Prevention of allergic rhinitis by aldose reductase inhibition in a murine model.

Umesh C.S. Yadav, Rakesh Mishra, Leopoldo Aguilera-Aguirre, Sanjiv Sur, Istvan Bolodgh, Kota V. Ramana, Satish K. Srivatsava

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Allergic rhinitis, one of the most common atopic diseases, is known to be elicited by Th2 cytokine-mediated inflammatory response. We have shown earlier that a polyol pathway enzyme aldose reductase (AR) regulates airway inflammation; however its role in allergic rhinitis is not known. We have investigated the role of AR in mediating pathological symptoms associated with allergic rhinitis in mice. The wild-type (WT) mice treated without or with AR inhibitor and AR knock out (AR(-/-)) mice were sensitized by two intraperitoneal injections of ragweed pollen extract (RWE) with adjuvant alum on days 0 and 4 followed by challenge on day 11 and/or 18 and 25. The allergic rhinitis symptoms were assessed by monitoring the nasal scratch, mast cell degranulation and release of tryptase in nasal lavage, infiltration of inflammatory cells, production of inflammatory cytokines and nasal epithelium remodeling. Sensitization and challenge of mice with RWE produced robust and reproducible pathological symptoms of allergic rhinitis as compared to control mice. AR inhibitor, fidarestat administered mice showed markedly reduced early phase response to allergen exposure such as nasal scratches, mast cells degranulation and release of tryptase in the nasal passage as well as late phase response such as inflammatory cell infiltration and release of Th2 type cytokines and nasal epithelial remodeling. Further, prevention of these events in AR(-/-)) mice suggests the role of AR in the mediation of allergic rhinitis. These results indicate an important role of AR in the mediation of RWE-induced allergic rhinitis in mice and prevention by AR inhibitor, fidarestat offers a novel therapeutic approach to ameliorate allergic rhinitis.

Original languageEnglish (US)
Pages (from-to)178-186
Number of pages9
JournalInflammation & allergy drug targets
Volume12
Issue number3
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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    Yadav, U. C. S., Mishra, R., Aguilera-Aguirre, L., Sur, S., Bolodgh, I., Ramana, K. V., & Srivatsava, S. K. (2013). Prevention of allergic rhinitis by aldose reductase inhibition in a murine model. Inflammation & allergy drug targets, 12(3), 178-186. https://doi.org/10.2174/1871528111312030004