Current Prospective of Aldose Reductase Inhibition in the Therapy of Allergic Airway Inflammation in Asthma

K.V.      Ramana; U.C.S.      Yadav; W.J.      Calhoun; S.K.      Srivastava

Abstract

The prevalence of asthma and costs of its care have been continuously increasing, but novel therapeutic options to treat this inflammatory disease have not been brought to the US market. Current therapies such as inhaled steroids, long-acting beta-agonist bronchodilators, antihistamines and immunomodulators may control the symptoms of allergic asthma but fail to modify the underlying disease. Excessive use of steroids and other immunosuppresents alter the patient's quality of life, produce undesirable toxicities, and increase the risk of other pathologies such as diabetes. Hence novel therapeutic options to manage asthma are desirable. In the present review, we have discussed the role of the polyol pathway enzyme aldose reductase (AR) in the amplification of allergic airway inflammation. Recent studies have indicated that AR inhibition prevents the NF-κB-dependent generation of pro-inflammatory cytokines and chemokines in mouse models of allergic airway inflammation indicating the potential use of AR inhibition as a novel tool to control allergic responses. Since orally available AR inhibitors have already undergone phase III clinical trials for diabetic neuropathy and appear to have a manageable side effects profile, they could be readily developed as potential new drugs for the treatment of asthma and related complications.

Keywords: Asthma, airway inflammation, aldose reductase, polyol pathway, heterogeneity, anti-inflammatory medications, oxidative stress, antioxidant, cytokines, molecular signaling, chemokines, metaplasia, airway remodeling, pulmonary fibrosis, corticosteroids