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Attenuation of half sulfur mustard gas‐induced acute lung injury in rats
Author(s) -
McClintock Shan D.,
Hoesel Laszlo M.,
Das Salil K.,
Till Gerd O.,
Neff Thomas,
Kunkel Robin G.,
Smith Milton G.,
Ward Peter A.
Publication year - 2006
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1115
Subject(s) - sulfur mustard , lung , sulfur , medicine , toxicology , anesthesia , chemistry , toxicity , biology , organic chemistry
Airway instillation into rats of 2‐chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co‐instillation with CEES of liposomes containing pegylated (PEG)‐catalase (CAT), PEG‐superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co‐instillation of liposomes containing the reducing agents, N‐acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti‐oxidant compounds maximally attenuated CEES‐induced lung injury by nearly 80%. Delayed airway instillation of anti‐oxidant‐containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES‐induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti‐oxidant enzymes delivered via liposomes. Copyright © 2005 John Wiley & Sons, Ltd.