The antiasthmatic activity of Rho-kinase inhibitor hydroxyfasudil in the settings of experimentally induced allergic airway inflammation

Abstract

Objective: This experimental study evaluates the anti-asthmatic potential of the Rho-kinase inhibitor hydroxyfasudil in experimental allergen ovalbumin (OVA)-induced allergic inflammation.

Methods: Chronic allergic respiratory inflammation was caused by 28 days-sensitisation of guinea pigs with allergen ovalbumin (OVA). Hydroxyfasudil was administered intraperitoneally for the last two weeks in two doses (1 mg/kg; 10 mg/kg). Evaluated parameters: Changes in vivo specific airway resistance (sRaw); The concentrations of inflammatory cytokines Th2 (IL-4, IL-13) and Th1 (TNF-α and IFN-γ) in the lung homogenate and levels of leucocytes in the bronchoalveolar lavage fluid (BALF); The determination of remodelling markers the growth factors TGF-ß, EGF, EGF receptor (EGFR) and collagen types III and V in lung homogenate.

Results: Hydroxyfasudil administration at a lower dose (1 mg/kg) significantly reduced sRaw after a week of therapy. We observed a reduction of IL-13, TNF-α and IFN-γ in lung homogenate and a lower presence of lymphocytes in BALF after 14 days of hydroxyfasudil administration at both tested doses. Hydroxyfasudil administered for 14 days effectively reduced at both doses the TGF-ß, EGFR, collagen type III and IV and modulated EGF growth factor levels.

Conclusions: These findings indicate that RhoA/Rho-kinase is involved in the pathophysiology of allergic airway inflammation and suggest that Rho-kinase inhibitors have therapeutic potential for asthma management.

Acknowledgements: This work was supported by grant APVV-19-033, VEGA 1/0314/21, VEGA 1/0253/19