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
Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32591