Oxidative Medicine and Cellular Longevity / 2021 / Article / Tab 2

Review Article

Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives

Table 2

Summary of some possible mechanisms related to the positive effects of molecular hydrogen in different diseases and COVID-19 treatment.

Possible MechanismType of StudyPrincipleReference

Molecular properties-related mechanismsIn vivoUnlike most antioxidants, can penetrate biomembranes and diffuse into the cytosol, mitochondria and nucleus and reach cell organelles[50]
Has a rapid gaseous diffusion rate making it highly effective for reducing cytotoxic radicals
Redox-related mechanismsRegulates the redox homeostasis after a ROS-related dissipation stage
Mild enough not to disrupt metabolic oxidoreduction reactions or interrupt ROS-induced disruption of cell signaling
Selectively reduce the strongest cytotoxic oxidants, OH and ONOO; whereas, the biological useful oxidants such as superoxide, hydrogen peroxide, nitric oxide are not altered
Protects nuclear DNA and mitochondria
Protects cells and tissues against strong oxidative stress
Decreases production of ROS
in silicoReduces the reversible cross-linked intramolecular disulfide bonds formed after an oxidative stress e.g. ROS[86]
Decreases the energy barrier of disulfide rupture
In vivoBalances the S-S/SH in favor of thiols[58]
Protects Inositol 1, 4, 5-trisphosphate receptors (IP3Rs) function
Protects the ATP-induced Ca2+ signal by reducing the H2O2-induced disulfide bonds in IP3Rs and restores protein function
Activates glutathione/thioredoxin systems involved in the modulation of disulfide bond formation during oxidative stress leading to reduced H2O2-induced disulfide bond formation
Repairs the processes of cell injury produced through high ROS generation
AnimalMitigates the oxidative damage[98]
selectively reduces OH attenuating ischemia/reperfusion-Induced organ damage
Increases superoxide dismutase (SOD) activity against ROS-mediated cellular damage
Increases activities of antioxidant enzymes
Can significantly decrease levels of oxidative products
HumanInduces superoxide dismutases (SODs) activity to quench ROS production[99]
HumanDecreases ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression[100]
AnimalDecreases oxidative damage[98]

Inflammatory reactions and apoptosis-related mechanismsAnimalInhibits the over-expression of inflammatory factors (IL-6, IL-8 and TNF-α)[98]
Downregulates the expression of proapoptotic Fas proteins
Up-regulates the expression of the anti-apoptotic protein Bcl2
Ameliorates LPS-induced bronchopulmonary dysplasia
Reduces LPS-induced oxidative stress production

Lung and alveoli-related mechanismsAnimalAmeliorates LPS-induced suppression of genes encoding fibroblast growth factor receptor 4 (FGFR4), VEGFR2, and HO-1, as well as LPS-induced overexpression of inflammatory marker proteins (TNFα and IL-6)[79]
Suppresses the induced expressions of inflammatory marker proteins (TNFα and IL-6)
Reduces ROS production in alveolar epithelial cells
AnimalAttenuates septic shock-induced organ injury[98]
Decreases neutrophil infiltrate in the alveoli
Reduces alveolar damage
Reduces levels of high-mobility group box 1 in serum and lung tissue improving the survival rate of mice with sepsis
Reduces the levels of IL-6, IL-8 and TNF-α
Down-regulates the levels of Fas protein and up-regulates the levels of Bcl2 protein, which may inhibit ALI by inducing apoptosis, and may protect lung function
Effectively prevents enterogenous sepsis
Significantly decreases the level of MDA and MPO
AnimalProtects against the alveolar destruction attenuating oxidative DNA damage and SIPS in the lungs[101]
Decreases the markers of oxidative DNA damage such as phosphorylated histone H2AX and 8-hydroxydeoxyguanosine, and senescence markers such as cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1, and b-galactosidase
Restores static lung compliance
Reduces airspace enlargement and parenchymal destruction
Attenuates cigarette smoke-induced oxidative DNA damage and premature senescence in the lungs
AnimalEnhances phagocytic activity of alveolar macrophages[102]
Attenuates lung injury
AnimalAttenuates alveolar epithelial barrier damage[60]
Improves alveolar gas exchange
Reduces cell damage caused by alveolar epithelial cell apoptosis and excessive autophagy
HumanH2/O2 mixture relieves dyspnea and alleviates patient discomfort during the perioperative period[81]

Small intestine injury-related mechanismsAnimalProtects the intestinal mucosa from mechanical injury[98]
Reduces the pathological changes of the small intestine
Inhibits bacterial translocation
Protects the function of other organs in the body

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