Protection from half-mustard-gas-induced acute lung injury in the rat

• Published in: Journal of applied toxicology 2002-07, Vol.22 (4), p.257-262
• Main Authors: McClintock, Shannon D., Till, Gerd O., Smith, Milton G., Ward, Peter A.
• Format: Article
• Language: English
• Subjects: Animals; antioxidants; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; complement; Complement System Proteins - deficiency; Complement System Proteins - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Elapid Venoms - pharmacology; Gas, fumes; Half-mustard gas; Injections, Intraperitoneal; Intubation, Intratracheal; Lung - drug effects; Lung - pathology; lung injury; Male; Medical sciences; Mustard Gas - administration & dosage; Mustard Gas - analogs & derivatives; Mustard Gas - toxicity; N-acetyl-L-cysteine; Neutropenia - immunology; neutrophils; Neutrophils - immunology; Rats; Rats, Long-Evans; Respiratory Distress Syndrome, Adult - chemically induced; Respiratory Distress Syndrome, Adult - pathology; Respiratory Distress Syndrome, Adult - prevention & control; Specific Pathogen-Free Organisms; Toxicology
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.856

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 125I‐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. Copyright © 2002 John Wiley & Sons, Ltd.