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Kudo N, Kouno R, Shibayama Y. SLC25A40 Facilitates Anticancer Drug Resistance in Human Leukemia K562 Cells. Biol Pharm Bull 2023; 46:1304-1309. [PMID: 37407483 DOI: 10.1248/bpb.b23-00293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
The chronic myelogenous leukemia cell line, K562/ADM is derived from the K562 cell line, which is resistant to doxorubicin (alias, adriamycin: ADM). P-glycoprotein levels are significantly higher in K562/ADM cells than in K562 cells. The overexpression of p-glycoprotein has been shown to cause drug resistance. Therefore, the present study investigated a novel mechanism underlying the drug resistance of K562/ADM cells. A gene ontology analysis demonstrated that the expression of solute carrier (SLC)-mediated transmembrane transport genes was significantly higher in K562/ADM cells than in K562 cells. The expression level of a member of the SLC family, SLC25A40 was higher in K562/ADM cells than in K562 cells. SLC25A40 is located near the ABCB1 gene. A real-time PCR analysis showed that the expression of SLC25A40, ABCB4, and ADAM22 was up-regulated. These genes are located close to SLC25A40. The down-regulation of SLC25A40 significantly decreased the mitochondrial concentration of glutathione and cell proliferation. Collectively, the present results demonstrated that the expression of SLC25A40 was up-regulated in K562/ADM cells, which enhanced to cell proliferation, and that the expression of SLC25A40 affected drug resistance to ADM.
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Affiliation(s)
- Nodoka Kudo
- Department of Drug Formulation, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
| | - Rikuma Kouno
- Department of Drug Formulation, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
| | - Yoshihiko Shibayama
- Department of Drug Formulation, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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Electrolyzed-Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects. Int J Mol Sci 2022; 23:ijms232314750. [PMID: 36499079 PMCID: PMC9738607 DOI: 10.3390/ijms232314750] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/16/2022] [Accepted: 11/18/2022] [Indexed: 11/29/2022] Open
Abstract
Numerous benefits have been attributed to alkaline-electrolyzed-reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured to be due to the intrinsic properties of ERW (e.g., negative oxidation-reduction potential (ORP), alkaline pH, H2 gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, free electrons, active hydrogen, mineral hydrides). The associated pseudoscientific marketing has contributed to the reluctance of mainstream science to accept ERW as having biological effects. Finally, through many in vitro and in vivo studies, each one of these propositions was examined and refuted one-by-one until it was conclusively demonstrated that H2 was the exclusive agent responsible for both the negative ORP and the observed therapeutic effects of ERW. This article briefly apprised the history of ERW and comprehensively reviewed the sequential research demonstrating the importance of H2. We illustrated that the effects of ERW could be readily explained by the known biological effects of H2 and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H2 concentration of ERW should be measured to ensure it is comparable to those used in clinical studies.
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Nakamura K. Electrolyzed water produced using carbon electrodes promotes the proliferation of normal cells while inhibiting cancer cells. Drug Discov Ther 2022; 16:191-195. [PMID: 35989283 DOI: 10.5582/ddt.2022.01045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We previously developed electrolyzed water (EW) using carbon electrodes and estimated its ability to inhibit the proliferation of human cervical carcinoma HeLa cells. In this study, we found that EW-containing media could not only inhibit HeLa cell proliferation, but were also capable of promoting the proliferation of normal human dermal fibroblasts (NHDF). In addition, the developed EW could reduce cytochrome c, as demonstrated by the cytochrome c reduction assay. Interestingly, EW with a greater pH, which was unable to inhibit HeLa cell proliferation, completely lost the ability to reduce cytochrome c. Our results indicate that EW has opposite effects on cancer and normal cell proliferation and has the ability to reduce cytochrome c. Based on our findings, we suggest the possibility that the reducing capacity of our developed EW may be involved in the significant inhibition of HeLa cell proliferation.
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Affiliation(s)
- Kyoko Nakamura
- Pharmaceutical Research and Technology Institute, Kindai University, Osaka, Japan
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Chilicka K, Rogowska AM, Szyguła R. Effects of Topical Hydrogen Purification on Skin Parameters and Acne Vulgaris in Adult Women. Healthcare (Basel) 2021; 9:144. [PMID: 33535651 PMCID: PMC7912839 DOI: 10.3390/healthcare9020144] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/23/2021] [Accepted: 01/29/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Acne vulgaris is a prevalent dermatological disease characterized by skin eruptions, which may decrease the sufferer's quality of life. Hydrogen purification treatment is a new procedure used in cosmetology to improve the skin parameters of the face. This study examined the effectiveness of hydrogen purification treatment to improve women's skin conditions with regard to acne vulgaris. METHODS In this study, 30 women participated who suffered from a high level of sebum and acne. The control group was comprised of 30 healthy women with a low level of sebum. The Hellgren-Vincent Scale and Derma Unit SSC 3 device were used to assess acne vulgaris severity and skin properties, respectively. Four hydrogen purification sessions were carried out at 7-day intervals, using the Hebe Hydrogenium+ generating alkaline water. RESULTS At baseline and 7 and 14 days after finishing the series of treatments, the levels of oiliness, moisture, and skin pH were tested. The main effects of treatment were significant in the following parameters: pH around the bottom lip, moisture between the eyebrows and around the nose, and oily skin in all three face sites. CONCLUSIONS The level of sebum decreased and moisture levels increased during hydrogen purification. Topical hydrogen purification is an effective and safe treatment for acne vulgaris.
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Affiliation(s)
- Karolina Chilicka
- Department of Health Sciences, Institute of Health Sciences, University of Opole, 45-060 Opole, Poland;
| | - Aleksandra M. Rogowska
- Department of Social Sciences, Institute of Psychology, University of Opole, 45-052 Opole, Poland;
| | - Renata Szyguła
- Department of Health Sciences, Institute of Health Sciences, University of Opole, 45-060 Opole, Poland;
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Outcomes Assessment of Sustainable and Innovatively Simple Lifestyle Modification at the Workplace - Drinking Electrolyzed-Reduced Water (OASIS-ERW): A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel) 2020; 9:antiox9070564. [PMID: 32605142 PMCID: PMC7402115 DOI: 10.3390/antiox9070564] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 05/30/2020] [Accepted: 05/30/2020] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress has been associated with many diseases as well as aging. Electrolyzed-reduced water (ERW) has been suggested to reduce oxidative stress and improve antioxidant potential. This study investigated the effects of drinking ERW on biomarkers of oxidative stress and health-related indices in healthy adults. We conducted a randomized, double-blind, placebo-controlled clinical trial on 65 participants, who were allocated into two groups. Of these, 61 received intervention (32 with ERW and 29 MW [mineral water]). All participants were instructed to drink 1.5 L/day of ERW or MW for eight weeks. Biomarkers of oxidative stress and health-related indices were assessed at baseline as well as after 4 weeks and 8 weeks of intervention. Of the primary outcome variables assessed, diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential showed a significant interaction between the groups and time, with d-ROMs levels significantly decreased at 8 weeks in ERW compared to those in MW. Among the secondary outcome variables, total, visceral, and subcutaneous fat mass significantly changed over time, with a significant association observed between the groups and time. Thus, daily ERW consumption may be a potential consideration for a sustainable and innovatively simple lifestyle modification at the workplace to reduce oxidative stress, increase antioxidant potential, and decrease fat mass.
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Yang WE, Ho YC, Tang CM, Hsieh YS, Chen PN, Lai CT, Yang SF, Lin CW. Duchesnea indica extract attenuates oral cancer cells metastatic potential through the inhibition of the matrix metalloproteinase-2 activity by down-regulating the MEK/ERK pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 63:152960. [PMID: 31280137 DOI: 10.1016/j.phymed.2019.152960] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/14/2019] [Accepted: 05/16/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND Duchesnea indica (Andr.) Focke, an herb in folk medicine used extensively in traditional Chinese medicine, has cytostatic properties as well as antioxidant and antimetastasis activities in various cancer cells. However, the effects and underlying mechanisms of Duchesnea indica extracts (DIEs) on human oral squamous cell carcinoma (OSCC) metastases remain unclear. PURPOSE In this study, we posit the hypothesis that DIE possesses antimetastatic effects on human OSCC cells. METHODS The effects of DIE on cell viability, motility, migration, and invasion were investigated. Gelatin zymography, Western blotting, migration and invasion assays were used to further study the underlying mechanisms involved in the antimetastatic effects of DIE in OSCC cells. RESULTS The results from MTT assay revealed that DIE did not affect the cell viability of OSCC cells. Moreover, DIE significantly attenuated OSCC cells' motility, migration, and invasion by reducing the MMP-2 protein expression and MMP-2 activity in a dose-dependent manner. In addition, DIE reduced the phosphorylation of both ERK1/2 and its upstream kinase but had no effect on the phosphorylation of p38 and JNK. CONCLUSION DIE triggers the antimetastatic activity in OSCC cells by suppressing the MMP-2 activity via the MEK/ERK signaling pathways. Therefore, these findings are promising for the use of DIE antimetastatic activity in oral cancer metastasis treatment.
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Affiliation(s)
- Wei-En Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yung-Chuan Ho
- School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
| | - Cheng-Ming Tang
- Graduate Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
| | - Yih-Shou Hsieh
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| | - Pei-Ni Chen
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| | - Chih-Ting Lai
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
| | - Chiao-Wen Lin
- Graduate Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
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Sipahi H, Reis R, Dinc O, Kavaz T, Dimoglo A, Aydın A. In vitro biocompatibility study approaches to evaluate the safety profile of electrolyzed water for skin and eye. Hum Exp Toxicol 2019; 38:1314-1326. [DOI: 10.1177/0960327119862333] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Electrolyzed water (EW) is a widely used disinfectant agent with high oxidation–reduction potential (ORP). Although EW has been used in many areas, such as food hygiene, agriculture, and animal husbandry, the studies presented in the literature are not enough to clarify the toxic effects of EW. The aim of this study is, therefore, to produce EWs at different pH, ORP, and chlorine concentrations and to assess their safety in terms of toxicology. At the beginning of the study, the antimicrobial activity of the EW types with respect to bacteria and fungus was investigated. EWs below pH 7 were all effective in inactivating Enterococcus hirae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans completely. In vitro studies of cell cultures revealed that different concentrations of EWs were not cytotoxic for the L929 cells under 10- to 80-fold dilutions. In addition, it has been determined that produced EWs did not have irritation potential, according to the in vitro EpiDerm™, reconstituted skin irritation test in the frames of biocompatibility tests. For the mucous membrane irritation test, the hen’s egg test-chorioallantoic membrane experiment was performed, and EWs were found to have no eye irritation. In conclusion, it has been shown that produced EWs with antimicrobial efficacy were found to be safe for skin and eye according to in vitro biocompatibility study studies. Thus, the establishment of a technological infrastructure for the EW production and the use of produced EW as an effective disinfectant in the food, medical, and agricultural areas should be encouraged.
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Affiliation(s)
- H Sipahi
- Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Yeditepe University, Istanbul, Turkey
| | - R Reis
- Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Yeditepe University, Istanbul, Turkey
- Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Karadeniz Technical University, Trabzon, Turkey
| | - O Dinc
- Institutue of Health Science, Department of Biotechnology, University of Health Sciences, Istanbul, Turkey
| | - T Kavaz
- Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Yeditepe University, Istanbul, Turkey
| | - A Dimoglo
- Faculty of Engineering, Department of Environmental Engineering, Duzce University, Konuralp, Duzce, Turkey
| | - A Aydın
- Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Yeditepe University, Istanbul, Turkey
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Electrochemically Reduced Water Delays Mammary Tumors Growth in Mice and Inhibits Breast Cancer Cells Survival In Vitro. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:4753507. [PMID: 30402124 PMCID: PMC6196883 DOI: 10.1155/2018/4753507] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 07/25/2018] [Accepted: 09/16/2018] [Indexed: 12/30/2022]
Abstract
Electrochemical reduced water (ERW) has been proposed to have beneficial effects on human health due to its rich content of H2 and the presence of platinum nanoparticles with antioxidant effects. Many studies have demonstrated that ERW scavenging properties are able to reduce the damage caused by oxidative stress in different experimental models. Although few in vivo studies have been reported, it has been demonstrated that ERW may display anticancer effects by induction of tumor cells apoptosis and reduction of both angiogenesis and inflammation. In this study, we show that ERW treatment of MCF-7, MDA-MB-453, and mouse (TUBO) breast cancer cells inhibited cell survival in a time-dependent fashion. ERW decreased ErbB2/neu expression and impaired pERK1/ERK2 and AKT phosphorylation in breast cancer cells. In addition, ERW treatment induced apoptosis of breast cancer cell lines independently of the status of p53 and ER and PR receptors. Our in vivo results showed that ERW treatment of transgenic BALB-neuT mice delayed the development of mammary tumors compared to the control. In addition, ERW induced a significant prolongation of tumor-free survival and a reduction in tumor multiplicity. Overall, these results suggest a potential beneficial role of ERW in inhibiting cancer cells growth.
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Lin CP, Chuang WC, Lu FJ, Chen CY. Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice. World J Gastroenterol 2017; 23:4920-4934. [PMID: 28785146 PMCID: PMC5526762 DOI: 10.3748/wjg.v23.i27.4920] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 03/31/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice.
METHODS In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.
RESULTS The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.
CONCLUSION HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.
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Franceschelli S, Gatta DMP, Pesce M, Ferrone A, Patruno A, de Lutiis MA, Grilli A, Felaco M, Croce F, Speranza L. New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW) on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State. Int J Mol Sci 2016; 17:ijms17091461. [PMID: 27598129 PMCID: PMC5037740 DOI: 10.3390/ijms17091461] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 08/03/2016] [Accepted: 08/12/2016] [Indexed: 12/24/2022] Open
Abstract
It is known that increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW) produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H2O2-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H2O2 on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.
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Affiliation(s)
- Sara Franceschelli
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Daniela Maria Pia Gatta
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Mirko Pesce
- Medicine and Health Science School, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Alessio Ferrone
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Antonia Patruno
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Maria Anna de Lutiis
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Alfredo Grilli
- Medicine and Health Science School, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Mario Felaco
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Fausto Croce
- Department of Farmacy, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
| | - Lorenza Speranza
- Department of Medicine and Science of Aging, University of Gabriele D'Annunzio, 66100 Chieti, Italy.
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Nakayama M, Kabayama S, Ito S. The hydrogen molecule as antioxidant therapy: clinical application in hemodialysis and perspectives. RENAL REPLACEMENT THERAPY 2016. [DOI: 10.1186/s41100-016-0036-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Electrochemically reduced water protects neural cells from oxidative damage. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:869121. [PMID: 25383141 PMCID: PMC4212634 DOI: 10.1155/2014/869121] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 08/19/2014] [Accepted: 09/02/2014] [Indexed: 12/17/2022]
Abstract
Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50–200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca2+ influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW.
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Kinjo T, Ye J, Yan H, Hamasaki T, Nakanishi H, Toh K, Nakamichi N, Kabayama S, Teruya K, Shirahata S. Suppressive effects of electrochemically reduced water on matrix metalloproteinase-2 activities and in vitro invasion of human fibrosarcoma HT1080 cells. Cytotechnology 2012; 64:357-71. [PMID: 22695858 DOI: 10.1007/s10616-012-9469-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 05/21/2012] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Tomoya Kinjo
- Division of Life Engineering, Graduate School of Systems Life Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan
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XQ2, a novel TPZ derivative, induced G2/M phase arrest and apoptosis under hypoxia in non-small cell lung cancer cells. Biosci Biotechnol Biochem 2010; 74:1181-7. [PMID: 20530905 DOI: 10.1271/bbb.90889] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hypoxia is one of the inevitable circumstances of various tumors. It controls various levels of regulation in tumor progression and results in tumor resistance to radiotherapy and chemotherapy. Here we investigated a synthetic TPZ derivative, N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide (XQ2), a novel compound that induced anti-cancer effects both in normoxia and in hypoxia, cell proliferation assay found that XQ2 exhibited a potent inhibitory effect on the tested cancer cell lines both in normoxia and in hypoxia. Flow cytometry and western blot studies indicated that XQ2 induces G2/M arrest and a caspase-dependent apoptosis in A549 cells. Additionally, intracellular reactive oxygen species (ROS) appear to play a key role in the anticancer effect of XQ2 in hypoxia. Taken together, our data suggest that XQ2 exerted anticancer action by suppressing the ROS level and triggering cell-cycle arrest and the caspase-dependent pathway, which is associated with apoptosis.
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Tsai CF, Hsu YW, Chen WK, Chang WH, Yen CC, Ho YC, Lu FJ. Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice. Food Chem Toxicol 2009; 47:2031-6. [PMID: 19477216 DOI: 10.1016/j.fct.2009.05.021] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2008] [Revised: 04/30/2009] [Accepted: 05/18/2009] [Indexed: 02/07/2023]
Abstract
The study investigated the protective effect of electrolyzed reduced water (ERW) against carbon tetrachloride (CCl(4))-induced liver damage. Male ICR mice were randomly divided into control, CCl(4), CCl(4)+silymarin, and CCl(4)+ERW groups. CCl(4)-induced liver lesions include leukocytes infiltration, hepatocyte necrosis, ballooning degeneration, mitosis, calcification, fibrosis and an increase of serum alanine aminotransferase (ALT), and aminotransferase (AST) activity. In addition, CCl(4) also significantly decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). By contrast, ERW or silymarin supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of hepatic enzyme markers (ALT and AST) and increased the activities of SOD, catalase, and GSH-Px in liver. Therefore, the results of this study show that ERW can be proposed to protect the liver against CCl(4)-induced oxidative damage in mice, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenging effect.
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Affiliation(s)
- Chia-Fang Tsai
- Institute of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 402, Taiwan
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