Abstract
AbstractRationaleChlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2exposures frequently occur in domestic and occupational environments, and in transportation accidents. There is a knowledge gap in large animal models of Cl2-induced acute lung injury (ALI) required to accurately model human etiology and for the development of targeted countermeasuresObjectiveTo develop a translational model of Cl2-induced ALI in swine to study toxico-pathophysiology and identify biomarkers useful for forensic analysis.MethodsSpecific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2gas (≤ 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation.ResultsExposure to Cl2resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Chlorine exposure resulted in increased total BALF and neutrophil counts, vascular leakage, and edema compared to the control group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung after Cl2-exposure.ConclusionsThe translational model developed in this study replicates key features of humans exposed to Cl2and is suitable to test medical countermeasures. Specific biomarkers of Cl2exposure have been identified in plasma and lung tissue samples.Take home messageWe developed a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute respiratory distress syndrome. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers.
Publisher
Cold Spring Harbor Laboratory
Reference54 articles.
1. Schneider T , Lütkefend T. Nowhere to Hide: The Logic of Chemical Weapons Use in Syria; 2019 February 2019.
2. News U , Itt O. Syrian air force used deadly chemical weapons in 2017 attacks, global watchdog finds. 2020 [cited 2020 05/07/2020]; Available from: https://news.un.org/en/story/2020/04/1061402
3. Formation of chlorinated lipids post-chlorine gas exposure
4. Hemstrom P , Larsson A , Elfsmark L , Astot C. l-alpha-Phosphatidylglycerol Chlorohydrins as Potential Biomarkers for Chlorine Gas Exposure. Anal Chem 2016.
5. Detection of 3-chlorinated tyrosine residues in human cells by flow cytometry;J Immunol Methods,2011
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