title: Nitrite therapy prevents chlorine gas toxicity in rabbits.
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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham AL 35294, United States.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Honavar
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, Birmingham AL 35294, United States; Center for Free Radical Biology and Lung Injury and Repair Center, University of Alabama at Birmingham, Birmingham AL 35294, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Doran
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham AL 35294, United States.
authors.forename: Karina
authors.initials: K
authors.lastname: Ricart
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, Birmingham AL 35294, United States; Center for Free Radical Biology and Lung Injury and Repair Center, University of Alabama at Birmingham, Birmingham AL 35294, United States.
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham AL 35294, United States; Center for Free Radical Biology and Lung Injury and Repair Center, University of Alabama at Birmingham, Birmingham AL 35294, United States. Electronic address: rakeshpatel@uabmc.edu.
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002713:Chlorine; D019610:Cytoprotection; D004195:Disease Models, Animal; D005740:Gases; D007273:Injections, Intramuscular; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009573:Nitrites / Q000008:administration & dosage / Q000494:pharmacology*; D011041:Poisoning / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
chemical_list: D005740:Gases; D016209:Interleukin-8; D009573:Nitrites; D020011:Protective Agents; D002713:Chlorine
keywords: Halogen; Inflammation; Nitric oxide