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Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice.

Faller S, Zimmermann KK, Strosing KM, Engelstaedter H, Buerkle H, Schmidt R, Spassov SG, Hoetzel A - Med Gas Res (2012)

Bottom Line: The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality.The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo.In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Hugstetter Str, 55, D-79106, Freiburg, Germany. simone.faller@uniklinik-freiburg.de.

ABSTRACT

Background: Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.

Methods: C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance.

Results: Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

Conclusion: Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

No MeSH data available.


Related in: MedlinePlus

Effect of LPS and hydrogen sulfide inhalation on lung damage. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Sections from the left lung lobe were stained with hematoxylin and eosin. High power fields were randomly assigned to measure alveolar wall thickness (A), to count total infiltrate numbers (B), and to calculate an acute lung injury (ALI) score (C). Data represent means ± SEM for n = 7-8/group. ANOVA on Ranks (A + B, Dunn`s posthoc test) and ANOVA (C; Student-Newman-Keuls posthoc test), *P < 0.05 vs. PBS + air group; #P < 0.05 vs. PBS + H2S group; §P < 0.05 vs. LPS + H2S group.
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Figure 2: Effect of LPS and hydrogen sulfide inhalation on lung damage. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Sections from the left lung lobe were stained with hematoxylin and eosin. High power fields were randomly assigned to measure alveolar wall thickness (A), to count total infiltrate numbers (B), and to calculate an acute lung injury (ALI) score (C). Data represent means ± SEM for n = 7-8/group. ANOVA on Ranks (A + B, Dunn`s posthoc test) and ANOVA (C; Student-Newman-Keuls posthoc test), *P < 0.05 vs. PBS + air group; #P < 0.05 vs. PBS + H2S group; §P < 0.05 vs. LPS + H2S group.

Mentions: In the presented model of pulmonary sepsis H + E staining of lung cryosections showed that as compared to control conditions (PBS + air, PBS + H2S, Figure 1A + B, respectively), LPS treatment clearly stimulated the formation of lung edema and the influx of immune-competent cells (LPS + air, Figure 1C). In sharp contrast, exposure to 80 ppm H2S markedly reduced LPS-induced lung damage (LPS + H2S, Figure 1D), reflected by decreased edema formation and cellular infiltration into the lung tissue. These findings were confirmed by quantitative analysis: H2S inhalation prevented alveolar wall thickening (Figure 2A) and cellular infiltration (Figure 2B), that was otherwise observed in LPS-treated animals kept in room air. In addition, a reduction of lung damage to control levels by H2S inhalation was also detected by rating an overall ALI score (Figure 2C), strongly suggesting a lung-protective role for H2S inhalation in LPS-induced ALI.


Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice.

Faller S, Zimmermann KK, Strosing KM, Engelstaedter H, Buerkle H, Schmidt R, Spassov SG, Hoetzel A - Med Gas Res (2012)

Effect of LPS and hydrogen sulfide inhalation on lung damage. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Sections from the left lung lobe were stained with hematoxylin and eosin. High power fields were randomly assigned to measure alveolar wall thickness (A), to count total infiltrate numbers (B), and to calculate an acute lung injury (ALI) score (C). Data represent means ± SEM for n = 7-8/group. ANOVA on Ranks (A + B, Dunn`s posthoc test) and ANOVA (C; Student-Newman-Keuls posthoc test), *P < 0.05 vs. PBS + air group; #P < 0.05 vs. PBS + H2S group; §P < 0.05 vs. LPS + H2S group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Effect of LPS and hydrogen sulfide inhalation on lung damage. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Sections from the left lung lobe were stained with hematoxylin and eosin. High power fields were randomly assigned to measure alveolar wall thickness (A), to count total infiltrate numbers (B), and to calculate an acute lung injury (ALI) score (C). Data represent means ± SEM for n = 7-8/group. ANOVA on Ranks (A + B, Dunn`s posthoc test) and ANOVA (C; Student-Newman-Keuls posthoc test), *P < 0.05 vs. PBS + air group; #P < 0.05 vs. PBS + H2S group; §P < 0.05 vs. LPS + H2S group.
Mentions: In the presented model of pulmonary sepsis H + E staining of lung cryosections showed that as compared to control conditions (PBS + air, PBS + H2S, Figure 1A + B, respectively), LPS treatment clearly stimulated the formation of lung edema and the influx of immune-competent cells (LPS + air, Figure 1C). In sharp contrast, exposure to 80 ppm H2S markedly reduced LPS-induced lung damage (LPS + H2S, Figure 1D), reflected by decreased edema formation and cellular infiltration into the lung tissue. These findings were confirmed by quantitative analysis: H2S inhalation prevented alveolar wall thickening (Figure 2A) and cellular infiltration (Figure 2B), that was otherwise observed in LPS-treated animals kept in room air. In addition, a reduction of lung damage to control levels by H2S inhalation was also detected by rating an overall ALI score (Figure 2C), strongly suggesting a lung-protective role for H2S inhalation in LPS-induced ALI.

Bottom Line: The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality.The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo.In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Hugstetter Str, 55, D-79106, Freiburg, Germany. simone.faller@uniklinik-freiburg.de.

ABSTRACT

Background: Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.

Methods: C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance.

Results: Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

Conclusion: Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

No MeSH data available.


Related in: MedlinePlus