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In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats.

Du Q, Wang C, Zhang N, Li G, Zhang M, Li L, Zhang Q, Zhang J - BMC Anesthesiol (2014)

Bottom Line: Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group.These effects were lessened by NaHS.Its regulatory effect on lung mitochondria is positively correlated with the dosage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Hebei Medical University, 361 Zhongshan Eastern Road, Shijiazhuang, 050017 China ; Intensive Care Unit, Hebei General Hospital, 348 Heping Western Road, Shijiazhuang, 050051 China.

ABSTRACT

Background: Acute lung injury (ALI) is a serious disease with high incidence in ICU, and impaired mitochondria function plays a significant role in ALI. In this study, we examined the possible roles of exogenous hydrogen sulfide (H2S) in lung mitochondria regulation in ALI rats.

Methods: The rat ALI model was induced by an intra-tongue vein Lipopolysaccharide (LPS) injection. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 40 Sprague-Dawley rats into five groups: control, LPS injury, LPS + low-dose NaHS (0.78 mg • kg(-1)), LPS + middle-dose NaHS (1.56 mg • kg(-1)), and LPS + high-dose NaHS (3.12 mg • kg(-1)). Rats were killed 3 h after NaHS administration. We calculated a semi-quantitative histological index of lung injury assessments and measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. We observed lung mitochondria ultrastructures with an electron microscope. We examined oxidative stress markers in lung mitochondria and the mitochondrial swelling and activity. We analyzed lung mitochondria and cytosol Cyt-c protein expression using Western blotting.

Results: Compared to the control group, the quantitative assessment score index, wet-to-dry weight ratios, and interleukin-1β content in the LPS injury group were significantly increased and the mitochondrial ultrastructure damaged. Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group. These effects were lessened by NaHS.

Conclusion: Exogenous H2S provided a protective effect against ALI by decreasing the mitochondrial lipid peroxidation level and protecting the cell structure in the LPS-induced rat models. Its regulatory effect on lung mitochondria is positively correlated with the dosage.

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Histologic changes of lung tissue in each group. Microphotographs of morphological changes of lung tissues (original magnification × 200). Hematoxylin and eosin staining:control: control group. LPS: LPS injury group. L: LPS + low-dose NaHS group. M: LPS + middle-dose NaHS group. H: LPS + high-dose NaHS group. In comparison, the LPS injury group showed diffuse edema in alveolar spaces and interstitium of the lung, hemorrhage, severe inflammatory cell infiltration and serous exudation in the alveolar space, and thickened interbular septa. These changes were lightly mitigated in the LPS + low-dose NaHS group, and were significantly mitigated in LPS + middle-dose NaHS group and high-dose NaHS group.
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Fig1: Histologic changes of lung tissue in each group. Microphotographs of morphological changes of lung tissues (original magnification × 200). Hematoxylin and eosin staining:control: control group. LPS: LPS injury group. L: LPS + low-dose NaHS group. M: LPS + middle-dose NaHS group. H: LPS + high-dose NaHS group. In comparison, the LPS injury group showed diffuse edema in alveolar spaces and interstitium of the lung, hemorrhage, severe inflammatory cell infiltration and serous exudation in the alveolar space, and thickened interbular septa. These changes were lightly mitigated in the LPS + low-dose NaHS group, and were significantly mitigated in LPS + middle-dose NaHS group and high-dose NaHS group.

Mentions: We found that the control group morphology was normal with light microscopy, and there was no alveolar edema fluid in the alveolar space. The alveolar wall was intact with no evidence of inflammatory cell infiltration or hemorrhage. Conversely, the LPS injury group showed diffuse edema in alveolar spaces, lung interstitium, hemorrhage, severe inflammatory cell infiltration, serous exudation in the alveolar space, and a thickened interbular septa like “hyaline membrane”. These changes were lightly mitigated in the LPS + low-dose NaHS group, and significantly mitigated in LPS + middle-dose and high-dose NaHS groups (Figure 1).Figure 1


In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats.

Du Q, Wang C, Zhang N, Li G, Zhang M, Li L, Zhang Q, Zhang J - BMC Anesthesiol (2014)

Histologic changes of lung tissue in each group. Microphotographs of morphological changes of lung tissues (original magnification × 200). Hematoxylin and eosin staining:control: control group. LPS: LPS injury group. L: LPS + low-dose NaHS group. M: LPS + middle-dose NaHS group. H: LPS + high-dose NaHS group. In comparison, the LPS injury group showed diffuse edema in alveolar spaces and interstitium of the lung, hemorrhage, severe inflammatory cell infiltration and serous exudation in the alveolar space, and thickened interbular septa. These changes were lightly mitigated in the LPS + low-dose NaHS group, and were significantly mitigated in LPS + middle-dose NaHS group and high-dose NaHS group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4279795&req=5

Fig1: Histologic changes of lung tissue in each group. Microphotographs of morphological changes of lung tissues (original magnification × 200). Hematoxylin and eosin staining:control: control group. LPS: LPS injury group. L: LPS + low-dose NaHS group. M: LPS + middle-dose NaHS group. H: LPS + high-dose NaHS group. In comparison, the LPS injury group showed diffuse edema in alveolar spaces and interstitium of the lung, hemorrhage, severe inflammatory cell infiltration and serous exudation in the alveolar space, and thickened interbular septa. These changes were lightly mitigated in the LPS + low-dose NaHS group, and were significantly mitigated in LPS + middle-dose NaHS group and high-dose NaHS group.
Mentions: We found that the control group morphology was normal with light microscopy, and there was no alveolar edema fluid in the alveolar space. The alveolar wall was intact with no evidence of inflammatory cell infiltration or hemorrhage. Conversely, the LPS injury group showed diffuse edema in alveolar spaces, lung interstitium, hemorrhage, severe inflammatory cell infiltration, serous exudation in the alveolar space, and a thickened interbular septa like “hyaline membrane”. These changes were lightly mitigated in the LPS + low-dose NaHS group, and significantly mitigated in LPS + middle-dose and high-dose NaHS groups (Figure 1).Figure 1

Bottom Line: Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group.These effects were lessened by NaHS.Its regulatory effect on lung mitochondria is positively correlated with the dosage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Hebei Medical University, 361 Zhongshan Eastern Road, Shijiazhuang, 050017 China ; Intensive Care Unit, Hebei General Hospital, 348 Heping Western Road, Shijiazhuang, 050051 China.

ABSTRACT

Background: Acute lung injury (ALI) is a serious disease with high incidence in ICU, and impaired mitochondria function plays a significant role in ALI. In this study, we examined the possible roles of exogenous hydrogen sulfide (H2S) in lung mitochondria regulation in ALI rats.

Methods: The rat ALI model was induced by an intra-tongue vein Lipopolysaccharide (LPS) injection. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 40 Sprague-Dawley rats into five groups: control, LPS injury, LPS + low-dose NaHS (0.78 mg • kg(-1)), LPS + middle-dose NaHS (1.56 mg • kg(-1)), and LPS + high-dose NaHS (3.12 mg • kg(-1)). Rats were killed 3 h after NaHS administration. We calculated a semi-quantitative histological index of lung injury assessments and measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. We observed lung mitochondria ultrastructures with an electron microscope. We examined oxidative stress markers in lung mitochondria and the mitochondrial swelling and activity. We analyzed lung mitochondria and cytosol Cyt-c protein expression using Western blotting.

Results: Compared to the control group, the quantitative assessment score index, wet-to-dry weight ratios, and interleukin-1β content in the LPS injury group were significantly increased and the mitochondrial ultrastructure damaged. Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group. These effects were lessened by NaHS.

Conclusion: Exogenous H2S provided a protective effect against ALI by decreasing the mitochondrial lipid peroxidation level and protecting the cell structure in the LPS-induced rat models. Its regulatory effect on lung mitochondria is positively correlated with the dosage.

Show MeSH
Related in: MedlinePlus