title: Hydrogen sulfide ameliorates tobacco smoke-induced oxidative stress and emphysema in mice.
abstract: OBJECTIVE
  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(2)S) 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(2)S donor NaHS (50 μmol/kg in 0.25 ml phosphate buffer saline, intraperitoneally) or vehicle daily before exposed to TS for 1 h/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.
  
  
  CONCLUSIONS
  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(2)S donors have therapeutic potential for the prevention and treatment of COPD caused by TS.
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Han
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.forename: Christiana
authors.initials: C
authors.lastname: Dimitropoulou
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D051267:NF-E2-Related Factor 2; D014028:Tobacco Smoke Pollution; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D019803:Glutathione Disulfide; D006862:Hydrogen Sulfide