Honavar Jaideep, Doran Stephen, Ricart Karina, Matalon Sadis, Patel Rakesh P
Department of Pathology, University of Alabama at Birmingham, Birmingham AL 35294, United States.
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.
Toxicol Lett. 2017 Apr 5;271:20-25. doi: 10.1016/j.toxlet.2017.02.019. Epub 2017 Feb 22.
Chlorine (Cl) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl 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-Cl 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 Cl toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl 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 Cl gas exposure injury.
氯气（Cl）暴露及其毒性在军事和工业领域仍然是一个令人担忧的问题。虽然氯气暴露后对肺部和其他组织的损伤已有文献记载，且主要潜在机制也已阐明，但尚未开发出在暴露后给药有效且适用于大规模伤亡情况的靶向治疗方法。我们最近的研究表明，在氯气暴露后通过肌肉注射（IM）给予亚硝酸盐可有效预防急性肺损伤并提高啮齿动物模型的存活率。本研究的目的是建立一个氯气毒性的兔模型，并测试亚硝酸盐在非啮齿动物模型中是否具有保护作用。将新西兰白兔暴露于氯气（600ppm，45分钟）会导致气道中蛋白质和中性粒细胞积聚显著增加，且在18小时内死亡率约为35%。在氯气暴露后30分钟通过单次肌肉注射给予1mg/kg或10mg/kg的亚硝酸盐，可在6小时时将急性肺损伤指标降低多达50%。此外，所有接受亚硝酸盐治疗的兔子在研究期间均存活。这些数据为开发亚硝酸盐作为暴露后治疗药物以减轻氯气暴露损伤提供了进一步的理论依据。
