Can hydrogen therapy help with severe sepsis?

This mouse study suggests hydrogen inhalation may help protect against intestinal damage in severe sepsis by activating protective cellular pathways. However, human studies are needed to confirm these benefits in patients.

How does hydrogen gas protect against sepsis damage?

Hydrogen appears to work through the Nrf2/HO-1/HMGB1 pathway, which produces protective proteins and reduces harmful inflammation in intestinal tissue. This helps the body better handle the stress of severe infection.

What did this sepsis study find about hydrogen treatment?

Mice with severe sepsis who inhaled hydrogen gas had dramatically improved survival rates (45% vs 0%) and better bacterial clearance. The treatment significantly reduced intestinal damage compared to untreated mice.

Is hydrogen inhalation safe for sepsis patients?

While this mouse study showed promising results, human safety and effectiveness haven't been established. Clinical trials would be needed before hydrogen therapy could be recommended for sepsis patients.

How was hydrogen gas administered in this study?

Mice inhaled 2% hydrogen gas for 60 minutes after sepsis induction. This concentration and timing showed protective effects, but optimal dosing for humans would need separate research.

Hydrogen Gas Protects Against Severe Sepsis Intestinal Damage in Mice

Authors: Ling Yin, Man Yang, Yang Yu, Keliang Xie, Yonghao Yu
Journal: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Year: 2020
DOI: 10.3760/cma.j.cn121430-20200717-00533
Study Type: Mouse
Outcome: Positive
Peer Reviewed: Yes
Country: China
Health Condition: Severe Sepsis
Body System: Gastrointestinal

TL;DR

Inhaling hydrogen gas significantly improved survival and reduced bacterial infection and intestinal damage in mice with severe sepsis, but only if they had a functioning Nrf2 gene, which is important for protecting cells from stress.

Key Finding

In mice with severe sepsis, hydrogen inhalation improved 7-day survival rates from 0% to 45% and reduced bacterial load, but only in mice with functional Nrf2 protein—suggesting Nrf2 is necessary for hydrogen's protective mechanism.

Summary

This mouse study tested whether breathing hydrogen gas could protect the intestines during severe sepsis (a life-threatening infection). Researchers gave some mice hydrogen to breathe and compared them to mice that breathed only air. Mice that received hydrogen had better survival rates and clearer infections, but only if they had a working version of a protein called Nrf2. When researchers removed the Nrf2 protein, hydrogen no longer helped, showing that this protein is essential for hydrogen's protective effect.

Practical Takeaway

This early animal evidence suggests hydrogen gas may help protect intestinal tissue during severe infection by activating a specific cellular pathway. However, this is a mouse study only, and it's unclear whether these results would apply to humans or what dose and delivery method would be appropriate. Much more research, including human trials, would be needed before hydrogen could be considered a treatment for sepsis.

Abstract

Objective: To investigate the protective effect of the hydrogen (H2) inhalation on intestinal injury in severe sepsis mice and its relationship with nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/high mobility group protein B1 (HMGB1) pathway. Methods: The 280 male wild-type (WT) and Nrf2 knockout (Nrf2-KO) ICR mice (6-8 weeks old, 20-25 g weight) were assigned into 8 groups randomly (WT and Nrf2-KO mice, 4 groups respectively, n = 35): Sham group, H2 inhalation group (Sham+H2 group), sepsis model group which was induced by cecal ligation and puncture (CLP group) and H2 treatment group (CLP+H2 group). In Sham group, except cecal ligation and perforation, the same surgery was used. The mice in Sham group and CLP group inhaled only air for 1 hour and 6 hours, respectively, while the mice in Sham+H2 group and CLP+H2 group inhaled 2% H2 for 60 minutes. After modeling, 20 mice randomly in each group were selected to measure 7-day natural survival rates; the remaining mice(15 mice) were killed in 24 hours after modeling, and the bacterial load was determined by collecting the peritoneal lavage fluid (PLF) of each mouse to measure the colony forming unit (CFU); and the intestinal tissue was taken after perfusion, and the intestinal tissue of 3 mice was used to extract protein for HO-1 and HMGB1 levels by using Western blotting. Intestinal tissue of 3 mice was extracted to prepare histomorphology sections for the identification of HO-1. Intestinal tissue of 3 mice was used to detect the expression of HMGB1 by immunofluorescence. Results: The 7-day survival rate of WT and Nrf2-KO mice in CLP group was zero; in WT mice, the 7-day survival rate of CLP+H2 group was significantly higher than that of CLP group (45% vs. 0%, P 0.05). Compared with Sham group, the CFU in the PLF of both mice in CLP group increased significantly. Compared with CLP group, 2% H2 treatment could significantly improve the bacterial clearance rate of WT mice with severe sepsis (CFU, ×103: 34.7±6.3 vs. 74.2±8.1, P 0.05). The results of Western blotting, immunohistochemical and immune-fluorescence showed that the expression of HO-1 and HMGB1 in the CLP group were higher than those in the Sham group. Compared with CLP group, the expression of HO-1 in WT mice of CLP+H2 group was significantly higher [HO-1 protein expression (HO-1/β-actin): 0.716±0.035 vs. 0.460±0.045, HO-1 positive expression (A value): 0.703±0.135 vs. 0.430±0.116, both P 0.05]. Conclusions: H2 can inhibit the intestinal injury of mice with severe sepsis through Nrf2/HO-1/HMGB1 pathway, and Nrf2 plays an important role in the treatment of intestinal injury with H2.