Hydrogen sulfide ameliorates tobacco smoke-induced oxidative stress and emphysema in mice

Weihong Han, Zheng Dong, Christiana Dimitropoulou, Yunchao Su

Research output: Contribution to journalArticle

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Abstract

Aims: The mutual interactions between reactive oxygen species, airway inflammation, and alveolar cell death play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In the present study, we investigated the possibility that hydrogen sulfide (H 2S) donor sodium hydrosulfide (NaHS) might be a novel option for intervention in COPD. Results: We used a mouse model of tobacco smoke (TS)-induced emphysema. Mice were injected with H 2S donor NaHS (50μmol/kg in 0.25ml phosphate buffer saline, intraperitoneally) or vehicle daily before exposed to TS for 1h/day, 5 days/week for 12 and 24 weeks. We found that NaHS ameliorated TS-induced increase in mean linear intercepts, the thickness of bronchial walls, and the numbers of total cell counts as well as neutrophils, monocytes, and tumor necrosis factor α in bronchial alveolar lavage. Moreover, NaHS reduced increases in right ventricular systolic pressure, the thickness of pulmonary vascular walls, and the ratio of RV/LV+S in TS-exposed mice. Further, TS exposure for 12 and 24 weeks reduced the protein contents of cystathionine γ-lyase (CGL), cystathionine β-synthetase (CBS), nuclear erythroid-related factor 2 (Nrf2), P ser473-Akt, as well as glutathione/oxidized glutathione ratio in the lungs. TS-exposed lungs exhibited large amounts of 8-hydroxyguanine-positive and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Treatment with NaHS increased P ser473-Akt and attenuated TS-induced reduction of CGL, CBS, and Nrf2 as well as glutathione/oxidized glutathione ratio in the lungs. NaHS also reduced amounts of 8-hydroxyguanine-positive, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and active caspase-3 in TS-exposed lungs. Additionally, knocking-down Akt protein abolished the protective effects of NaHS against TS-induced apoptosis and downregulation of Nrf2, CGL, and CBS in pulmonary artery endothelial cells. Conclusion: These results indicate that NaHS protects against TS-induced oxidative stress, airway inflammation, and remodeling and ameliorates the development of emphysema and pulmonary hypertension. H 2S donors have therapeutic potential for the prevention and treatment of COPD caused by TS.

Original languageEnglish (US)
Pages (from-to)2121-2134
Number of pages14
JournalAntioxidants and Redox Signaling
Volume15
Issue number8
DOIs
StatePublished - Oct 15 2011

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Hydrogen Sulfide
Oxidative stress
Tobacco
Emphysema
Smoke
Oxidative Stress
Pulmonary diseases
Lung
Chronic Obstructive Pulmonary Disease
Glutathione Disulfide
DNA Nucleotidylexotransferase
Labeling
Glutathione
Cells
Cystathionine
Cystathionine beta-Synthase
Inflammation
Airway Remodeling
Alveolar Epithelial Cells
sodium bisulfide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Hydrogen sulfide ameliorates tobacco smoke-induced oxidative stress and emphysema in mice. / Han, Weihong; Dong, Zheng; Dimitropoulou, Christiana; Su, Yunchao.

In: Antioxidants and Redox Signaling, Vol. 15, No. 8, 15.10.2011, p. 2121-2134.

Research output: Contribution to journalArticle

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N2 - Aims: The mutual interactions between reactive oxygen species, airway inflammation, and alveolar cell death play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In the present study, we investigated the possibility that hydrogen sulfide (H 2S) donor sodium hydrosulfide (NaHS) might be a novel option for intervention in COPD. Results: We used a mouse model of tobacco smoke (TS)-induced emphysema. Mice were injected with H 2S donor NaHS (50μmol/kg in 0.25ml phosphate buffer saline, intraperitoneally) or vehicle daily before exposed to TS for 1h/day, 5 days/week for 12 and 24 weeks. We found that NaHS ameliorated TS-induced increase in mean linear intercepts, the thickness of bronchial walls, and the numbers of total cell counts as well as neutrophils, monocytes, and tumor necrosis factor α in bronchial alveolar lavage. Moreover, NaHS reduced increases in right ventricular systolic pressure, the thickness of pulmonary vascular walls, and the ratio of RV/LV+S in TS-exposed mice. Further, TS exposure for 12 and 24 weeks reduced the protein contents of cystathionine γ-lyase (CGL), cystathionine β-synthetase (CBS), nuclear erythroid-related factor 2 (Nrf2), P ser473-Akt, as well as glutathione/oxidized glutathione ratio in the lungs. TS-exposed lungs exhibited large amounts of 8-hydroxyguanine-positive and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Treatment with NaHS increased P ser473-Akt and attenuated TS-induced reduction of CGL, CBS, and Nrf2 as well as glutathione/oxidized glutathione ratio in the lungs. NaHS also reduced amounts of 8-hydroxyguanine-positive, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and active caspase-3 in TS-exposed lungs. Additionally, knocking-down Akt protein abolished the protective effects of NaHS against TS-induced apoptosis and downregulation of Nrf2, CGL, and CBS in pulmonary artery endothelial cells. Conclusion: These results indicate that NaHS protects against TS-induced oxidative stress, airway inflammation, and remodeling and ameliorates the development of emphysema and pulmonary hypertension. H 2S donors have therapeutic potential for the prevention and treatment of COPD caused by TS.

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