Hydrogen in the treatment of human diseasesScientific Research

Hydrogen: A Novel Option in Human Disease Treatment

Mengling Yang,1 Yinmiao Dong,1 Qingnan He,1 Ping Zhu,2 Quan Zhuang,3 Jie Shen,1 Xueyan Zhang,4 and Mingyi Zhao1

https://doi.org/10.1155/2020/8384742

Abstract

H2 has shown anti-inflammatory and antioxidant capacity in multiple clinical studies, and is recommended in the latest novel coronavirus pneumonia (NCP) treatment guidelines in China. Clinical experiments have surprisingly found that H2 gas can protect the lungs and extrapulmonary organs of NCP patients from pathological stimuli. The possible mechanism for the action of H2 gas is unclear. H2 gas modulates anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (including apoptosis, autophagy, pyroptosis, ferroptosis, and the circadian clock), and has the potential to treat many Potential for systemic disease. This article provides an overview of basic research and recent clinical applications of hydrogen in multi-organ diseases to develop clinical management strategies for various diseases.

Conclusions

Hydrogen has great potential in regulating oxidative stress, inflammation, organelle energy metabolism and programmed cell death. Numerous animal experiments and clinical studies have demonstrated the protective effects of hydrogen on many organs and systems.

Research in this area has increased over the past 15 years. However, the details of the specific molecular mechanisms behind the therapeutic effects of hydrogen remain unclear. For example, whether hydrogen can actually be used to regulate ferroptosis, pyroptosis, or the biological clock is unclear. Since H2 does not have only unidirectional (opposite) effects on autophagy like rapamycin or leucine, is it possible to regulate autophagy or apoptosis in a specific direction?

Previous studies have clearly explained the anti-oxidative stress effects of hydrogen. However, some recent clinical studies have shown that H2 can also induce oxidative stress under certain conditions. H2 ventilation can induce a slight increase in ROS, which activates Nrf2, NF-κB signaling pathway and heat shock response. H2-induced ROS production was also observed in cancer cells. The specific mechanism of hydrogen-induced increase in oxidative stress should be elucidated by further experiments. These and other questions related to the mechanism of hydrogen deserve further study.

A number of factors limit the clinical use of hydrogen.First, hydrogen is considered unsafe at concentrations above 4% because such high levels are explosive and can have cytotoxic effects. Previous studies have shown that hydrogen concentration should be stabilized above 2% to prevent acute oxidative stress. But even 2% hydrogen is not completely safe. Most clinical ventilators are equipped with platinum thermometers because H2 and O2 can overheat platinum surfaces at room temperature. Second, there is a lack of specialized equipment that can manage hydrogen at effective concentrations while ensuring hydrogen safety. Third, there are few large-scale controlled human studies on the effects of hydrogen.

Fourth, Liu and colleagues showed that inhaled H2 resulted in a slower increase in H2 concentrations compared to intraperitoneal, intravenous, or oral administration. However, elevated H2 concentrations persisted for at least 60 minutes after inhalation. Therefore, the mode of administration of H2 should be chosen carefully [7]. Therefore, the dose-specific effects or side effects of hydrogen in humans remain unclear.

Data on the known mechanisms of hydrogen action suggest that hydrogen can reduce damage to multiple organs in NCP patients. A comparison of different hydrogen forms demonstrates the value of HW in effectively treating such patients.

Hydrogen is cheap and safe, and can be administered in a number of ways. We anticipate that the full clinical potential of hydrogen will be realized when large-scale clinical trials confirm the therapeutic efficacy and safety of hydrogen.

 

Abbreviation

NCP:Novel coronavirus pneumonia
H2:Hydrogen
I/R:Ischemia/reperfusion
HRS:H2-rich saline
HW:H2-rich water
ROS:Reactive oxygen species
ER:Endoplasmic reticulum
EMT:Epithelial-mesenchymal transition
CVD:Cardiovascular diseases
NAFLD:Nonalcoholic fatty liver disease
AKI:Acute kidney injury
MDA:Malondialdehyde
Nrf2:Nuclear erythroid 2-related factor 2
PGC-1α:Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha.

 

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