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Ōsaka, Japan

Spulber S.,Karolinska Institutet | Edoff K.,Karolinska Institutet | Hong L.,Karolinska Institutet | Morisawa S.,Nihon Trim Co Ltd. | And 2 more authors.
PLoS ONE | Year: 2012

Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen. © 2012 Spulber et al. Source


Kinjo T.,Kyushu University | Ye J.,Kyushu University | Ye J.,Xiamen University | Yan H.,Kyushu University | And 7 more authors.
Cytotechnology | Year: 2012

It has been demonstrated that hydrogen peroxide (H 2O 2) is directly associated with elevated matrix metalloproteinase-2 (MMP-2) expression in several cell lines. Electrochemically reduced water (ERW), produced near the cathode during electrolysis, and scavenges intracellular H 2O 2 in human fibrosarcoma HT1080 cells. RT-PCR and zymography analyses revealed that when HT1080 cells were treated with ERW, the gene expression of MMP-2 and membrane type 1 MMP and activation of MMP-2 was repressed, resulting in decreased invasion of the cells into matrigel. ERW also inhibited H 2O 2-induced MMP-2 upregulation. To investigate signal transduction involved in MMP-2 downregulation, mitogen-activated protein kinase (MAPK)-specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (MAPK/extracellular regulated kinase kinase 1 inhibitor) and c-Jun NH 2-terminal kinase inhibitor II, were used to block the MAPK signal cascade. MMP-2 gene expression was only inhibited by SB203580 treatment, suggesting a pivotal role of p38 MAPK in regulation of MMP-2 gene expression. Western blot analysis showed that ERW downregulated the phosphorylation of p38 both in H 2O 2-treated and untreated HT1080 cells. These results indicate that the inhibitory effect of ERW on tumor invasion is due to, at least in part, its antioxidative effect. © Springer Science+Business Media B.V. 2012. Source


Yan H.,Kyushu University | Kinjo T.,Kyushu University | Tian H.,Kyushu University | Hamasaki T.,Kyushu University | And 3 more authors.
Bioscience, Biotechnology and Biochemistry | Year: 2011

Electrolyzed reduced water (ERW) contains a large amount of molecular hydrogen and asmall amount of Pt nanoparticles (Pt NPs). We have found that ERW significantly extended the lifespan of Caenorhabditis elegans in a novel culture medium designated Water Medium.In this study, we found that synthetic Pt NPs at ppb levels significantly extended the nematode lifespan and scavenged reactive oxygen species (ROS) in the nematode induced by paraquat treatment. In contrast, a high concentration of dissolved molecular hydrogen had no significant effect on the lifespan of the nematode. These findings suggest that the Pt NPs in ERW, rather than the molecular hydrogen, extend the longevity of the nematode, at least partly by scavenging ROS. Source


Nakanishi H.,Kyushu University | Hamasaki T.,Kyushu University | Kinjo T.,Kyushu University | Yan H.,Kyushu University | And 4 more authors.
Nano Biomedicine and Engineering | Year: 2013

Prolonged exposure to excessive reactive oxygen species (ROS) increases risk factorsfor many diseases. Therefore, elimination of ROS as well as prevention of its production becomes critically important. In the present study, we evaluated the levels of cytotoxicity and ROS scavenging activity induced by synthetic platinum nanoparticles (PtNPs). Average size of synthesized PtNPs was 2.2 nm. Synthetic PtNPs were found to scavenge both induced and endogenous H2O2 significantly in L6 rat skeletal muscle cells at a very low concentration (10-2 mg/l). To investigate the mechanism of action, the hierarchical oxidative stress model was used as an experimental model. To evaluate this possibility, we assessedglutathione concentration and gene levels of several antioxidant enzymes in PtNPs-treated(10-3-10 mg/l) L6 cells. Reduced glutathione (GSH) was increased in the range of 10-3-1 mg/l, but not in the 10 mg/l PtNP-treated cells. The GSH/GSSG ratio increased significantly at 1 mg/l and decreased in the 10 mg/l PtNPtreated cells. Most of the gene transcripts for oxidative stress inducible heme oxygenase-1 (HO-1), glutathione reductase (GR), copper-zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and catalase were increased significantly by PtNPs at 10-1-10 mg/l.Such upregulatory effects induced by synthetic PtNPs at high concentrations (1-10 mg/l) in L6 cells can be explained by the hierarchical oxidative stress model. However, the cellular responses induced by low levels (10-3-10-2 mg/l) of PtNPs could not be fully explained by this model. © 2013 H. Nakanishi et al. Source


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Nihon Trim Co. | Date: 2006-01-17

Drinking water containing electrolytes; drinking water containing an alkaline solution; and/or ionized drinking water.

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