|
| Possible Mechanism | Type of Study | Principle | Reference |
|
| Molecular properties-related mechanisms | In vivo | Unlike 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 mechanisms | Regulates 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 silico | Reduces the reversible cross-linked intramolecular disulfide bonds formed after an oxidative stress e.g. ROS | [86] |
| Decreases the energy barrier of disulfide rupture |
| In vivo | Balances 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 |
| Animal | Mitigates 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 |
| Human | Induces superoxide dismutases (SODs) activity to quench ROS production | [99] |
| Human | Decreases ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression | [100] |
| Animal | Decreases oxidative damage | [98] |
|
| Inflammatory reactions and apoptosis-related mechanisms | Animal | Inhibits 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 mechanisms | Animal | Ameliorates 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 |
| Animal | Attenuates 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 |
| Animal | Protects 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 |
| Animal | Enhances phagocytic activity of alveolar macrophages | [102] |
| Attenuates lung injury |
| Animal | Attenuates alveolar epithelial barrier damage | [60] |
| Improves alveolar gas exchange |
| Reduces cell damage caused by alveolar epithelial cell apoptosis and excessive autophagy |
| Human | H2/O2 mixture relieves dyspnea and alleviates patient discomfort during the perioperative period | [81] |
|
| Small intestine injury-related mechanisms | Animal | Protects 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 |
|
