Nitric-Oxide-Releasing Dexamethasone Derivative NCX-1005 Improves Lung Function and Attenuates Inflammation in Experimental Lavage-Induced ARDS.

Acute respiratory distress syndrome (ARDS) is a common complication of critical illness and remains a major source of morbidity and mortality in the intensive care unit (ICU). ARDS is characterised by diffuse lung inflammation, epithelial and endothelial deterioration, alveolar-capillary leak and oedema formation, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory activity of nitric-oxide-releasing dexamethasone derivative NCX-1005 as a potential novel drug for ARDS. Adult rabbits with lavage-induced ARDS were treated with dexamethasone i.v. (0.5 mg/kg; DEX) and nitro-dexamethasone i.v. (0.5 mg/kg, NCX-1005) or were untreated (ARDS). Controls represented healthy ventilated animals. The animals were subsequently oxygen-ventilated for an additional 4 h and respiratory parameters were recorded. Lung oedema, inflammatory cell profile in blood and bronchoalveolar lavage, levels of the cytokines (IL-1β, IL-6, IL-8, TNF-α), and oxidative damage (TBARS, 3NT) in the plasma and lung were evaluated. Nitric oxide-releasing dexamethasone derivative NCX-1005 improved lung function, reduced levels of cytokines, oxidative modifications, and lung oedema formation to similar degrees as dexamethasone. Only NCX-1005 prevented the migration of neutrophils into the lungs compared to dexamethasone. In conclusion, the nitric oxide-releasing dexamethasone derivative NCX-1005 has the potential to be effective drug with anti-inflammatory effect in experimental ARDS.