PMID- 25818978 OWN - NLM STAT- MEDLINE DCOM- 20150812 LR - 20161125 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 196 IP - 1 DP - 2015 Jun 1 TI - Hydrogen gas inhibits high-mobility group box 1 release in septic mice by upregulation of heme oxygenase 1. PG - 136-48 LID - S0022-4804(15)00155-9 [pii] LID - 10.1016/j.jss.2015.02.042 [doi] AB - BACKGROUND: Sepsis is a potentially fatal whole-body inflammation caused by severe infection. Hydrogen gas (H2) is effective for treating sepsis. In this study, we hypothesized that the protective function of H2 in mice with septic lung injury occurred through the activation of heme oxygenase 1 (HO-1) and its upstream regulator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). MATERIALS AND METHODS: Male institute of cancer research mice were subjected to sepsis by cecal ligation and puncture (CLP) with the presence or absence of H2. Beginning at 1 and 6 h after CLP or sham operation, respectively, 2% H2 was inhaled for 1 h. We intraperitoneally injected the HO-1 inhibitor zinc protoporphyrin IX (40 mg/kg) 1 h before CLP. To assess the severity of septic lung injury, we observed the 7-d survival rate, wet/dry weight ratio of lung, lung histopathologic score, oxygenation index, and so forth. Serum and homogenates from the lung, liver, and kidney were acquired for measuring the levels of high-mobility group box 1 (HMGB1) at 6, 12, and 24 h after CLP or sham operation. Furthermore, the protein and messenger RNA expression of Nrf2, HO-1, and HMGB1 was measured at 6, 12, and 24 h. RESULTS: Septic mice had a lower survival rate and more severe lung injury compared with the sham group. However, therapy with H2 increased the survival rate and alleviated the severity of lung injury, reduced the HMGB1 level, and increased the HO-1 and Nrf2 levels in septic mice. Moreover, the HO-1 inhibitor zinc protoporphyrin IX significantly eliminated the protective effect of H2 on septic lung injury. CONCLUSIONS: H2 plays a significant role in regulating the release of the inflammatory cytokine HMGB1 in septic mice, which is partially mediated through the activation of HO-1 as a downstream molecule of Nrf2. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Li, Yuan AU - Li Y AD - Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China. FAU - Xie, Keliang AU - Xie K AD - Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China. Electronic address: xiekeliang2009@hotmail.com. FAU - Chen, Hongguang AU - Chen H AD - Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China. FAU - Wang, Guolin AU - Wang G AD - Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China. FAU - Yu, Yonghao AU - Yu Y AD - Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China. Electronic address: yuyonghao@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150227 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (HMGB1 Protein) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Protoporphyrins) RN - 15442-64-5 (zinc protoporphyrin) RN - 7YNJ3PO35Z (Hydrogen) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) SB - IM MH - Animals MH - HMGB1 Protein/*antagonists & inhibitors MH - Heme Oxygenase-1/genetics/*physiology MH - Hydrogen/*pharmacology MH - Lung/pathology MH - Male MH - Membrane Proteins/genetics/*physiology MH - Mice MH - NF-E2-Related Factor 2/genetics MH - Peroxidase/metabolism MH - Protoporphyrins/pharmacology MH - Sepsis/*drug therapy/metabolism/pathology MH - Signal Transduction MH - Up-Regulation OTO - NOTNLM OT - Acute lung injury OT - Heme oxygenase 1 OT - High-mobility group box 1 OT - Hydrogen gas OT - Sepsis EDAT- 2015/03/31 06:00 MHDA- 2015/08/13 06:00 CRDT- 2015/03/31 06:00 PHST- 2014/11/22 00:00 [received] PHST- 2015/02/15 00:00 [revised] PHST- 2015/02/18 00:00 [accepted] PHST- 2015/03/31 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2015/08/13 06:00 [medline] AID - S0022-4804(15)00155-9 [pii] AID - 10.1016/j.jss.2015.02.042 [doi] PST - ppublish SO - J Surg Res. 2015 Jun 1;196(1):136-48. doi: 10.1016/j.jss.2015.02.042. Epub 2015 Feb 27.