X-Message-Number: 32592 Date: Sun, 23 May 2010 10:25:22 -0700 (PDT) From: Subject: hydrogen & carbon monoxide as solution additives? II Am J Transplant. 2010 Apr;10(4):763-72. Epub 2010 Feb 25. Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs. Yoshida J, Ozaki KS, Nalesnik MA, Ueki S, Castillo-Rama M, Faleo G, Ezzelarab M, Nakao A, Ekser B, Echeverri GJ, Ross MA, Stolz DB, Murase N. Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA. Abstract I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury. PMID: 20199500 Invest Ophthalmol Vis Sci. 2010 Jan;51(1):487-92. Epub 2009 Oct 15. Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury. Oharazawa H, Igarashi T, Yokota T, Fujii H, Suzuki H, Machide M, Takahashi H, Ohta S, Ohsawa I. Department of Ophthalmology, Musashikosugi Hospital, Nippon Medical School, Kanagawa, Japan. Abstract PURPOSE: Retinal ischemia-reperfusion (I/R) injury by transient elevation of intraocular pressure (IOP) is known to induce neuronal damage through the generation of reactive oxygen species. Study results have indicated that molecular hydrogen (H(2)) is an efficient antioxidant gas that selectively reduces the hydroxyl radical (*OH) and suppresses oxidative stress-induced injury in several organs. This study was conducted to explore the neuroprotective effect of H(2)-loaded eye drops on retinal I/R injury. METHODS: Retinal ischemia was induced in rats by raising IOP for 60 minutes. H(2)-loaded eye drops were prepared by dissolving H(2) gas into a saline to saturated level and administered to the ocular surface continuously during the ischemia and/or reperfusion periods. One day after I/R injury, apoptotic cells in the retina were quantified, and oxidative stress was evaluated by markers such as 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina. RESULTS: When H(2)-loaded eye drops were continuously administered, H(2) concentration in the vitreous body immediately increased and I/R-induced *OH level decreased. The drops reduced the number of retinal apoptotic and oxidative stress marker-positive cells and prevented retinal thinning with an accompanying activation of Muller glia, astrocytes, and microglia. The drops improved the recovery of retinal thickness by >70%. CONCLUSIONS: H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury. PMID: 19834032 [Could hydrogen extend human lifespan by suppressing infections?] Shock. 2009 Dec 7. [Epub ahead of print] Protective Effects of Hydrogen Gas on Murine Polymicrobial Sepsis via Reducing Oxidative Stress and HMGB1 Release. Xie K, Yu Y, Pei Y, Hou L, Chen S, Xiong L, Wang G. 1Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, P. R. China. Tel: +86-22-60361519. 2Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, P. R. China. Tel: +86-29-84775337. Abstract Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units (ICU). Excessive production of reactive oxygen species (ROS) plays an important role in the pathogenesis of sepsis. Recently, it has been suggested that molecular hydrogen (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (*OH, the most cytotoxic ROS) and effectively protects against organ damage induced by ischemia/reperfusion. Therefore, we hypothesized that H2 treatment had a beneficial effect on sepsis. In the present study, we found that H2 inhalation starting at 1 and 6 hours after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration- and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase (MPO) activity, wet-to-dry (W/D) weight ratio, protein concentration in bronchoalveolar lavage (BAL), serum biochemical parameters, and organ histopathological scores at 24 hours after CLP operation, which was significantly attenuated by 2% H2 treatment. In addition, we found that the beneficial effects of H2 treatment on sepsis and sepsis-associated organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes and reduced levels of high-mobility group box 1 (HMGB1) in serum and tissue. Thus, H2 inhalation may be an effective therapeutic strategy for septic patients. PMID: 19997046 [Could hydrogen inhibit cancer growth? We'd need a little more proof than this!] Biol Pharm Bull. 2008 Jan;31(1):19-26. Inhibitory effect of electrolyzed reduced water on tumor angiogenesis. Ye J, Li Y, Hamasaki T, Nakamichi N, Komatsu T, Kashiwagi T, Teruya K, Nishikawa R, Kawahara T, Osada K, Toh K, Abe M, Tian H, Kabayama S, Otsubo K, Morisawa S, Katakura Y, Shirahata S. Graduate School of Systems Life Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan. 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. PMID: 18175936 Free text> http://www.jstage.jst.go.jp/article/bpb/31/1/19/_pdf J Food Sci. 2007 Jun;72(5):S298-302. Effect of pH on the taste of alkaline electrolyzed water. Koseki M, Tanaka Y, Noguchi H, Nishikawa T. Yamawaki Gakuen Junior College, 4-10-36, Akasaka, Minato-ku, Tokyo 107-8371, Japan Abstract The pH dependence of the taste of alkaline electrolyzed water (AEW) made by electrolyzing bottled mineral waters was examined by sensory evaluation. For water with a calcium concentration of 79 or 93 mg/L, the taste of AEW with a pH of 9.5 was considered better than that of the unelectrolyzed water. In contrast, for water with a calcium concentration of 10 mg/L, the taste of the unelectrolyzed water was preferred to that of AEW with a pH of 9.5. Electrolysis reduced the calcium concentrations in waters with calcium concentrations of 79 or 93 mg/L, but did not change the calcium concentration in water with a calcium concentration of 10 mg/L. Electrolysis probably improved the taste of water with a higher calcium concentration by reducing the calcium concentration; however, the effect of electrolysis on water with a calcium concentration of 10 mg/L is likely to be the result of the pH increase alone. PMID: 17995745 [If this stuff is so great why isn't everybody at the AMA guzzling it? Appl Biochem Biotechnol. 2006 Nov;135(2):133-44. Electrolyzed-reduced water protects against oxidative damage to DNA, RNA, and protein. Lee MY, Kim YK, Ryoo KK, Lee YB, Park EJ. Department of Genetic Engineering, Soonchunhyang University, Asan, Chungnam 336-600, Korea. Abstract The generation of reactive oxygen species is thought to cause extensive oxidative damage to various biomolecules such as DNA, RNA, and protein. In this study, the preventive, suppressive, and protective effects of in vitro supplementation with electrolyzed-reduced water on H2O2-induced DNA damage in human lymphocytes were examined using a comet assay. Pretreatment, cotreatment, and posttreatment with electrolyzed-reduced water enhanced human lymphocyte resistance to the DNA strand breaks induced by H2O2 in vitro. Moreover, electrolyzed-reduced water was much more effective than diethylpyrocarbonate-treated water in preventing total RNA degradation at 4 and 25 degrees C. In addition, electrolyzed-reduced water completely prevented the oxidative cleavage of horseradish peroxidase, as determined using sodium dodecyl sulfate-polyacrylamide gels. Enhancement of the antioxidant activity of ascorbic acid dissolved in electrolyzed-reduced water was about threefold that of ascorbic acid dissolved in nonelectrolyzed deionized water, as measured by a xanthine-xanthine oxidase superoxide scavenging assay system, suggesting an inhibitory effect of electrolyzed reduced water on the oxidation of ascorbic acid. PMID: 17159237 Biochem Biophys Res Commun. 1997 May 8;234(1):269-74. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Shirahata S, Kabayama S, Nakano M, Miura T, Kusumoto K, Gotoh M, Hayashi H, Otsubo K, Morisawa S, Katakura Y. Institute of Cellular Regulation Technology, Graduate School of Genetic Resources Technology, Kyushu University, Fukuoka, Japan Abstract Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules, which brings about a variety of diseases as well as aging. The ideal scavenger for active oxygen should be 'active hydrogen'. 'Active hydrogen' can be produced in reduced water near the cathode during electrolysis of water. Reduced water exhibits high pH, low dissolved oxygen (DO), extremely high dissolved molecular hydrogen (DH), and extremely negative redox potential (RP) values. Strongly electrolyzed-reduced water, as well as ascorbic acid, (+)-catechin and tannic acid, completely scavenged O.-2 produced by the hypoxanthine-xanthine oxidase (HX-XOD) system in sodium phosphate buffer (pH 7.0). The superoxide dismutase (SOD)-like activity of reduced water is stable at 4 degrees C for over a month and was not lost even after neutralization, repeated freezing and melting, deflation with sonication, vigorous mixing, boiling, repeated filtration, or closed autoclaving, but was lost by opened autoclaving or by closed autoclaving in the presence of tungsten trioxide which efficiently adsorbs active atomic hydrogen. Water bubbled with hydrogen gas exhibited low DO, extremely high DH and extremely low RP values, as does reduced water, but it has no SOD-like activity. These results suggest that the SOD-like activity of reduced water is not due to the dissolved molecular hydrogen but due to the dissolved atomic hydrogen (active hydrogen). Although SOD accumulated H2O2 when added to the HX-XOD system, reduced water decreased the amount of H2O2 produced by XOD. Reduced water, as well as catalase and ascorbic acid, could directly scavenge H2O2. Reduce water suppresses single-strand breakage of DNA b active oxygen species produced by the Cu(II)-catalyzed oxidation of ascorbic acid in a dose-dependent manner, suggesting that reduced water can scavenge not only O2.- and H2O2, but also 1O2 and .OH. PMID: 9169001 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32592