Nitrite therapy prevents chlorine gas toxicity in rabbits

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 (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl₂ exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h 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.