Protection from half-mustard-gas-induced acute lung injury in the rat.
The chemical warfare agent analog, 2-chloroethyl ethyl sulfide, known as 'half-mustard gas' (HMG), is less toxic and less of an environmental hazard than the full molecule and has been shown to produce an acute lung injury in rats when instilled via intrapulmonary injection. This injury is characterized by massive, localized hemorrhage and edema into the alveolar compartment and can be quantitated by measuring extravasation of (125)I-bovine serum albumin into the extravascular compartment. Employing this rat model of HMG-induced lung injury, we observed significant attenuation of the pulmonary injury when experimental animals were complement or neutrophil depleted prior to HMG challenge. Significant protection also was provided by the use of antioxidants such as catalase, dimethyl sulfoxide, dimethyl thiourea, resveratrol and N-acetyl-L-cysteine (NAC). The last compound showed protection from lung injury as high as 70% and was still effective even when given up to 90 min after exposure of the lungs to HMG. These data suggest that acute lung injury caused by exposure to HMG may be related partially to complement mediated pathways and the generation by neutrophils of toxic oxygen species The data indicate that NAC is an effective antidote against HMG-induced acute lung injury in the rat.
McClintock
Shannon D
SD
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Till
Gerd O
GO
Smith
Milton G
MG
Ward
Peter A
PA
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000172:deficiency / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009151:Mustard Gas / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D009503:Neutropenia / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D020318:Rats, Long-Evans; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms
D000975:Antioxidants; D004546:Elapid Venoms; C031278:2-chloroethyl ethyl sulfide; D003165:Complement System Proteins; D009151:Mustard Gas