Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy‑mediated NLRP3 inflammasome inactivation in sepsis

Hongguang Chen, Jingcheng Feng, Ke-Liang Xie, Linlin Zhang, Xiaoyin Meng, Xing Mao, Yang Zhang, Yaoqi Wang, Yonghao Yu, Yuan Li

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DOI: 10.3892/ijmm.2019.4311 DOI is the universal ID for this study.

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Sepsis is a highly heterogeneous syndrome that is caused by a dysregulated host response to infection. The disproportionate inflammatory response to invasive infection is a triggering event inducing sepsis. The activation of inflammasomes in sepsis can amplify inflammatory responses. It has been reported that damaged mitochondria contribute to NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome‑related sepsis. Our previous study revealed that hydrogen (H2) exerts anti‑inflammatory effects in sepsis but the detailed mechanism remains to be elucidated. In the present study, septic mice induced by cecal ligation and puncture (CLP) and macrophages induced by lipopolysaccharide (LPS) were used as models of sepsis in vivo and in vitro, respectively. An inducer and inhibitor of autophagy and the NLRP3 inflammasome were administered to investigate the detailed mechanism of action of H2 treatment in sepsis. The results demonstrated that LPS and ATP led to NLRP3 inflammasome pathway activation, excessive cytokine release, mitochondrial dysfunction and the activation of autophagy. CLP induced organ injury and NLRP3 pathway activation. H2 treatment ameliorated vital organ damage, the inflammatory response, mitochondrial dysfunction and NLRP3 pathway activation, and promoted autophagy in macrophages induced by LPS and in CLP mice. However, the inhibitor of autophagy and the inducer of NLRP3 reversed the protective effect of H2 against organ damage, the inflammatory response and mitochondrial dysfunction in vivo and in vitro. Collectively, the results demonstrated that H2 alleviated mitochondrial dysfunction and cytokine release via autophagy‑mediated NLRP3 inflammasome inactivation.

Publish Year 2019
Country China
Rank Positive
Journal International Journal of Molecular Medicine
Primary Topic Whole Body
Secondary TopicSepsis
Model Mouse
Tertiary TopicEndoplasmic Reticulum Function
Vehicle Saline (Dissolved)
pH N/A
Application Injection