A hypothesis on biological protection from space radiation through the use of new therapeutic gases as medical counter measures
© Schoenfeld et al; licensee BioMed Central Ltd. 2012
Received: 12 September 2011
Accepted: 4 April 2012
Published: 4 April 2012
Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is biological damage that is associated with increased oxidative stress. It is therefore important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as chemical radioprotectors for radical scavenging and as biological signaling molecules for management of the body's response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it can be concluded that this approach may have therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion (IR) injury, acute respiratory distress syndrome, Parkinson's and Alzheimer's disease, cataracts, and aging. We envision applying these therapies through inhalation of gas mixtures or ingestion of water with dissolved gases.
Keywordsspace radiation radiolysis radiochemistry radiation shielding therapeutic medical gas reactive oxygen species oxidative stress countermeasure
The Challenge of Space Radiation
Galactic Cosmic Rays (GCR), solar energetic particles (SEP), and trapped energetic particles in a planetary magnetic field are natural sources of radiation in space. GCRs consist of highly energetic nuclei, predominately protons and He, but also trace amounts of C, O, Ne, Si, Ca, and Fe ions. Particle energies can range from 100 MeV to 10 GeV per nucleon . Although the high charge and energy (HZE) nuclei are in trace amounts, they are still of concern because they can cause more damage than protons since they are more highly ionizing. As well, even though particle fluxes are typically low, they are chronic and can significantly increase with solar events . Furthermore, GCRs and SEPs impinging on shielding material, atmosphere, or surface of a planet or satellite can produce secondary radiation, including energetic neutrons, from nuclear fragmentation of the primary ion and target atoms. This can introduce an additional component to the radiation field which makes shielding from HZE quite challenging and poses one of the principal unknowns in understanding the HZE effects with human tissue . Furthermore, while our bodies do possess a natural repair mechanism, radiation with a high linear energy transfer (LET) rate, like space radiation, is attributed to be more likely to cause double strand breaks in DNA that are relatively more difficult for our natural repair mechanisms to fix correctly . While a week or month of this radiation at the dose rates naturally present likely will not have serious consequences, several year durations in space could. The traditional paradigm for radiation protection is to minimize exposure time, maximize distance from radiation sources, and use shielding to attenuate and absorb radiation before it can deposit its energy in humans. In regards to minimizing exposure time, new propulsive technologies could reduce trip times but have yet to be developed and would not address the ability to remain at a location for long durations. It is impractical to maximize distance from cosmic radiation sources. In regards to shielding, aspects of attenuation by mass or deflection by magnetic fields or charge repulsion have been considered. Due to the phenomena of secondary radiation, shielding by other matter may require a significant amount of mass which could be impractical within current mass constraints in space systems. Due to the high energy of the space radiation, magnetic field and charge strengths required for deflection may be currently impractical because of mass and power constraints in modern space systems along with other system design implications. In short, shielding space radiation is seemingly quite challenging. However, advances in biochemistry may reveal some more tools for radiation protection .
Parallels between Radiation Chemistry of Water & Radiobiology
Radiolysis is the decomposition of water from exposure to ionizing radiation. Radiation chemistry of water has been well studied since the onset of nuclear power production, as water has been the most often used coolant. Since mammalian cells are composed of about 80% water, it seemed natural that there exist similarities between radiation chemistry of water and radiation biology. It is these similarities from which analogues for radioprotective measures were inspired.
Chain of Events Initiated by Chemically Reactive Species
Radiolysis in nuclear systems causes a chain of events that ultimately manifest into systematic problems like corrosion and gas generation. Ionizing radiation creates chemically reactive radicals H3O+, e-, H+, H, and OH by ionizing and/or breaking the bonds of water molecules. These radicals then initiate a chain of chemical reactions within the water which can result in the formation of molecular decomposition products such as H2, O2, HO2 and H2O2. BWR recirculation water contains oxygen and hydrogen peroxide in the concentration range from 100 to 300 ppb, and about 10 ppb of dissolved hydrogen (less than stoichiometric ratio of 8 to 1) . These oxidizing species alter the water composition and therefore its electrochemical character which facilitates the manifestation of problems like corrosion or gas generation. As such, the nature in which systematic problems develop can be viewed as stemming from a chain of events that are initiated by ionization and propagated by a scheme of chemical reactions with the net result or outcome depending upon the ensuing chemistry.
This scenario is similar in nature to a biological system and the pathogenesis of radiation related ailments and disease. Ionization of key biological molecules can lead to chemical reactions which transform these molecules. This alters their biochemical function and can result in changes of their biochemical properties. Modification of biochemical properties propagates from a cellular level to organ and systematic changes that ultimately manifest into clinical symptoms and ailments. Ionization of the molecules can be initiated both directly (by radiation) and indirectly (by free radicals and reactive oxygen species (ROS) created by radiolysis). Free radicals and ROS like O2-, 1O2, ·OH, ·OOH, NO· and H2O2 can cause cell injury or death by oxidative stress [5, 6]. Oxidative stress to the cell results from such things as DNA damage or lipid peroxidation. Disease can then develop as a direct result of radiation damage or due to a system impairment caused by radiation damage such as the case of radiation-induced damage of chromosomes in lymphocytes compromising the immune system's ability to prevent tumor development . Overall, the greatest risks from radiation exposure are assumed to be cancer , cataracts, and damage to the central nervous system . Thus the nature of the problem seems similar to nuclear systems in that systematic manifestations result from a chain of events initiated by ionization and propagated, in this case, by ensuing chemical reactions and biological responses.
Interestingly enough, oxidative stress has been implicated to play a role in the development of other diseases as well [10, 11]. That is, the normal production and development of a variety of disorders and diseases has also been associated with an increase of oxidative stress and inflammation similar to that which would be caused by exposure to radiation. For example, certain detrimental effects from space radiation on the dopaminergic system are similar to functional changes that occur from Parkinson's disease , diabetogenic problems associated with increased C-peptide excretion and insulin resistance , as well as constipation due to malfunction of the intestine. Oxidative stress during space flight can cause a loss of protein after reductive remodeling of skeletal muscle due to undernutrition . Diseases in which oxidative stress is implicated, and thus which could also be affected by the countermeasures proposed in this paper, include cardiovascular disease, cancer , chronic inflammatory disease , hypertension , ischemia/reperfusion injury , acute respiratory distress syndrome (ARDS) , neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease [18, 19] and aging .
Radical Scavenging & Antioxidants
Similarly, in a biological system, antioxidants have been seen to protect against oxidative stress and prevent the pathological process of a wide range of disease . The effect of antioxidants in reducing oxidative stress can be attributed to their ability to protect tissues from free radicals  hinting towards a scavenging mechanism. Turner  indicates, "A number of radiosensitizing chemicals and drugs are known. Some sensitize hypoxic cells, but have little or no effect on normally aerated cells. Other agents act as radioprotectors reducing biological effectiveness...which scavenge free radicals. Still other chemicals modifiers have little effect on cell killing but substantially enhance some multistep processes, such as oncogenic cell transformation." Thus it appears that antioxidants act similarly to radical scavengers in nuclear coolant systems in that they chemically protect against indirect ionization by preferentially reacting with the reactive species and thus reducing their ability to cause oxidative stress.
A Scenario of Competing Processes with a Critical Point & Natural Repair Mechanisms
In a biological system, it appears to be a similar scenario between biochemical damage and repair processes. Free radicals and ROS were identified as the root cause of oxidative stress and while their production is attributed to exposure to external sources like X-rays, ozone, cigarette smoke, air pollutants and industrial chemicals , they are also generated naturally during a variety of energy-generating biochemical reactions and cellular functions . In fact, the ROS actually serve a necessary function as signaling molecules that critically modulate the activation of the immune system and thus participate in antibacterial defense . Thus, neutralization of all free radicals would not be desirable. Oxidative stress occurs when there is an imbalance between antioxidants and ROS and free radicals  such as when ROS concentrations increase due to radiation exposure generating them by ionization. Chopping  observes, "The cell is protected by different DNA repair mechanisms which try to restore the damage. We don't know the details, except when the repair goes wrong (e.g. a replacement of a lost nucleotide by a 'wrong" base pair, etc.)... The cell contains natural radical scavengers. As long as they are in excess of the radiolysis products, the DNA may be protected. When the products exceed the amount of scavengers, radiation damage and cancer induction may occur. In principle, there could thus be a threshold dose for radiation damage, at which the free radicals formed exceed the capacity of scavenging. The scavenging capacity may differ from individual to individual depending on his/her physical condition." Experimental investigations regarding long-duration space flights in particular clearly showed increased oxidative stress markers and a reduction in antioxidants after these flights [30, 7]. Kennedy et al.  demonstrated that exposure to space radiation may compromise the capacity of the host antioxidant defense system and that this adverse biological effect can be prevented, at least partially, by dietary supplementation with agents expected to have effects on antioxidant activities. Interestingly and similarly so, the radiation resistance of the bacteria Deinococcus radiodurans that can grow under chronic γ radiation (50 Gy/hr) or recover from acute doses greater than 10 kGy has been attributed to the role of antioxidants in mitigating the extent of oxidative damage [32–34]. Thus there appear to be similarities between the nuclear and biological systems in how use of scavengers can enhance and bolster the favorable process thereby increasing the natural radiation resistance of the system. Chopping  points out that several radiation protection agents are known and probably function as scavengers for the products of water radiolysis. However, the oxygen effect to promote ROS production isn't seen for the higher LET α radiation where the OER is 1, as opposed to 3 as for the case of X-rays, implying that direct damage such as double strand DNA breaks becomes the more dominant type of damage process for higher LET radiation. Therefore, for the high LET space radiation, scavenging alone may not be an effective mitigation approach. Thus, we envision a strategy that interrupts the chain of events leading to biological disease during the chemical and biological stages. In particular, we propose a strategy that (1) bolsters antioxidant capacity (2) supports natural repair processes and (3) manages biological response to radiation insult. This approach could have a great effect for increasing the threshold tolerance for radiation damage before it propagates into systematic symptoms, disease and ailments.
Radiation protection by a conjunctive bio-chemical approach
Over the course of the last century, a wealth of knowledge has been accumulated on the effect of radiation on biological systems. Areas spanning in scope from DNA damage up to changes in physiology have received extensive study. To date, biology studies of radiation damage have largely focused on components of DNA repair systems such ataxia telangiectasia mutated gene (ATM). More recently, however, it has been found that modification of key molecular targets can protect tissue from radiation induced fibrosis in mice exposed to doses up to 25 Gy [35, 36]. It has also been found that changes in APOE (Apolipoprotein E) genotype dramatically influences survival following Total Body Irradiation (TBI) in murine models. These results imply that modification of key molecular targets to induce biological changes in the host can protect tissue from radiation damage. Turner  notes that, "for carcinogensis or transformation, for example, such biological promoters (radioprotectors) can dwarf the effects of physical factors, such as LET and dose rate, on dose-response relationships."
radical scavenging of toxic decomposition products of free radicals and ROS
repair of biological molecules by donation of H atoms since hydrogen bonds are among the weakest in biological molecules and such are the first to be broken 
interaction with cellular components (binding, altering metabolic pathway, etc.)
Interaction with cellular components can have biological effects that lend to radioprotection like hypoxia, alteration of metabolic state, and anti-apoptotic and anti-inflammatory properties. Tissue hypoxia decreases the radiosensitivity of cells by minimizing the O2 effect and can be produced chemically by impairing oxygen transport (binding up hemogloblin with another molecule) or biologically by either restricting blood flow (vasoconstrictor drug, hypocapnia, etc.) or lowering blood pressure (vasodilator drug). Vasodilation along with other circulatory enhancements may also enhance the natural repair mechanism as it is believed to be more effective in a living organism, where the cells are in continuous exchange with the surrounding cells and body fluids, than in the tissue samples often studied in the laboratory . Inducing a hypometabolic state which resembles hibernation, may contribute to tolerance against oxidative stress. Metabolic rates in hibernating marmots and ground squirrels help delay the onset of obvious damage. Also, survival times for guinea pigs that have received massive doses of radiation (> 6000 rads) have been extended from several hours to about 4 days through the use of central nervous system depressants (pentobarbital) where it has been attributed to partial protection from central nervous system syndrome . Furthermore, a hypometabolic status may also prove to be an ideal therapy for various shock or trauma states in which dramatic reduction in metabolic demands may be highly protective . Anti-apoptotic properties can mitigate organ damage such as in IR injury by reducing the amount of cellular self destruction. Interference with mitosis and DNA synthesis may slow cells in their radio-resistant phase of cell division or afford more time for natural repair of the cell prior to replication of the damage.
We hypothesize that therapeutic medical gases can serve as radioprotectors and biological signaling molecules to work conjunctively in preventing, protecting, and repairing radiation damage
Medical gases might prove to have lower chemical toxicity and thereby permit increased dose administration. If so, this could improve effectiveness as many of the radiation protective agents are limited to being administered in small doses due to their chemical toxicity . Furthermore, incorporating the biological aspect with the chemical aspect of scavenging radiolysis byproducts may prove to be particularly effective for space radiation than using low LET radioprotectors as direct damage such as DNA double strand breaks likely become the more dominant damage mechanisms for the higher LET radiation . NO, CO, H2S and H2 are gaseous signaling molecules in humans. These molecules act as transmitters of information between cells by chemically interacting with cell receptors to trigger a response within the cell. These comprise some of the medical gases of interest and many of them act both on the chemical level in the form of antioxidant radical scavenging and on the biological level in the form anti-inflammatory, anti-apoptotic, and other biological effects. Extensive and more detailed information about these gases in a therapeutic role can be found in reference  which provides a detailed description of medical gases of interest and their properties and  provides detailed information pertaining in particular to H2.
We hypothesize that hydrogen can repair biological radicals by H atom donation and/or supplement antioxidant capacity either directly as an antioxidant or indirectly as a signaling molecule to trigger production of natural antioxidant enzymes
Cited Properties of H2 as a Medical Gas with Suggested Chemical/Biological Mechanisms.
radical scavenging antioxidant
• selectively reduces hydroxyl radicals (•OH) and reactive nitrogen oxide species (NO2 and N2O3) but did not eliminate O2- or H2O2 when tested in in vitro .
• does not decrease the steady-state levels of nitric oxide (NO)  which may be beneficial as endogenous NO signaling pathways modulate pulmonary vascular tone and leukocyte/endothelial interactions .
• diminished lipid peroxidation as indicated by MDA levels when compared to air-treated grafts .
• drinking hydrogen-containing water with concentrations as low as 0.04 mM, significantly reduced the loss of dopaminergic neurons, decreased accumulation of DNA damage, and lipid peroxidation in mice with Parkinson's disease induced by oral administration of MPTP .
• postulated to inhibit caspase-3 activation .
It is highly diffusible and as such may potentially reach subcellular compartments, such as mitochondria and nuclei, which are the primary site of ROS generation and DNA damage  and are also notoriously difficult to target pharmacologically.
Its hyporeactivity with other gases at therapeutic concentrations may allow hydrogen to be administered with other therapeutic gases, including inhaled anaesthesia agents .
H2 may spare the innate immune system while still allowing phagocytosis of infecting organisms. When tested in vitro, it did not eliminate O2- or H2O2 which have important functions in neutrophils and macrophages as they must generate ROS in order to kill some types of bacteria engulfed by phagocytosis . It is not clear whether a similar reaction preferentially occurs under complex biological conditions. Experimental studies have demonstrated that hydrogen has potent therapeutic efficacies on both parasite infection  and polymicrobial sepsis .
No adverse effects have been found in humans drinking hydrogen water in a study that examined the effects of drinking hydrogen-rich water (HW) for radiation-induced late adverse effects [44, 45]. Studies showed that the consumption of HW for 6 months resulted in significant decrease of serum levels of derivatives of Reactive Oxidative Metabolites (dROMs) and an increase of biological antioxidant power determined by Free Radical Analytical System (FRAS). No severe adverse effects were seen during follow up period. These results suggest that drinking HW improved Quality of Life (QOL), associated with decrease of oxidative injury markers, in patients with radiotherapy.
Hydrogen has only recently been considered for therapeutic applications for radiation exposure [46, 47] and recent results are beginning to preliminarily demonstrate its radioprotective effects in cultured cells and rats when exposed to 4-8 Gy of γ-irradiation from a Co-60 source . Qian, et al  found that a hydrogen rich PBS treatment applied to human lymphocyte AHH-1 cells increased cell vitality in that it decreased cellular lactate dehydrogenase (LDH) leakage and attenuated apoptosis. When the treatment was applied in vivo to male BALB/c rats, they found it attenuated intestinal injury, helped sustain levels of natural antioxidant enzymes GSH & SOD, and reduced both lipid peroxidation (as indicated by MDA) and oxidative stress (as indicated by DNA base damage/lesion 8-OHdG). The protective effects appear to be concentration dependent, at least within the range of their test (up to 0.4 mmol/L), and are more effective as a pre-treatment before exposure rather than after. This may imply a protective mechanism from an antioxidant role either by the hydrogen itself or by it 'signaling' the production of natural anti-oxidant enzymes. While there appears to be insignificant differences in levels of natural antioxidant enzymes GSH & SOD from the treatment in this experiment, other experiments have indicated hydrogen treatment appears to increase antioxidant enzymes such as catalase, SOD or heme oxygenase-1 [39, 44]. None the less, a protective effect seems apparent and questions of how much hydrogen can be absorbed by ingestion, inhalation or injection and how long it will remain effective along with other questions remain to be addressed.
We hypothesize that NO and thrombospondin-1 signaling might be used conjunctively to manage response to radiation insult for tissue preservation
Cited Properties of NO as a Medical Gas with Suggested Chemical/Biological Mechanisms.
radical scavenging antioxidant
• NO reacts with peroxy and oxy radicals generated during the process of lipid peroxidation. The reactions between NO and these ROS can terminate lipid peroxidation and protect tissues from ROS-induced injuries .
• induces the rate-limiting antioxidant enzyme, heme oxygenase (HO)-1 thus imparting resistance to H2O2 induced cell death .
• in bacteria, activates the redox-sentive transcriptional regulator protein (oxyR), resulting in the subsequent expression of protein protective against ROS .
• inhibiting P-selectin expression and leukocyte recruitment .
• vasodilator through relaxation of vascular tone by stimulating soluble guanylate cyclase (sGC) and increased cGMP content in vascular smooth muscle cells .
We hypothesize that small, therapeutic concentrations of CO and/or when used in conjunction with other medical gases can decrease radiosensitivity without the deleterious effects of excessive CO
Cited Properties of CO as a Medical Gas with Suggested Chemical/Biological Mechanisms.
radical scavenging antioxidant
• binds to the heme moiety of mitochondrial cytochrom c oxidase. By binding to the heme, CO may prevent degradation of heme proteins which induce tissue injury by rapidly promoting peroxidation of the lipid membranes of cells [74, 75].
• impedes O2 transport as it binds to hemoglobin with an affinity 240 times higher than that of O2.
We hypothesize that H2S administered in small, therapeutic concentrations can enhance antioxidant activity and aid in tissue preservation. Furthermore, it may support natural DNA repair mechanisms by temporarily slowing cell cycle progression so that more time is afforded to operate before detrimental errors are copied
Cited Properties of H2S as a Medical Gas with Suggested Chemical/Biological Mechanisms.
radical scavenging antioxidant
• antioxidant inhibitor of peroxynitrite-mediated processes via activation of N-methly-D-aspartate (NMDA) receptors .
• shield cultured neurons from oxidative damage by increasing levels of glutathione .
• inhibits myeloperoxidase and destroys H2O2 .
• mediates mitochondrial preservation in post hypoxic conditions that are ideal for mitochondrial permeability transition pore (MPTP) that would cause the mitochondria to break down and lead to cell death .
• reduces IR induced apoptosis via reduction of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) .
• H2S activated STAT3 and Protein Kinase C (PKC) inhibits the pro-apoptotic factor Bad and upregulated the prosurvival proteins Bcl-2 and Bcl-xl by altering phosphorylation .
• H2S influences inactivation of pro-apoptotic pathways through survival pathway of extracellular-signal regulated kinase (ERK1/2)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI-3-kinase) .
• inhibit leukocyte adherence in the rat mesenteric microcirculation during vascular inflammation .
• transiently and reversibly inhibiting mitochondrial respiration .
• produces a "suspended animation-like" metabolic status with hypothermia and reduced oxygen demand in pigs (who received it intravenously) . and mice (who received hydrogen sulfide via inhalation) [89, 90].
• mice breathing 80 ppm of H2S for 6 hr reduced heart rate, core body temperature, respiratory rate and physical activity where as blood pressure remained unchanged .
Possible administration methods
Hydrogen or combinations of other medical gases could be administered to astronauts by inhalation, ingestion or injection. Inhalation could be achieved though a ventilator circuit, facemask, nasal cannula, or creating a spacesuit or spacecraft atmosphere which is composed of or contains a non-flammable gas mixture of these therapeutic medical gases. The use of Hydreliox, an exotic breathing gas mixture of 49% hydrogen, 50% helium and 1% oxygen for prevention of decompression sickness and nitrogen narcosis during very deep technical diving , is one example of human inhalation of hydrogen gas mixtures even though this particular mixture is suited only for deep technical diving applications. Drinking hydrogen-rich water (HW) appears to have comparable effects to hydrogen inhalation . Although inhaled hydrogen gas may act more rapidly, oral intake of hydrogen-rich water is another method which may be more practical for daily life or suitable for continuous consumption in preventive or therapeutic uses. Ingestion of gas dissolved solutions may prove to be more portable, easily administered, and a safe means of delivering molecular hydrogen . Gas rich water in which the gases have been dissolved could be prepared by bubbling gases into solution under pressure or other dissolution methods like swept gas diffusion. However, consideration will have to be given to loss of gas over time by dissolution and diffusion. Alternatively, some therapeutic gases such as hydrogen could be generated in solution by chemical reaction with the solution such as magnesium (Mg + 2H2O · Mg(OH)2 + H2). In this case for example, a magnesium stick could be inserted into the water just prior to drinking. However, consideration will also have to be given to ingestion of the produced byproducts as well. Though oral administration is safe and convenient, hydrogen can be lost from solution by dissolution and diffusion and some hydrogen is lost in the stomach or intestine, making it difficult to control the concentration of hydrogen administrated. Administration of hydrogen via an injectable hydrogen-rich solution may allow delivery of more accurate concentrations of hydrogen . This method of administration has been demonstrated for hydrogen in rats .
We hypothesize a systems approach of using various therapeutic medical gases as chemical radioprotectors in conjunction with biological signaling molecules to disrupt the chain of events initiated by radiation exposure and interfere with pathogenesis of disease. This could have a profound positive effect as it addresses prevention, protection, and repair. This represents a novel and feasible preventative/therapeutic strategy to address radiation-induced adverse events and thus the challenge of space radiation. While more studies are warranted to apply this therapy for space travel and determine details of optimum gas mixtures and therapy administration plans, it appears that it represents a potentially novel, therapeutic, and preventative strategy that may also ameliorate symptoms for other oxidative stress related diseases as has been shown in relevant ground-based (animal) models.
Any opinions expressed are those of the authors and do not necessarily reflect the views of NASA.
List of abbreviations
Acute Respiratory Distress Syndrom
ataxia telangiectasia mutated gene
Boiling Water Reactor
derivatives of Reactive Oxidative Metabolites
Free Radical Analytical System
Galactic Cosmic Rays
Hydrogen Water Chemistry
High Z and Energy (Z - Atomic #)
Linear Energy Transfer
Open Circuit Potential
Oxygen Enhancement Ratio
parts per billion
parts per million
Quality of Life
Reactive Oxygen Species
Solar Energetic Particles
Total Body Irradiation.
This work was originally published in Proceedings of Nuclear and Emerging Technologies for Space 2011, Albuquerque, NM, February 7-10, 2011, paper 3284 and is republished with permission from the American Nuclear Society. Copyright 2011 by the American Nuclear Society, La Grange Park, Illinois.
- Ad Hoc Committee on the Solar System Radiation Environment and NASA's Vision for Space Exploration: A Workshop Space Studies Board Division on Engineering and Physical Sciences. Space Radiation Hazards and the Vision for Space Exploration. 2006, Washington DC: The National Academies Press, 7-37.
- Parker EN: Shielding Space Travelers. Scientific American. 2006, 40-47.
- Chopping G, Liljenzin J, Rydberg J: Radiation Biology and Radiation Protection. Radiochemistry and Nuclear Chemistry. 2002, Butterworth-Heinemann, 474-513. 3View Article
- Lin C: Radiation Chemistry in Reactor Coolant. Radiochemistry in Nuclear Power Reactors. 1996, Washington, DC: National Academy Press, 125-142.
- Nakao A, Kaczorowski DJ, Sugimoto R, Billiar TR, McCurry KR: Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury. J Clin Biochem Nutr. 2008, 42: 78-88. 10.3164/jcbn.2008013.PubMed CentralView ArticlePubMed
- Hanaoka K: Antioxidant Effects of Water Produced by Electrolysis of Sodium Chloride Solutions. Journal of Applied Electrochemistry. 2001, 31: 1307-1313. 10.1023/A:1013825009701.View Article
- Testard I, Ricoul M, Hoffschir F, Flury-Herard A, Dutrillaux B, Fedorenko B, Gerasimenko V, Sabatier L: Radiation-induced Chromosome Damage in Astronauts' Lymphocytes. Int J Radiat Biol. 1996, 70: 403-411. 10.1080/095530096144879.View ArticlePubMed
- Barr YR, Bacal K, Jones JA, Hamilton DR: Breast Cancer and Spaceflight: Risk and Management. Aviat Space Environ Med. 2007, 78: A26-37.PubMed
- Koike Y, Frey MA, Sahiar F, Dodge R, Mohler S: Effects of HZE Particle on the Nigrostriatal Dopaminergic System in a Future Mars Mission. Acta Astronaut. 2005, 56: 367-378. 10.1016/j.actaastro.2004.05.068.View ArticlePubMed
- Packer L, Fuchs JJ: Vitamin C in Health and Disease. 1997, New York: Marcel Dekker
- Sohal RS, Weindurch R: Oxidative Stress, Caloric Restriction, and Aging. Science. 1996, 273: 59-63. 10.1126/science.273.5271.59.PubMed CentralView ArticlePubMed
- Tobin BW, Uchakin PN, Leeper-Woodford SK: Insulin secretion and sensitivity in space flight: diabetogenic effects. Nutrition. 2002, 18: 842-8. 10.1016/S0899-9007(02)00940-1.View ArticlePubMed
- Stein TP: Space Flight and Oxidative Stress. Nutrition. 2002, 18: 867-871. 10.1016/S0899-9007(02)00938-3.View ArticlePubMed
- Cerutti PA, Trump BF: Inflammation and oxidative stress in carcinogenesis. Cancer Cells. 1991, 3: 1-7.PubMed
- Ha H, Park J, Kim YS, Endou H: Oxidative stress and chronic allograft nephropathy. Yonsei Med J. 2004, 45: 1049-1052.View ArticlePubMed
- Watson T, Goon PK, Lip GY: Endothelial Progenitor Cells, Endothelial Dysfunction, Inflammation, and Oxidative Stress in Hypertension. Antioxid Redox Signal. 2008, 10: 1079-1788. 10.1089/ars.2007.1998.View ArticlePubMed
- Tasaka S, Amaya F, Hashimoto S, Ishizaka A: Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome. Antioxid Redox Signal. 2008, 10: 739-753. 10.1089/ars.2007.1940.View ArticlePubMed
- Nunomura A, Moreira PI, Takeda A, Smith MA, Perry G: Oxidative RNA damage and neurodegeneration. Curr Med Chem. 2007, 14: 2968-2975. 10.2174/092986707782794078.View ArticlePubMed
- Loh KP, Huang SH, De Silva R, Tan BK, Zhu YZ: Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res. 2006, 3: 327-337. 10.2174/156720506778249515.View ArticlePubMed
- Wei YH, Lu CY, Wei CY, Ma YS, Lee HC: Oxidative stress in human aging and mitochondrial disease consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol. 2001, 44: 1-11.PubMed
- Schoenfeld MP: A Review of Radiolysis Concerns for Water Shielding in Fission Surface Power Applications. Proceedings of Space Technology and Applications International Forum 2008 (STAIF 2008). Edited by: El-Genk M. 2008, New York: AIP Conference Proceedings 969, 337-347.
- Lillard RS, Pile DL, Butt DP: The Corrosion of Materials in Water Irradiated by 800 MeV Protons. Journal of Nuclear Materials. 2000, 278: 277-289. 10.1016/S0022-3115(99)00248-2.View Article
- Nakao A, Sugimoto R, Billiar TR, McCurry KR: Therapeutic Antioxidant Medical Gas. J Clin Biochem Nutr. 2009, 44: 1-13. 10.3164/jcbn.08-193R.PubMed CentralView ArticlePubMed
- Turner JE: Chemical and Biological Effects of Radiation. Atoms, Radiation, and Radiation Protection. 1995, New York: John Wiley & Sons, Inc, 421-422. 2
- Bjergbakke E, Draganic ZD, Sehested K, Draganic IG: Radiolytic Products in Waters Part I: Computer Simulation of Some Radiolytic Processes in the Laboratory. Radioehimiea Acta. 1989, 48: 65-71.
- Hart EJ, McDonell WR, Gordon S: The Decomposition of Light and Heavy Water Boric Acid Solutions by Nuclear Reactor Radiations. Proceedings of International Conference on the Peaceful Uses of Atomic Energy. 1955, Geneva. New York: United Nations P/839, 7: 597-
- Dean RT: Biochemistry and Pathology of Radical-Mediated Protein Oxidation. Biochem J. 1997, 324: 1-18.PubMed CentralView ArticlePubMed
- Reth M: Hydrogen peroxide as second messenger in lymphocyte activation. Nat Immunol. 2002, 3: 1129-1134. 10.1038/ni1202-1129.View ArticlePubMed
- Halliwell B, Gutteridge JM, Cross CE: Free Radicals, Antioxidants, and Human Disease: Where are we Now?. J Lab Clin Med. 1992, 119: 598-620.PubMed
- Hollander J, Gore M, Fiebig R, Mazzeo R, Ohishi S, Ohno H, Ji L: Spaceflight downregulates antioxidant defense systems in rat liver. Free Radic Biol Med. 1998, 24: 385-90. 10.1016/S0891-5849(97)00278-5.View ArticlePubMed
- Kennedy AR, Guan J, Ware JH: Countermeasures against space radiation induced Oxidative Stress in Mice. Radiat Environ Biophys. 2007, 46: 201-203. 10.1007/s00411-007-0105-4.View ArticlePubMed
- Daly MJ, Gaidamakova EK, Matrosova VY, Vasilenko A, Zhai M, Venkateswaran A, Hess M, Omelchenko MV, Kostandarithes HM, Makarova KS, Wackett LP, Fredrickson JK, Ghosal D: Accumulation of Mn(II) in Deinococcus radiodurans Facilitates Gamma Radiation Resistance. Scienceexpress. 2004
- Daly MJ, Gaidamakova EK, Matrosova VY, Vasilenko A, Zhai M, Leapman RD, Lai B, Ravel B, Li SW, Kemner KM, Fredrickson JK: Protein Oxidation Implicated as the Primary Determinant of Bacterial Radioresistance. PLoS Biol. 2007, 5 (4): 0769-0779.View Article
- Ghosal D, Omelchenko MV, Gaidamakova EK, Matrosova VY, Vasilenko A, Venkateswaran , Zhai M, Kostandarithes HM, Brim H, Makarova KS, Wackett LP, Fredrickson JK, Daly MJ: How radiation Kills Cells: Survival of Deinococcus radiodurans and Shewanella oneidenis under Oxidative Stress. FEMS Microbiology Reviews. 2005
- Isenberg JS, Maxhimer JB, Hyodo F, Pendra ML, Ridnour LA, DeGraff WG, Tsokos M, Wink DA, Roberts DD: Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury. Am J Pathol. 2008, 173 (4): 1100-1112. 10.2353/ajpath.2008.080237.PubMed CentralView ArticlePubMed
- Maxhimer JB, Soto-Pantoja DR, Ridnour LA, Shih HB, DeGraff WG, Tsokos M, Wink DA, Isenberg JS, Roberts DD: Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling. Sci Transl Med. 2009, 1 (3): 3ra7-10.1126/scitranslmed.3000139.PubMed CentralPubMed
- Casarett AP: Modification of Radiation Injury. Radiation Biology. 1968, New Jersey: Prentice-Hall, Inc, 249-262.
- Lefer DJ: A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide. Proceedings of the National Academy of Sciences. 2007, 104 (46): 17907-17908. 10.1073/pnas.0709010104.View Article
- Huang C, Kawamura T, Toyoda Y, Nakao A: Recent Advances in Hydrogen Research as a Therapeutic Medical Gas. Free Radical Research. 2010, 44 (9): 971-982. 10.3109/10715762.2010.500328.View ArticlePubMed
- Ohsawa I, Masahiro I, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen Acts as a Therapeutic Antioxidant by Selectively Reducing Cytotoxic Oxygen Radicals. Nat Med. 2007, 13: 688-694. 10.1038/nm1577.View ArticlePubMed
- Nakao A, Kaczorowski DJ, Wang Y, Cardinal JS, Buchholz BM, Sugiomoto R, Tobita K, Lee S, Toyoda Y, Billiar TR, McCurry KR: Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both. J Heart Lung Transplant. 2010, 29: 544-553. 10.1016/j.healun.2009.10.011.View ArticlePubMed
- Gharib B, Hanna S, Abdallahi O, Lepidi H, Gardette B, De Reggi M: Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation. C R Acad Sci. 2001, 3 (324): 719-724.View Article
- Xie K, Yu Y, Pei Y, Hou L, Chen S, Xiong L, Wang G: Protective Effects of Hydrogen Gas on Murine Polymicrobial Sepsis via Reducing Oxidative Stress and HMGB1 Release. Shock. 2009
- Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakano K, Ohta M, Adachi T, Obayashi H, Yoshikawa T: Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008, 28: 137-143. 10.1016/j.nutres.2008.01.008.View ArticlePubMed
- Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N: Effectiveness of Hydrogen Rich Water on Antioxidant Status on Subjects with Potential Metabolic Syndrome--An Open Label Pilot Study. J Clin Biochem Nutr. 2010, 46: 140-149. 10.3164/jcbn.09-100.PubMed CentralView ArticlePubMed
- Liu C, Cui J, Sun Q, Cai J: Hydrogen Therapy may be an effective and specific Novel Treatment for Acute Radiation Syndrome. Medical Hypotheses. 2009
- Schoenfeld MP, Ansari RR, Zakrajsek JF, Billiar TR, Toyoda Y, Wink DA, Nakao A: Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight. Med Hypotheses. 2010
- Qian L, Cao F, Cui J, Huang Y, Zhou X, Liu S, Cai J: Radioprotective effect of Hydrogen in Cultured Cells and Mice. Free Radical Research. 2010, 44 (3): 275-282. 10.3109/10715760903468758.View ArticlePubMed
- Isenberg JS: Regulation of nitric oxide signaling by thrombospondin-1: implications for anti-angiogenic therapies. Nat Rev Cancer. 2009, 9 (3): 2009-View Article
- Bolli R: Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. J Mol Cell Cardiol. 2001, 33: 1897-1918. 10.1006/jmcc.2001.1462.View ArticlePubMed
- Han W, Lijun W, Shaopeng C, Yu KN: Exogenous Carbon Monoxide Protects the Bystander Chinese Hamster Ovary Cells in Mixed Coculture System After Alpha-Particle Irradiation. Carcinogenesis. 2010, 31 (2): 275-280. 10.1093/carcin/bgp301.View ArticlePubMed
- Motterlini R, Mann BE, Foresti R: Therapeutic applications of carbon monoxide-releasing molecules. Expert Opin Investig Drugs. 2005, 14: 1305-1318. 10.1517/135437184.108.40.2065.View ArticlePubMed
- Nakao A, Toyokawa H, Tsung A, Nalesnik MA, Stolz DB, Kohmoto J, Ikeda A, Tomiyama K, Harada T, Takahashi T, Yang R, Fink MP, Morita K, Choi AM, Murase N: Ex vivo application of carbon monoxide in university of wisconsin solution to prevent intestinal cold ischemia/reperfusion injury. Am J Transplant. 2006, 6: 2243-2255. 10.1111/j.1600-6143.2006.01465.x.View ArticlePubMed
- Redl H, Bahrami S, Schlag G, Traber DL: Clinical detection of LPS and animal models of endotoxemia. Immunobiology. 1993, 187: 330-345. 10.1016/S0171-2985(11)80348-7.View ArticlePubMed
- Klimisch HJ, Chevalier HJ, Harke HP, Dontenwill W: Uptake of carbon monoxide in blood of miniature pigs and other mammals. Toxicology. 1975, 3: 301-310. 10.1016/0300-483X(75)90031-1.View ArticlePubMed
- King A, Lefer D: Cytoportective actions of hydrogen sulfide in ischaemia-reperfusion injury. Exp Physiol. 2011, 1-7. 00.00
- Elrod J, Calvert J, Morrison J, Doeller J, Kraus D, Tao L, Jiao X, Scalia R, Kiss L, Szabó C, Kimura H, Chow C, Lefer D: Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA. 2007, 104: 15560-15565. 10.1073/pnas.0705891104.PubMed CentralView ArticlePubMed
- Kamoun P: Endogenous Production of Hydrogen Sulfide in Mammals. Amino Acids. 2004, 26: 243-254.View ArticlePubMed
- Lowicka E, Beltowski J: Hydrogen Sulfide (H2S)--the Third Gas of Interest for Pharmacologist. Pharmacol Rep. 2007, 59: 4-24.PubMed
- Abraini JH, Gardette-Chauffour MC, Martinez E, Rostain JC, Lemaire C: Psychophysiological Reactions in Humans During an Open Sea Dive to 500 m with a Hydrogen-Helium-Oxygen mixture. J Appl Physiol. 1994, 76: 1113-1118.PubMed
- Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S: Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009, 64: 753-761. 10.1007/s00280-008-0924-2.View ArticlePubMed
- Cardinal JS, Zhan J, Wang Y, Sugimoto R, Tsung A, McCurry KR, Billiar TR, Nakao A: Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int. 2009, 77: 101-109.View ArticlePubMed
- Cai J, Kang Z, Liu K, Liu W, Li R, Zhang JH, Luo X, Sun X: Neuroprotective Effects of Hydrogen Saline in Neonatal Hypoxia-ischemia Rat Model. Brain Res. 2009, 1256: 129-137.View ArticlePubMed
- Pinsky DJ, Naka Y, Chowdhury NC, Liao H, Oz MC, Michler RE, Kubaszewski E, Malinski T, Stern DM: The nitric oxide/cyclic GMP pathway in organ transplantation: critical role in successful lung preservation. Proc Natl Acad Sci. 1994, 91: 12086-12090. 10.1073/pnas.91.25.12086.PubMed CentralView ArticlePubMed
- Buchholz BM, Kaczorowski DJ, Sugimoto R, Yang R, Wang Y, Billiar TR, McCurry KR, Bauer AJ, Nakao A: Hydrogen inhalation ameliorates oxidative stress in transplantation induced 170 intestinal graft injury. Am J Transplant. 2008, 8: 2015-24. 10.1111/j.1600-6143.2008.02359.x.View ArticlePubMed
- Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Tanaka Y, Nakabeppu Y, Noda M: Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4- 173 phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PLoS One. 2009, 4 (9): e7247-10.1371/journal.pone.0007247.PubMed CentralView ArticlePubMed
- Sun Q, Kang Z, Cai J, Liu W, Liu Y, Zhang JH, Denoble PJ, Tao H, Sun X: Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats. Exp Biol Med. 2009, 234: 1212-1219. 10.3181/0812-RM-349.View Article
- Mao YF, Zheng XF, Cai JM, You XM, Deng XM, Zhang JH, Jiang L, Sun XJ: Hydrogen-rich saline reduces lung injury induced by intestinal ischemia/reperfusion in rats. Biochem Biophys Res Commun. 2009, 381: 602-605. 10.1016/j.bbrc.2009.02.105.View ArticlePubMed
- Chen XL, Zhang Q, Zhao R, Medford RM: Superoxide, H2O2, and iron are required for TNF-alpha-induced MCP-1gene expression in endothelial cells: role of Rac1 and NADPH oxidase. Am J Physiol Heart Circ Physiol. 2004, 286: 1001-1007.View Article
- Padmaja S, Huie RE: The reaction of nitric oxide with organic peroxyl radicals. Biochem Biophys Res Commun. 1993, 195: 539-544. 10.1006/bbrc.1993.2079.View ArticlePubMed
- Kim YM, Bergonia H, Lancaster JR: Nitrogen oxide-induced autoprotection in isolated rat hepatocytes. FEBS Lett. 1995, 374: 228-232. 10.1016/0014-5793(95)01115-U.View ArticlePubMed
- Nunoshiba T, deRojas-Walker T, Wishnok JS, Tannenbaum SR, Demple B: Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. Proc Natl Acad Sci. 1993, 90: 9993-9997. 10.1073/pnas.90.21.9993.PubMed CentralView ArticlePubMed
- Ahluwalia A, Foster P, Scotland RS, McLean PG, Mathur A, Perretti M, Moncada S, Hobbs AJ: Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitment. Proc Natl Acad Sci. 2004, 101: 1386-13891. 10.1073/pnas.0304264101.PubMed CentralView ArticlePubMed
- Nath KA, Balla J, Croatt AJ, Vercellotti GM: Heme protein-mediated renal injury: a protective role for 21-aminosteroids in vitro and in vivo. Kidney Int. 1995, 47: 592-602. 10.1038/ki.1995.75.View ArticlePubMed
- Kumar S, Bandyopadhyay U: Free heme toxicity and its detoxification systems in human. Toxicol Lett. 2005, 157 (3): 175-188. 10.1016/j.toxlet.2005.03.004.View ArticlePubMed
- Bilban M, Bach FH, Otterbein SL, Ifedigbo E, d'Avila JC, Esterbauer H, Chin BY, Usheva A, Robson SC, Wagner O, Otterbein LE: Carbon monoxide orchestrates a protective response through PPARgamma. Immunity. 2006, 24 (5): 601-610. 10.1016/j.immuni.2006.03.012.View ArticlePubMed
- Taillé C, El-Benna J, Lanone S, Boczkowski J, Motterlini R: Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the antiproliferative effect of carbon monoxide in human airway smooth muscle. J Biol Chem. 2005, 280: 25350-25360. 10.1074/jbc.M503512200.View ArticlePubMed
- Zuckerbraun BS, Chin BY, Bilban M, d'Avila JC, Rao J, Billiar TR, Otterbein LE: Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species. FASEB J. 2007, 21: 1099-1106. 10.1096/fj.06-6644com.View ArticlePubMed
- Lee BS, Heo J, Kim YM, Shim SM, Pae HO, Kim YM, Chung HT: Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells. Biochem Biophys Res Commun. 2006, 343: 965-972. 10.1016/j.bbrc.2006.03.058.View ArticlePubMed
- Sawle P, Foresti R, Mann BE, Johnson TR, Green CJ, Motterlini R: Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br J Pharmacol. 2005, 145: 800-810. 10.1038/sj.bjp.0706241.PubMed CentralView ArticlePubMed
- Hegazi RA, Rao KN, Mayle A, Sepulveda AR, Otterbein LE, Plevy SE: Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med. 2005, 202: 1703-1713. 10.1084/jem.20051047.PubMed CentralView ArticlePubMed
- Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Cheung NS, Halliwell B, Moore PK: The Novel Neuromodulator Hydrogen Sulfide: An Endogenous Peroxynitrite 'scavenger'?. J Neurochem. 2004, 90: 765-768. 10.1111/j.1471-4159.2004.02617.x.View ArticlePubMed
- Kimura Y, Kimura H: Hydrogen Sulfide Protects Neurons from Oxidative Stress. FASEB J. 2004, 18: 1165-1167.PubMed
- Oh GS, Pae HO, Lee BS, Kim BN, Kim JM, Kim HR, Jeon SB, Jeon WK, Chae HJ, Chung HT: Hydrogen Sulfide Inhibits Nitric Oxide Production and Nuclear Factor-kappaB via heme oxygenase-1 Expression in RAW264.7 Macrophages Stimulated 2 with Lipopolysaccharide. Free Radic Biol Med. 2006, 41: 106-119. 10.1016/j.freeradbiomed.2006.03.021.View ArticlePubMed
- Qingyou Z, Junbao D, Weijin Z, Hui Y, Chaoshu T, Chunyu Z: Impact of Hydrogen Sulfide on Carbon Monoxide/Heme Oxygenase Pathway in the Pathogenesis of Hypoxic Pulmonary Hypertension. Biochem Biophys Res Commun. 2004, 371: 30-37.View Article
- Laggner H, Muellner MK, Schreier S, Sturm B, Hermann M, Exner M, Gmeiner BM, Kapiotis S: Hydrogen sulphide: a novel physiological inhibitor of LDL atherogenic modification by HOCl. Free Radic Res. 2007, 41: 741-747. 10.1080/10715760701263265.View ArticlePubMed
- Sodha NR, Clements RT, Feng J, Liu Y, Bianchi C, Horvath EM, Szabo C, Sellke FW: The Effects of Therapeutic Sulfide on Myocardial Apoptosis in Response to Ischemia-Reperfusion injury. Eur J Cardiothorac Surg. 2008, 33: 906-913. 10.1016/j.ejcts.2008.01.047.PubMed CentralView ArticlePubMed
- Simon F, Giudici R, Duy CN, Schelzig H, Oter S, Gröger M, Wachter U, Vogt J, Speit G, Szabó C, Radermacher P, Calzia E: Hemodynamic and Metabolic Effects of Hydrogen Sulfide During Porcine Ischemia/Reperfusion Injury. Shock. 2008,
- Blackstone E, Morrison M, Roth MB: H2S induces a suspended animation-like state in mice. Science. 2005, 308: 518-10.1126/science.1108581.View ArticlePubMed
- Blackstone E, Roth MB: Suspended animation-like state protects mice from lethal hypoxia. Shock. 2007, 27: 370-372. 10.1097/SHK.0b013e31802e27a0.View ArticlePubMed
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