"Treatment with inhibitor of Rho-kinase in guinea pigs with chronic allergic infiltration: modulation of eosinophilic inflammation, expression of inflammatory cytokines, elastic fiber and airway reactivity.

• Grant number: 10/02943-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2010
• End date: January 31, 2011
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Homar Toledo Charafeddine
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Asthma is a chronic inflammatory condition of airways, impacting on public health worldwide and is associated with the economic, psychological and social. One of several substances related to inflammatory events in asthma is a protein called Rho kinase, the use of this inhibitor protein (Rho kinase Y-27632) showed inhibition of inflammatory cells, hyperresponsiveness and bronchoconstriction characteristic of asthma in animal models of allergic sensitization . The purpose of this study is to evaluate in an experimental model of asthma, with 32 guinea pigs, the effect of treatment with Rho kinase inhibitor on respiratory mechanics, the content of elastic fibers, the eosinophil response and the expression of inflammatory cytokines (IL-2 and IL-4). For this purpose the animals will be divided into 4 groups, submitted to: inhalation with saline solution (SF), inhalation solution of ovalbumin (OVA) inhalation with saline solution and treatment with inhibitor of Rho kinase (Rho + SF) and inhalation of ovalbumin solution and treatment with inhibitor of Rho kinase (Rho + OVA). One by one, the animals in the OVA and OVA + Rho will be submitted to inhalation of aerosol OVA diluted in NaCl 0.9%, for 15 minutes or until symptoms of respiratory distress, increasing doses, the first 4 inhalations will be 1 mg.ml-1, 5 and 6 received inhalations of 2.5 mg.ml-1 and 7th inhalation of 5 g.ml-1, the inhalations are made 2 times per week for 4 weeks, the animals inhaled with saline (group SF and SF + Rho) shall be subject to the same protocol. From the 5th OVA inhalation group and SF + Rho + Rho, will be the guinea pigs inhaled a selective inhibitor of Rho kinase (Y-27632) 30 minutes after the initial inhalation.