Title: Nitrite therapy prevents chlorine gas toxicity in rabbits.
Authors: Honavar, Jaideep; Doran, Stephen; Ricart, Karina; Matalon, Sadis; Patel, Rakesh P
Published In Toxicol Lett, (2017 Apr 05)
Abstract: Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2exposure 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-Cl2exposure 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 Cl2toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl2exposure 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 Cl2gas exposure injury.
PubMed ID: 28237808
MeSH Terms: Acute Lung Injury/etiology; Acute Lung Injury/metabolism; Acute Lung Injury/pathology; Acute Lung Injury/prevention & control*; Animals; Bronchoalveolar Lavage Fluid/chemistry; Chlorine*; Cytoprotection; Disease Models, Animal; Gases; Injections, Intramuscular; Interleukin-8/metabolism; Lung/drug effects*; Lung/metabolism; Lung/pathology; Male; Neutrophil Infiltration/drug effects; Nitrites/administration & dosage; Nitrites/pharmacology*; Poisoning/etiology; Poisoning/metabolism; Poisoning/pathology; Poisoning/prevention & control*; Protective Agents/administration & dosage; Protective Agents/pharmacology*; Rabbits; Time Factors