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Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model.

ABSTRACT: BACKGROUND:Hydrogen gas (H2) inhalation during hemorrhage stabilizes post-resuscitation hemodynamics, improving short-term survival in a rat hemorrhagic shock and resuscitation (HS/R) model. However, the underlying molecular mechanism of H2 in HS/R is unclear. Endothelial glycocalyx (EG) damage causes hemodynamic failure associated with HS/R. In this study, we tested the hypothesis that H2 alleviates oxidative stress by suppressing xanthine oxidoreductase (XOR) and/or preventing tumor necrosis factor-alfa (TNF-?)-mediated syndecan-1 shedding during EG damage. METHODS:HS/R was induced in rats by reducing mean arterial pressure (MAP) to 35?mm Hg for 60?min followed by resuscitation. Rats inhaled oxygen or H2 + oxygen after achieving shock either in the presence or absence of an XOR inhibitor (XOR-I) for both the groups. In a second test, rats received oxygen alone or antitumor necrosis factor (TNF)-? monoclonal antibody with oxygen or H2. Two hours after resuscitation, XOR activity, purine metabolites, cytokines, syndecan-1 were measured and survival rates were assessed 6?h after resuscitation. RESULTS:H2 and XOR-I both suppressed MAP reduction and improved survival rates. H2 did not affect XOR activity and the therapeutic effects of XOR-I and H2 were additive. H2 suppressed plasma TNF-? and syndecan-1 expression; however, no additional H2 therapeutic effect was observed in the presence of anti-TNF-? monoclonal antibody. CONCLUSIONS:H2 inhalation after shock stabilized hemodynamics and improved survival rates in an HS/R model independent of XOR. The therapeutic action of H2 was partially mediated by inhibition of TNF-?-dependent syndecan-1 shedding.

SUBMITTER: Tamura T

PROVIDER: S-EPMC7458091 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model.

Tamura Tomoyoshi T Sano Motoaki M Matsuoka Tadashi T Yoshizawa Joe J Yamamoto Ryo R Katsumata Yoshinori Y Endo Jin J Homma Koichiro K Kajimura Mayumi M Suzuki Masaru M Kobayashi Eiji E Sasaki Junichi J

Shock (Augusta, Ga.) 20200901 3

<h4>Background</h4>Hydrogen gas (H2) inhalation during hemorrhage stabilizes post-resuscitation hemodynamics, improving short-term survival in a rat hemorrhagic shock and resuscitation (HS/R) model. However, the underlying molecular mechanism of H2 in HS/R is unclear. Endothelial glycocalyx (EG) damage causes hemodynamic failure associated with HS/R. In this study, we tested the hypothesis that H2 alleviates oxidative stress by suppressing xanthine oxidoreductase (XOR) and/or preventing tumor ne ...[more]

PMID: 32804466

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Project description:Although intensity-modulated radiation therapy (IMRT) has been developed as an alternative to conventional radiotherapy, reducing bone marrow damage is limited. Thus, a novel technology is needed to further mitigate IMRT-induced bone marrow damage. Molecular hydrogen (H2) was recently reported as a preventive and therapeutic antioxidant that selectively scavenges hydroxyl radical (·OH) and peroxynitrite (ONOO-). This observational study aimed to examine whether H2 gas treatment improves IMRT-induced bone marrow damage in cancer patients. The study was performed at Clinic C4 in Tokyo, Japan between May 2015 and November 2016. During this period, all enrolled patients received IMRT once per day for 1 to 4 weeks. After each time of IMRT, the patients of control group (n = 7, 3 men and 4 women, age range: 26-70 years) received mild hyperbaric oxygen therapy in health care chamber for 30 minutes, and the patients of H2 group (n = 16, 8 men and 8 women, age range: 35-82 years) received 5% H2 gas in health care chamber for 30 minutes once per day. Radiation-induced bone marrow damage was evaluated by hematological examination of peripheral blood obtained before and after IMRT, and the data were expressed by the ratio after to before treatment. The total number of radiation times and total exposure doses of radiation were similar between the control and H2 groups. IMRT with health care chamber therapy significantly reduced white blood cells and platelets, but not red blood cells, hemoglobin and hematocrit. In contrast, H2 gas treatment significantly alleviates the reducing effects of white blood cells and platelets (P = 0.0011 and P = 0.0275, respectively). Tumor responses to IMRT were similar between the two groups. The results obtained demonstrated that H2 gas inhalation therapy alleviated IMRT-induced bone marrow damage without compromising the anti-tumor effects of IMRT. The present study suggests that this novel approach of H2 gas inhalation therapy may be applicable to IMRT-induced bone marrow damage in cancer patients. The study protocol was approved by an Ethics Committee Review of Tokyo Clinic and Research Institute ICVS Incorporated (Tokyo, Japan) on February 1, 2019, and was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000035864) on February 20, 2019.

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Dataset Information

Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model.

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Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model.

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