Attenuation of half sulfur mustard gas-induced acute lung injury in rats.
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.
McClintock
Shannon D
SD
The University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA.
Hoesel
Laszlo M
LM
Das
Salil K
SK
Till
Gerd O
GO
Neff
Thomas
T
Kunkel
Robin G
RG
Smith
Milton G
MG
Ward
Peter A
PA
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D002374:Catalase / Q000008:administration & dosage / Q000627:therapeutic use; D002619:Chemical Warfare Agents / Q000506:poisoning*; D003165:Complement System Proteins / Q000502:physiology; D016503:Drug Delivery Systems; D057487:Enzyme Therapy; D004798:Enzymes / Q000008:administration & dosage; D008081:Liposomes; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000506:poisoning; D051381:Rats; D020318:Rats, Long-Evans; D019163:Reducing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use
D000975:Antioxidants; D002619:Chemical Warfare Agents; D004798:Enzymes; D008081:Liposomes; D019163:Reducing Agents; C031278:2-chloroethyl ethyl sulfide; D003165:Complement System Proteins; D002374:Catalase; D013482:Superoxide Dismutase; D009151:Mustard Gas