ovalbumin and amlexanox

We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

Topics: Aminopyridines; Animals; Anti-Allergic Agents; Antigens; Cromolyn Sodium; Cyclosporine; Dinitrobenzenes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Edema; Haptens; Hindlimb; Hypersensitivity, Delayed; Male; ortho-Aminobenzoates; Ovalbumin; Passive Cutaneous Anaphylaxis; Promethazine; Pyridines; Pyrimidinones; Quinolones; Rats; Rats, Wistar

The pharmacodynamics of Amlexanox (AA-673), an azoxanthone derivative recently developed as an ocular anti-allergic drug, were studied in normal and anaphylactic rat conjunctiva. Ocular anaphylaxis was induced by topical application of dithiothreitol and antigen challenge (egg albumin). The drug concentration was measured at 5, 30, 60 and 120 min after instillation of AA-673 0.25% ophthalmic solution. Histamine concentrations in the pretreated and untreated anaphylactic conjunctiva were compared. In both groups the drug concentration decreased exponentially with time, showing a marked delay in the anaphylactic group. There was a significant difference in histamine values between the pretreated and untreated groups.

Topics: Aminopyridines; Animals; Chromatography, High Pressure Liquid; Conjunctiva; Dithiothreitol; Histamine; Hypersensitivity; Male; Ovalbumin; Rats; Rats, Inbred Strains