Nitrite therapy prevents chlorine gas toxicity in rabbits

Academic Article

Abstract

  • © 2017 Elsevier B.V. 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 (600 ppm, 45 min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18 h. Nitrite administered 30 min post Cl2 exposure by a single IM injection, at 1 mg/kg or 10 mg/kg, prevented indices of acute lung injury at 6 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.
  • Published In

  • Toxicology Letters  Journal
  • Digital Object Identifier (doi)

    Author List

  • Honavar J; Doran S; Ricart K; Matalon S; Patel RP
  • Start Page

  • 20
  • End Page

  • 25
  • Volume

  • 271