N-Acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury

O Koksel,L Cinel,L Tamer,U Oral,A Ozdulger,I Cinel

doi:10.1186/cc2671

Abstract

Since oleic acid (OA) induces morphologic and cellular changes similar to those observed in human acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), it has become a widely used model to investigate the effects of several agents on pathogenesis of lung injury. The antioxidant, anti-inflammatory and antiapoptotic properties of N-acetylcysteine (NAC) have been documented in many lung injury models [1]. In this study, we evaluated the role of NAC in an OA-induced lung injury model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in lung tissue. Five groups (sham, NAC, OA, pre-OA-NAC and post-OA-NAC) were determined. ALI/ARDS was induced by intravenous (IV) administration of OA. The pre-OA-NAC group received IV NAC 15 min before OA infusion and the post-OA-NAC group received IV NAC 2 hours after OA infusion. In both of the NAC treatment groups, blood and tissue samples were collected 4 hours after OA infusion, independent of the time of NAC infusion. The MPO activity, MDA and 3-NT levels in lung homogenates were found to be increased in the OA group, and the administration of NAC significantly reduced tissue MPO, MDA and 3-NT levels (P = 0.0001). Lung histopathology was also protected by NAC in this OA-induced experimental lung injury model. In conclusion, the present study demonstrates that oleic acid induces myeloperoxydase activation and consequently increases 3-NT and MDA levels in lung tissue. Our data suggest that elevated 3-NT levels in lung tissue represent the role of excessive formation of peroxynitrite and the efficacy of NAC treatment in the prevention of peroxynitrite-mediated OA-induced lung injury. Due to its antioxidant and anti-inflammatory properties, NAC seems to be a promising agent in treatment of critically ill patients with lung injury states.

Highlights

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Summary

Introduction

In contrast to conventional surgical tracheostomy, percutaneous dilational tracheostomy (PDT) in different variants is spreading rapidly in intensive care units today. The objectives of the current study were (1) to assess the prognostic significance of plasma concentrations of NSE for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiopulmonary resuscitation (CPR), and (2) to compare the prognostic information provided by NSE measurements with that provided by conventional risk indicators (clinical neurological examination and computerised tomography [CT] scan of the brain). Independent pulmonary ventilation was introduced in the 1930s and allows the utilization of different ventilatory strategies for each lung to improve gas exchange, respiratory mechanics or both in patients with heterogeneous lung diseases It is not clear whether the lower inflection point (LIP) on the inspiratory limb or the point of maximum curvature (PMC) on the deflation limb of the pressure–volume (PV) curve should be used for the positive end-expiratory pressure (PEEP) setting in acute lung injury (ALI). The long-term outcome, health-related quality of life (HRQL), and ICU and hospital costs of medical ICU patients were assessed

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