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      Therapeutic effect of molecular hydrogen in corneal UVB-induced oxidative stress and corneal photodamage

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          Abstract

          The aim of this study is to examine whether molecular hydrogen (H 2) is able to reduce oxidative stress after corneal damage induced by UVB irradiation. We previously found that UVB irradiation of the cornea caused the imbalance between the antioxidant and prooxidant enzymes in the corneal epithelium, followed by the imbalance between metalloproteinases and their physiological inhibitors (imbalances in favour of prooxidants and metalloproteinases) contributing to oxidative stress and development of the intracorneal inflammation. Here we investigate the effect of H 2 dissolved in PBS in the concentration 0.5 ppm wt/vol, applied on rabbit corneas during UVB irradiation and healing (UVB doses 1.01 J/cm 2 once daily for four days). Some irradiated corneas remained untreated or buffer treated. In these corneas the oxidative stress appeared, followed by the excessive inflammation. Malondiladehyde and peroxynitrite expressions were present. The corneas healed with scar formation and neovascularization. In contrast, in H 2 treated irradiated corneas oxidative stress was suppressed and malondiladehyde and peroxynitrite expressions were absent. The corneas healed with the restoration of transparency. The study provides the first evidence of the role of H 2 in prevention of oxidative and nitrosative stress in UVB irradiated corneas, which may represent a novel prophylactic approach to corneal photodamage.

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          Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.

          Molecular hydrogen (H2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H2. There are several methods to ingest or consume H2; inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.
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            Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications

            Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
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              Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model.

              Cerebral hypoxia-ischemia (HI) represents a major cause of brain damage in the term newborn. This study aimed to examine the short and long-term neuroprotective effect of hydrogen saline (H(2) saline) using an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to left common carotid artery ligation and then 90 min hypoxia (8% oxygen at 37 degrees C). H(2) saturated saline was administered by peritoneal injection (5 ml/kg) immediately and again at 8 h after HI insult. At 24 h after HI, the pups were decapitated and brain morphological injury was assessed by 2,3,5-triphenyltetrazolium chloride (TTC), Nissl, and TUNEL staining. Acute cell death, inflammation and oxidative stress were evaluated at 24 h by studying caspase-3 activity, MDA measurement as well as Iba-1 immunochemistry in the brain. At 5 weeks after HI, spontaneous activity test and Morris water maze test were conducted. We observed that H(2) saline treatment reduced the caspase activity, MDA, Iba-1 levels, the infarct ratio, and improved the long-term neurological and neurobehavioral functions. H(2) saline has potentials in the clinical treatment of HI and other ischemia-related cerebral diseases.
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                Author and article information

                Contributors
                cejkova@biomed.cas.cz
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 December 2017
                21 December 2017
                2017
                : 7
                : 18017
                Affiliations
                [1 ]ISNI 0000 0004 0404 6946, GRID grid.424967.a, Institute of Experimental Medicine of the Czech Academy of Sciences, ; 14220 Prague 4, Czech Republic
                [2 ]ISNI 0000 0004 1937 116X, GRID grid.4491.8, Faculty of Natural Science, , Charles University, ; Vinicna 7, 12843 Prague 2, Czech Republic
                [3 ]ISNI 0000 0000 9852 649X, GRID grid.43582.38, Loma Linda University School of Medicine, ; Loma Linda, CA 92350 USA
                Article
                18334
                10.1038/s41598-017-18334-6
                5740126
                29269749
                16215612-c988-40ce-b93e-15175145fab0
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 October 2017
                : 8 December 2017
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