Liposomal antioxidants provide prolonged protection against acute respiratory distress syndrome

Background. We have previously shown that N-acetylcysteine (NAC), an antiox idant, in the resuscitation after shock prevents lung injury in response to lipopolysaccharide (LPS) by inhibiting chemokine generation by alveolar ma crophages in the lung. However, the protection was short-hived. We hypothes ized that liposomal (Lip) NAC delivered intratracheally might be delivered directly to the target cells and exert prolonged effect. Methods. Sprague-Dawley rats were bled to a blood pressure of 40 mm Hg for 1 hour and resuscitated with shed blood and equal volume of Ringer's lactat e. In some studies 500 mg/kg NAC was included in the resuscitation fluid. T hirty minutes later, 150 mu l LipNAC (9.4 mg/kg NAC) was given intratrachea lly One hour and 18 hours after resuscitation, LPS (30 mu g/g) or saline wa s given intratracheally. Lung injury was assessed by permeability to I-125- albumin, bronchoalveolar lavage neutrophils and living myeloperoxidase. The cytokine-induced neutrophil chemoattractant (CINC) expression in the lung was assessed by Northern blot. Results. At the early time point, both NAC and LipNAC protected the lung wi th the effects in significantly reducing the increases in transpulmonary al bumin flux, neutrophil influx and myeloperoxidase in the lungs of shock/LPS rats. However; by the late time point, only LipNAC retained its salutary e ffect. This correlated well with persistent ability to prevent CINC increas e. In. addition, Lip alpha-tocopherol (alpha-T) and LipNAC/alpha-T were tes ted and determined to be effective to protect the lung. Conclusions. Liposomal encapsulation of antioxidants at low dose provides l ong lasting protection against acute respiratory distress syndrome after sh ock. This may represent a novel treatment approach.