Research Paper Volume 11, Issue 4 pp 1226—1239

Methane alleviates sepsis-induced injury by inhibiting pyroptosis and apoptosis: in vivo and in vitro experiments

Zeyu Li1, *,, Yifan Jia1, *,, Yang Feng2, *,, Ruixia Cui1,3, , Runchen Miao1, , Xing Zhang1, , Kai Qu1, , Chang Liu1,4, , Jingyao Zhang1,4, ,

  • 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People's Republic of China
  • 2 Department of Immunology, Shaanxi University of Chinese Medicine, Xianyang Shaanxi 712046, People's Republic of China
  • 3 Department of ICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People's Republic of China
  • 4 Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People's Republic of China
* Equal contribution

Received: January 2, 2019       Accepted: February 12, 2019       Published: February 18, 2019      

https://doi.org/10.18632/aging.101831
How to Cite

Copyright: Li et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Methane has been reported to have anti-oxidative, anti-apoptotic and anti-inflammatory properties. We investigated the potential protective effects of methane on sepsis-induced injury and determined the related mechanisms. C57BL/6 mice received laparotomy with cecal ligation and puncture (CLP) to create a septic model, followed by methane-rich saline (MRS) treatment after CLP. MRS treatment improved the 5-day survival rate and organ functions and alleviated pathological damage of the mice, as well as reduced excessive inflammatory mediators, such as tumor necrosis factor-α and interleukin-6. MRS treatment also decreased the levels of oxidative stress index proteins, decreased the apoptosis of cells and inhibited nod-liker receptor protein (NLRP)3-mediated pyroptosis in the lung and intestine. In in vitro experiments, RAW264.7 and primary peritoneal macrophages were treated with lipopolysaccharide (LPS) plus adenosine-triphosphate (ATP) to induce inflammation and pyroptosis. Consistent with the in vivo results, methane-rich medium (MRM) treatment also reduced the levels of excessive inflammatory mediators, and decreased the levels of ROS, inhibited apoptosis and pyroptosis. Our results indicate that methane offers a protective effect for septic mice via its anti-inflammation, anti-oxidation, anti-pyroptosis and anti-apoptosis properties.

Abbreviations

MRS: methane-rich saline; MRM: methane-rich medium treatment; CLP: cecal ligation and puncture; Sham control: sham-operated group; CLP+NS: normal saline treatment group with cecal ligation and puncture; CLP+MRS: methane-rich saline treatment with cecal ligation and puncture; NM: normal medium control; MRM: methane medium control; NM+L+A: normal medium with LPS and ATP; MRM+L+A: methane-rich medium with LPS and ATP; ROS: reactive oxygen species; MPO: myeloperoxidase; SOD: superoxide dismutase; GSH: reduced glutathione; MDA: malondialdehyde; DHE: dihydroethidium; NF-κB: nuclear factor-kappa B; NLRP3: NOD-like receptor protein 3.