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      Hydrogen-rich saline may be an effective and specific novel treatment for osteoradionecrosis of the jaw

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          Abstract

          Hydrogen, a therapeutic medical gas, can exert antioxidant activity via selectively reducing cytotoxic reactive oxygen species such as hydroxyl radicals. Hydrogen-rich saline is an alternative form of molecular hydrogen that has been widely used in many studies, including metabolic syndrome, cerebral, hepatic, myocardial ischemia/reperfusion, and liver injuries with obstructive jaundice, with beneficial results. Osteoradionecrosis of the jaw is a serious complication following radiotherapy for head and neck cancers. It has long been known that most radiation-induced symptoms are caused by free radicals generated by radiolysis of H 2O, and the hydroxyl radical is the most reactive of these. Reducing the hydroxyl radical can distinctly improve the protection of cells from radiation damage. We hypothesized that hydrogen-rich saline might be an effective and specific method of managing and preventing osteoradionecrosis of the jaw.

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          Most cited references 44

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          Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions.

           E Stadtman (1992)
          Basic mechanisms that underlie the oxygen free radical-promoted oxidation of free amino acids and amino acid residues of proteins are derived from radiolysis studies. Results of these studies indicate that the most common pathway for the oxidation of simple aliphatic amino acids involves the hydroxyl radical-mediated abstraction of a hydrogen atom to form a carbon-centered radical at the alpha-position of the amino acid or amino acid residue in the polypeptide chain. Addition of O2 to the carbon-centered radicals leads to formation of peroxy radical derivatives, which upon decomposition lead to production of NH3 and alpha-ketoacids, or to production of NH3, CO2, and aldehydes or carboxylic acids containing one less carbon atom. As the number of carbon atoms in the amino acid is increased, hydrogen abstraction at other positions in the carbon chain becomes more important and leads either to the formation of hydroxy derivatives, or to amino acid cross-linked products as a consequence of carbon-centered radical recombination processes. alpha-Hydrogen abstraction plays a minor role in the oxidation of aromatic amino acids by radiolysis. Instead, the aromatic ring is the primary site of attack leading to hydroxy derivatives, to ring scission, and in the case of tyrosine to the formation of Tyr-Tyr cross-linked dimers. The basic pattern for the oxidation of amino acids by metal ion-catalyzed reactions (Fenton chemistry) is similar to the alpha-hydrogen abstraction pathway. But unlike the case of oxidation by radiolysis, this Fenton pathway is the major mechanism for the oxidation of all aliphatic amino acids, regardless of chain length, as well as for the oxidation of aromatic amino acids. Curiously, the Fe(III)-catalyzed oxidation of free amino acids is almost completely dependent upon the presence of bicarbonate ion, and is greatly stimulated by iron chelators at chelator/Fe(III) ratios less than 1.0, and is inhibited at chelator/Fe(III) ratios greater than 1.0. It is deduced that the most active catalytic complex is composed of two equivalents of HCO3-, an amino acid, and at least one equivalent of iron; however, two forms of iron, an iron-chelate and another form, must somehow be involved. In contrast to the situation with radiolysis, the aromatic rings of aromatic amino acids are only minor targets for metal-catalyzed reactions. All amino acid residues in proteins are subject to attack by hydroxyl radicals generated by ionizing radiation; however, the aromatic amino acids and sulfur-containing amino acids are most sensitive to oxidation.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome—An Open Label Pilot Study

            Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5–2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55–0.65 mM), by the following chemical reaction; Mg + 2H2O → Mg (OH)2 + H2. The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.
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              Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury.

              Ischemia/reperfusion (I/R) injury during small intestinal transplantation (SITx) frequently causes complications including dysmotility, inflammation and organ failure. Recent evidence indicates hydrogen inhalation eliminates toxic hydroxyl radicals. Syngeneic, orthotopic SITx was performed in Lewis rats with 3 h of cold ischemic time. Both donor and recipient received perioperative air or 2% hydrogen inhalation. SITx caused a delay in gastrointestinal transit and decreased jejunal circular muscle contractile activity 24 h after surgery. Hydrogen treatment resulted in significantly improved gastrointestinal transit, as well as jejunal smooth muscle contractility in response to bethanechol. The transplant induced upregulation in the inflammatory mediators CCL2, IL-1 beta, IL-6 and TNF-alpha were mitigated by hydrogen. Hydrogen significantly diminished lipid peroxidation compared to elevated tissue malondialdehyde levels in air-treated grafts demonstrating an antioxidant effect. Histopathological mucosal erosion and increased gut permeability indicated a breakdown in posttransplant mucosal barrier function which was significantly attenuated by hydrogen treatment. In recipient lung, hydrogen treatment also resulted in a significant abatement in inflammatory mRNA induction and reduced neutrophil recruitment. Hydrogen inhalation significantly ameliorates intestinal transplant injury and prevents remote organ inflammation via its antioxidant effects. Administration of perioperative hydrogen gas may be a potent and clinically applicable therapeutic strategy for intestinal I/R injury.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                14 October 2015
                : 11
                : 1581-1585
                Affiliations
                Department of Cranio-facial Trauma and Orthognathic Surgery Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi’an, People’s Republic of China
                Author notes
                Correspondence: Lei Tian, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi’an, 710032, People’s Republic of China, Tel +86 29 8477 6109, Fax +86 29 8477 6097, Email tianleison@ 123456163.com
                Article
                tcrm-11-1581
                10.2147/TCRM.S90770
                4610769
                © 2015 Chen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Hypothesis

                Medicine

                reactive oxygen species, hydrogen, osteoradionecrosis

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