کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5562117 | 1562602 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Chlorine gas induces acute lung injury and death in rabbits.
- Post-chlorine exposure administration of IM nitrite improves 18Â h survival.
- Post-chlorine exposure administration of IM nitrite prevents lung leak and airway accumulation of neutrophils.
Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600Â ppm, 45Â min) caused significant increases in protein and neutrophil accumulation in the airways and â¼35% mortality over 18Â h. Nitrite administered 30Â min post Cl2 exposure by a single IM injection, at 1Â mg/kg or 10Â mg/kg, prevented indices of acute lung injury at 6Â h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury.
Journal: Toxicology Letters - Volume 271, 5 April 2017, Pages 20-25