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Toxicol Lett. 2019 Sep 15;312:204-213. doi: 10.1016/j.toxlet.2019.04.019. Epub 2019 Apr 30.

Phosgene inhalation causes hemolysis and acute lung injury.

Author information

1
Department of Anesthesiology and Perioperative Medicine, Birmingham, AL, 35205-3703, United States; Division of Molecular and Translational Biomedicine, Birmingham, AL, 35205-3703, United States; Pulmonary Injury and Repair Center, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
2
Pulmonary Injury and Repair Center, Birmingham, AL, 35205-3703, United States; Department of Pediatrics, Division of Neonatology, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
3
Department of Anesthesiology and Perioperative Medicine, Birmingham, AL, 35205-3703, United States; Division of Molecular and Translational Biomedicine, Birmingham, AL, 35205-3703, United States; School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
4
School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; Department of Pharmacology, Mobile, AL, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
5
School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; Department of Biochemistry and Molecular Biology, St. Louis, MO, 63104, United States; St. Louis University, St. Louis, MO, 63104, United States.
6
School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; Department of Biochemistry and Molecular Biology, St. Louis, MO, 63104, United States.
7
Department of Pathology, Division of Cellular and Molecular Pathology, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
8
Pulmonary Injury and Repair Center, Birmingham, AL, 35205-3703, United States; Department of Pathology, Division of Cellular and Molecular Pathology, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States.
9
Department of Anesthesiology and Perioperative Medicine, Birmingham, AL, 35205-3703, United States; Division of Molecular and Translational Biomedicine, Birmingham, AL, 35205-3703, United States; Pulmonary Injury and Repair Center, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States. Electronic address: smatalon@uabmc.edu.

Abstract

Phosgene (Carbonyl Chloride, COCl2) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis of solvents (degreasers, cleaners). It is a sweet smelling gas, and therefore does not prompt escape by the victim upon exposure. Supplemental oxygen and ventilation are the only available management strategies. This study was aimed to delineate the pathogenesis and identify novel biomarkers of acute lung injury post exposure to COCl2 gas. Adult male and female C57BL/6 mice (20-25 g), exposed to COCl2 gas (10 or 20 ppm) for 10 min in environmental chambers, had a dose dependent reduction in PaO2 and an increase in PaCO2, 1 day post exposure. However, mortality increased only in mice exposed to 20 ppm of COCl2 for 10 min. Correspondingly, these mice (20 ppm) also had severe acute lung injury as indicated by an increase in lung wet to dry weight ratio, extravasation of plasma proteins and neutrophils into the bronchoalveolar lavage fluid, and an increase in total lung resistance. The increase in acute lung injury parameters in COCl2 (20 ppm, 10 min) exposed mice correlated with simultaneous increase in oxidation of red blood cells (RBC) membrane, RBC fragility, and plasma levels of cell-free heme. In addition, these mice had decreased plasmalogen levels (plasmenylethanolamine) and elevated levels of their breakdown product, polyunsaturated lysophosphatidylethanolamine, in the circulation suggesting damage to cellular plasma membranes. This study highlights the importance of free heme in the pathogenesis of COCl2 lung injury and identifies plasma membrane breakdown product as potential biomarkers of COCl2 toxicity.

KEYWORDS:

BAL proteins; Free heme; Inflammation; Plasmalogens; Red blood cell fragility

PMID:
31047999
PMCID:
PMC6653688
[Available on 2020-09-15]
DOI:
10.1016/j.toxlet.2019.04.019
[Indexed for MEDLINE]
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