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Elevated carbon monoxide to carbon dioxide ratio in the exhaled breath of mice treated with a single dose of lipopolysaccharide.

Langeroudi AG, Hirsch CM, Estabragh AS, Meinardi S, Blake DR, Barbour AG - Open Forum Infect Dis (2014)

Bottom Line: Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood.The magnitude of increase was similar to what was observed with a bacteremia model.These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine ; Microbiology and Molecular Genetics.

ABSTRACT

Background: Analysis of volatile organic chemicals in breath holds promise for noninvasive diagnosis and monitoring of patients, but investigation of this in experimental mouse models has been limited. Of particular interest is endogenous production of carbon monoxide as a biomarker of inflammation and, more particularly, during sepsis.

Methods: Using a nose-only collection procedure for unanesthetized individual adult mice and sensitive gas chromatography of carbon monoxide (CO) and carbon dioxide (CO2) of sampled breath, we investigated the responses of mice to one-time injections with different doses of purified Escherichia coli lipopolysaccharide. Two strains of mice were examined: BALB/c and C3H, including an endotoxin-resistant mutant (HeJ) as well as the wild type (HOuJ).

Results: The CO to CO2 ratio increased in a dose-responsive manner within hours in treated BALC/c mice but not control mice. The CO/CO2 values declined to the range of control mice within 48-72 h after the injection of lipopolysaccharide. Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood. C3H/HOuJ mice, but not the HeJ mice, had similar increases of the CO/CO2 ratio in response to the endotoxin.

Conclusions: Carbon monoxide concentrations in exhaled breath of at least 2 strains of mice increase in response to single injections of endotoxin. The magnitude of increase was similar to what was observed with a bacteremia model. These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis.

No MeSH data available.


Related in: MedlinePlus

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) of heme oxygenase-1 gene (HMOX1) transcripts in the whole blood of C3H/HeOuJ (wild-type) mice injected with lipopolysaccharide (LPS) at hour 0. The results were normalized per 1000 β-actin transcripts determined by RT-qPCR. Each vertical bar represents a value from an individual mouse at that time of euthanasia and blood collection.
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OFU085F2: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) of heme oxygenase-1 gene (HMOX1) transcripts in the whole blood of C3H/HeOuJ (wild-type) mice injected with lipopolysaccharide (LPS) at hour 0. The results were normalized per 1000 β-actin transcripts determined by RT-qPCR. Each vertical bar represents a value from an individual mouse at that time of euthanasia and blood collection.

Mentions: We next examined the specificity of the CO response to endotoxin by studying C3H/HeJ (Tlr4Lps-d) mice, which, as the consequence of a spontaneous mutation in the Toll-like receptor 4 gene, are more resistant to endotoxin. These were compared with mice, which are congenic but wild-type with respect to endotoxin sensitivity. We first assessed the effect on HMOX1 expression in the blood of individual mice at 4, 18, and 42 postinjection of 0, 50, 100, or 250 µg LPS. The responses of the C3H lineage mice were similar to what was observed with BALB/c lineage mice (Figure 2). In the subsequent experiment, C3H/HeOuJ or C3H/HeJ mice received LPS at 10 µg/g of body weight (5 HeJ and 6 HeOuJ mice) or water alone (3 HeOuJ mice). Breaths were collected before the injections and then at 4 hours and 24 hours postinjection, followed by euthanasia. The mean and variances of preinjection body weights of the groups were not significantly different (Table 2).Table 2.


Elevated carbon monoxide to carbon dioxide ratio in the exhaled breath of mice treated with a single dose of lipopolysaccharide.

Langeroudi AG, Hirsch CM, Estabragh AS, Meinardi S, Blake DR, Barbour AG - Open Forum Infect Dis (2014)

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) of heme oxygenase-1 gene (HMOX1) transcripts in the whole blood of C3H/HeOuJ (wild-type) mice injected with lipopolysaccharide (LPS) at hour 0. The results were normalized per 1000 β-actin transcripts determined by RT-qPCR. Each vertical bar represents a value from an individual mouse at that time of euthanasia and blood collection.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4281777&req=5

OFU085F2: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) of heme oxygenase-1 gene (HMOX1) transcripts in the whole blood of C3H/HeOuJ (wild-type) mice injected with lipopolysaccharide (LPS) at hour 0. The results were normalized per 1000 β-actin transcripts determined by RT-qPCR. Each vertical bar represents a value from an individual mouse at that time of euthanasia and blood collection.
Mentions: We next examined the specificity of the CO response to endotoxin by studying C3H/HeJ (Tlr4Lps-d) mice, which, as the consequence of a spontaneous mutation in the Toll-like receptor 4 gene, are more resistant to endotoxin. These were compared with mice, which are congenic but wild-type with respect to endotoxin sensitivity. We first assessed the effect on HMOX1 expression in the blood of individual mice at 4, 18, and 42 postinjection of 0, 50, 100, or 250 µg LPS. The responses of the C3H lineage mice were similar to what was observed with BALB/c lineage mice (Figure 2). In the subsequent experiment, C3H/HeOuJ or C3H/HeJ mice received LPS at 10 µg/g of body weight (5 HeJ and 6 HeOuJ mice) or water alone (3 HeOuJ mice). Breaths were collected before the injections and then at 4 hours and 24 hours postinjection, followed by euthanasia. The mean and variances of preinjection body weights of the groups were not significantly different (Table 2).Table 2.

Bottom Line: Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood.The magnitude of increase was similar to what was observed with a bacteremia model.These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine ; Microbiology and Molecular Genetics.

ABSTRACT

Background: Analysis of volatile organic chemicals in breath holds promise for noninvasive diagnosis and monitoring of patients, but investigation of this in experimental mouse models has been limited. Of particular interest is endogenous production of carbon monoxide as a biomarker of inflammation and, more particularly, during sepsis.

Methods: Using a nose-only collection procedure for unanesthetized individual adult mice and sensitive gas chromatography of carbon monoxide (CO) and carbon dioxide (CO2) of sampled breath, we investigated the responses of mice to one-time injections with different doses of purified Escherichia coli lipopolysaccharide. Two strains of mice were examined: BALB/c and C3H, including an endotoxin-resistant mutant (HeJ) as well as the wild type (HOuJ).

Results: The CO to CO2 ratio increased in a dose-responsive manner within hours in treated BALC/c mice but not control mice. The CO/CO2 values declined to the range of control mice within 48-72 h after the injection of lipopolysaccharide. Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood. C3H/HOuJ mice, but not the HeJ mice, had similar increases of the CO/CO2 ratio in response to the endotoxin.

Conclusions: Carbon monoxide concentrations in exhaled breath of at least 2 strains of mice increase in response to single injections of endotoxin. The magnitude of increase was similar to what was observed with a bacteremia model. These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis.

No MeSH data available.


Related in: MedlinePlus