Effect of inducible nitric oxide inhibition on oxidative stress markers and pulmonary allergic inflammation in mice

• Grant number: 08/10303-2
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2009
• End date: November 30, 2011
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Heloisa Helena de Araujo Ferreira
• Grantee: Heloisa Helena de Araujo Ferreira
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Oxidative stress has an essential role in asthma pathogenesis due the development of oxygen and nitrogen reactive species, as O2*-, *OH or ONOO-, that is produced by binding between *NO and O2*-. Normally, lungs has an integrated antioxidant system to minimize oxidant stress, that include superoxide dismutase enzyme (SOD), catalase or glutathione system (GPx) and H2S that rapidly detoxify oxygen or nitrogen reactive products to avoid damage and cellular dead. However, airways antioxidant capacity is reduced in asthma, mainly due to the reduced SOD activity in bronchial epithelial cells. The unbalance between oxidant/antioxidant species as seen in asthma induces activation of the transcription factor NF-kB, that provokes expression of a variety of genes involved in allergic reaction as IL-4, IL-5 e TNF-a, RANTES, eotaxin, adhesion molecules and iNOS. Besides, our previous results suggested that persistent inhibition of *NO synthesis in mice could result in an airway inflammation as bad as that produced by OVA exposure itself (seen in non-treated mice). Thus, the anti-inflammatory or pro-inflammatory effect of *NO synthesis inhibitors on the lungs response may be dependent on phase of allergic response. The objective of this research is to study the influence of iNOS on oxidative stress markers in asthma and verify H2S and *NO-pathway relationship on antioxidant capacity of airways. (AU)