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

• Published in: Aging (Albany, NY.) NY.), 2019-02, Vol.11 (4), p.1226-1239
• Main Authors: Li, Zeyu, Jia, Yifan, Feng, Yang, Cui, Ruixia, Miao, Runchen, Zhang, Xing, Qu, Kai, Liu, Chang, Zhang, Jingyao
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cytokines - genetics; Cytokines - metabolism; Gene Expression Regulation - drug effects; Macrophages, Peritoneal - drug effects; Male; Methane - administration & dosage; Mice; Mice, Inbred C57BL; Peritonitis - complications; Pyroptosis - drug effects; RAW 264.7 Cells; Research Paper; Saline Solution - administration & dosage; Saline Solution - chemistry; Sepsis - etiology; Sepsis - therapy
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101831

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.