Hydrogen Gas Protects Liver from Sepsis Damage in Mouse Study
- Authors
- Xinling Chen, Wenting Suo, Qiuling Li, Yun Chen, Yao Deng, Luyao Xu, Jiaying Dai, Ning Zhang, Jiean Xu, Jinwen Xu, Xiaodong Zhang, Wen Su, Chengqin Lu, Shuangling Yang, Hongzhi Yang, Hequan Zhu, Haimei Liu, Wenhai Guo, Yaxing Zhang
- Journal
- Frontiers in Immunology
- Year
- 2026
- DOI
- 10.3389/fimmu.2026.1759535
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Hepatic
TL;DR
Intraperitoneal hydrogen pretreatment reduced LPS-induced acute liver injury in mice by lowering oxidative stress, suppressing TLR4/NF-κB/MAPK inflammatory signaling, and inhibiting NLRP3-related pyroptosis.
Key Finding
Hydrogen gas pretreatment reduced liver damage from bacterial toxin exposure in mice by suppressing inflammatory signaling pathways and preventing a damaging form of cell death called pyroptosis.
Summary
Researchers tested whether hydrogen gas could protect mouse livers from damage caused by lipopolysaccharide (a bacterial toxin that triggers sepsis-like conditions). They found that hydrogen gas given by injection before the toxin exposure reduced liver inflammation, lowered markers of liver damage in the blood, and prevented a type of cell death called pyroptosis by blocking inflammatory signaling pathways in the liver.
Practical Takeaway
This mouse study suggests hydrogen gas may have potential to protect the liver during severe infection, but the findings cannot yet be applied to humans. The study used injected hydrogen gas rather than hydrogen water, and human trials would be needed to determine if similar benefits occur in people with sepsis or liver disease.
Abstract
Background: The liver is extremely vulnerable to endotoxin-induced damage during sepsis. Hydrogen gas (H2) is a colorless and odorless gas molecule with anti-oxidative and anti-inflammatory actions. However, the effects of H2 intraperitoneal injection on sepsis-induced acute liver injury and the possible mechanisms remain unclear. Methods: Biochemical analysis, H&E staining, immunoblotting, immunofluorescence, and TUNEL staining were used to investigate the effects and mechanisms of H2 intraperitoneal injection on lipopolysaccharide (LPS)-induced acute liver injury in mice. AML12 cells and pharmacological rescue experiment were used to confirmed the target of H2. Results: H2 pretreatment by intraperitoneal injection improved LPS-induced acute liver injury in mice as indicated by reducing inflammatory cells infiltration in the liver, down-regulating serum ALT and AST levels, decreasing hepatic 3-nitrotyrosine, MDA, and MPO levels, and up-regulating hepatic GSH levels. Mechanistically, H2 suppressed TLR4 to IKK-NF-κB and to MAPK (ERK, p38 and JNK) signaling, and thus reducing pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-18 levels in the liver of LPS-challenged mice. Moreover, the hepatic pyroptosis signaling including NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) to GSDMD, Caspase-8/11 to GSDMD, Caspase-3 to GSDME, and TUNEL staining in LPS-challenged mice were all reversed by H2 treatment. The pharmacological rescue experiments by agonist (nigericin) and antagonist (MCC950) of NLRP3 further confirm the action of H2 on NLRP3 in vitro. Conclusions: H2 pretreatment by intraperitoneal injection alleviated LPS-induced acute liver injury in mice by modulating redox homeostasis, TLR4-mediated innate immune signaling, NLRP3 inflammasome activation and pyroptosis signaling.