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.
Highlights
Sepsis, a systemic inflammatory response syndrome caused by polymicrobial infections, is a major cause of mortality in hospital patients [1]
The survival rates of the cecal ligation and puncture (CLP)+methane‐rich saline (MRS) groups varied with the different concentrations of MRS
We used Hematoxylin and eosin (HE) staining to evaluate the protective effect of MRS on the lungs intestines 12 and 24 h after CLP (Figure 2A)
Summary
A systemic inflammatory response syndrome caused by polymicrobial infections, is a major cause of mortality in hospital patients [1]. The activation of Kupffer cells can activate the nuclear factor-kappa B (NF-κB) signaling pathway, which further accelerates the www.aging‐us.com production of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), which form the cytokine cascade, and eventually leads to cell apoptosis and multiple organ dysfunction [3, 4]. Many 1-2 nm pores are formed on the cell membrane, causing the cell membrane to lose integrity and the ability to import and export control material, eventually leading to the dissolution of the cell membrane, the release of cellular contents, and further induction of an inflammatory response in other cells [5]. Excessive reactive oxidative species (ROS) produced by inflammatory reactions cause activation of NLRP3, which indicates that ROS can induce pyroptosis-induced multiple organ dysfunction [8]. The pharmacological inhibition of the NLRP3 pathway might constitute a potent protective strategy during sepsis
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