Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats

Ito, Mikako; Hirayama, Masaaki; Yamai, Kazuaki; Goto, Sachiko; Ito, Masafumi; Ichihara, Masatoshi; Ohno, Kinji

doi:10.1186/2045-9912-2-15

Cited by 93 publications

(88 citation statements)

References 23 publications

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“…Asterisks indicate statistical significance as determined by Student's t test (*p \ 0.05) for D, E, F, and one-way ANOVA and Tukey's multiple-comparison test (***p \ 0.001) for H stronger effect than administration of either alone. We previously showed that HRW, but not HCA, was effective in a Parkinson's disease rat model; however, by inducing a blood concentration of H 2 similar to that produced by HRW, intermittent administration of HCA resulted in intermediate effects between HRW and the normal HCA treatment [12]. This result suggests that H 2 bioactivity depends not only on its blood concentration but also on changes in the H 2 Fig.…”

Section: Discussionmentioning

confidence: 83%

“…We have previously investigated the differences between HRW and HCA using Parkinson's disease model rats [12]; however, neither other report has compared the therapeutic effects between HRW and HCA nor demonstrated their different molecular actions. To explore this, we selected nine genes from Supplementary Fig.…”

Section: Hrw and Hca Additively Alter Gene Expression In Liver And Otmentioning

confidence: 99%

“…The rats were either administered 4 ml of HRW into the stomach through a gastric tube or exposed to 2 % H 2 gas/98 % air (HCA) in a plastic cage. Meanwhile, 3-week continuous administration of HCA to mice was performed as described previously with slight modification [12]. Mice in standard plastic cages were placed in a 60-L air-tight acrylic chamber, which was continuously supplied with 10 L/min HCA.…”

Section: Animals and H 2 Administrationmentioning

confidence: 99%

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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: 83%

Section: Hrw and Hca Additively Alter Gene Expression In Liver And Otmentioning

confidence: 99%

Section: Animals and H 2 Administrationmentioning

confidence: 99%

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

et al. 2015

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“…Hydrogen-saturated water (1.6 ppm or 0.8 mM) was prepared daily, using an AquelaBlue electrolysis instrument (Miz Co Ltd, Fujisawa, Japan). 11 Rats were housed ad libitum to food and water, including hydrogen-saturated water in group H, under a natural day/night cycle. Rats were acclimated for 7 days before any experimental procedures were conducted.…”

Section: Methods Animal Modelsmentioning

confidence: 99%

Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects

Kishimoto

Kato

Ito

et al. 2015

The Journal of Thoracic and Cardiovascular Surgery

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“…Hydrogen gas (H 2 ) was recently revealed as a signaling modulator with multiple biological functions in clinical trails (Ohsawa et al, 2007;Itoh et al, 2009;Ito et al, 2012). It was previously found that a hydrogenase system could generate H 2 in bacteria and green algae (Meyer, 2007;Esquível et al, 2011).…”

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confidence: 99%

Reactive Oxygen Species-Dependent Nitric Oxide Production Contributes to Hydrogen-Promoted Stomatal Closure in Arabidopsis

et al. 2014

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The signaling role of hydrogen gas (H 2 ) has attracted increasing attention from animals to plants. However, the physiological significance and molecular mechanism of H 2 in drought tolerance are still largely unexplored. In this article, we report that abscisic acid (ABA) induced stomatal closure in Arabidopsis (Arabidopsis thaliana) by triggering intracellular signaling events involving H 2 , reactive oxygen species (ROS), nitric oxide (NO), and the guard cell outward-rectifying K + channel (GORK). ABA elicited a rapid and sustained H 2 release and production in Arabidopsis. Exogenous hydrogen-rich water (HRW) effectively led to an increase of intracellular H 2 production, a reduction in the stomatal aperture, and enhanced drought tolerance. Subsequent results revealed that HRW stimulated significant inductions of NO and ROS synthesis associated with stomatal closure in the wild type, which were individually abolished in the nitric reductase mutant nitrate reductase1/2 (nia1/2) or the NADPH oxidasedeficient mutant rbohF (for respiratory burst oxidase homolog). Furthermore, we demonstrate that the HRW-promoted NO generation is dependent on ROS production. The rbohF mutant had impaired NO synthesis and stomatal closure in response to HRW, while these changes were rescued by exogenous application of NO. In addition, both HRW and hydrogen peroxide failed to induce NO production or stomatal closure in the nia1/2 mutant, while HRW-promoted ROS accumulation was not impaired. In the GORK-null mutant, stomatal closure induced by ABA, HRW, NO, or hydrogen peroxide was partially suppressed. Together, these results define a main branch of H 2 -regulated stomatal movement involved in the ABA signaling cascade in which RbohF-dependent ROS and nitric reductase-associated NO production, and subsequent GORK activation, were causally involved.

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Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats

Cited by 93 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 ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects

Reactive Oxygen Species-Dependent Nitric Oxide Production Contributes to Hydrogen-Promoted Stomatal Closure in Arabidopsis

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