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Nitrite therapy improves survival postexposure to chlorine gas.
- Source :
- American Journal of Physiology: Lung Cellular & Molecular Physiology; 12/1/2014, Vol. 307 Issue 11, pL888-L894, 7p
- Publication Year :
- 2014
-
Abstract
- Exposure to relatively high levels of chlorine (Cl<subscript>2</subscript>) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl<subscript>2</subscript> exposure, could prevent Cl<subscript>2</subscript> gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl<subscript>2</subscript> gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ~20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl<subscript>2</subscript> exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl<subscript>2</subscript>-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl<subscript>2</subscript> gas exposure that is amenable to administration in mass-casualty scenarios. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10400605
- Volume :
- 307
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Lung Cellular & Molecular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 99857803
- Full Text :
- https://doi.org/10.1152/ajplung.00079.2014