PMID- 25895145
OWN - NLM
STAT- MEDLINE
DCOM- 20160310
LR  - 20181113
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 44
IP  - 1
DP  - 2015 Jul
TI  - Hydrogen Gas Alleviates the Intestinal Injury Caused by Severe Sepsis in Mice by 
      Increasing the Expression of Heme Oxygenase-1.
PG  - 90-8
LID - 10.1097/SHK.0000000000000382 [doi]
AB  - Hydrogen gas (H2) has antioxidative, anti-inflammatory, and antiapoptotic effects 
      and may have beneficial effects in severe sepsis. The purpose of this study was 
      to investigate the mechanisms underlying these protective effects. Male Institute 
      for Cancer Research mice were randomized into 6 groups: sham; sham + H2; severe 
      sepsis; severe sepsis + H2; severe sepsis + zinc protoporphyrin IX (ZnPPIX), a 
      heme oxygenase-1 (HO-1) inhibitor; and severe sepsis + H2 + ZnPPIX. Cecal 
      ligation and puncture (CLP) was used to induce sepsis. Mice in the H2 groups 
      received inhaled 2% H2 for 1 h at 1 h and 6 h after CLP or sham operation. Mice 
      in the ZnPPIX groups received 40-mg/kg ZnPPIX by intraperitoneal injection 1 h 
      before CLP. Tin protoporphyrin IX (TinPPIX), another HO-1 inhibitor, was also 
      used in part for this study. Mice in the TinPPIX groups received 50-mg/kg TinPPIX 
      through subcutaneous injection 6 h before CLP. The levels of biochemical markers, 
      oxidative products, inflammatory mediator, the number of intestinal apoptotic 
      cells, and the colony-forming unit numbers in the peritoneal lavage fluid were 
      much higher in the severe sepsis group compared with the sham group. Intestinal 
      injury in animals with severe sepsis was worse than that in animals in the sham 
      group. H2 therapy in the animals with severe sepsis was associated with reduced 
      intestinal injury, decreased numbers of colony-forming unit and apoptotic cells, 
      reduced levels of biochemical markers, oxidative products, and high-mobility 
      group box 1 protein. The protective effects of H2 were reversed by ZnPPIX and 
      TinPPIX. Protein and messenger RNA expressions of HO-1 and nuclear 
      factor-erythroid 2 p45-related factor 2 (Nrf2) in the intestine were increased in 
      the severe sepsis group compared to the sham group, and H2 further increased 
      their expressions in the severe septic mice. Zinc protoporphyrin IX and TinPPIX 
      inhibited the expression of HO-1 protein. Hydrogen has the capacity to protect 
      mice from organ injury in severe sepsis through a mechanism involving HO-1.
FAU - Li, Yuan
AU  - Li Y
AD  - *Department of Anesthesiology, General Hospital of Tianjin Medical University, 
      Tianjin, China; daggerTianjin Institute of Anesthesiology, Tianjin, China; double daggerDepartment 
      of Cardiology, Tianjin People's Hospital, Tianjin, China; and  section signDepartment of 
      Anesthesiology, Tianjin Chest Hospital, Tianjin, China.
FAU - Li, Qi
AU  - Li Q
FAU - Chen, Hongguang
AU  - Chen H
FAU - Wang, Tao
AU  - Wang T
FAU - Liu, Lingling
AU  - Liu L
FAU - Wang, Guolin
AU  - Wang G
FAU - Xie, Keliang
AU  - Xie K
FAU - Yu, Yonghao
AU  - Yu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Membrane Proteins)
RN  - 0 (Protoporphyrins)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - 7YNJ3PO35Z (Hydrogen)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/*drug effects
MH  - Heme Oxygenase-1/*biosynthesis
MH  - Hydrogen/*pharmacology
MH  - Intestines/*enzymology/pathology
MH  - Male
MH  - Membrane Proteins/*biosynthesis
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Protoporphyrins/pharmacology
MH  - Sepsis/*drug therapy/enzymology/pathology
EDAT- 2015/04/22 06:00
MHDA- 2016/03/11 06:00
CRDT- 2015/04/21 06:00
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/03/11 06:00 [medline]
AID - 10.1097/SHK.0000000000000382 [doi]
PST - ppublish
SO  - Shock. 2015 Jul;44(1):90-8. doi: 10.1097/SHK.0000000000000382.