Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

Liu, Chi; Kurokawa, Ryōsuke; Fujino, Masayuki; Hirano, Shin‐ichi; Sato, Bunpei; Li, Xiaokang

doi:10.1038/srep05485

Cited by 97 publications

(104 citation statements)

References 23 publications

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“…Moreover, the changes in the liver H 2 concentration reported by Kamimura et al were similar to ours [16]. Recently, Liu et al estimated the H 2 concentration in systemic rat organs using gas chromatography after administration of high concentrations of HRW or HCA by a method similar to ours [25]. They mainly showed H 2 concentrations in blood and organs after administration of H 2 super-rich water or saline from several routes.…”

Section: Discussionmentioning

confidence: 52%

Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents

et al. 2015

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Molecular hydrogen (H2) is an agent with potential applications in oxidative stress-related and/or inflammatory disorders. H2 is usually administered by inhaling H2-containing air (HCA) or by oral intake of H2-rich water (HRW). Despite mounting evidence, the molecular mechanism underlying the therapeutic effects and the optimal method of H2 administration remain unclear. Here, we investigated whether H2 affects signaling pathways and gene expression in a dosage- or dose regimen-dependent manner. We first examined the H2 concentrations in blood and organs after its administration and found that oral intake of HRW rapidly but transiently increased H2 concentrations in the liver and atrial blood, while H2 concentrations in arterial blood and the kidney were one-tenth of those in the liver and atrial blood. In contrast, inhalation of HCA increased H2 equally in both atrial and arterial blood. We next examined whether H2 alters gene expression in normal mouse livers using DNA microarray analysis after administration of HCA and HRW. Ingenuity Pathway Analysis revealed that H2 suppressed the expression of nuclear factor-kappa B (NF-κB)-regulated genes. Western blot analysis showed that H2 attenuated ERK, p38 MAPK, and NF-κB signaling in mouse livers. Finally, we evaluated whether the changes in gene expression were influenced by the route of H2 administration and found that the combination of both HRW and HCA had the most potent effects on signaling pathways and gene expression in systemic organs, suggesting that H2 may act not only through a dose-dependent mechanism but also through a complex molecular network.

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Section: Discussionmentioning

confidence: 52%

Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents

et al. 2015

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“…It was prepared freshly and sterilized by gamma radiation before injection. The concentration of hydrogen-rich saline was measured by oxidimetry method with a reagent containing methylene blue and colloidal platinum (Miz Company, Kanagawa, Japan) [25], and it was maintained at about 0.55 mmol/L to keep the concentrations of hydrogen in the heart and liver above 20 ppb/g [26]. …”

Section: Methodsmentioning

confidence: 99%

Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis

Gao

Yang

Fan

et al. 2016

Mediators of Inflammation

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Doxorubicin (DOX) remains the most effective anticancer agent which is widely used in several adult and pediatric cancers, but its application is limited for its cardiotoxicity and hepatotoxicity. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for many diseases. In this study, we found that intraperitoneal injection of hydrogen-rich saline (H2 saline) ameliorated the mortality, cardiac dysfunction, and histopathological changes caused by DOX in rats. Meanwhile, serum brain natriuretic peptide (BNP), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), tissue reactive oxygen species (ROS), and malondialdehyde (MDA) levels were also attenuated after H2 saline treatment. What is more, we further demonstrated that H2 saline treatment could inhibit cardiac and hepatic inflammation and apoptosis relative proteins expressions by western blotting test. In conclusion, our results revealed a protective effect of H2 saline on DOX-induced cardiotoxicity and hepatotoxicity in rats by inhibiting inflammation and apoptosis.

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“…Continuous H 2 dissolution or production by water electrolysis during the whole preservation period may possibly solve such problems; however, complex equipment is necessary to avoid the risk of explosion. Moreover, the liver is the largest solid organ in the human body, deeply located in the right subphrenic space; therefore, sufficient H 2 delivery to transplanted livers in situ seems rather difficult compared with other organs . Thus, we finally conceived of the direct injection of an aqueous H 2 solution into liver grafts ex vivo, named HyFACS.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Flush After Cold Storage as a New End‐Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury

Tamaki¹,

Hata²,

Okamura³

et al. 2018

Liver Transpl

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Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.

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Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

Cited by 97 publications

References 23 publications

Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents

Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents

Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis

Hydrogen Flush After Cold Storage as a New End‐Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury

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