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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S. Ohta / Biochimica et Biophysica Acta 1820 (2012) 586–594 587 Fig. 1. Illustration of the generation and scavenging systems of reactive oxygen species (ROS) in mitochondria. Superoxide radical anions (•O2−) are generated by the reaction of oxygen (O2) with an electron leaked from the electron transport chain of mitochondria. •O2− is non-enzymatically or enzymatically converted to hydrogen peroxide (H2O2) with Mn-superoxide dismutase (Mn-SOD), and detoxified with Glutatione peroxidase (GPx) to water. Some H2O2 are converted to the most reactive ROS, hydroxyl radicals (•OH) by the Fenton reaction. •OH damages DNA, proteins and membranes. Additionally, nitric oxide (NO•) reacts with •O2− to generate peroxynitrite (ONOO−). Molecular hydrogen (H2) cannot directly react with •O2−, H2O2 and NO, but can with •OH. which functions in cell signaling [12–14] and has favorable distribution characteristics in its own physical ability to penetrate biomembranes and diffuse through barriers into cellular components. Here, we review the recent progress toward therapeutic and preventive applications of hydrogen. 2. ROS as one of the major causes of acute and chronic diseases Oxidative stress arises from an excess of free oxidizing radicals. As the first step in generating ROS, the majority of •O2− is generated in mitochondria by electron leakage from the electron transport chain [2,4–6]. Acute oxidative stress may arise from a variety of different situations: inflammation, heavy exercise, cardiac infarction, cessation of operative bleeding, organ transplantation, and others. The accelerated generation of ROS by reperfusion of the ischemic myocardium is a potential mediator of reperfusion injury [15–18]. During myocardial reperfusion, •O2− is generated within the injured mitochondria via electron leakage from the electron transport chain. Superoxide dismutase converts •O2− to H2O2, which is metabolized by glutathione peroxidase or catalase to generate H2O. Highly reactive •OH is generated from H2O2 via the Fenton or Weise reaction in the presence of catalytically active metals, such as Fe2+ and Cu+ [19,20]. These ROS mediate myocardial injury by inducing mitochondrial permeability transition pore (PTP) opening, causing a loss of mitochondrial membrane potential, and leading to mitochondrial swelling with membrane rupture [21]. Many attempts have been made to inhibit ROS production to limit the extent of reperfusion injury. The administration of ROS scavengers at the time of reperfusion has produced conflicting results that can be partially explained by the dual role of ROS in ischemia–reperfusion hearts [22,23]. The majority of detrimental effects associated with lethal reperfusion injury are attributed to •OH. By comparison, •O2− and H2O2 have less oxidative energy and, paradoxically, are implicated as crucial signaling components in the establishment of tolerance to oxidative stress. The inhibition of both pathways may be deleterious since ROS signaling during the first few minutes of myocardial reperfusion is essential for beneficial ischemic post-conditioning [24,25]. It is widely accepted that persistent oxidative stress is one of the causes of lifestyle-related diseases, aging, and cancer. ROS are generated inside the body in various situations in daily life, such as hard exercise, smoking, being exposed to ultraviolet rays or air pollution, aging, stress, and so on [26–29]. Inside the body of every aerobic organism, ROS are generated when breathing activity consumes oxygen. These ROS are generated under the condition of excessively high membrane potential at the mitochondrial inner membrane. Thereby, uncoupling proteins control the membrane potential to suppress the production of ROS and then consequently to repress diabetes [30–32]. 3. Characteristics of molecular hydrogen Hydrogen is the most abundant element in the universe, constituting nearly 75% of the universe's mass; however, hydrogen is absent on the earth in its monoatomic form and found in water and organic or inorganic compounds. Hydrogen gas, with the molecular formula H2, is a colorless, odorless, tasteless and highly combustible diatomic gas. The earth's atmosphere contains less than 1 ppm of hydrogen gas [33]. Molecular hydrogen is rather less active and behaves as an inert gas in the absence of catalysts or at body temperature. H2 does not react with most compounds, including oxygen gas at room temperature. Hydrogen gas is flammable only at temperature higher than 527 °C, and explodes by the rapid chain reaction with oxygen only in the explosive range of the H2 concentration (4–75%, vol/vol). Although H2 has had a reputation for being a highly flammable diatomic gas since the explosion of the Hindenburg airship in 1937, there is no risk of combustion at levels less than 4%. Furthermore, safety standards are established for high concentrations of H2 gas for inhalation since high pressure H2 gas is used in deep diving gas mixes to prevent decompression sickness and arterial gas thrombi [34]. The safety of hydrogen for humans is demonstrated by its application in Hydreliox, an exotic, breathing gas mixture of 49% hydrogen, 50% helium and 1% oxygen, which is used for the prevention of

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