Protective mechanism of reduced water against alloxan-induced pancreatic β-cell damage: Scavenging effect against reactive oxygen species

Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Japan.
Cytotechnology (Impact Factor: 1.75). 12/2002; 40(1-3):139-49. DOI: 10.1023/A:1023936421448
Source: PubMed


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.

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Available from: Yoshinori Katakura, Oct 13, 2015
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    • "On the other hand, AERW exhibited a decreased suppressive effect on invasion (Fig. 1b), indicating that active substances in ERW may be heatunstable or volatile. These results were consistent with those reported previously (Li et al. 2002). ERW mainly contains Pt nanoparticles and hydrogen molecules , and is likely to contain Pt nanoparticles with adsorbed active hydrogen converted from hydrogen molecules by the catalytic action of Pt nanoparticles (Minaev and A ˚ gren 1999; Roucoux et al. 2002; Isobe et al. 2003; Li et al. 2011; Supplementary material Table 3; Shirahata et al. 2012). "
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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. DOI:10.1007/s10616-012-9469-7 · 1.75 Impact Factor
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    • "Synthesized Pt nanoparticles also activated hydrogen molecules to hydrogen atoms by their catalysis action. Natural reduced waters (NRWs) such as Hita Tenryosui water in Japan and Nordenau water in Germany also exhibited ROS-scavenging activities (Li et al., 2002). We propose an active hydrogen mineral nanoparticles hypothesis of reduced water to explain the mechanism of action of both ERW and NRW (Fig. 3). "
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    ABSTRACT: In Japan, research on functional water, especially on reduced water, is developing at a rapid pace. Reduced water such as electrochemically reduced water and natural reduced water can scavenge reactive oxygen species in cultured cells. Reduced waters are expected to have preventive and positive effects on oxidative stress-related diseases such as diabetes, cancer, arteriosclerosis, neurodegenerative diseases, and side effects of hemodialysis. It has been suggested that the active agents in reduced water are hydrogen (atoms and molecules), mineral nanoparticles, and mineral nanoparticle hydrides.
    Trends in Food Science & Technology 02/2012; 23(2). DOI:10.1016/j.tifs.2011.10.009 · 4.65 Impact Factor
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    • "The present in vitro and in vivo studies showed that the mice fed with ERW throughout the experimental period had a reduced incidence of diabetes, which was accompanied by improved diabetic indexes. Therefore, our results together with the previous report by Li et al. suggest that b-cell loss occurring gradually over several years could be prevented or retarded by taking ERW for a long period of time (Li et al. 2002). "
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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. DOI:10.1007/s10616-010-9317-6 · 1.75 Impact Factor
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