Análise fisiológica dos efeitos de um bacteriófago em fusão com um peptídeo inibidor de PLA2 (F7-PLI) em modelo experimental murino de asma alérgica

Abstract

Allergic asthma is an inflammatory disease of high prevalence, characterized by obstructing the airways and can be identified by variable and recurrent symptoms such as: airflow limitation, cough, dyspnea and tiredness. Clinical studies have shown that, as the disease progresses, recurrent airway inflammation can lead to repeated attacks (exacerbations), bronchoconstriction, and bronchial hyperreactivity. This inflammation can be attributed to elevated levels of lysophosphatidylcholine (LPC) in the lungs, which in asthmatic individuals and animal models of asthma increases the levels of phospholipase A2 (PLA2) enzymes, which is of great importance in airway remodeling. It was observed that the activation of the PLA2 family is a key process for the production of precursors in the biosynthesis of inflammatory mediators and when inhibited, offers an attractive therapeutic approach in the development of new agents for the treatment of asthma. In view of these facts, the objective of this work was to analyze the physiological effects of a PLA2 inhibitor phage (F7-PLI) in an experimental model of ovalbumin-induced allergic asthma in Swiss webster mice. Seven different treatments (n = 7 per group) were used, containing non-asthmatic animals treated with saline (SAL) and asthmatic animals (OVA) treated with Dexamethasone, phage expressing a peptide mimetic inhibitor of PLA2 and wild phage, respectively. Asthma was induced by sensitizing the animals to Ovalbumin and Aluminum Hydroxide - AL (OH) 3 which then received an antigen challenge. After 48h of the last challenge, the respiratory electrophysiological parameters of the mice were analyzed and the bronchoalveolar lavage (BAL) was collected to analyze the metabolites in the FTIR. The results were expressed as mean ± SEM and compared by analysis of variance ANOVA. The current volume and minute volume were higher in asthmatic animals treated with F7PLI phage compared to healthy animals (SAL). Thus, it can be concluded that the inhibition of the PLA2 enzyme in mice sensitized with ovalbumin and treated with peptide inhibitor PLA2 mimetic can improve the respiratory function of these animals, as a consequence of the reduction of inflammation of the airways.