The pharmacological profile of ovalbumin-induced paw oedema in rats.
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.
Feitosa
R F G
RF
Institute of Biomedicine, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil. rgfeitosa@ig.com.br
Melcíades
G B
GB
Assreuy
A M S
AM
Rocha
M F G
MF
Ribeiro
R A
RA
Lima
A A M
AA
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004487:Edema / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology
D018926:Anti-Allergic Agents; D001381:Azepines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D010047:Ovalbumin; D002746:Chlorpromazine; D007665:Ketotifen