Hydrogen Gas Therapy Protects Intestines During Severe Infection in Mice

Authors
Journal
Drug Design, Development and Therapy
Year
DOI
10.2147/DDDT.S271191
Study Type
Mouse
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Sepsis
Body System
Gastrointestinal

TL;DR

Inhaling hydrogen gas significantly improves survival and reduces intestinal damage in mice with sepsis by affecting certain proteins and metabolic pathways.

Key Finding

Inhaling 2% hydrogen gas significantly improved survival rates and reduced intestinal damage in mice with polymicrobial sepsis, with the protective effect linked to changes in 199 different proteins involved in thyroid hormone and nitrogen metabolism.

Summary

Researchers used mice with a severe infection (sepsis) to test whether inhaling hydrogen gas could protect the intestines from damage. They found that mice breathing 2% hydrogen gas survived longer, had fewer bacteria in their blood, and showed less intestinal damage compared to untreated mice. Using advanced protein analysis, they identified 199 proteins that changed when hydrogen was used, suggesting the gas works by affecting how the body processes thyroid hormones and nitrogen.

Practical Takeaway

This mouse study provides early evidence that hydrogen gas inhalation may help protect intestines during severe infections, but these results cannot yet be applied to humans. Much more research, including human clinical trials, would be needed to determine if hydrogen gas could be a useful treatment for sepsis in patients.

Abstract

Objective: Sepsis-associated intestinal injury has a higher morbidity and mortality in patients with sepsis, but there is still no effective treatment. Our research team has proven that inhaling 2% hydrogen gas (H2) can effectively improve sepsis and related organ damage, but the specific molecular mechanism of its role is not clear. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis was used for studying the effect of H2 on intestinal injury in sepsis. Methods: Male C57BL/6J mice were used to prepare a sepsis model by cecal ligation and puncture (CLP). The 7-day survival rates of mice were measured. 4-kd fluorescein isothiocyanate-conjugated Dextran (FITC-dextran) blood concentration measurement, combined with hematoxylin-eosinstain (HE) staining and Western blotting, was used to study the effect of H2 on sepsis-related intestinal damage. iTRAQ-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used for studying the proteomics associated with H2 for the treatment of intestinal injury. Results: H2 can significantly improve the 7-day survival rates of sepsis mice. The load of blood and peritoneal lavage bacteria was increased, and H2 treatment can significantly reduce it. CLP mice had significant intestinal damage, and inhalation of 2% hydrogen could significantly reduce this damage. All 4194 proteins were quantified, of which 199 differentially expressed proteins were associated with the positive effect of H2 on sepsis. Functional enrichment analysis indicated that H2 may reduce intestinal injury in septic mice through the effects of thyroid hormone synthesis and nitrogen metabolism signaling pathway. Western blot showed that H2 was reduced by down-regulating the expressions of deleted in malignant brain tumors 1 protein (DMBT1), insulin receptor substrate 2 (IRS2), N-myc downregulated gene 1 (NDRG1) and serum amyloid A-1 protein (SAA1) intestinal damage in sepsis mice. Conclusion: A total of 199 differential proteins were related with H2 in the intestinal protection of sepsis. H2-related differential proteins were notably enriched in the following signaling pathways, including thyroid hormone synthesis signaling pathway, nitrogen metabolism signaling pathways, digestion and absorption signaling pathways (vitamins, proteins and fats). H2 reduced intestinal injury in septic mice by down-regulating the expressions of SAA1, NDRG1, DMBT1 and IRS2.