title: In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats.
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.
  
  
  CONCLUSIONS
  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.
authors.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.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Du
authors.affiliation: Clinical research center, Hebei General Hospital, 348 Heping Western Road, Shijiazhuang, 050051 China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Children's Hospital of Hebei Province, 133 Jianhua Southern Avenue, Shijiazhuang, 050031 China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Centers for Disease Control and Prevention, 97 Huaian Eastern Road, Shijiazhuang, 050021 China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of chest surgery, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051 China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Centers for Disease Control and Prevention, 97 Huaian Eastern Road, Shijiazhuang, 050021 China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei Centers for Disease Control and Prevention, 97 Huaian Eastern Road, Shijiazhuang, 050021 China.
authors.forename: Qingzeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, 361 Zhongshan Eastern Road, Shijiazhuang, 050017 China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000097:blood*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D013440:Sulfides; D008315:Malondialdehyde; D045304:Cytochromes c; D013482:Superoxide Dismutase; C025451:sodium bisulfide
keywords: Acute lung injury; Exogenous hydrogen sulfide; Lipopolysaccharide; Mitochondria; Mitochondrial lipid peroxidation