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N-Acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury
Critical Care volume 8, Article number: P204 (2004)
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 . 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.
Ozdulger A, Cinel I, Koksel O, et al.: The protective effect of N -acetylecysteine on apoptotic lung injury in CLP-induced sepsis model. Shock 2003, 19: 366-372. 10.1097/00024382-200304000-00012
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Koksel, O., Cinel, I., Tamer, L. et al. N-Acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury. Crit Care 8 (Suppl 1), P204 (2004). https://doi.org/10.1186/cc2671