The online version of this article (doi:10.1186/1471-2253-14-117) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
QD designed the study, participated in the laboratory investigations and the design of the protocol, and wrote the manuscript. CW carried out the Western blotting, participated in the laboratory investigations, and performed the statistical analysis and helped draft the manuscript. NZ and GL participated in the laboratory investigations and wrote the manuscript. MZ, QZ, HZ, and LL participated in analysis and interpretation. JZ directed the study. All authors have read and approved the final version of the manuscript.
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.
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.
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.
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.
Faller S, Zimmermann KK, Strosing KM: Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice. Med Gas Res. 2012, 2: 2-6. 10.1186/2045-9912-2-2. CrossRef
Huang XL, Ma HJ, Zhou XH: Effect of exogenous hydrogen sulfide on polymorphonuclear neutrophil accumulation in acute lung injury rat induced by lipopolysaccharides and its mechanism. Chin J Appl Physiol. 2010, 26: 477-480.
Liaudet L, Rosenblatt-Velin N, Pacher : Role of peroxynitrite in the cardiovascular dysfunction of septic shock. Curr Vasc Pharmacol. 2013, 11: 196-207. PubMed
Fielhaber JA, Carroll SF, Dydensborg AB, Shourian M, Triantafillopoulos A, Harel S, Hussain SN, Bouchard M, Qureshi ST, Kristof AS: Inhibition of Mammalian Target of Rapamycin Augments Lipopolysaccharide-Induced Lung Injury and Apoptosis. J Immunol. 2012, 188: 4535-4542. 10.4049/jimmunol.1003655. CrossRefPubMed
Liu G, Cheresh P, Kamp DW: Molecular basis of asbestos-induced lung disease. Annu Rev Patho. 2013, 24: 161-187. CrossRef
Ufnal M, Żera T: The role of nitric oxide, hydrogen sulfide and carbon monoxide in the regulation of the circulatory system and their pharmacotherapeutic potential. Kardiol Pol. 2010, 68 (Suppl 5): S436-S440. PubMed
Lowicka E, BeLtowski J: Hydrogen sulfide (H 2S) - the third gas of interest for pharmacologists. Pharmacol Rep. 2007, 59: 4-24. PubMed
Yu YP, Chin XL, Liu LJ: A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury. Sci World J. 2014, 2014: 432318-
Zivkovic V, Jakovljevic V, Pechanova O, Srejovic I, Joksimovic J, Selakovic D, Barudzic N, Djuric DM: Effects of DL-homocysteine thiolactone on cardiac contractility, coronary flow, and oxidative stress markers in the isolated rat heart: the role of different gasotransmitters. Biomed Res Int. 2013, 2013: 318-471. CrossRef
Wang C, Wang HY, Liu ZW, Fu Y, Zhao B: Effect of endogenous hydrogen sulfide on oxidative stress in oleic acid-induced acute lung injury in rats. Chin Med J (Engl). 2011, 124: 3476-3480.
Faller S, Spassov SG, Zimmermann KK, Ryter SW, Buerkle H, Loop T, Schmidt R, Strosing KM, Hoetzel A: Hydrogen sulfide prevents hyperoxia-induced lung injury by downregulating reactive oxygen species formation and angiopoietin-2 release. Curr Pharm Des. 2013, 19: 2715-2721. 10.2174/1381612811319150006. CrossRefPubMed
Bhatia M: Role of hydrogen sulfide in the pathology of inflammation. Scientifica (Cairo). 2012, 2012: 159680-
Smith Kendra M, Mrozek Jeanne D, Simonton Susan C, Bing Dennis R, Meyers Pat A, Connett John E, Mammel MC: Prolonged partical liquid ventilation using conventional and high frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome. Crit Care Med. 1997, 25: 1888-1897. 10.1097/00003246-199711000-00030. CrossRef
Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG: Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis. 1979, 120: 893-899. PubMed
Siriporn C: Chattipakorn, Savitree Thummasorn, Jantira Sanit, Nipon Chattipakorn: Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart. J Geriatr Cardiol. 2014, 11: 151-157.
The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000, 342: 1301-1308. CrossRef
Villar J, Blanco J, Añón JM, Santos-Bouza A, Blanch L, Ambrós A, Mosteiro F, Basaldúa S, Fernández RL, Kacmarek RM, ALIEN Network: The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011, 37: 1932-1941. 10.1007/s00134-011-2380-4. CrossRefPubMed
Choi JS, Lee HS, Seo KH, Na JO, Kim YH, Uh ST, Park CS, Oh MH, Lee SH, Kim YT: The effect of post-treatment N-acetylcysteine in LPS-induced acute lung injury of rats. Tuberc Respir Dis (Seoul). 2012, 73: 22-31. 10.4046/trd.2012.73.1.22. CrossRef
Dogan SA, Trifunovic A: Modelling mitochondrial dysfunction in mice. Physiol Res. 2011, 60: S61-70. PubMed
Chouteau JM, Obiako B, Gorodnya OM, Pastukh VM, Ruchko MV, Wright AJ, Wilson GL, Gillespie MN: Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs. Am J Physiol Lung Cell Mol Physiol. 2011, 301: L892-898. 10.1152/ajplung.00210.2011. CrossRefPubMedPubMedCentral
Gu ZY, Ling YL, Xu XH, Meng AH, Li SJ: Effect of peroxynitrite on the reactivity of rabbit pulmonary arteriesin vitro. Acta PhysiolSc. 2003, 55: 469-474.
Spiller F, Orrico MIL, Nascimento DC, Czaikoski PG, Souto FO, Alves-Filho JC, Freitas A, Carlos D, Montenegro MF, Neto AF, Ferreira SH, Rossi MA, Hothersall JS, Assreuy J, Cunha FQ: Hydrogen sulfide improves neutrophil migration and survival in sepsis via K +ATP channel activation. Am J Respir Crit Care Med. 2010, 182: 360-368. 10.1164/rccm.200907-1145OC. CrossRefPubMed
Tokuda K, Kida K, Marutani E, Crimi E, Bougaki M, Khatri A, Kimura H, Ichinose F: Inhaled hydrogen sulfide prevents endotoxin-induced systemic inflammation and improves survival by altering sulfide metabolism in mice. Antioxid Redox Signal. 2012, 17: 11-21. 10.1089/ars.2011.4363. CrossRefPubMedPubMedCentral
Aslami H, Pulskens WP, Kuipers MT, Bos AP, van Kuilenburg ABP, Wanders RJ, Roelofsen J, Roelofs JJ, Kerindongo RP, Beurskens CJ, Schultz MJ, Kulik W, Weber NC, Juffermans NP: Hydrogen sulfide donor NaHS reduces organ injury in a rat model of pneumococcal pneumosepsis, associated with improved bio-energetic status. PLoS One. 2013, 8: e63497-10.1371/journal.pone.0063497. CrossRefPubMedPubMedCentral
Madurga A, Mižíková I, Ruiz-Camp J, Vadász I, Herold S, Mayer K, Fehrenbach H, Seeger W, Morty RE: Systemic hydrogen sulfide administration partially restores normal alveolarization in an experimental animal model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2014, 306: L684-97. 10.1152/ajplung.00361.2013. CrossRefPubMed
- In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats
- BioMed Central
Neu im Fachgebiet AINS
Meistgelesene Bücher aus dem Fachgebiet AINS
Mail Icon II