title: Validation of guinea pig model of allergic rhinitis by oral and topical drugs.
abstract: Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in the studies of rhinitis. Systemic sensitization and challenge with ovalbumin-induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers, positive skin reactions and nasal lavage IL-4 concentration. Histopathology of nasal mucosa showed infiltration of eosinophils and other inflammatory cells consistent with the symptoms. Topical sensitization of ovalbumin yielded inconsistent symptoms of rhinitis. In systemic sensitization model, repeated challenge of ovalbumin caused similar response for at least 3 consecutive challenges. The symptoms were affected by relative humidity in the air and dosing volume of topical drugs. Sneezing and lacrimation were reduced by acute oral administration of the H1 receptor antagonists and steroids or the prophylactic oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist montelukast or acute topical antihistamines, mast cell stabilizer sodium cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical steroid. Nose rubbing was reduced significantly by some oral and topical antihistamines. Oral steroids offered excellent protection against all symptoms. Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2 weeks had no effect on sneezing or rubbing. However, it caused complete inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant oxymetazoline caused reduction in congestion. These results suggest that differential responsiveness to symptoms of rhinitis by a new agent can be very well profiled in the model in congruence with the mediation pathways and mechanism of action of drugs. The model provides complete symptomatic characterization of rhinitis and is a good tool for its study.
authors.affiliation: Sun Pharma Advanced Research Company Limited, Atladara, Tandalja Road, Vadodara, Gujarat, 390 020, India.
authors.forename: Prashant C
authors.initials: PC
authors.lastname: Bahekar
authors.forename: Jigar H
authors.initials: JH
authors.lastname: Shah
authors.forename: Upendra B
authors.initials: UB
authors.lastname: Ayer
authors.forename: Sanjay N
authors.initials: SN
authors.lastname: Mandhane
authors.forename: Rajamannar
authors.initials: R
authors.lastname: Thennati
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006813:Humidity; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012912:Sneezing / Q000187:drug effects / Q000276:immunology
chemical_list: D018926:Anti-Allergic Agents; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin