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. 2002 Jun;11(3):155–163. doi: 10.1080/09622935020138000

The pharmacological profile of ovalbumin-induced paw oedema in rats.

R F G Feitosa 1, G B Melcíades 1, A M S Assreuy 1, M F G Rocha 1, R A Ribeiro 1, A A M Lima 1
PMCID: PMC1781661  PMID: 12137244

Abstract

Rats are commonly used in anaphylaxis models, mainly in intestinal anaphylaxis. Hypersensitivity mechanisms are complex and they are not clearly defined. Ovalbumin (OVA) is commonly used for studies on the hypersensitivity mechanism. However, the potential pro-inflammatory mediators induced by this antigen in the model of paw oedema in immunized rats are still not completely understood. This work examines the pharmacological modulation of several mediators involved in rat hind paw immune oedema induced by OVA. Wistar rats were previously immunized (14-18 days) with OVA (30 microg, intraperitoneally) or sham-sensitized with aluminum hydroxide (control). The paw volumes were measured before the antigenic stimuli and 1, 2, 3 and 4 h after the intraplantar injection of OVA (10 microg/paw). Subcutaneous injection of dexamethasone, diphenhydramine, cyproheptadine, chlorpromazine or methysergide significantly inhibited (p < 0.05) the allergic paw oedema. The dual inhibitor of cyclooxygenase and lipoxygenase (NDGA), the cyclooxygenase inhibitor (indomethacin), the lipoxygenase inhibitor (MK-886), the PAF antagonist (WEB 2086), the mast cell stabilizer (ketotifen), and the anti-histamine (meclizine) did not inhibit the immune oedema. In addition, thalidomide and pentoxifylline (anti-tumour necrosis factor drugs) were ineffective against OVA-induced oedema. The fact that indomethacin, MK-886, NDGA and WEB 2086 are unable to inhibit this allergic oedema indicates that the dexamethasone action seems not to be via phospholipase A2, but possibly due to the synthesis and/or the inhibitory activity of cytokines. The paw oedema inhibition by diphenhydramine, but not by meclizine, may suggest a different mechanism, which is independent of the effect of histamine. These data indicate that allergic oedema is more sensitive to anti-serotonin drugs, mainly anti-5-HT2, suggesting that the principal mediator of this inflammatory response is serotonin.

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Selected References

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  1. Amorim C. Z., Cordeiro R. S., Vargaftig B. B. Interference of antihistamines and anti-allergic drugs with antigen-induced paw edema in boosted and unboosted mice. Eur J Pharmacol. 1992 Jun 17;216(3):429–434. doi: 10.1016/0014-2999(92)90441-6. [DOI] [PubMed] [Google Scholar]
  2. BOSHELL B. R., MACLAREN J., METCALFE J. Asymptomatic bacteriuria in pregnancy. Surg Gynecol Obstet. 1962 May;114:583–586. [PubMed] [Google Scholar]
  3. Bissonnette E. Y. Histamine inhibits tumor necrosis factor alpha release by mast cells through H2 and H3 receptors. Am J Respir Cell Mol Biol. 1996 Jun;14(6):620–626. doi: 10.1165/ajrcmb.14.6.8652190. [DOI] [PubMed] [Google Scholar]
  4. Businco L., Cantani A. Food allergy in children: diagnosis and treatment with sodium cromoglycate. Allergol Immunopathol (Madr) 1990 Nov-Dec;18(6):339–348. [PubMed] [Google Scholar]
  5. Casey F. B., Tokuda S. A comparative study of the mechanisms of passive cutaneous anaphylaxis induced by mouse IgG, rabbit IgG, and rabbit F (ab')2 antibodies. I. The role of serotonin and histamine. Int Arch Allergy Appl Immunol. 1973;44(6):737–744. doi: 10.1159/000230978. [DOI] [PubMed] [Google Scholar]
  6. Di Rosa M., Giroud J. P., Willoughby D. A. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol. 1971 May;104(1):15–29. doi: 10.1002/path.1711040103. [DOI] [PubMed] [Google Scholar]
  7. Dinarello C. A. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis. 1991 Jun;163(6):1177–1184. doi: 10.1093/infdis/163.6.1177. [DOI] [PubMed] [Google Scholar]
  8. Endres S., Fülle H. J., Sinha B., Stoll D., Dinarello C. A., Gerzer R., Weber P. C. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology. 1991 Jan;72(1):56–60. [PMC free article] [PubMed] [Google Scholar]
  9. Guo Y., Mochizuki T., Morii E., Kitamura Y., Maeyama K. Role of mast cell histamine in the formation of rat paw edema: a microdialysis study. Eur J Pharmacol. 1997 Jul 23;331(2-3):237–243. doi: 10.1016/s0014-2999(97)01002-9. [DOI] [PubMed] [Google Scholar]
  10. Honrubia M. A., Rodriguez J., Dominguez R., Lozoya E., Manaut F., Seijas J. A., Villaverde M. C., Calleja J. M., Cadavid M. I., Maayani S. Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and structure-activity relationships of a series of cyproheptadine analogues. Chem Pharm Bull (Tokyo) 1997 May;45(5):842–848. doi: 10.1248/cpb.45.842. [DOI] [PubMed] [Google Scholar]
  11. Jahnová E., Horváthová M., Gazdík F. Expression of adhesion molecules and effect of disodium cromoglycate treatment in asthmatics. Physiol Res. 1998;47(6):439–443. [PubMed] [Google Scholar]
  12. Kaneta S., Kanbara H., Fujihira E., Mitsuya M. Mouse IgE-mediated paw anaphylaxis in mice and rats. Int Arch Allergy Appl Immunol. 1986;80(3):333–335. doi: 10.1159/000234075. [DOI] [PubMed] [Google Scholar]
  13. Kim D. Y., Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol. 2000 Oct;95(10):2698–2709. doi: 10.1111/j.1572-0241.2000.03177.x. [DOI] [PubMed] [Google Scholar]
  14. Landucci E. C., Antunes E., Donato J. L., Faro R., Hyslop S., Marangoni S., Oliveira B., Cirino G., de Nucci G. Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2. Br J Pharmacol. 1995 Feb;114(3):578–583. doi: 10.1111/j.1476-5381.1995.tb17178.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee H. Z., Wu C. Serotonin-induced protein kinase C activation in cultured rat heart endothelial cells. Eur J Pharmacol. 2000 Sep 8;403(3):195–202. doi: 10.1016/s0014-2999(00)00495-7. [DOI] [PubMed] [Google Scholar]
  16. Lesser M. L., Braun H. I., Helson L. Statistical methods for measuring and comparing treatment efficacies: applications to nude mice experimentation. Exp Cell Biol. 1980;48(2):126–137. doi: 10.1159/000162981. [DOI] [PubMed] [Google Scholar]
  17. Liston H., Bennett L., Usher B., Jr, Nappi J. The association of the combination of sumatriptan and methysergide in myocardial infarction in a premenopausal woman. Arch Intern Med. 1999 Mar 8;159(5):511–513. doi: 10.1001/archinte.159.5.511. [DOI] [PubMed] [Google Scholar]
  18. Maling H. M., Webster M. E., Williams M. A., Saul W., Anderson W., Jr Inflammation induced by histamine, serotonin, bradykinin and compound 48-80 in the rat: antagonists and mechanisms of action. J Pharmacol Exp Ther. 1974 Nov;191(2):300–310. [PubMed] [Google Scholar]
  19. Moreira A. L., Sampaio E. P., Zmuidzinas A., Frindt P., Smith K. A., Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med. 1993 Jun 1;177(6):1675–1680. doi: 10.1084/jem.177.6.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nisijima K., Yoshino T., Yui K., Katoh S. Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res. 2001 Jan 26;890(1):23–31. doi: 10.1016/s0006-8993(00)03020-1. [DOI] [PubMed] [Google Scholar]
  21. Perdue M. H., Chung M., Gall D. G. Effect of intestinal anaphylaxis on gut function in the rat. Gastroenterology. 1984 Mar;86(3):391–397. [PubMed] [Google Scholar]
  22. Pierce P. A., Xie G. X., Peroutka S. J., Green P. G., Levine J. D. 5-Hydroxytryptamine-induced synovial plasma extravasation is mediated via 5-hydroxytryptamine2A receptors on sympathetic efferent terminals. J Pharmacol Exp Ther. 1995 Oct;275(1):502–508. [PubMed] [Google Scholar]
  23. Pollice P. F., Rosier R. N., Looney R. J., Puzas J. E., Schwarz E. M., O'Keefe R. J. Oral pentoxifylline inhibits release of tumor necrosis factor-alpha from human peripheral blood monocytes : a potential treatment for aseptic loosening of total joint components. J Bone Joint Surg Am. 2001 Jul;83-A(7):1057–1061. doi: 10.2106/00004623-200107000-00012. [DOI] [PubMed] [Google Scholar]
  24. Rocha M. F., Maia M. E., Bezerra L. R., Lyerly D. M., Guerrant R. L., Ribeiro R. A., Lima A. A. Clostridium difficile toxin A induces the release of neutrophil chemotactic factors from rat peritoneal macrophages: role of interleukin-1beta, tumor necrosis factor alpha, and leukotrienes. Infect Immun. 1997 Jul;65(7):2740–2746. doi: 10.1128/iai.65.7.2740-2746.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scott R. B., Tan D. T., Miampamba M., Sharkey K. A. Anaphylaxis-induced alterations in intestinal motility: role of extrinsic neural pathways. Am J Physiol. 1998 Oct;275(4 Pt 1):G812–G821. doi: 10.1152/ajpgi.1998.275.4.G812. [DOI] [PubMed] [Google Scholar]
  26. Shida T. [A comparison of the pharmacological actions between DSCG (disodium cromoglycate) and BDP (beclomethasone dipropionate) in the treatment of bronchial asthma]. Nihon Rinsho. 1996 Nov;54(11):3011–3016. [PubMed] [Google Scholar]
  27. Trichard C., Paillère-Martinot M. L., Attar-Levy D., Recassens C., Monnet F., Martinot J. L. Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients. Am J Psychiatry. 1998 Apr;155(4):505–508. doi: 10.1176/ajp.155.4.505. [DOI] [PubMed] [Google Scholar]
  28. Tromp S. C., Tangelder G. J., Slaaf D. W., Reneman R. S., van Velzen S., Engels W., van Breda E., oude Egbrink M. G. The role of mast cells and histamine in leukocyte-endothelium interactions in four rat strains. Pflugers Arch. 1998 Jul;436(2):255–261. doi: 10.1007/s004240050630. [DOI] [PubMed] [Google Scholar]
  29. WILHELM D. L. The mediation of increased vascular permeability in inflammation. Pharmacol Rev. 1962 Jun;14:251–280. [PubMed] [Google Scholar]
  30. Wang J. P., Chen Y. H., Kuo S. C. Inhibition of hind-paw edema and cutaneous vascular plasma extravasation by 2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) in mice. Naunyn Schmiedebergs Arch Pharmacol. 1996 Dec;354(6):779–784. doi: 10.1007/BF00166905. [DOI] [PubMed] [Google Scholar]
  31. Wolf C., Schunack W. Synthesis and pharmacology of combined histamine H1-/H2-receptor antagonists containing diphenhydramine and cyproheptadine derivatives. Arch Pharm (Weinheim) 1996 Feb;329(2):87–94. doi: 10.1002/ardp.19963290206. [DOI] [PubMed] [Google Scholar]
  32. Yamaki K., Thorlacius H., Xie X., Lindbom L., Hedqvist P., Raud J. Characteristics of histamine-induced leukocyte rolling in the undisturbed microcirculation of the rat mesentery. Br J Pharmacol. 1998 Feb;123(3):390–399. doi: 10.1038/sj.bjp.0701614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yeh S. Y., Dersch C., Rothman R., Cadet J. L. Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats. Synapse. 1999 Sep 1;33(3):207–217. doi: 10.1002/(SICI)1098-2396(19990901)33:3<207::AID-SYN5>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  34. da Motta J. I., Cunha F. Q., Vargaftig B. B., Ferreira S. H. Drug modulation of antigen-induced paw oedema in guinea-pigs: effects of lipopolysaccharide, tumour necrosis factor and leucocyte depletion. Br J Pharmacol. 1994 May;112(1):111–116. doi: 10.1111/j.1476-5381.1994.tb13038.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Lima V., Bezerra M. M., de Menezes Alencar V. B., Vidal F. D., da Rocha F. A., de Castro Brito G. A., de Albuquerque Ribeiro R. Effects of chlorpromazine on alveolar bone loss in experimental periodontal disease in rats. Eur J Oral Sci. 2000 Apr;108(2):123–129. doi: 10.1034/j.1600-0722.2000.00766.x. [DOI] [PubMed] [Google Scholar]

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