| Molecular Hydrogen Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice Through Reducing Inflammation and Apoptosis. | |
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MedLine Citation:
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PMID: 22508291 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Recently, our and other studies have found that hydrogen gas (H2) treatment can ameliorate the lung injury induced by sepsis, ventilator, hyperoxia, and ischemia-reperfusion. However, the molecular mechanisms by which H2 ameliorates lung injury remain unclear. In the current study, we investigated whether H2 or hydrogen-rich saline (HS) could exert protective effects in a mouse model of ALI induced by intratracheal administration of lipopolysaccharide (LPS) via inhibiting the nuclear factor κB (NF-κB) signaling pathway-mediated inflammation and apoptosis. Two percent of H2 was inhaled for 1 h beginning at 1 and 6 h after LPS administration, respectively. We found that LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology and histologic scores, wet-to-dry weight ratio, and oxygenation index (PaO2/FIO2), as well as total protein in the bronchoalveolar lavage fluid (BALF), which was attenuated by H2 treatment. Hydrogen gas treatment inhibited LPS-induced pulmonary early and late NF-κB activation. Moreover, H2 treatment dramatically prevented the LPS-induced pulmonary cell apoptosis in LPS-challenged mice, as reflected by the decrease in TUNEL (deoxynucleotidyl transferase dUTP nick end labeling) staining-positive cells and caspase 3 activity. Furthermore, H2 treatment markedly attenuated LPS-induced lung neutrophil recruitment and inflammation, as evidenced by downregulation of lung myeloperoxidase activity, total cells, and polymorphonuclear neutrophils in BALF, as well as proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, interleukin 6, and high-mobility group box 1) and chemokines (keratinocyte-derived chemokine, macrophage inflammatory protein [MIP] 1α, MIP-2, and monocyte chemoattractant protein 1) in BALF. In addition, i.p. injection of 10 mL/kg hydrogen-rich saline also significantly attenuated the LPS-induced ALI. Collectively, these results demonstrate that molecular hydrogen treatment ameliorates LPS-induced ALI through reducing lung inflammation and apoptosis, which may be associated with the decreased NF-κB activity. Hydrogen gas may be useful as a novel therapy to treat ALI. ABBREVIATIONS: ALI-acute lung injury; ARDS-acute respiratory distress syndrome; BALF-bronchoalveolar lavage fluid; ELISA-enzyme-linked immunosorbent assay; H2-hydrogen gas; HMGB1-high-mobility group box 1; HS-hydrogen-rich saline; i.t.-intratracheal; KC-keratinocyte-derived chemokine; LPS-lipopolysaccharide; MCP-1-monocyte chemoattractant protein 1; MIP-1α-macrophage inflammatory protein 1α; MIP-2-macrophage inflammatory protein 2; MPO-myeloperoxidase; PBS-phosphate-buffered saline; PMNs-polymorphonuclear neutrophils; TUNEL-deoxynucleotidyl transferase dUTP nick end labeling; W/D-wet-to-dry. |
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Authors:
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Keliang Xie; Yonghao Yu; Yi Huang; Lina Zheng; Jipeng Li; Hongguang Chen; Huanzhi Han; Lichao Hou; Gu Gong; Guolin Wang |
Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 37 ISSN: 1540-0514 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-4-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: - |
Other Details:
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Languages: ENG Pagination: 548-555 Citation Subset: - |
Affiliation:
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*Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin; †Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province; ‡Department of Anesthesiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi Province; §Department of Gastrointestinal Surgery, State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province; and ∥Department of Anesthesiology, General Hospital of Chengdu Military Command, Chengdu, Sichuan Province, People's Republic of China. |
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