X-Message-Number: 32591
Date: Sun, 23 May 2010 10:21:43 -0700 (PDT)
From: 
Subject: hydrogen & carbon monoxide as solution additives? I


[Hydrogen and carbon monoxide offer synergistic protection against ischemic 
damage, and may reduce ice formation in the bargain. Since free radicals are 
known to partly mediate vitrification solution toxicity, then adding hydrogen 
derived from water electrolysis should also reduce vitrification solution 
toxicity. Problems with poor diffusion which can limit the usefulness of high 
molecular weight antioxidants such as glutathione, should not be a problem with 
hydrogen.]

J Heart Lung Transplant. 2010 May;29(5):544-53. Epub 2009 Dec 24.

Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled 
hydrogen or carbon monoxide, or both.

Nakao A, Kaczorowski DJ, Wang Y, Cardinal JS, Buchholz BM, Sugimoto R, Tobita K,
Lee S, Toyoda Y, Billiar TR, McCurry KR. Department of Surgery, Thomas E Starzl
Transplantation Institute, University of Pittsburgh, Pittburgh, Pennsylvania 
15213, USA.
Abstract

    BACKGROUND: Recent advances in novel medical gases, including hydrogen and 
    carbon monoxide (CO), have demonstrated significant opportunities for 
    therapeutic use. This study was designed to evaluate the effects of inhaled 
    hydrogen or CO, or both, on cold ischemia/reperfusion (I/R) injury of the 
    myocardium. METHODS: Syngeneic heterotopic heart transplantation was 
    performed in rats after 6 or 18 hours of cold ischemia in Celsior solution. 
    Survival, morphology, apoptosis and marker gene expression were assessed in 
    the grafts after in vivo inhalation of hydrogen (1% to 3%), CO (50 to 250 
    ppm), both or neither. Both donors and recipients were treated for 1 hour 
    before and 1 hour after reperfusion. RESULTS: After 6-hour cold ischemia, 
    inhalation of hydrogen (>2%) or CO (250 ppm) alone attenuated myocardial 
    injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial 
    injury, and treatment with hydrogen or CO alone failed to demonstrate 
    significant protection. Dual treatment with hydrogen and CO significantly 
    attenuated I/R graft injury, reducing the infarcted area and decreasing in 
    serum troponin I and creatine phosphokinase (CPK). Hydrogen treatment alone 
    significantly reduced malondialdehyde levels and serum high-mobility group 
    box 1 protein levels as compared with air-treated controls. In contrast, CO 
    only marginally prevented lipid peroxidation, but it suppressed I/R-induced 
    mRNA upregulation for several pro-inflammatory mediators and reduced graft 
    apoptosis. CONCLUSIONS: Combined therapy with hydrogen and CO demonstrated 
    enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory 
    mechanisms, and may be a clinically feasible approach for preventing cold 
    I/R injury of the myocardium. Copyright (c) 2010 International Society for 
    Heart and Lung Transplantation. Published by Elsevier Inc. All rights 
    reserved.
PMID: 20036162


[I also wonder whether hydrogen would extend human lifespan by multiple 
mechanisms, including suppression of tumor growth, stroke damage, and 
infections. However it is something of an understatement to say that further 
research on this topic is indicated. Whether or not hydrogen-enriched 
electrolyzed water really can extend human lifespan, it at least appears to be 
safe for 28 days.]

Toxicol Ind Health. 2010 May;26(4):203-16. Epub 2010 Mar 4.

Biological safety of neutral-pH hydrogen-enriched electrolyzed water upon 
mutagenicity, genotoxicity and subchronic oral toxicity.

Saitoh Y, Harata Y, Mizuhashi F, Nakajima M, Miwa N. Laboratory of Cell-Death 
Control Biotechnology, Faculty of Life and Environmental Sciences, Prefectural 
University of Hiroshima, Nanatsuka, Shobara, Hiroshima, Japan.
Abstract

    Hydrogen-dissolved water has been suggested to be effective for alleviating 
    the oxidative stress. In the present study, neutral-pH hydrogen-enriched 
    electrolyzed water (NHE-water; dissolved hydrogen: 0.90-1.14 parts per 
    million [ppm]; oxido-reduced potential: -150 approximately -80 mV), which 
    was prepared with a water-electrolysis apparatus equipped with a 
    non-diaphragm cell and a highly compressed activated-carbon block, was 
    evaluated for the mutagenic and genotoxic potentials, at concentrations up 
    to 100% dose/plate, and for the subchronic toxicity. NHE-water did not 
    induce reverse mutations in Salmonella typhimurium strains TA100, TA1535, 
    TA98 and TA1537, and Escherichia coli strain WP2uvrA, in either the absence 
    or presence of rat liver S9 for exogenous metabolic activation. Similarly, 
    NHE-water did not induce chromosome aberrations in Chinese hamster lung 
    fibroblast cells (CHL/IU), in short-term (6-hour) tests, with or without rat
    liver S9, or in a continuous treatment (24-hour) test. To evaluate the 
    subchronic toxicity, Crj:CD(SD) specific pathogen free (SPF)-rats were 
    administered with NHE-water at a dose of 20 mL/kg/day for 28 days via 
    intragastric infusion. NHE-water-related toxic changes were not seen in 
    terms of any items such as clinical symptoms, body weight, food consumption,
    urinalysis, hematology, blood chemistry, necropsy, each organ weight and 
    histopathology. Thus, the no-observable-adverse-effect level (NOAEL) for 
    NHE-water was estimated to be greater than 20 mL/kg/day under the conditions
    examined, demonstrating the consistency with the expected safety for a 
    human with a body weight of 60 kg to drink the NHE-water up to at least 1.2 
    L/day.
PMID: 20203135

[Carbon monoxide also looks very interesting.]

BMC Gastroenterol. 2010 May 5;10(1):42. [Epub ahead of print]

Carbon monoxide-Releasing Molecule-2 (CORM-2) attenuates acute hepatic ischemia 
reperfusion injury in rats.
Wei Y, Chen P, de Bruyn M, Zhang W, Bremer E, Helfrich W.
Abstract

    ABSTRACT: BACKGROUND: Hepatic ischemia-reperfusion injury (I/Ri) is a 
    serious complication occurring during liver surgery that may lead to liver 
    failure. Hepatic I/Ri induces formation of reactive oxygen species, 
    hepatocyte apoptosis, and release of pro-inflammatory cytokines, which 
    together causes liver damage and organ dysfunction. A potential strategy to 
    alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and 
    cytoprotective effects of carbon monoxide (CO) by application of so-called 
    CO-releasing molecules (CORMs). Here, we assessed whether CO released from 
    CORM-2 protects against hepatic I/Ri in a rat model. METHODS: Forty male 
    Wistar rats were randomly assigned into four groups (n=10). Sham group 
    underwent a sham operation and received saline. I/R group underwent hepatic 
    I/R procedure by partial clamping of portal structures to the left and 
    median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic
    ischemia and subsequently received saline. CORM-2 group underwent the same 
    procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 
    group underwent the same procedure and received iCORM-2 (8 mg/kg), which 
    does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was 
    assessed by measuring serum damage markers AST and ALT, liver histology 
    score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver 
    extracts, serum levels of pro-inflammatory cytokines TNF-alpha and IL-6, and
    hepatic neutrophil infiltration. RESULTS: A single systemic infusion with 
    CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum 
    AST/ALT levels and an improved liver histology score. Treatment with CORM-2 
    also up-regulated expression of the anti-apoptotic protein Bcl-2, 
    down-regulated caspase-3 activation, and significantly reduced the levels of
    apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly 
    inhibited the activity of the pro-inflammatory transcription factor 
    NF-kappaB as measured in nuclear extracts of liver homogenates. Moreover, 
    CORM-2 treatment resulted in reduced serum levels of pro-inflammatory 
    cytokines TNF-alpha and IL-6 and down-regulation of the adhesion molecule 
    ICAM-1 in the endothelial cells of liver. In line with these findings, 
    CORM-2 treatment reduced the accumulation of neutrophils in the liver upon 
    I/Ri. Similar treatment with an inactive variant of CORM-2 (iCORM-2) did not
    have any beneficial effect on the extent of liver I/Ri. CONCLUSIONS: CORM-2
    treatment at the time of reperfusion had several distinct beneficial 
    effects on severity of hepatic I/Ri that may be of therapeutic value for the
    prevention of tissue damage as a result of I/Ri during hepatic surgery.
PMID: 20444253
Free text>
http://www.biomedcentral.com/content/pdf/1471-230x-10-42.pdf

[Hydrogen itself treats carbon monoxide poisoning.]

Med Hypotheses. 2010 Mar 29. [Epub ahead of print]
Hydrogen as a novel and effective treatment of acute carbon monoxide poisoning.

Shen M, He J, Cai J, Sun Q, Sun X, Huo Z. Department of Emergency, Changhai 
Hospital,168 Changhai Road, Shanghai 200433, PR China.
Abstract

    Hydrogen is a major component of interstellar space and the fuel that 
    sustains the stars. However, it is seldom regarded as a therapeutic gas. A 
    recent study provided evidence that hydrogen inhalation exerted antioxidant 
    and anti-apoptotic effects and protected the brain against 
    ischemia-reperfusion injury by selectively reducing hydroxyl radical and 
    peroxynitrite. It has been known that the mechanisms underlying the brain 
    injury after acute carbon monoxide poisoning are interwoven with multiple 
    factors including oxidative stress, free radicals, and neuronal nitric oxide
    synthase as well as abnormal inflammatory responses. Studies have shown 
    that free radical scavengers can improve the neural damage. Based on the 
    findings abovementioned, we hypothesize that hydrogen therapy may be an 
    effective, simple, economic and novel strategy in the treatment of acute 
    carbon monoxide poisoning. Copyright C 2010 Elsevier Ltd. All rights 
    reserved.
PMID: 20347528

Nephrol Dial Transplant. 2010 Apr 12. [Epub ahead of print]

A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced 
by water electrolysis: a clinical trial.

Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S. 1 Tohoku University 
Hospital, Department of Blood Purification (Sendai).
Abstract

    Background. Chronic inflammation in haemodialysis (HD) patients indicates a 
    poor prognosis. However, therapeutic approaches are limited. Hydrogen gas 
    (H(2)) ameliorates oxidative and inflammatory injuries to organs in animal 
    models. We developed an HD system using a dialysis solution with high levels
    of dissolved H(2) and examined the clinical effects. Methods. Dialysis 
    solution with H(2) (average of 48 ppb) was produced by mixing dialysate 
    concentrates and reverse osmosis water containing dissolved H(2) generated 
    by a water electrolysis technique. Subjects comprised 21 stable patients on 
    standard HD who were switched to the test HD for 6 months at three sessions 
    a week. Results. During the study period, no adverse clinical signs or 
    symptoms were observed. A significant decrease in systolic blood pressure 
    (SBP) before and after dialysis was observed during the study, and a 
    significant number of patients achieved SBP <140 mmHg after HD (baseline, 
    21%; 6 months, 62%; P < 0.05). Changes in dialysis parameters were minimal, 
    while significant decreases in levels of plasma monocyte chemoattractant 
    protein 1 (P < 0.01) and myeloperoxidase (P < 0.05) were identified. 
    Conclusions. Adding H(2) to haemodialysis solutions ameliorated inflammatory
    reactions and improved BP control. This system could offer a novel 
    therapeutic option for control of uraemia.
PMID: 20388631

Neuroscience. 2010 Apr 25. [Epub ahead of print]

Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in 
a focal ischemia rat model.

Chen CH, Manaenko A, Zhan Y, Liu WW, Ostrowki RP, Tang J, Zhang JH. Department 
of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA; 
Department of Anatomy and Embryology, Peking University Health Science Center, 
Beijing, PR China.
Abstract

    Hyperglycemia is one of the major factors for hemorrhagic transformation 
    after ischemic stroke. In this study, we tested the effect of hydrogen gas 
    on hemorrhagic transformation in a rat focal cerebral ischemia model. 
    Sprague-Dawley rats (n=72) were divided into the following groups: sham; 
    sham treated with hydrogen gas (H(2)); Middle Cerebral Artery Occlusion 
    (MCAO); and MCAO treated with H(2) (MCAO+H(2)). All rats received an 
    injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. 
    Following a 90 min ischemic period, hydrogen was inhaled for 2 h during 
    reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 
    6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic 
    score, oxidative stress (evaluated by measuring the level of 8 
    Hydroxyguanosine (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), and 
    matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after 
    ischemia. We found that hydrogen inhalation for 2 h reduced infarct and 
    hemorrhagic volumes and improved neurological functions. This effect of 
    hydrogen was accompanied by a reduction of the expression of 8OHG, HNE, and 
    nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the 
    blood glucose level from 500+/-32.51 to 366+/-68.22 mg/dl at 4 h after 
    dextrose injection was observed in hydrogen treated animals. However, the 
    treatment had no significant effect on the expression of ZO-1, occludin, 
    collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced brain 
    infarction, hemorrhagic transformation, and improved neurological function 
    in rats. The potential mechanisms of decreased oxidative stress and glucose 
    levels after hydrogen treatment warrant further investigation. Copyright C 
    2010 IBRO. Published by Elsevier Ltd. All rights reserved.
PMID: 20423721

Cryobiology. 2010 Apr 27. [Epub ahead of print]

Gaseous persufflation with carbon monoxide during ischemia protects the isolated
liver and enhances energetic recovery.

Koetting M, Leuvenink H, Dombrowski F, Minor T. Department for General, Visceral
and Transplantation Surgery, University Hospital of Essen, Germany.
Abstract

    BACKGROUND: The benefit of carbon monoxide as applied by controlled, 
    continuous gaseous persufflation during liver preservation on postischemic 
    graft recovery was investigated in an isolated rat liver model. METHODS: 
    Livers from male Wistar rats were retrieved 30min after cardiac arrest of 
    the donor and subjected to 18h of cold storage. Some grafts were subjected 
    to gaseous persufflation with carbon monoxide (CO, dissolved in nitrogen) 
    during static cold storage at a concentration of 50ppm or 250ppm. Graft 
    viability was assessed thereafter upon warm reperfusion in vitro. RESULTS: 
    CO-persufflation significantly reduced cellular enzyme loss (maximal at 
    50ppm) and functional recovery (bile production and energy charge) upon 
    reperfusion by about 50%. The effect was associated with a reduction of free
    radical-induced lipid peroxidation, lower vascular perfusion resistance, 
    and improved mitochondrial ultrastructure. CONCLUSION: Viability of cold 
    stored liver grafts can be notably augmented by gaseous ex vivo application 
    of low dose CO to the isolated organ. Copyright C 2010. Published by 
    Elsevier Inc.
PMID: 20430019

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