Vet Pharmacol Ther 1994 Dec;17(6):459-69.
    pubmed: 7707492doi: 10.1111/j.1365-2885.1994.tb00278.xgoogle scholar: lookup
  33. Tsai HJ, Hwang SH, Morisseau C, Yang J, Jones PD, Kasagami T, Kim IH, Hammock BD. Pharmacokinetic screening of soluble epoxide hydrolase inhibitors in dogs.. Eur J Pharm Sci 2010 Jun 14;40(3):222-38.
    pmc: PMC3285443pubmed: 20359531doi: 10.1016/j.ejps.2010.03.018google scholar: lookup
  34. van Loon JP, de Grauw JC, van Dierendonck M, L'ami JJ, Back W, van Weeren PR. Intra-articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model.. Equine Vet J 2010 Jul;42(5):412-9.
    pubmed: 20636777doi: 10.1111/j.2042-3306.2010.00077.xgoogle scholar: lookup
  35. Viñuela-Fernández I, Jones E, Chase-Topping ME, Price J. Comparison of subjective scoring systems used to evaluate equine laminitis.. Vet J 2011 May;188(2):171-7.
    pubmed: 20541956doi: 10.1016/j.tvjl.2010.05.011google scholar: lookup
  36. Wagner K, Inceoglu B, Dong H, Yang J, Hwang SH, Jones P, Morisseau C, Hammock BD. Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models.. Eur J Pharmacol 2013 Jan 30;700(1-3):93-101.
    pmc: PMC3578047pubmed: 23276668doi: 10.1016/j.ejphar.2012.12.015google scholar: lookup
  37. Wagner K, Inceoglu B, Gill SS, Hammock BD. Epoxygenated fatty acids and soluble epoxide hydrolase inhibition: novel mediators of pain reduction.. J Agric Food Chem 2011 Apr 13;59(7):2816-24.
    pmc: PMC3483885pubmed: 20958046doi: 10.1021/jf102559qgoogle scholar: lookup
  38. Wagner K, Inceoglu B, Hammock BD. Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception.. Prostaglandins Other Lipid Mediat 2011 Nov;96(1-4):76-83.
    pmc: PMC3215909pubmed: 21854866doi: 10.1016/j.prostaglandins.2011.08.001google scholar: lookup
  39. Wagner K, Lee KS, Yang J, Hammock BD. Epoxy fatty acids mediate analgesia in murine diabetic neuropathy.. Eur J Pain 2017 Mar;21(3):456-465.
    pmc: PMC5300894pubmed: 27634339doi: 10.1002/ejp.939google scholar: lookup
  40. Wagner K, Vito S, Inceoglu B, Hammock BD. The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling.. Prostaglandins Other Lipid Mediat 2014 Oct;113-115:2-12.
    pmc: PMC4254344pubmed: 25240260doi: 10.1016/j.prostaglandins.2014.09.001google scholar: lookup

Citations

This article has been cited 13 times.
  1. Matsumoto N, Singh N, Lee KS, Barnych B, Morisseau C, Hammock BD. The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms. Prostaglandins Other Lipid Mediat 2022 Oct;162:106662.
    doi: 10.1016/j.prostaglandins.2022.106662pubmed: 35779854google scholar: lookup
  2. Xu J, Qiu X, Yu G, Ly M, Yang J, Silva RM, Zhang X, Yu M, Wang Y, Hammock B, Pinkerton KE, Zhao D. Soluble epoxide hydrolase inhibitor can protect the femoral head against tobacco smoke exposure-induced osteonecrosis in spontaneously hypertensive rats. Toxicology 2022 Jan 15;465:153045.
    doi: 10.1016/j.tox.2021.153045pubmed: 34801612google scholar: lookup
  3. Gowler PRW, Turnbull J, Shahtaheri M, Gohir S, Kelly T, McReynolds C, Yang J, Jha RR, Fernandes GS, Zhang W, Doherty M, Walsh DA, Hammock BD, Valdes AM, Barrett DA, Chapman V. Clinical and Preclinical Evidence for Roles of Soluble Epoxide Hydrolase in Osteoarthritis Knee Pain. Arthritis Rheumatol 2022 Apr;74(4):623-633.
    doi: 10.1002/art.42000pubmed: 34672113google scholar: lookup
  4. McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD. Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development. Molecules 2021 Aug 19;26(16).
    doi: 10.3390/molecules26165034pubmed: 34443621google scholar: lookup
  5. Tucker L, Trumble TN, Groschen D, Dobbs E, Baldo CF, Wendt-Hornickle E, Guedes AGP. Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis. Front Vet Sci 2021;8:685824.
    doi: 10.3389/fvets.2021.685824pubmed: 34422942google scholar: lookup
  6. Mavangira V, Kuhn MJ, Abuelo A, Morisseau C, Hammock BD, Sordillo LM. Activity of sEH and Oxidant Status during Systemic Bovine Coliform Mastitis. Antioxidants (Basel) 2021 May 20;10(5).
    doi: 10.3390/antiox10050812pubmed: 34065244google scholar: lookup
  7. Bittar IP, Neves CA, Araújo CT, Oliveira YVR, Silva SL, Borges NC, Franco LG. Dose-Finding in the Development of an LPS-Induced Model of Synovitis in Sheep. Comp Med 2021 Apr 1;71(2):141-147.
    doi: 10.30802/AALAS-CM-20-000032pubmed: 33568256google scholar: lookup
  8. Wang Y, Wagner KM, Morisseau C, Hammock BD. Inhibition of the Soluble Epoxide Hydrolase as an Analgesic Strategy: A Review of Preclinical Evidence. J Pain Res 2021;14:61-72.
    doi: 10.2147/JPR.S241893pubmed: 33488116google scholar: lookup
  9. Shihadih DS, Harris TR, Kodani SD, Hwang SH, Lee KSS, Mavangira V, Hamamoto B, Guedes A, Hammock BD, Morisseau C. Selection of Potent Inhibitors of Soluble Epoxide Hydrolase for Usage in Veterinary Medicine. Front Vet Sci 2020;7:580.
    doi: 10.3389/fvets.2020.00580pubmed: 33005645google scholar: lookup
  10. Teixeira JM, Abdalla HB, Basting RT, Hammock BD, Napimoga MH, Clemente-Napimoga JT. Peripheral soluble epoxide hydrolase inhibition reduces hypernociception and inflammation in albumin-induced arthritis in temporomandibular joint of rats. Int Immunopharmacol 2020 Oct;87:106841.
    doi: 10.1016/j.intimp.2020.106841pubmed: 32736189google scholar: lookup
  11. Bracken OV, Jalali P, Glanville JRW, Benvenutti L, Chambers ES, Trahair H, Motwani M, Feehan KT, Evans JG, Carvalho JS, De Maeyer RPH, Akbar AN, Lih FB, Zeldin DC, Bishop-Bailey D, Edin ML, Gilroy DW. Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans. Nat Commun 2026 Jan 16;17(1):431.
    doi: 10.1038/s41467-025-67961-5pubmed: 41545341google scholar: lookup
  12. Larsson N, McReynolds CB, Hwang SH, Wan D, Yang J, Lindberg R, Lehtipalo S, Claesson J, Liljeström AI, Lind A, Brolin A, Mettävainio MI, Hammock BD, Morisseau C, Nording ML. Inhibition of soluble epoxide hydrolase in endotoxin induced pig lung injury. Front Pharmacol 2025;16:1652349.
    doi: 10.3389/fphar.2025.1652349pubmed: 41001346google scholar: lookup
  13. McReynolds C, Hammock B, Morisseau C. Regulatory lipid vicinal diols counteract the biological activity of epoxy fatty acids and can act as biomarkers and mechanisms for disease progression. Pharmacol Ther 2023 Aug;248:108454.
    doi: 10.1016/j.pharmthera.2023.108454pubmed: 37268114google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.