Hydrogen Gas Reduces Organ Damage and Inflammation in Sepsis
- Authors
- Hongguang Chen, Xing Mao, Xiaoyin Meng, Yuan Li, Jingcheng Feng, Linlin Zhang, Yang Zhang, Yaoqi Wang, Yonghao Yu, Ke-Liang Xie
- Journal
- International Journal of Molecular Medicine
- Year
- 2019
- DOI
- 10.3892/ijmm.2019.4311
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Immune System
TL;DR
Hydrogen gas treatment can reduce organ damage and inflammation in sepsis by improving mitochondrial health and decreasing harmful inflammatory responses through a process called autophagy.
Key Finding
Hydrogen treatment reduced sepsis-induced organ damage and excessive inflammation in mice by activating autophagy (cellular cleanup), which then deactivated the NLRP3 inflammasome pathway and restored mitochondrial function.
Summary
This study examined how hydrogen gas might help protect organs during sepsis (a life-threatening condition caused by the body's extreme response to infection). Researchers used mice with sepsis and immune cells exposed to bacterial toxins to test whether hydrogen could reduce inflammation and organ damage. They found that hydrogen appeared to work by activating a cellular cleanup process called autophagy, which then turned off a harmful inflammatory pathway called NLRP3. When researchers blocked autophagy, hydrogen's protective effects disappeared, suggesting this cleanup process is essential to how hydrogen works.
Practical Takeaway
While these results are promising, they come from animal studies only and do not yet demonstrate that hydrogen would have the same effects in humans with sepsis. The findings suggest a potential mechanism for how hydrogen might help in severe infection, but clinical trials in humans would be needed before any therapeutic claims could be made. This early-stage research indicates hydrogen warrants further investigation for sepsis treatment, but it is not yet established as a clinical intervention.
Abstract
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.