Protection of half sulfur mustard gas–induced lung injury in guinea pigs by antioxidant liposomes

The purpose of this study was to develop antioxidant liposomes as an antidote for mustard gas–induced lung injury in a guinea pig model. Five liposomes (LIP‐1, LIP‐2, LIP‐3, LIP‐4, and LIP‐5) were tested with differing levels of phospholipid, cholesterol, phosphatidic acid, tocopherol (α, γ, δ), N‐acetylcysteine (NAC), and glutathione (GSH). A single dose (200 µL) of liposome was administered intratracheally 5 min or 1 h after exposure to 2‐chloroethyl ethyl sulfide (CEES). The animals were sacrificed either 2 h after exposure (for lung injury study) or 30 days after exposure (for histology study). The liposomes offered 9%–76% protection against lung injury. The maximum protection was with LIP‐2 (71.5% protection) and LIP‐4 (75.4%) when administered 5 min after CEES exposure. Delaying the liposome administration 1 h after CEES exposure decreased the efficacy. Both liposomes contained 11 mM α‐tocopherol, 11 mM γ‐tocopherol, and 75 mM NAC. However, LIP‐2 contained additionally 5 mM δ‐tocopherol. Overall, LIP‐2 and LIP‐4 offered significant protection by controlling the recruitment of neutrophils, eosinophils, and the accumulation of septal and perivascular fibrin and collagen. However, LIP‐2 showed better protection than LIP‐4 against the accumulation of red blood cells in the bronchi, alveolar space, arterioles and veins, and fibrin and collagen deposition in the alveolar space. The antifibrotic effect of the liposomes, particularly LIP‐2, was further evident by a decreased level of lipid peroxidation and hydroxyproline in the lung. Thus, antioxidant liposomes containing both NAC and vitamin E are an effective antidote against CEES‐induced lung injury. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:143–153, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20279