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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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Lung Ultrastructure. Effect of H2S on mitochondrial ultrastructure in lung cells, as determined by transmission electron microscopy analysis, in LPS-Induced ALI rat model (original magnification × 25000). There were significant differences in the ultrastructure of mitochondria in lung cells in the control group (control) and LPS injury group (LPS). The mitochondria in lung cells from the LPS group were swollen with disrupted or disintegrated cristae and the osmiophilic lamellar bodies were fusion or disappeared. This mitochondrial damage was lightly mitigated in the LPS + low-dose NaHS group (L), and were significantly mitigated in LPS + middle-dose NaHS group (M) and high-dose NaHS group (H). Arrows indicate mitochondria in lung cells. Bar, 500 nm.
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Fig2: Lung Ultrastructure. Effect of H2S on mitochondrial ultrastructure in lung cells, as determined by transmission electron microscopy analysis, in LPS-Induced ALI rat model (original magnification × 25000). There were significant differences in the ultrastructure of mitochondria in lung cells in the control group (control) and LPS injury group (LPS). The mitochondria in lung cells from the LPS group were swollen with disrupted or disintegrated cristae and the osmiophilic lamellar bodies were fusion or disappeared. This mitochondrial damage was lightly mitigated in the LPS + low-dose NaHS group (L), and were significantly mitigated in LPS + middle-dose NaHS group (M) and high-dose NaHS group (H). Arrows indicate mitochondria in lung cells. Bar, 500 nm.

Mentions: There were significant differences between the mitochondrial ultrastructure in the control and LPS groups’ lung cells. The mitochondria in lung cells from the LPS injury group were swollen with disrupted or disintegrated cristae, and the osmiophilic lamellar bodies had fused or disappeared. This mitochondrial damage was slightly mitigated in the LPS + low-dose NaHS group and significantly mitigated in the LPS + middle-dose and high-dose NaHS groups (Figure 2).Figure 2


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)

Lung Ultrastructure. Effect of H2S on mitochondrial ultrastructure in lung cells, as determined by transmission electron microscopy analysis, in LPS-Induced ALI rat model (original magnification × 25000). There were significant differences in the ultrastructure of mitochondria in lung cells in the control group (control) and LPS injury group (LPS). The mitochondria in lung cells from the LPS group were swollen with disrupted or disintegrated cristae and the osmiophilic lamellar bodies were fusion or disappeared. This mitochondrial damage was lightly mitigated in the LPS + low-dose NaHS group (L), and were significantly mitigated in LPS + middle-dose NaHS group (M) and high-dose NaHS group (H). Arrows indicate mitochondria in lung cells. Bar, 500 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Lung Ultrastructure. Effect of H2S on mitochondrial ultrastructure in lung cells, as determined by transmission electron microscopy analysis, in LPS-Induced ALI rat model (original magnification × 25000). There were significant differences in the ultrastructure of mitochondria in lung cells in the control group (control) and LPS injury group (LPS). The mitochondria in lung cells from the LPS group were swollen with disrupted or disintegrated cristae and the osmiophilic lamellar bodies were fusion or disappeared. This mitochondrial damage was lightly mitigated in the LPS + low-dose NaHS group (L), and were significantly mitigated in LPS + middle-dose NaHS group (M) and high-dose NaHS group (H). Arrows indicate mitochondria in lung cells. Bar, 500 nm.
Mentions: There were significant differences between the mitochondrial ultrastructure in the control and LPS groups’ lung cells. The mitochondria in lung cells from the LPS injury group were swollen with disrupted or disintegrated cristae, and the osmiophilic lamellar bodies had fused or disappeared. This mitochondrial damage was slightly mitigated in the LPS + low-dose NaHS group and significantly mitigated in the LPS + middle-dose and high-dose NaHS groups (Figure 2).Figure 2

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