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Molecular hydrogen antioxidant to reduce oxidative stress

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Molecular hydrogen antioxidant to reduce oxidative stress ( molecular-hydrogen-antioxidant-reduce-oxidative-stress )

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Biochimica et Biophysica Acta 1820 (2012) 586–594 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbagen Review Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases☆ Shigeo Ohta ⁎ Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396, Kosugi-machi, Nakahara-ku, Kawasaki-city, Kanagawa-pref. 211-8533, Japan article info Article history: Received 31 March 2011 Received in revised form 9 May 2011 Accepted 12 May 2011 Available online 20 May 2011 Keywords: Antioxidant Hydrogen Hydrogen medicine Mitochondrion Oxidative stress Prevention 1. Introduction Mitochondria are central to oxidative phosphorylation and much of the metabolism, and are also involved in many aspects of cell death [1]. Consequently, mitochondrial dysfunction contributes to a wide range of human pathologies. In many of these, excessive oxidative damage is a major factor because the mitochondrial respiratory chain is a significant source of damaging reactive oxygen species (ROS), superoxide (•O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) [2], as illustrated in Fig. 1; however, despite the clinical importance of mitochondrial oxidative damage, antioxidants have had limited therapeutic success [3–8]. Oxidative stress arises from the strong cellular oxidizing potential of excess ROS. Acute oxidative stress may arise from a variety of situations: inflammation, heavy exercise, cardiac infarction, cessation of operative bleeding, organ transplantation, and others [6]. On the ☆ This article is part of a Special Issue entitled Biochemistry of Mitochondria. ⁎ Tel.: +81 44 733 9267; fax: +81 44 733 9268. E-mail address: ohta@nms.ac.jp. 0304-4165/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.bbagen.2011.05.006 abstract Background: Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process; however, there has been little success in developing an effective antioxidant with no side effect. We have reported that molecular hydrogen has potential as an effective antioxidant for medical applications [Ohsawa et al., Nat. Med. 13 (2007) 688–694]. Scope of review: We review the recent progress toward therapeutic and preventive applications of hydrogen. Since we published the first paper in Nature Medicine, effects of hydrogen have been reported in more than 38 diseases, physiological states and clinical tests in leading biological/medical journals. Based on this cumulative knowledge, the beneficial biological effects of hydrogen have been confirmed. There are several ways to intake or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water, taking a hydrogen bath, injecting hydrogen-dissolved saline, dropping hydrogen-dissolved saline into the eyes, and increasing the production of intestinal hydrogen by bacteria. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti- inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders. Major conclusions: Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive. General significance: Hydrogen is a novel antioxidant with great potential for actual medical applications. This article is part of a Special Issue entitled Biochemistry of Mitochondria. © 2011 Elsevier B.V. All rights reserved. other hand, persistent oxidative stress is accepted as one of the causes of many common diseases, cancer and the aging process; however, most clinical trials with dietary antioxidants failed to show marked success in preventing oxidative stress-related diseases [9]. Thus, it is very important to find an effective antioxidant with no side effects. We found that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [10]. In the three and a half years since the first hydrogen paper was published in Nature Medicine, hydrogen effects have been reported in 38 diseases and physiological states [11], establishing overwhelming support for the beneficial biological effects of hydrogen have been established. There are several ways to ingest or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water (hydrogen water), taking a hydrogen-dissolved bath, injecting hydrogen-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eyes, and increasing the production of intestinal hydrogen by bacteria. Further- more, H2 exhibits not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. H2 has a number of advantages as a potential antioxidant: it is mild enough not to disturb metabolic redox reactions or to affect ROS,

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