The anti-asthmatic potential of Rho-kinase inhibitor hydroxyfasudil in the model of experimentally induced allergic airway inflammation

Objective: This experimental study evaluated the anti-asthmatic potential of the Rho-kinase inhibitor hydrox-yfasudil in the settings of allergen-induced allergen-induced experimental asthma. Methods: Chronic allergic airway inflammation was caused by 28 days-sensitisation of guinea pigs with oval-bumin (OVA). Hydroxyfasudil was administered intraperitoneally in two doses for the last two weeks (1 mg/kg b. w.; 10 mg/kg b.w.). The degree of allergic inflammation was determined based on concentrations of inflam-matory Th2 cytokines (IL-4, IL-13), Th1 cytokines (TNF-alpha and IFN-gamma) in the lung homogenate and leukocyte count in the bronchoalveolar lavage fluid (BALF). The markers of remodelling and fibrosis, the growth factors (TGF-81, EGF), EGF receptor, collagen type III and V were estimated in lung homogenate. The changes in specific airway resistance (sRaw) were used as an in vivo bronchial hyperreactivity parameter.Results: Hydroxyfasudil administration at both doses significantly reduced sRaw after a week of therapy. We observed a decline of IL-13, TNF-alpha and IFN-gamma in lung homogenate and a lower presence of lymphocytes in BALF after 14 days of hydroxyfasudil administration at both tested doses. Hydroxyfasudil 14 days-treatment at both doses effectively reduced the concentrations of TGF-81, EGF receptors, collagen type III and V in BALF and modulated EGF levels. Conclusions: These findings indicate that RhoA/Rho-kinase is involved in the pathophysiology of allergic airway inflammation and suggest that Rho-kinase inhibitor hydroxyfasudil has therapeutic potential for asthma management.

Automated summary

Objective: This experimental study evaluated the therapeutic potential of the Rho-kinase inhibitor hydroxyfasudil in managing allergen-induced asthma. The results showed that treatment with hydroxyfasudil for one week significantly reduced airway resistance and, after 14 days, decreased the number of inflammatory cells in bronchoalveolar lavage fluid and concentrations of cytokines and growth factors in lung tissue.