Hydrogen Gas Protects Against Life-Threatening Sepsis Organ Damage

Authors
Journal
International Immunopharmacology
Year
DOI
10.1016/j.intimp.2019.106049
Study Type
Mouse
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Sepsis
Body System
Respiratory

TL;DR

Hydrogen treatment can help protect against organ damage in sepsis by reducing cell stress and enhancing the cell's cleanup processes.

Key Finding

In mice with sepsis, hydrogen gas reduced organ injury and improved organ function by activating the cell's cleanup system (autophagy) and reducing cellular stress in the endoplasmic reticulum.

Summary

This study used mice with sepsis (a severe infection causing organ damage) to investigate how hydrogen gas might protect organs. Researchers found that sepsis triggers two harmful cellular processes: endoplasmic reticulum stress (a type of cellular damage) and impaired autophagy (the cell's cleanup system). When hydrogen was given to septic mice, it reduced endoplasmic reticulum stress, improved autophagy function, and decreased inflammation and organ damage in the lungs, liver, and kidneys.

Practical Takeaway

This is early laboratory research in mice only, not humans. While the findings suggest hydrogen may have protective effects against sepsis-related organ damage through specific cellular mechanisms, much more research—including human studies—would be needed before any therapeutic claims could be made. The results are interesting but cannot yet be applied to human sepsis treatment.

Abstract

Aims: Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Although much progress has been made in understanding the pathophysiology of sepsis, further discussion and study of the detailed therapeutic mechanisms are needed. Autophagy and endoplasmic reticulum stress are two pathways of the complicated regulatory network of sepsis. Herein, we focus on the cellular mechanism in which autophagy and endoplasmic reticulum stress participate in hydrogen (H2)-protected sepsis-induced organ injury. Materials and methods: Male C57BL/6 mice were randomly divided into the following groups: control group, cecal ligation puncture (CLP) group, CLP + tunicamycin(TM) group, CLP + 4-phenyl butyric acid (4-PBA) group, CLP + rapamycin (Rap) group, CLP + 3-methyladenine (3-MA) group, CLP + H2 group, CLP + H2 + 3-MA group, and CLP + H2 + TM group. After the experiment was completed, autophagosome was detected by transmission electron microscopy; protein PKR-like ER kinase (PERK), p-PERK, Eukaryotic translation initiation factor-2α (eIF2α), p-eIF2α, inositol-requiring enzyme1α(IRE1α), C/EBP homologous protein(CHOP), activating transcription factor(ATF), XBP-1, microtubule-associated protein 1 light(LC3), Beclin1, PTEN-induced putative kinase 1(PINK1), Parkin, and p65 subunit of Nuclear factor kappa B(NF-κb) were measured by Western blot; myeloperoxidase(MPO) activity in lung, bronchoalveolar lavage(BAL) total protein, lung wet-to-dry(W/D) ratio, serum biochemical indicators, 7-day survival rate, and pathological injury scores of lung, liver, and kidney were tested; and cytokines tumor necrosis factor-α(TNF-α), Interleukin(IL)-1β, and IL-6 and high mobility group box protein (HMGB)1 were detected by enzyme-linked immunosorbent assay(ELISA). Results: We demonstrated that sepsis induced endoplasmic reticulum stress. Moreover, it was found that an increase in endoplasmic reticulum impaired autophagy activity in sepsis, and the absence of endoplasmic reticulum stress attenuated tissue histological injury and dysfunction of lung, liver, and kidney in septic mice. Intriguingly, hydrogen alleviated the endoplasmic reticulum stress via the autophagy pathway and also mitigated inflammation and organ injury. Conclusion: Hydrogen provided protection from organ injury induced by sepsis via autophagy activation and endoplasmic reticulum stress pathway inactivation.