Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner

Hongguang Chen, Jingcheng Feng, Keliang Xie, Mengying Yan, Xing Mao, Yang Yu, Yanyan Wang, Yong-Hao Yu

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DOI: 10.1016/j.intimp.2019.03.021 DOI is the universal ID for this study.

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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.

Publish Year 2019
Country China
Rank Positive
Journal International Immunopharmacology
Primary Topic Liver
Secondary TopicSepsis
Model Mouse
Tertiary TopicMultiple Organ Dysfunction Syndrome
Vehicle Gas
pH N/A
Application Inhalation