Hydrogen: A Novel Option in Human Disease Treatment

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Hydrogen: A Novel Option in Human Disease Treatment ( hydrogen-novel-option-human-disease-treatment )

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2 Oxidative Medicine and Cellular Longevity •OH ONOO− ROS Nrf-2 HO-1 TNF-𝛼 NF-𝜅B INF-𝛾 Fas FasL IL-1𝛼 IL-1𝛽 IL-6 IL-8 IL-10 H2 GRP78 TRAF2 miR-210 OXPHOS Th1/Th2 balance Figure 1: Biological effects of H2. H2 exhibits selective antioxidative and anti-inflammatory activities and can regulate ER stress, mitochondria, and immune function. H2 selectively scavenges ⋅OH and ONOO-, upregulates Nrf-2 and HO-1, and downregulates the expression of proinflammatory and inflammatory cytokines that include TNF-α, NF-κB, INF-γ, Fas, FasL, IL-1α, IL-1β, IL-6, IL-8, and IL- 10, as well as downregulates ER stress-related factors that include GRP78 and TRAF2. H2 also reduces miR-210 and activates OXPHOS in mitochondria. Finally, H2 increases CD4+CD25+Foxp3+Treg cells and maintains the Th1/Th2 balance. water (HW), bathing in HW, and using HRS eyedrops. As well, the production of intestinal H2 by bacteria can be increased via oral administration of acarbose and lactulose. Liu and his colleagues demonstrated that the hydrogen con- centration reached a peak of 5 min after oral and intraperito- neal administration, and in only 1 min following intravenous administration [7]. Beginning on 31 December 2019 in Wuhan, China, ill- ness and pneumonia named coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to become a pan- demic. The seventh edition of Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) issued by China National Health Commission recommended the inhalation of oxygen mixed with hydrogen gas (33.3% O2 and 66.6% H2), bringing H2 to the forefront of contemporary therapeutic medical gas research. The preventive and therapeutic effects of H2 have been intensively investigated for various pathological processes. In this review, we summarize the most recently published litera- ture concerning the use of H2 in respiratory, cardiovascular, nervous, digestive, reproductive, urinary, motor, and sensory system diseases, as well as for the treatment of metabolic syn- drome and cancer. We also briefly discuss some known mech- anisms underlying the action of H2. We hope that this information will increase the understanding of the therapeutic activities of H2 and inform future H2-based therapies. 2. Mechanisms of the Action of H2 To fully explain the preventive and therapeutic effects of H , 2 biological effects and possible mechanisms are summarized in Figures 1 and 2. 2.1. Anti-Inflammatory Effect of H2. The anti-inflammatory effect of H2 has already been reported in many studies. In the early stage of inflammation, H2 can reduce the infiltration of neutrophils and M1 macrophages, and the release of proinflammatory factors by downregulating the expression of intercellular cell adhesion molecule-1 (ICAM-1), granulocyte-macrophage colony-stimulating factor (GM- CSF), and granulocyte colony-stimulating factor (G-CSF) [4]. H2 can also inhibit the expression of proinflammatory cytokines during the progress of inflammation and has been revealed in many animal models to decrease the overexpres- sion of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF- α) [8], interferon-gamma (INF-γ), and late proinflammatory cytokines, such as high-mobility group box-1 protein (HMGB1) [9]. Tanaka and colleagues [10] conducted a gene array analysis of lung grafts from donor rats pretreated with hydrogen ventilation. The authors described that pretreat- ment with H2 obviously elevated the expression of two stress-response proteins: heat shock protein A5 (HSPA5) and dual-specificity phosphatase 1 (DUSP1). HSP70 protein CD4 CD25 u a y i r d n o I h m c o m t i FOXP3 Treg u u m n e o t a r l e g g e l R a t i o n

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