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. 2020 Nov;1480(1):104-115.
doi: 10.1111/nyas.14422. Epub 2020 Jul 9.

Circulating and tissue biomarkers as predictors of bromine gas inhalation

Juan Xavier Masjoan Juncos  1 , Shazia Shakil  1 , Aamir Ahmad  1 , Duha Aishah  1 , Charity J Morgan  2 , Louis J Dell'Italia  3   4 , David A Ford  5 , Aftab Ahmad  1 , Shama Ahmad  1
Affiliations

Circulating and tissue biomarkers as predictors of bromine gas inhalation

Juan Xavier Masjoan Juncos et al. Ann N Y Acad Sci. 2020 Nov.

Abstract

The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br2 ) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br2 and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury, as indicated by BALF protein content, and free bromostearic acid levels correlated with plasma cTnI levels. Thus, BFAs and cardiac injury biomarkers can identify Br2 exposure and predict the severity of organ damage.

Keywords: biomarkers; brominated fatty acid; bromine; halogens; heart; injury; lung; plasma.

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Figures

Figure 1.
Figure 1.
Schematic representation of the experimental design and sample collection after bromine (Br2) inhalation. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Rats were euthanized according to the euthanasia criterion after monitoring their clinical symptoms and pooled into their corresponding time points and samples were collected for the analysis of BFAs. Unexposed controls were also utilized for comparisons.
Figure 2.
Figure 2.
Formation of reactive brominated lipids in the lungs, blood, and heart after Br2 inhalation. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Lung (A), plasma (B), and heart (C) tissues were analyzed for the production of BFAs by MS, demonstrating the formation of (free or esterified/total) 2-bromopalmitic (red bars) and 2-bromostearic (yellow bars) acids. The blue and green bars are the respective endogenous CFAs. Data are means ± SE; n = 5−6 for each group. *P < 0.05 versus the naïve/0 ppm group.
Figure 3.
Figure 3.
Reactive brominated lipid content in the lungs, blood, and heart correlates with blood oxygenation. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Lung (A), plasma (B), and heart (C) tissues were analyzed for the production of BFAs by MS, demonstrating the formation of (free or esterified/total) 2-bromopalmitic (blue circle) and 2-bromostearic (red square) acids. Pulse oximetry was performed as described in the methods to measure the oxygenation. The lipid biomarker values were correlated with oxygen saturation using Spearman’s correlation. The correlation coefficient r and P values are shown on each figure for the corresponding biomarker.
Figure 4.
Figure 4.
Reactive brominated lipid content in the lungs, blood, and heart correlates with lung injury. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Lung (A), plasma (B), and heart (C) tissues were analyzed for the production of BFAs by MS, demonstrating the formation of (free or esterified/total) 2-bromopalmitic (blue circle) and 2-bromostearic (red square) acids. Bronchoalveolar fluid (BALF) was collected after euthanasia and analyzed for total protein content. The lipid biomarker values were correlated with BALF protein using Spearman’s correlation. The correlation coefficient r and P values are shown on each figure for the corresponding biomarker.
Figure 5.
Figure 5.
Reactive brominated lipid content in the lungs, blood, and heart correlates with the HR. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Lung (A), plasma (B), and heart (C) tissues were analyzed for the production of BFAs by MS, demonstrating the formation of (free or esterified/total) 2-bromopalmitic (blue circle) and 2-bromostearic (red square) acids. The HR was measured by pulse oximetry. The lipid biomarker values were correlated with the HR using Spearman’s correlation. The correlation coefficient r and P values are shown on each figure for the corresponding biomarker.
Figure 6.
Figure 6.
Reactive brominated lipid content in the lungs, blood, and heart correlates with cTnI. Sprague−Dawley rats were exposed to 600 ppm Br2 for 60 minutes. Lung (A), plasma (B), and heart (C) tissues were analyzed for the production of BFAs by MS, demonstrating the formation of (free or esterified/total) 2-bromopalmitic (blue circle) and 2-bromostearic (red square) acids. Blood was collected from descending aorta after euthanasia and plasma analyzed for cTnI by ELISA. The lipid biomarker values were correlated with cTnI using Spearman’s correlation. The correlation coefficient r and P values are shown on each figure for the corresponding biomarker.
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