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Global Translational Medicine Hydrogen for acute lung injury

Figure 11. The summary of the meta-analysis.
clinical trials, thereby improving the feasibility of translating expression level of MPO, reducing neutrophil infiltration
preclinical research. However, it is important to note that the and suppressing the release of inflammatory cytokines such
results of this meta-regression are limited to rats and mice, and as IL-1, IL-6, IL-8, and TNF-α cytokines in lung tissues. Ying
their applicability to other animal species remains uncertain. and He found that molecular hydrogen could ameliorate
[34]
Furthermore, the GRADE assessment revealed that 40% of the OA-induced ALI symptoms and inhibit the expression
[31]
indicators in the included studies had low or very low quality, of NF-κB p65 proteins. Similarly, Liang et al. showed
which showed that most of the investigators did not adhere to that molecular hydrogen could inhibit p38MAPK protein
relevant animal experiment guidelines, causing certain biases activation, reduce downstream TNF-α expression, and
in the experiments. Therefore, it is essential for researchers attenuate inflammatory cell infiltration. Most importantly,
to systematically search for all relevant experimental animal these studies revealed that hydrogen not only inhibits the
studies before designing or initiating new animal experiments secretion of inflammatory cells such as neutrophils but also
or clinical trials . ameliorates ALI symptoms, modulates the expression of
[47]
p38MAPK and NF-κB proteins, and blocks the release of
4.3. Anti-inflammation mechanisms of hydrogen cytokines. However, further studies are needed to identify
Alveolar edema and pulmonary interstitial edema are the molecular mechanism of hydrogen in alleviating ALI.
hallmarks of ALI . These symptoms are often the result of Furthermore, several studies have shown that
[48]
changes in the permeability of alveolar-capillary barriers. hydrogen can inhibit pulmonary fibrosis by regulating
Neutrophils play a key role in the progression of ALI as macrophage polarization. Macrophages can exhibit two
they are the first cells recruited to the inflammatory site . phenotypes, M1 and M2 . Under normal physiological
[49]
[55]
Orfanos et al. reported that neutrophil infiltration in conditions, alveolar macrophages are predominantly of
[50]
ALI can be divided into three stages: (i) Neutrophil capture the M2 phenotype. However, during infection or injury,
and rolling; (ii) neutrophil adhesion; and (iii) neutrophil M2 macrophages can polarize into the M1 phenotype
transmigration. In the first stage, endothelial cells are and release a large number of inflammatory mediators,
affected by cytokines like TNF-α, interleukin-1 (IL-1), or inducing ALI to enter the exudation phase . If injury and
[56]
LPS and then release abundant adhesion molecules of the inflammation continue to occur, alveolar macrophages
selectin family such as E-selectin and P-selectin to capture polarize will toward the M2 phenotype and release IL-6,
activated-neutrophils . In the next stage, cytokines TGF-β, IL-4, and other cytokines, leading to ALI entering
[51]
continue to be released, prompting the endothelium to the fibrosis stage [56,57] . Audi et al. demonstrated that
[10]
release reactive oxygen species (ROS) and intercellular repeated inhalation of hydrogen could reduce persistent
adhesion molecule-1, facilitating cell adhesion . Finally, inflammation and prevent irreversible alveolar fibrosis.
[52]
neutrophils transmigrate through the endothelium and
cause infiltration. Myeloperoxidase, the main component 4.4. Antioxidant mechanisms of hydrogen
of neutrophil activation and secretion, serves as an The excessive production of ROS is the cause of damage
indicator of the degree of neutrophil infiltration in the to pulmonary vascular endothelial cells and dysfunction
alveolar cavity [53,54] . Several included studies used MPO of alveolar epithelial cells . Li et al. demonstrated that
[23]
[58]
from bronchoalveolar lavage fluid as the indicator to reflect hydrogen can eliminate ROS and enhance the expression of
neutrophil infiltration [20,22,26,27,29,33,34,37,38] . All these studies Nrf2 molecule. Under physiological conditions, Nrf2 molecule
have demonstrated that molecular hydrogen can inhibit the is localized in the cytoplasm and forms a complex with the

Volume 2 Issue 3 (2023) 11 https://doi.org/10.36922/gtm.0379