Publications (18)16.84 Total impact
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Article: Suppressive effects of electrochemically reduced water on matrix metalloproteinase-2 activities and in vitro invasion of human fibrosarcoma HT1080 cells.
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ABSTRACT: It has been demonstrated that hydrogen peroxide (H(2)O(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(2)O(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(2)O(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(2)O(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.Cytotechnology 06/2012; 64(3):357-71. · 1.21 Impact Factor -
Article: Erratum to: Suppressive effects of natural reduced waters on alloxan-induced apoptosis and type 1 diabetes mellitus.
Cytotechnology 05/2012; 64(3):299. · 1.21 Impact Factor -
Article: Suppressive effects of natural reduced waters on alloxan-induced apoptosis and type 1 diabetes mellitus.
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ABSTRACT: Insulin-producing cells express limited activities of anti-oxidative enzymes. Therefore, reactive oxygen species (ROS) produced in these cells play a crucial role in cytotoxic effects. Furthermore, diabetes mellitus (DM) development is closely linked to higher ROS levels in insulin-producing cells. Hita Tenryosui Water(®) (Hita T. W., Hita, Japan) and Nordenau water (Nord. W., Nordenau, Germany), referred to as natural reduced waters (NRWs), scavenge ROS in cultured cells, and therefore, might be a possibility as an alternative to conventional pharmacological agents against DM. Therefore, this study aimed to investigate the role of NRWs in alloxan (ALX)-induced β-cell apoptosis as well as in ALX-induced diabetic mice. NRWs equally suppressed DNA fragmentation levels. Hita T. W. and Nord. W. ameliorated ALX-induced sub-G(1) phase production from approximately 40% of control levels to 8.5 and 11.8%, respectively. NRWs restored serum insulin levels (p < 0.01) and reduced blood glucose levels (p < 0.01) in ALX-induced mice. Hita T. W. restored tissue superoxide dismutase (SOD) (p < 0.05) activity but not tissue catalase activity. Hita T. W. did not elevate SOD or catalase activity in HIT-T15 cells. Nord. W. restored SOD (p < 0.05) and catalase (p < 0.05) activity in both cultured cells and pancreatic tissue to normal levels. Even though variable efficacies were observed between Hita T. W. and Nord. W., both waters suppressed ALX-induced DM development in CD-1 male mice by administering NRWs for 8 weeks. Our results suggest that Hita T. W. and Nord. W. protect against ALX-induced β-cell apoptosis, and prevent the development of ALX-induced DM in experimental animals by regulating ALX-derived ROS generation and elevating anti-oxidative enzymes. Therefore, the two NRWs tested here are promising candidates for the prevention of DM development.Cytotechnology 12/2011; 64(3):281-97. · 1.21 Impact Factor -
Article: Anti-diabetes effect of water containing hydrogen molecule and Pt nanoparticles.
BMC proceedings 11/2011; 5 Suppl 8:P18. -
Article: The neuroprotective effects of electrolyzed reduced water and its model water containing molecular hydrogen and Pt nanoparticles.
BMC proceedings 11/2011; 5 Suppl 8:P69. -
Article: Mechanism of the lifespan extension of Caenorhabditis elegans by electrolyzed reduced water--participation of Pt nanoparticles.
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ABSTRACT: Electrolyzed reduced water (ERW) contains a large amount of molecular hydrogen and a small 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.Bioscience Biotechnology and Biochemistry 07/2011; 75(7):1295-9. · 1.28 Impact Factor -
Article: Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus.
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ABSTRACT: Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing β-cells. Here, we showed that electrolyzed reduced water prevented alloxan-induced DNA fragmentation and the production of cells in sub-G1 phase in HIT-T15 pancreatic β-cells. Blood glucose levels in alloxan-induced type 1 diabetes model mice were also significantly suppressed by feeding the mice with electrolyzed reduced water. These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic β-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.Cytotechnology 11/2010; 63(2):119-31. · 1.21 Impact Factor -
Article: Extension of the lifespan of Caenorhabditis elegans by the use of electrolyzed reduced water.
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ABSTRACT: Electrolyzed reduced water (ERW) has attracted much attention because of its therapeutic effects. In the present study, a new culture medium, which we designated Water medium, was developed to elucidate the effects of ERW on the lifespan of Caenorhabditis elegans. Wild-type C. elegans had a significantly shorter lifespan in Water medium than in conventional S medium. However, worms cultured in ERW-Water medium exhibited a significantly extended lifespan (from 11% to 41%) compared with worms cultured in ultrapure water-Water medium. There was no difference between the lifespans of worms cultured in ERW-S medium and ultrapure water-S medium. Nematodes cultured in ultrapure water-Water medium showed significantly higher levels of reactive oxygen species than those cultured in ultrapure water-S medium. Moreover, ERW-Water medium significantly reduced the ROS accumulation induced in the worms by paraquat, suggesting that ERW-Water medium extends the longevity of nematodes at least partly by scavenging ROS.Bioscience Biotechnology and Biochemistry 10/2010; 74(10):2011-5. · 1.28 Impact Factor -
Chapter: Growth Suppression of HL60 and L6 Cells by Atomic Hydrogen
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ABSTRACT: We previously reported electrolyzed reduced water (ERW) which produced near the cathode by electrolysis has a reductive activity. We also revealed that ERW contains both molecular hydrogen and platinum nanoparticles (Pt nps) derived from platinum-coated titanium electrodes. Pt nps have catalysis activity converting molecular hydrogen to atomic hydrogen. Thus, we regard a solution containing both dissolved hydrogen and Pt nps as a model water of ERW (H2/Pt nps solution), and then we tried to examine the physiological effects of H2/Pt nps solution. To our knowledge, there is no report on physiological effects of H2/Pt nps solution. Here, we report the effects of H2/Pt nps solution on the growth of promyelocytic cell line, HL60 cells and myogenic cell lines, L6 cells. H2/Pt nps solution suppressed cell growth in the presence of both hydrogen and Pt nps in a dose dependent manner. The result of sub-G1 analysis suggests that H2/Pt nps solution induces apoptosis in both HL60 and L6 cells. The labeled Pt nps in HL60 cells were detected in liposome, suggesting Pt nps is incorporated by endocytosis. These results suggest that atomic hydrogen catalyzed by Pt nps induced significant cell growth suppression and atomic hydrogen may be one of new signal of cell function. KeywordsPlatinum-Nanoparticles-Apoptosis-Atomic hydrogen-Antioxidant-ROS06/2010: pages 323-325; -
Chapter: Anti-Diabetes Effects of Hita Tenryou-Sui Water®, a Natural Reduced Water
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ABSTRACT: It has been reported that a natural reduced water derived from a deep well in Japan (trademark, Hita Tenryousui water®; Nakanoshima, Hita city, Oita, Japan) scavenged intracellular reactive oxygen species (ROS) and protected a hamster pancreas β cell line HIT-T15 from oxidative damage by alloxan, a type 1 diabetes inducer. Here we demonstrated that the water also suppressed the fasted blood glucose levels of the alloxan-induced type 1-diabetes mice. Protein tyrosine phosphatase (PTP) is a redox-regulatable signal enzyme and activation of PTP in Type 2-diabetes patients is noted to be responsible to inactivation of insulin receptor. Hita Tenryousui water® suppressed the PTP activity, leading the activation of insulin receptor. This water stimulated glucose uptake into myotubes and showed a tendency to improve the impaired sugar tolerance of Type 2-diabetes model mice. An open clinical test of Hita Tenryousui water® against 65 patients with hyperglycemia and 50 patients with hyperlipemia for 2 months resulted in significant improvement of impaired blood sugar, plasma triglycerol and total cholesterol levels (P<0.05). These facts suggest that daily intake of natural reduced water will be beneficial to prevent and improve diabetes mellitus. KeywordsDiabetes-Hita tenryosui water-Natural reduced water-Reactive oxygen species-Protein tyrosine phosphatase06/2010: pages 307-313; -
Chapter: Suppressive Effect of ERW on Lipid Peroxidation and Plasma Triglyceride Level
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ABSTRACT: Electrolyzed reduced water (ERW) containing hydrogen molecules and Pt nanoparticles is expected as a new antioxidant. Thiobarbituric acid reactive substances (TBARS) assay revealed that ERW had an inhibitory effect on the oxidation of low-density lipoproteins (LDL). In addition, ERW significantly suppressed LDL oxidation in the medium cultured J.774.A1 macrophage like cells. ERW inhibited Cu2+ ion-catalyzed oxidation of LDL ex vivo. ERW lowered lipid peroxide level in blood red cells and plasma triglyceride in rats fed a basal diet containing 2% cholesterol. These results suggest that ERW has anti-LDL oxidation and anti-hyperlipidemia effects. KeywordsElectrolyzed reduced water-Hyperlipidemia-LDL-Oxidation06/2010: pages 315-321; -
Chapter: “Nordenau Phenomenon” – Application of Natural Reduced Water to Therapy
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ABSTRACT: This prospective observation study examines changes in the relevant tests parameters of 411 diabetes patients drinking natural reduced water from the “Nordenau Spring”, as well as a correlation of these changes with the fluctuation of the reactive oxygen species in their blood. The average age of the test persons is 71.5 years and the daily consumption of reduced water is as much as two liters. The average duration of stay in Nordenau is 6 days. The diagnostic parameters such as blood sugar, HbA1c, cholesterol, LDL, HDL, and serum creatinine concentration are tested twice - at the beginning and at the end of the participants stay in Nordenau. Additionally a random sample of reactive oxygen species in the blood of 136 patients is taken in order to find out its possible causal connections to the diabetes relevant test parameters.HbA1c has been considered as the substantial test parameter in order to break down the whole group into responder and non-responder categories. One hundred and eighty six tested persons or 45% of the total have been assigned to the responder group, meaning that the patients’ HbA1c and blood sugar improved significantly. Furthermore we evaluated among the responder group a portion of patients who in the same time significantly improved their cholesterol, LDL, HDL and serum creatinine concentration average value. This stage of our follow up study regarding type II diabetes patients estimates number needed to treat on four patients in order to achieve the significant improvement of all diabetes relevant parameters. This is a very good quotient; moreover it could be achieved entirely without side effects. The significant improvement of diabetes relevant parameters like blood fats and creatinine can be also beneficial to other diseases like high blood pressure, circulatory disturbance, renal insufficiency or atherosclerotic dementia. In addition to our previous tests, we administered to a random sample group of 136 patients a blood free oxygen radicals test (FORT). The test resulted in a decrease of the ROS of 70.6% of the group or 96 patients. Taking account of the fact that the natural reduced water as well as the electrolyzed reduced water obviously improves in a very short time and entirely without side effects very important metabolic parameters, it can be said that the reduced water shall be considered a useful supplement to the usual orthodox medication of ROS-associated diseases. KeywordsDiabetes-Noredenau water-reactive oxygen species-reduced water08/2009: pages 265-271; -
Article: Kinetic analysis of superoxide anion radical-scavenging and hydroxyl radical-scavenging activities of platinum nanoparticles.
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ABSTRACT: There are few reports on the physiological effects of metal nanoparticles (nps), especially with respect to their functions as scavengers for superoxide anion radical (O2(.-)) and hydroxyl radical (.OH). We tried to detect the scavenging activity of Pt nps using a hypoxanthine-xanthine oxidase system for O2(.-) and using a Fenton and a UV/H2O2 system for .OH. Electron spin resonance analysis revealed that 2 nm particle size Pt nps have the ability to scavenge O2(.-) and .OH. The calculated rate constant for the O2(.-)-scavenging reaction was 5.03 +/- 0.03 x 10(7) M (-1) s (-1). However, the analysis of the Fenton and UV/H 2O 2 system in the presence of Pt nps suggested that the .OH-scavenging reaction cannot be determined in both systems. Among particle sizes tested from 1 to 5 nm, 1 nm Pt nps showed the highest O2(.-)-scavenging ability. Almost no cytotoxicity was observed even after adherent cells (TIG-1, HeLa, HepG2, WI-38, and MRC-5) were exposed to Pt nps at concentrations as high as 50 mg/L. Pt nps scavenged intrinsically generated reactive oxygen species (ROS) in HeLa cells. Additionally, Pt nps significantly reduced the levels of intracellular O2(.-) generated by UVA irradiation and subsequently protected HeLa cells from ROS damage-induced cell death. These findings suggest that Pt nps may be a new type of antioxidant capable of circumventing the paradoxical effects of conventional antioxidants.Langmuir 08/2008; 24(14):7354-64. · 4.19 Impact Factor -
Article: Inhibitory effect of electrolyzed reduced water on tumor angiogenesis.
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ABSTRACT: Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Tumor cells are exposed to higher oxidative stress compared to normal cells. Numerous reports have demonstrated that the intracellular redox (oxidation/reduction) state is closely associated with the pattern of VEGF expression. Electrolyzed reduced water (ERW) produced near the cathode during the electrolysis of water scavenged intracellular H(2)O(2) and decreased the release of H(2)O(2) from a human lung adenocarcinoma cell line, A549, and down-regulated both VEGF transcription and protein secretion in a time-dependent manner. To investigate the signal transduction pathway involved in regulating VEGF expression, mitogen-activated kinase (MAPK) specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (ERK1/2 inhibitor) and JNKi (c-Jun N-terminal protein kinase inhibitor) were applied. The results showed that only PD98059 blocks VEGF expression, suggesting an important role for ERK1/2 in regulating VEGF expression in A549 cells. As well, ERW inhibited the activation of extracellular signal-regulated kinase (ERK) in a time-dependent manner. Co-culture experiments to analyze in vitro tubule formation assay revealed that A549 cell-derived conditioned medium significantly stimulated the formation of vascular tubules in all analyzed parameters; tubule total area, tubule junction, number of tubules, and total tubule length. ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.Biological & Pharmaceutical Bulletin 01/2008; 31(1):19-26. · 1.66 Impact Factor -
Article: Catalyser-21(TM), a mineral water derived from leaf soil, inhibits tumor cell invasion and angiogenesis.
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ABSTRACT: Catalyser-21(TM) is a mineral water derived from natural leaf soil containing various organic and inorganic substances. Previous reports suggested a possibility that Catalyser-21(TM) has antioxidative potential and could inhibit angiogenesis and cancer cell invasiveness. Angiogenesis is a prerequisite for cancer cells to spread to surrounding tissues. Vascular endothelial growth factor (VEGF) is a major angiogenic factor in the formation of blood capillaries by cancer cells to supply nutrients and oxygen for their sustained growth. Matrix metalloproteinase-2 (MMP-2) is another key enzyme for cancer cell metastasis. To assess the anti-angiogenic activity of Catalyser-21(TM), we first examined cell viability using a human cervical cancer cell line, HeLa, and a fibrosarcoma cell line, HT1080. The results showed that Catalyser-21(TM) decreased the viability of both cell types in a dose-dependent manner. Flow cytometric analysis proved that Catalyser-21(TM) scavenges intracellular H(2)O(2) in both cell types. RT-PCR demonstrated that both VEGF and MMP-2 gene transcription was suppressed after Catalyser-21(TM) treatment. Both Matrigel and tubule formation experiments showed an effect of Catalyser-21(TM). These results suggest that Catalyser-21(TM) has potential as an anti-tumor agent.Cytotechnology 01/2008; 55(2-3):61-70. · 1.21 Impact Factor -
Article: Electrolyzed Reduced Water Supplemented with Platinum Nanoparticles Suppresses Promotion of Two-stage Cell Transformation.
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ABSTRACT: In the two-stage cell transformation theory, cancer cells first receive initiation, which is mainly caused by DNA damage, and then promotion, which enhances transformation. Murine Balb/c 3T3 cells are widely used for transformation experiments because they lose contact inhibition ability when transformed. Electrolyzed reduced water (ERW), which is produced near a cathode during electrolysis of water, is an alkaline drinking water that is beneficial to health. ERW contains a high concentration of dissolved hydrogen and scavenge reactive oxygen species (ROS), along with a small amount of platinum (Pt) nanoparticles (Pt nps) derived from Pt-coated titanium electrodes. Pt nps stably disperse in aqueous solution for a long time, and convert hydrogen molecules to active hydrogen (atomic hydrogen) that can scavenge ROS. Therefore, ERW supplemented with synthesized Pt nps is a model strong reduced water. This is the first report that ERW supplemented with synthesized Pt nps strongly prevents transformation of Balb/c 3T3 cells. ERW was prepared by electrolysis of 0.002 M NaOH solution using a batch-type electrolysis device. Balb/c 3T3 cells were treated with 3-methyl cholanthrene (MCA) as an initiation substance, followed by treatment with phorbol-12-myristate-13-acetate (PMA) as a promotion substance. MCA/PMA-induced formation of a transformation focus was strongly suppressed by ERW supplemented with Pt nps but not by ERW or Pt nps individually. ERW supplemented with Pt nps suppressed transformation at the promoter stage, not at initiation, suggesting that ERW supplemented with Pt nps suppressed the PMA-induced augmentation of intracellular ROS. ERW supplemented with Pt nps is a potential new antioxidant against carcinogenesis.Cytotechnology 02/2005; 47(1-3):97-105. · 1.21 Impact Factor -
Article: Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: Scavenging effect against reactive oxygen species.
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ABSTRACT: Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules, resulting in many diseases. Reduced water (RW) such as hydrogen-rich electrolyzed reduced water and natural reduced waters like Hita Tenryosui water in Japan and Nordenau water in Germany that are known to improve various diseases, could protect a hamster pancreatic beta cell line, HIT-T15 from alloxan-induced cell damage. Alloxan, a diabetogenic compound, is used to induce type 1 diabetes mellitus in animals. Its diabetogenic effect is exerted via the production of ROS. Alloxan-treated HIT-T15 cells exhibited lowered viability, increased intracellular ROS levels, elevated cytosolic free Ca(2+) concentration, DNA fragmentation, decreased intracellular ATP levels and lowering of glucose-stimulated release of insulin. RW completely prevented the generation of alloxan-induced ROS, increase of cytosolic Ca(2+) concentration, decrease of intracellular ATP level, and lowering of glucose-stimulated insulin release, and strongly blocked DNA fragmentation, partially suppressing the lowering of viability of alloxan-treated cells. Intracellular ATP levels and glucose-stimulated insulin secretion were increased by RW to 2-3.5 times and 2-4 times, respectively, suggesting that RW enhances the glucose-sensitivity and glucose response of beta-cells. The protective activity of RW was stable at 4 degrees C for over a month, but was lost by autoclaving. These results suggest that RW protects pancreatic beta-cells from alloxan-induced cell damage by preventing alloxan-derived ROS generation. RW may be useful in preventing alloxan-induced type 1-diabetes mellitus.Cytotechnology 12/2002; 40(1-3):139-49. · 1.21 Impact Factor -
Chapter: Electrolyzed Reduced Water Prolongs Caenorhabditis elegans’ Lifespan
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ABSTRACT: Electrolyzed reduced water (ERW) has been reported to scavenge intracellular reactive oxygen species (ROS) and improve oxidative stress-related diseases. A new culture method using water medium for Caenorhabditis elegans (C.elegans) was developed in order to elucidate the effects of ERW on the lifespan of nematode. ERW significantly extended the lifespan of C. elegans and alleviated the ROS Level in nematode in water medium, but not in conventional S-medium. These results suggested that the nematode lifespan was elongated at least in part by ROS-scavenging action of ERW. KeywordsC. Elegans-Electrolyzed reduced water-Lifespan-Nematode-Reactive oxygen species01/1970: pages 289-293;
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1970–2012
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Kyushu University
- • Faculty of Agriculture
- • Graduate School of Systems Life Sciences
Fukuoka-shi, Fukuoka-ken, Japan
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