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

• DOI: 10.18632/aging.101831
• Publication Date: 2019-02-19T00:13:39Z
• Authors: Zeyu Li; Yifan Jia; Yang Feng; Ruixia Cui; Runchen Miao; Xing Zhang; Kai Qu; Chang Liu; Jingyao Zhang
• Keywords: Male; 0301 basic medicine; Apoptosis; Peritonitis; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; RAW 264.7 Cells; Gene Expression Regulation; Sepsis; Macrophages, Peritoneal; Pyroptosis; Animals; Cytokines; Saline Solution; Methane; Research Paper

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.