FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
BMC veterinary research2012; 8; 160; doi: 10.1186/1746-6148-8-160

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse.

Abstract: Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices. Results: After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP) differed significantly from each other (p = 0.002). The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period. Conclusions: In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.
Get Full Text
Publication Date: 2012-09-10 PubMed ID: 22963524PubMed Central: PMC3485115DOI: 10.1186/1746-6148-8-160Google 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
  • Research Support
  • Non-U.S. Gov't

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.

The research article presents findings on the non-genomic action of beclomethasone dipropionate, a glucocorticoid, in reducing bronchoconstriction caused by leukotriene C4 on cut lung slices of horses. It hints at a possible rapid non-genomic response mechanism that glucocorticoids may involve in treating recurrent airway obstruction in horses.

Objective of the Research

  • The objective of this study was to examine the effects of the glucocorticoid beclomethasone dipropionate on bronchoconstriction in the lungs of horses. The aim was to gain more understanding of how glucocorticoids, proven effective in treating airway obstruction in horses, work to reduce inflammation and bronchoconstriction.

Methodology

  • Scientists used precision-cut lung slices (PCLS) from horses to analyse the action of beclomethasone. Horses used for the study were not subjected to euthanasia due to respiratory-related illnesses.
  • The lung slices were exposed to Leukotriene C4, a known mediator of inflammation and bronchoconstriction.
  • The contraction of the bronchioles in the lung slices in response to Leukotriene C4, with and without the presence of beclomethasone, were studied and compared.

Findings

  • The results of the research showed that after 30 minutes of incubation in PCLS, beclomethasone significantly reduced the contraction of bronchioles instilled with leukotriene C4.
  • The half maximal effective concentration (EC50) values of contractions induced by leukotriene C4, with and without beclomethasone, differed significantly.
  • This significant difference in effect and the rapid response of beclomethasone suggests a likely non-genomic mechanism at play. Non-genomic mechanisms involve faster cellular responses as compared to nuclear-targeted, or genomic, responses that involve transcriptional activities and require a longer time.

Implications and Conclusions

  • In human neuroendocrinology, high levels of glucocorticoids have been associated with non-genomic mechanisms, suggesting similar possibilities in horses.
  • The use of a high concentration of beclomethasone on lung slices in the study also hints at such non-genomic mechanisms in the lower airways of horses when treated with high-dose inhaled glucocorticoids.
  • However, further research is needed to confirm this suspected non-genomic mechanism of glucocorticoids at a molecular level.

Cite This Article

APA
Fugazzola M, Barton AK, Niedorf F, Kietzmann M, Ohnesorge B. (2012). Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse. BMC Vet Res, 8, 160. https://doi.org/10.1186/1746-6148-8-160

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 8
Pages: 160

Researcher Affiliations

Fugazzola, Maria
  • University of Veterinary Sciences Hanover, Clinic for Horses, Hanover, Germany. maria.fugazzola@gmail.com
Barton, Ann-Kristin
    Niedorf, Frank
      Kietzmann, Manfred
        Ohnesorge, Bernhard

          MeSH Terms

          • Animals
          • Anti-Asthmatic Agents / pharmacology
          • Beclomethasone / pharmacology
          • Bronchoconstriction / drug effects
          • Female
          • Horses
          • Leukotriene C4 / pharmacology
          • Lung / drug effects
          • Lung / physiology
          • Male

          References

          This article includes 36 references
          1. Barnes PJ. Molecular mechanisms of glucocorticoid action in asthma.. Pulm Pharmacol Ther 1997;10(1):3-19.
            doi: 10.1006/pupt.1997.0079pubmed: 9344828google scholar: lookup
          2. Alangari AA. Genomic and non-genomic actions of glucocorticoids in asthma.. Ann Thorac Med 2010 Jul;5(3):133-9.
            doi: 10.4103/1817-1737.65040pmc: PMC2930650pubmed: 20835306google scholar: lookup
          3. Reichardt HM, Tuckermann JP, Bauer A, Schütz G. Molecular genetic dissection of glucocorticoid receptor function in vivo.. Z Rheumatol 2000;59 Suppl 2:II/1-5.
            doi: 10.1007/s003930050001pubmed: 11155788google scholar: lookup
          4. Gibson PG, Saltos N, Fakes K. Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial.. Am J Respir Crit Care Med 2001 Jan;163(1):32-6.
            pubmed: 11208622doi: 10.1164/ajrccm.163.1.9807061google scholar: lookup
          5. Lavoie JP. In: Heaves (recurrent airway obstruction): practical management of acute episodes and prevention of exacerbations Current Therapy in Equine Medicine2003. Robinson ME, Sprayberry KA, editor. St. Louis, Saunders;
          6. Hanania NA. The impact of inhaled corticosteroid and long-acting beta-agonist combination therapy on outcomes in COPD.. Pulm Pharmacol Ther 2008;21(3):540-50.
            doi: 10.1016/j.pupt.2007.12.004pubmed: 18280761google scholar: lookup
          7. Corcoran BM, Mair TS, Taylor DJ. Drugs used in the treatment of disorders of the respiratory system. The Veterinary Formulary sixth edition 2005.
          8. Léguillette R. Recurrent airway obstruction--heaves.. Vet Clin North Am Equine Pract 2003 Apr;19(1):63-86, vi.
            doi: 10.1016/S0749-0739(02)00067-6pubmed: 12747662google scholar: lookup
          9. Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P. Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.. J Vet Intern Med 2006 Mar-Apr;20(2):399-406.
            doi: 10.1111/j.1939-1676.2006.tb02875.xpubmed: 16594601google scholar: lookup
          10. Davis E, Rush BR. Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management.. Vet Clin North Am Equine Pract 2002 Dec;18(3):453-67, vi.
            doi: 10.1016/S0749-0739(02)00026-3pubmed: 12516928google scholar: lookup
          11. Ainsworth DM, Cheetam J. Disorders of the respiratory system. Equine Internal Medicine third edition; pp. 340–344.
          12. Nagase T, Fukuchi Y, Dallaire MJ, Martin JG, Ludwig MS. In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4.. Am J Respir Crit Care Med 1995 Jul;152(1):81-6.
            pubmed: 7599867doi: 10.1164/ajrccm.152.1.7599867google scholar: lookup
          13. Drazen JM. Leukotrienes as mediators of airway obstruction.. Am J Respir Crit Care Med 1998 Nov;158(5 Pt 3):S193-200.
            pubmed: 9817745doi: 10.1164/ajrccm.158.supplement_2.13tac180google scholar: lookup
          14. Lavoie JP, Léguillette R, Pasloske K, Charette L, Sawyer N, Guay D, Murphy T, Hickey GJ. Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction.. Am J Vet Res 2002 Apr;63(4):579-85.
            doi: 10.2460/ajvr.2002.63.579pubmed: 11939323google scholar: lookup
          15. Lindberg A, Robinson NE, Näsman-Glaser B, Jensen-Waern M, Lindgren JA. Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction.. Am J Vet Res 2004 Mar;65(3):289-95.
            doi: 10.2460/ajvr.2004.65.289pubmed: 15027674google scholar: lookup
          16. Marr KA, Lees P, Page CP, Cunningham FM. Inhaled leukotrienes cause bronchoconstriction and neutrophil accumulation in horses.. Res Vet Sci 1998 May-Jun;64(3):219-24.
            doi: 10.1016/S0034-5288(98)90129-1pubmed: 9690607google scholar: lookup
          17. Schwalfenberg B. Untersuchung der Leukotrienwirkung am Pferdebronchus mittels. Tierärztliche Hochschule, Dissertation, Hannover; 2007.
          18. Barton AK, Niedorf F, Gruber AD, Kietzmann M, Ohnesorge B. Pharmacological studies of bronchial constriction inhibited by parasympatholytics and cilomilast using equine precision-cut lung slices.. Berl Munch Tierarztl Wochenschr 2010 May-Jun;123(5-6):229-35.
            pubmed: 20496830
          19. Vietmeier J, Niedorf F, Bäumer W, Martin C, Deegen E, Ohnesorge B, Kietzmann M. Reactivity of equine airways--a study on precision-cut lung slices.. Vet Res Commun 2007 Jul;31(5):611-9.
            doi: 10.1007/s11259-007-3501-ypubmed: 17252319google scholar: lookup
          20. Barton AK, Niedorf F, Rohwer J, Kietzmann M, Ohnesorge B. Pilot study on passive sensitization against ovalbumin using equine precision-cut lung slices (PCLS). Pferdeheilkunde 2010;26:789–796.
          21. Martin C, Uhlig S, Ullrich V. Videomicroscopy of methacholine-induced contraction of individual airways in precision-cut lung slices.. Eur Respir J 1996 Dec;9(12):2479-87.
            doi: 10.1183/09031936.96.09122479pubmed: 8980957google scholar: lookup
          22. Devillier P. [Pharmacology of glucocorticoids and ENT pathology].. Presse Med 2001 Dec 22-29;30(39-40 Pt 2):59-69.
            pubmed: 11819915
          23. van der Velden VH. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.. Mediators Inflamm 1998;7(4):229-37.
            doi: 10.1080/09629359890910pmc: PMC1781857pubmed: 9792333google scholar: lookup
          24. Ferguson DC, Hoenig M. Glucocorticoids, mineralocorticoids, and steroid synthesis inhibitors. Veterinary Pharmacology and Therapeutics Iowa State University Press, Ames (USA); 2001. pp. 649–668.
          25. Croxtall JD, Choudhury Q, Flower RJ. Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism.. Br J Pharmacol 2000 May;130(2):289-98.
            doi: 10.1038/sj.bjp.0703272pmc: PMC1572055pubmed: 10807665google scholar: lookup
          26. Muto S, Ebata S, Okada K, Saito T, Asano Y. Glucocorticoid modulates Na+/H+ exchange activity in vascular smooth muscle cells by nongenomic and genomic mechanisms.. Kidney Int 2000 Jun;57(6):2319-33.
            doi: 10.1046/j.1523-1755.2000.00092.xpubmed: 10844602google scholar: lookup
          27. Harvey BJ, Alzamora R, Healy V, Renard C, Doolan CM. Rapid responses to steroid hormones: from frog skin to human colon. A homage to Hans Ussing.. Biochim Biophys Acta 2002 Nov 13;1566(1-2):116-28.
            doi: 10.1016/S0005-2736(02)00589-8pubmed: 12421543google scholar: lookup
          28. Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids.. Nat Clin Pract Rheumatol 2008 Oct;4(10):525-33.
            doi: 10.1038/ncprheum0898pubmed: 18762788google scholar: lookup
          29. Lecoq L, Vincent P, Lavoie-Lamoureux A, Lavoie JP. Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils.. Vet Immunol Immunopathol 2009 Mar 15;128(1-3):126-31.
            doi: 10.1016/j.vetimm.2008.10.303pubmed: 19036458google scholar: lookup
          30. Wehling M, Lösel R. Non-genomic steroid hormone effects: membrane or intracellular receptors?. J Steroid Biochem Mol Biol 2006 Dec;102(1-5):180-3.
            doi: 10.1016/j.jsbmb.2006.09.016pubmed: 17113980google scholar: lookup
          31. de Kloet ER, Karst H, Joëls M. Corticosteroid hormones in the central stress response: quick-and-slow.. Front Neuroendocrinol 2008 May;29(2):268-72.
            doi: 10.1016/j.yfrne.2007.10.002pubmed: 18067954google scholar: lookup
          32. Chanoine F, Grenot C, Heidmann P, Junien JL. Pharmacokinetics of butixocort 21-propionate, budesonide, and beclomethasone dipropionate in the rat after intratracheal, intravenous, and oral treatments.. Drug Metab Dispos 1991 Mar-Apr;19(2):546-53.
            pubmed: 1676668
          33. Zaitsu M, Hamasaki Y, Aoki Y, Miyazaki S. A novel pharmacologic action of glucocorticosteroids on leukotriene C4 catabolism.. J Allergy Clin Immunol 2001 Jul;108(1):122-4.
            doi: 10.1067/mai.2001.116000pubmed: 11447392google scholar: lookup
          34. Ammann VJ, Vrins AA, Lavoie JP. Effects of inhaled beclomethasone dipropionate on respiratory function in horses with chronic obstructive pulmonary disease (COPD).. Equine Vet J 1998 Mar;30(2):152-7.
            doi: 10.1111/j.2042-3306.1998.tb04475.xpubmed: 9535072google scholar: lookup
          35. Rush BR, Flaminio MJ, Matson CJ, Hakala JE, Shuman W. Cytologic evaluation of bronchoalveolar lavage fluid from horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively.. Am J Vet Res 1998 Aug;59(8):1033-8.
            pubmed: 9706209
          36. Urbach V, Harvey BJ. Rapid and non-genomic reduction of intracellular [Ca(2+)] induced by aldosterone in human bronchial epithelium.. J Physiol 2001 Nov 15;537(Pt 1):267-75.
            doi: 10.1111/j.1469-7793.2001.0267k.xpmc: PMC2278946pubmed: 11711579google scholar: lookup

          Citations

          This article has been cited 3 times.
          1. Michalaki C, Dean C, Johansson C. The Use of Precision-Cut Lung Slices for Studying Innate Immunity to Viral Infections. Curr Protoc 2022 Aug;2(8):e505.
            doi: 10.1002/cpz1.505pubmed: 35938685google scholar: lookup
          2. Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
            doi: 10.1111/jvim.16189pubmed: 34085342google scholar: lookup
          3. Liu G, Betts C, Cunoosamy DM, Åberg PM, Hornberg JJ, Sivars KB, Cohen TS. Use of precision cut lung slices as a translational model for the study of lung biology. Respir Res 2019 Jul 19;20(1):162.
            doi: 10.1186/s12931-019-1131-xpubmed: 31324219google scholar: lookup
          Subscribe to our newsletter
          Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.