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2014 ; 307
(11
): L888-94
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Nitrite therapy improves survival postexposure to chlorine gas
#MMPMID25326579
Honavar J
; Doran S
; Oh JY
; Steele C
; Matalon S
; Patel RP
Am J Physiol Lung Cell Mol Physiol
2014[Dec]; 307
(11
): L888-94
PMID25326579
show ga
Exposure to relatively high levels of chlorine (Cl?) 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? exposure, could prevent Cl? gas
toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl? 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? exposure improved survival and
resulted in loss of nitrite-dependent survival protection. Interestingly, female
mice were more sensitive to Cl?-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? gas exposure that is amenable to
administration in mass-casualty scenarios.
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