Hydrogen Gas Protects Liver During Life-Threatening Sepsis in Mice
- Authors
- Mengying Yan, Yang Yu, Xing Mao, Jingcheng Feng, Yanyan Wang, Hongguang Chen, Keliang Xie, Yong-Hao Yu
- Journal
- International Immunopharmacology
- Year
- 2019
- DOI
- 10.1016/j.intimp.2019.03.021
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Hepatic
TL;DR
Inhaling hydrogen gas can help mice recover from liver damage caused by sepsis by affecting a specific cellular cleanup process.
Key Finding
Hydrogen gas inhalation (2% for 3 hours) improved survival rates and reduced liver damage markers in septic mice, with the protective effect dependent on a specific cellular pathway called FUNDC1-mediated mitophagy.
Summary
Researchers studied whether hydrogen gas could protect the liver during sepsis (a severe infection) in mice. They found that mice breathing 2% hydrogen gas for 3 hours after sepsis showed better survival rates, less liver damage, and improved liver function compared to untreated mice. The protective effect appeared to work through a cellular cleanup process called mitophagy (where cells remove damaged mitochondria, which are the energy-producing parts of cells).
Practical Takeaway
This early evidence from animal studies suggests hydrogen gas inhalation may help protect the liver during severe infections, but this is preliminary research in mice only. Human studies would be needed to determine if these results apply to people with sepsis. The specific mechanism identified (FUNDC1-dependent mitophagy) may be important for understanding how hydrogen could work therapeutically, but more research is required before any clinical applications.
Abstract
Sepsis-induced hepatic dysfunction is considered as an independent risk factor of multiple organ dysfunction syndrome (MODS) and death. Mitophagy, a selective form of autophagy, plays a major role in sepsis-induced organ damage. We have demonstrated that hydrogen gas (H2), a selective antioxidant, exerts protective effects in septic mice. Here, we hypothesize that the therapeutic effects of H2 on septic animals with liver damages may be exerted through regulation of the Fun14 domain-containing protein 1 (FUDNC1)-induced mitophagy pathway. Male C57BL/6J mice were subjected to sham or cecal ligation and puncture (CLP) operation and treated with 2% H2 gas inhalation for 3 h starting at 1 h after sham or CLP surgery. To verify the role of FUNDC1, the cell-penetrating peptide P (NH2-GRKKRRQRRRPQDYESDDESYEVLDLTEY-COOH) (1 mg/kg) that functions as a FUNDC1 inhibitor was intraperitoneally injected into mice 24 h before the sham or CLP operation. To evaluate the severity of septic liver injury, the 7-day survival rate, liver histopathologic score, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respiration control ratio (RCR), and FUDNC1, P-18-FUDNC1, P62, LC3B-II, Tim23, and caspase-1 levels were evaluated after the sham or CLP operation. The results demonstrated that 2% H2 gas inhalation resulted in an increase in the 7-day survival rate, ALT and AST levels, RCR, and P62 and LC3B-II expression but decreased the histological score and FUDNC1, P-18-FUDNC1, Tim23, and caspase-1 levels after sepsis. However, no significant differences were reported between the CLP + peptide P and CLP + H2 + peptide P groups. These observations indicate that 2% H2 gas inhalation for 3 h may serve as an effective therapeutic strategy for sepsis-induced liver injury through the regulation of FUNDC1-dependent mitophagy.