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Journal of veterinary internal medicine2020; 34(4); 1631-1641; doi: 10.1111/jvim.15783

Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys.

Abstract: Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species. Objective: To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures. Methods: Six healthy adult female donkeys. Methods: Endotoxemia was induced by an IV infusion of LPS for 30 minutes. Animals either received 20 mL of saline or 0.6 mg/kg of meloxicam IV after LPS infusion. The experiments lasted 6 hours. Blood samples were collected serially for hematology, serum biochemistry, interleukin measurement, and leukocyte gene expression analysis. Vital signs were recorded throughout the study. Monocyte cultures were used to test the effects of meloxicam on LPS-activated monocytes. Results: Lipopolysaccharide induced fever, leukopenia, and neutropenia of similar magnitude in both groups, but meloxicam attenuated increases in plasma lactate, tumor necrosis factor-alpha (TNFα), and interleukin 1β concentrations compared to controls. No differences were detected between groups for cytokine mRNA expression. Furthermore, meloxicam decreased TNFα release in LPS-activated monocyte cultures. Conclusions: Meloxicam could be a feasible option for the treatment of endotoxemia and SIRS in donkeys. Additional studies are necessary to investigate possible meloxicam-related posttranscriptional regulation and to compare this drug with other nonsteroidal anti-inflammatory drugs (NSAIDs) in animals with endotoxemia.
Publication Date: 2020-05-28 PubMed ID: 32463537PubMed Central: PMC7379049DOI: 10.1111/jvim.15783Google Scholar: Lookup
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  • Journal Article

Summary

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This research article focuses on the use of meloxicam for treating endotoxemia-related systemic inflammation in donkeys. It further probes how gene expression and pathophysiology respond to endotoxemia along with the effects of meloxicam on such responses.

Objective of the Research

  • The main goal of the study was to understand the pathophysiology and gene expression changes associated with endotoxemia in donkeys and assess the impacts of meloxicam on these effects in donkeys and equine monocyte cultures.

Methodology

  • Six healthy adult female donkeys were employed in the study. Endotoxemia was induced by an intravenous infusion of lipopolysaccharide (LPS) for 30 minutes.
  • The donkeys were either given 20 ml of saline or 0.6 mg/kg of meloxicam IV after LPS infusion. Each experiment lasted 6 hours.
  • Blood samples were taken periodically for hematology, serum biochemistry, interleukin measurement, and leukocyte gene expression analysis. Vital signs of the donkeys were monitored throughout the tests.
  • Monocyte cultures were used to test the effect of meloxicam on LPS-triggered monocytes.

Results

  • LPS induced fever, leukopenia, and neutropenia of similar magnitude in both the control and the meloxicam treated groups. However, it was observed that meloxicam dampened increases in plasma lactate, tumor necrosis factor-alpha (TNFα), and interleukin 1β concentrations compared to the control group.
  • No significant differences were noted between the two groups in terms of cytokine mRNA expression. Importantly, meloxicam was found to reduce the release of TNFα in LPS-activated monocyte cultures.

Conclusions

  • The observations from the study suggest that meloxicam might be a viable treatment option for endotoxemia and associated systemic inflammatory response syndrome (SIRS) in donkeys.
  • However, further investigations would be necessary to understand possible posttranscriptional regulation linked to meloxicam, and how this drug compares to other nonsteroidal anti-inflammatory drugs (NSAIDs) in animals with endotoxemia.

Cite This Article

APA
Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. (2020). Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med, 34(4), 1631-1641. https://doi.org/10.1111/jvim.15783

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 4
Pages: 1631-1641

Researcher Affiliations

Mendoza Garcia, Francisco Javier
  • Department of Animal Medicine and Surgery, University of Cordoba, Campus Rabanales, Road Madrid-Cadiz km 396, 14104, Cordoba, Spain.
Gonzalez-De Cara, Carlos
  • Department of Animal Medicine and Surgery, University of Cordoba, Campus Rabanales, Road Madrid-Cadiz km 396, 14104, Cordoba, Spain.
Aguilera-Aguilera, Raul
  • Egabro Veterinary Practice, Cabra, Cordoba, Spain.
Buzon-Cuevas, Antonio
  • Department of Animal Medicine and Surgery, University of Cordoba, Campus Rabanales, Road Madrid-Cadiz km 396, 14104, Cordoba, Spain.
Perez-Ecija, Alejandro
  • Department of Animal Medicine and Surgery, University of Cordoba, Campus Rabanales, Road Madrid-Cadiz km 396, 14104, Cordoba, Spain.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cells, Cultured
  • Endotoxemia / chemically induced
  • Endotoxemia / drug therapy
  • Endotoxemia / veterinary
  • Equidae
  • Female
  • Interleukin-1beta / blood
  • Lactic Acid / blood
  • Lipopolysaccharides / toxicity
  • Meloxicam / pharmacology
  • Monocytes
  • Systemic Inflammatory Response Syndrome / chemically induced
  • Systemic Inflammatory Response Syndrome / drug therapy
  • Systemic Inflammatory Response Syndrome / veterinary
  • Tumor Necrosis Factor-alpha / blood

Grant Funding

  • Plan Andaluz de Investigacion from the Consejeria de Salud de la Junta de Andalucia (Spain)
  • Plan Propio de Investigacion from the University of Cordoba (Spain)
  • Programa Operativo de fondos FEDER Andalucia (Spain)

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 46 references
  1. Burden F, Thiemann A. Donkeys are different.. J Equine Vet Sci 2015;35:376‐382.
  2. Mendoza FJ, Perez‐Ecija RA, Toribio RE. Thyroid hormone concentrations differ between donkeys and horses.. Equine Vet J 2013;45:214‐218.
    pubmed: 22909401
  3. Veronesi MC, Gloria A, Panzani S, Sfirro MP, Carluccio A, Contri A. Blood analysis in newborn donkeys: hematology, biochemistry, and blood gases analysis.. Theriogenology 2014;82:294‐303.
    pubmed: 24831574
  4. Mendoza FJ, Estepa JC, Gonzalez‐De Cara CA. Energy‐related parameters and their association with age, gender, and morphometric measurements in healthy donkeys.. Vet J 2015;204:201‐207.
    pubmed: 25920762
  5. Perez‐Ecija A, Mendoza FJ. Characterisation of clotting factors, anticoagulant protein activities and viscoelastic analysis in healthy donkeys.. Equine Vet J 2017;49:734‐738.
    pubmed: 28323357
  6. Mejia‐Pereira S, Perez‐Ecija A, Buchanan BR, Toribio RE, Mendoza FJ. Evaluation of dynamic testing for pituitary pars intermedia dysfunction diagnosis in donkeys.. Equine Vet J 2019;51:481‐488.
    pubmed: 30362589
  7. Mendoza FJ, Aguilera‐Aguilera R, Gonzalez‐De Cara CA. Characterization of the intravenous glucose tolerance test and the combined glucose‐insulin test in donkeys.. Vet J 2015;206:371‐376.
    pubmed: 26515163
  8. Senior JM. Not small horses: improving treatments for donkeys.. Vet Rec 2013;173:292‐293.
    pubmed: 24077145
  9. Kelmer G. Update on treatments for endotoxemia.. Vet Clin North Am Equine Pract 2009;25:259‐270.
    pubmed: 19580938
  10. Mendoza FJ, Toribio RE, Perez‐Ecija A. Donkey internal medicine ‐ part I: metabolic, endocrine, and alimentary tract disturbances.. J Equine Vet Sci 2018;65:66‐74.
  11. Sykes BW, Furr MO. Equine endotoxaemia‐astate‐of‐the‐art review of therapy.. Aust Vet J 2005;83:45‐50.
    pubmed: 15971817
  12. Toribio RE, Kohn CW, Hardy J, Rosol TJ. Alterations in serum parathyroid hormone and electrolyte concentrations and urinary excretion of electrolytes in horses with induced endotoxemia.. J Vet Intern Med 2005;19:223‐231.
    pubmed: 15822568
  13. Werners AH, Bryant CE. Pattern recognition receptors in equine endotoxaemia and sepsis.. Equine Vet J 2012;44:490‐498.
    pmc: PMC7199481pubmed: 22607193
  14. Parkinson NJ, Buechner‐Maxwell VA, Witonsky SG, Pleasant RS, Werre SR, Ahmed SA. Characterization of basal and lipopolysaccharide‐induced microRNA expression in equine peripheral blood mononuclear cells using next‐generation sequencing.. PLoS One 2017;12:e0177664.
    pmc: PMC5446123pubmed: 28552958
  15. El‐Ashker M, El‐Sebaei M, Aamer H. The influence of experimentally‐induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus).. Vet Med 2017;62:117‐124.
  16. Werners AH, Bull S, Fink‐Gremmels J. Endotoxaemia: a review with implications for the horse.. Equine Vet J 2005;37:371‐383.
    pubmed: 16028631
  17. Nieto JE, MacDonald MH, Braim AE. Effect of lipopolysaccharide infusion on gene expression of inflammatory cytokines in normal horses in vivo.. Equine Vet J 2009;41:717‐719.
    pubmed: 19927593
  18. Gonzalez‐De Cara CA, Perez‐Ecija A, Aguilera‐Aguilera R. Temperament test for donkeys to be used in assisted therapy.. Appl Anim Behav Sci 2017;186:64‐71.
  19. Barton MH, Bruce EH, Moore JN, Norton N, Anders B, Morris DD. Effect of tumor necrosis factor antibody given to horses during early experimentally induced endotoxemia.. Am J Vet Res 1998;59:792‐797.
    pubmed: 9622754
  20. Barton MH, Parviainen A, Norton N. Polymyxin B protects horses against induced endotoxaemia in vivo.. Equine Vet J 2004;36:397‐401.
    pubmed: 15253079
  21. Figueiredo MD, Moore JN, Vandenplas ML, Sun WC, Murray TF. Effects of the second‐generation synthetic lipid a analogue E5564 on responses to endotoxin in [corrected] equine whole blood and monocytes.. Am J Vet Res 2008;69:796‐803.
    pubmed: 18518661
  22. Peiro JR, Barnabe PA, Cadioli FA. Effects of lidocaine infusion during experimental endotoxemia in horses.. J Vet Intern Med 2010;24:940‐948.
    pubmed: 20649751
  23. Alcott CJ, Sponseller BA, Wong DM. Clinical and immunomodulating effects of ketamine in horses with experimental endotoxemia.. J Vet Intern Med 2011;25:934‐943.
    pubmed: 21745244
  24. Naylor RJ, Taylor AH, Knowles EJ. Comparison of flunixin meglumine and meloxicam for post operative management of horses with strangulating small intestinal lesions.. Equine Vet J 2014;46:427‐434.
    pubmed: 24372991
  25. Toth F, Frank N, Elliott SB. Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses.. Am J Vet Res 2008;69:82‐88.
    pubmed: 18167091
  26. Toth F, Frank N, Geor RJ. Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin‐induced alterations in glucose and insulin dynamics in horses.. Am J Vet Res 2010;71:60‐68.
    pubmed: 20043782
  27. Kwon S, Moore JN, Robertson TP, Hurley DJ, Wagner B, Vandenplas ML. Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae.. Vet Immunol Immunopathol 2013;155:1‐8.
    pubmed: 23820116
  28. McGovern KF, Lascola KM, Smith SA. The effects of hyperglycemia and endotoxemia on coagulation parameters in healthy adult horses.. J Vet Intern Med 2013;27:347‐353.
    pubmed: 23480666
  29. Tadros EM, Frank N, Donnell RL. Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.. Am J Vet Res 2013;74:1010‐1019.
    pubmed: 23802673
  30. Sheats MK. A comparative review of equine SIRS, sepsis, and neutrophils.. Front Vet Sci 2019;6:69.
    pmc: PMC6424004pubmed: 30931316
  31. Frellstedt L, McKenzie HC, Barrett JG. Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro.. Vet Immunol Immunopathol 2012;149:97‐102.
    pubmed: 22658835
  32. Suagee JK, Corl BA, Crisman MV, Pleasant RS, Thatcher CD, Geor RJ. Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light‐breed horses.. J Vet Intern Med 2013;27:157‐163.
    pubmed: 23216530
  33. Moore JN, Norton N, Barton MH. Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.. Equine Vet J 2007;39:243‐248.
    pubmed: 17520976
  34. Cook VL, Holcombe SJ, Gandy JC, Corl CM, Sordillo LM. Ethyl pyruvate decreases proinflammatory gene expression in lipopolysaccharide‐stimulated equine monocytes.. Vet Immunol Immunopathol 2011;141:92‐99.
    pubmed: 21419499
  35. Henry MM, Moore JN. Endotoxin‐induced procoagulant activity in equine peripheral blood monocytes.. Circ Shock 1988;26:297‐309.
    pubmed: 3208423
  36. Sinclair MD, Mealey KL, Matthews NS, Peck KE, Taylor TS, Bennett BS. Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys.. Am J Vet Res 2006;67:1082‐1085.
    pubmed: 16740106
  37. David F, Farley J, Huang H. Cytokine and chemokine gene expression of IL‐1beta stimulated equine articular chondrocytes.. Vet Surg 2007;36:221‐227.
    pubmed: 17461946
  38. Castagnetti C, Mariella J, Pirrone A, Cinotti S, Mari G, Peli A. Expression of interleukin‐1beta, interleukin‐8, and interferon‐gamma in blood samples obtained from healthy and sick neonatal foals.. Am J Vet Res 2012;73:1418‐1427.
    pubmed: 22924724
  39. Sanchez‐Matamoros A, Kukielka D, De las Heras AI. Development and evaluation of a SYBR green real‐timeRT‐PCR assay for evaluation of cytokine gene expression in horse.. Cytokine 2013;61:50‐53.
    pubmed: 23103121
  40. Epstein A, Nir E, Eyngor M. Dynamic of cytokine gene transcription (TNF‐α, IL‐1β, IL‐6,IL‐8) in surgically treated colic horses by use of real‐time PCR (RT‐PCR).. Isr J Vet Med 2016;71:24‐30.
  41. Urayama S, Tanaka A, Kusano K. Oral administration of meloxicam suppresses low‐dose endotoxin challenge‐induced pain in thoroughbred horses.. J Equine Vet Sci 2019;77:139‐143.
    pubmed: 31133308
  42. Koenig J, Cote N. Equine gastrointestinal motility‐ileus and pharmacological modification.. Can Vet J 2006;47:551‐559.
    pmc: PMC1461410pubmed: 16808227
  43. Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL. Phenylbutazone prevents the endotoxin‐induced delay in gastric emptying in horses.. Can J Vet Res 1998;62:214‐217.
    pmc: PMC1189478pubmed: 9684051
  44. Tadros EM, Frank N. Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.. Am J Vet Res 2012;73:1394‐1402.
    pubmed: 22924721
  45. Clark A. Post‐transcriptional regulation of pro‐inflammatory gene expression.. Arthritis Res 2000;2:172‐174.
    pmc: PMC129998pubmed: 11094425
  46. Bachstetter AD, Van Eldik LJ. The p38 MAP kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the CNS.. Aging Dis 2010;1:199‐211.
    pmc: PMC3377763pubmed: 22720195

Citations

This article has been cited 7 times.
  1. Davias C, Mendoza FJ, De Las Heras A, Gonzalez-De-Cara C, Buzon-Cuevas A, Perez-Ecija A. Hematologic Ratios in Donkeys: Reference Intervals and Response to Experimentally Induced Endotoxemia. Animals (Basel) 2025 Aug 4;15(15).
    doi: 10.3390/ani15152272pubmed: 40805061google scholar: lookup
  2. Mendoza FJ, Toribio RE. An Overview of Donkey Neonatology. Animals (Basel) 2025 Jul 6;15(13).
    doi: 10.3390/ani15131986pubmed: 40646885google scholar: lookup
  3. Mendoza FJ, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara CA, De Las Heras A, Perez-Ecija A. Hemodynamic Response to Lipopolysaccharide Infusion and Effect of Meloxicam Administration on Cardiac Function in Donkeys. Animals (Basel) 2024 Dec 18;14(24).
    doi: 10.3390/ani14243660pubmed: 39765564google scholar: lookup
  4. Sousa LN, Winter IC, Varela DD, Luvison EZ, Guzmán JFC, Machado AMV, Figueiredo RDV, Pena GT, Dos Santos ACS, Faleiros RR, Carvalho AM. Lidocaine's Ineffectiveness in Mitigating Lipopolysaccharide-Induced Pain and Peristaltic Effects in Horses. Animals (Basel) 2024 Nov 2;14(21).
    doi: 10.3390/ani14213147pubmed: 39518869google scholar: lookup
  5. Zhi J, Qiao K, Xie L, Pascottini OB, Opsomer G, Dong Q. The In Vitro Effects of Carprofen on Lipopolysaccharide-Induced Neutrophil Extracellular Trap Formation in Dairy Cows. Animals (Basel) 2024 Mar 21;14(6).
    doi: 10.3390/ani14060985pubmed: 38540082google scholar: lookup
  6. Perez-Ecija A, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara C, Mendoza Garcia FJ. Reference intervals of acute phase proteins in healthy Andalusian donkeys and response to experimentally induced endotoxemia. J Vet Intern Med 2021 Jan;35(1):580-589.
    doi: 10.1111/jvim.16015pubmed: 33336874google scholar: lookup
  7. Perez-Ecija A, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara CA, Mendoza FJ. Blood Storage Conditions Affect Hematological Analysis in Samples From Healthy Donkeys and Donkeys With Experimentally-Induced Endotoxemia. Front Vet Sci 2020;7:640.
    doi: 10.3389/fvets.2020.00640pubmed: 33134340google scholar: lookup