Can hydrogen gas help treat sepsis-related lung damage?

Laboratory research suggests hydrogen gas therapy may protect lung cells from sepsis-induced damage by regulating calcium levels. However, this study was conducted in lab cells and mice, so human clinical trials are needed to confirm effectiveness and safety.

How does hydrogen gas protect lung cells during sepsis?

Hydrogen gas works by blocking excess calcium entry into lung blood vessel cells through specific proteins called STIM1 and Orai1. This helps maintain protective barriers in lung tissue and prevents harmful fluid leakage.

What did this study find about hydrogen therapy for lung injury?

The study found that hydrogen gas treatment significantly reduced lung damage in both laboratory-grown cells and mice exposed to sepsis-like conditions. The therapy preserved lung barrier function and reduced inflammation.

Is hydrogen gas therapy safe for sepsis patients?

While this laboratory study shows promising results, it was not conducted in humans. Clinical trials would be necessary to determine the safety and effectiveness of hydrogen gas therapy in actual sepsis patients.

What causes lung damage during sepsis?

During sepsis, the body's inflammatory response damages lung blood vessel cells, disrupting calcium balance and breaking down protective barriers. This allows fluid to leak into air spaces, making breathing difficult and potentially life-threatening.

Hydrogen Gas Protects Lungs from Sepsis-Related Damage in Lab Study

Authors: Yuan Li, Hongguang Chen, Ruichen Shu, Xuan Zhang, Guiyue Wang, Yiqing Yin
Journal: Shock
Year: 2023
DOI: 10.1097/SHK.0000000000002279
Study Type: Cell Culture
Outcome: Positive
Peer Reviewed: Yes
Country: China
Health Condition: Sepsis
Body System: Respiratory

TL;DR

Hydrogen gas treatment helps reduce lung damage and improves the health of lung blood vessel cells in sepsis by managing calcium levels within the cells.

Key Finding

Hydrogen gas reduced calcium-related damage to lung blood vessel cells by blocking the STIM1/Orai1 calcium channel pathway, preserving the cells' protective barrier function in sepsis-like conditions.

Summary

This study investigated how hydrogen gas protects lung cells from damage caused by bacterial toxins (lipopolysaccharides) that mimic sepsis, a life-threatening infection response. Researchers found that hydrogen gas reduced harmful calcium buildup inside lung blood vessel cells by blocking specific calcium channels (STIM1 and Orai1), which helped preserve the cells' barrier function and reduced lung fluid accumulation in both laboratory cell cultures and mice.

Practical Takeaway

This early laboratory and animal study suggests hydrogen may have potential protective effects against sepsis-related lung injury through a specific cellular mechanism. However, these results are from cell cultures and mice only—human studies are needed to determine whether hydrogen water or gas would have similar effects in people with sepsis or acute lung injury.

Abstract

Background: Sepsis is a type of life-threatening organ dysfunction that is caused by a dysregulated host response to infection. The lung is the most vulnerable target organ under septic conditions. Pulmonary microvascular endothelial cells (PMVECs) play a critical role in acute lung injury (ALI) caused by severe sepsis. The impairment of PMVECs during sepsis is a complex regulatory process involving multiple mechanisms, in which the imbalance of calcium (Ca2+) homeostasis of endothelial cells is a key factor in its functional impairment. Our preliminary results indicated that hydrogen gas (H2) treatment significantly alleviates lung injury in sepsis, protects PMVECs from hyperpermeability, and decreases the expression of plasma membrane stromal interaction molecule 1 (STIM1), but the underlying mechanism by which H2 maintains Ca2+ homeostasis in endothelial cells in septic models remains unclear. Thus, the purpose of the present study was to investigate the molecular mechanism of STIM1 and Ca2+-release-activated- Ca2+ channel protein1 (Orai1) regulation by H2 treatment and explore the effect of H2 treatment on Ca2+ homeostasis in lipopolysaccharide (LPS)-induced PMVECs and LPS-challenged mice. Methods: We observed the role of H2 on LPS-induced ALI of mice in vivo. The lung wet/dry (W/D) weight ratio, total protein in the bronchoalveolar lavage (BAL) fluid and Evans blue dye (EBD) assay were used to evaluate the pulmonary endothelial barrier damage of LPS-challenged mice. The expression of STIM1 and Orai1 were also detected using epifluorescence microscopy. Moreover, we also investigated the role of H2- rich medium in regulating PMVECs under LPS treatment, which induced injury similar to sepsis in vitro. The expression of STIM1 and Orai1 as well as the Ca2+ concentration in PMVECs were examined. Results: In vivo, we found that H2 alleviated ALI of mice through decreasing lung W/D weight ratio, total protein in the BAL fluid and permeability of lung. In addition, H2 also decreased the expression of STIM1 and Orai1 in pulmonary microvascular endothelium. In vitro, LPS treatment increased the expression levels of STIM1 and Orai1 in PMVECs, while H2 reversed these changes. Furthermore, H2 ameliorated Ca2+ influx under sepsis-mimicking conditions. Treatment with the sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA) inhibitor, thapsigargin (TG), resulted in a significant reduction in cell viability as well as a reduction in the expression of junctional proteins, including VE-cadherin and occludin. Treatment with the store-operated Ca2+ entry (SOCE) inhibitor, YM-58483 (BTP2), increased the cell viability and expression of junctional proteins. Conclusions: The present study suggested that H2 treatment alleviates LPS-induced PMVEC dysfunction by inhibiting SOCE mediated by STIM1 and Orai1 in vitro and in vivo.