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Molecular Hydrogen as a Novel Antioxidant in Sports Science

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Molecular Hydrogen as a Novel Antioxidant in Sports Science ( molecular-hydrogen-as-novel-antioxidant-sports-science )

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2 Oxidative Medicine and Cellular Longevity Table 1: Advantages and disadvantages of molecular hydrogen. Advantages Easily penetrates the cellular membrane and rapidly diffuses into organelles Selectively reduces ⋅OH and ONOO- and does not affect physiological reactive species Can be supplied to the body through multiple routes of administration Can be used with minimal side effects as it is excreted by exhaling Disadvantages Dwells in the body for a short time The optimal intake protocol has not been established The effects of long-term intake are unknown Small number of studies can be used with minimal side effects as it is excreted by exhal- ing. Despite several disadvantages (Table 1), the aforemen- tioned advantages of H2 use are expected to lead to an increase in research regarding its application in sports science. The purpose of this review is to provide evidence regard- ing the effects of H2 intake on changes in physiological and biochemical parameters, centering on exercise-induced oxi- dative stress, as well as illustrate the mechanisms underlying the biological actions of H2. More specifically, this review describes findings from previous studies regarding the effects of each method of H2 administration. Moreover, we also summarize possible future directions for this area of research. 2. Biological Actions of Molecular Hydrogen Although the antioxidative action of H2 was suggested in the study by Dole et al. [10] in 1975, its biological action has been overlooked for many years. Later, in 2007, it was reported that H2 selectively removes ⋅OH and ONOO-, which are strong oxidants, in vitro and that H2 suppresses oxidative stress after ischemia and reperfusion injury in vivo [3]. Since then, H2 has attracted widespread interest as a novel antiox- idant and numerous previous studies have reported on the effectiveness of H2 for various diseases and disease models associated with oxidative stress [1, 4–8]. However, the direct removal of ⋅OH and ONOO- alone cannot fully explain the beneficial effects exerted by H2 in these diseases. Therefore, the indirect effects of H2 on the regulation of intracellular signaling pathways and gene expression have been investi- gated [1, 4–8]. Specifically, it has been shown that H2 activates Nrf2 (nuclear factor-erythroid-derived 2-like-2) under oxidative stress conditions to increase the gene expression of antioxidant enzymes such as superoxide dis- mutase (SOD) and catalase [1, 4–8]. H2 has also been shown to downregulate the transcription factor NF-κB and inflam- matory cytokines (e.g., interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF-α)) in oxidative stress-induced inflam- mation [1, 4–8]. Moreover, recent studies have suggested that H2 suppresses lipid peroxidation associated with free radical chain reactions [11] H2 Direct actions ‧ OH and ONOO- ↓ Free radical chain reaction ↓ Biological actions Antioxidation Anti-inflammation Indirect actions Antioxidant enzymes Pro-inflammatory cytokines Oxidative stress-related diseases ↓ Figure 1: Possible simplified biological actions of molecular hydrogen: focusing on antioxidant and anti-inflammatory actions. Taken together, the antioxidant action of H2 is consid- ered to be not only direct, by selective removal of reactive species [3] and suppression of free radical chain reactions for lipid peroxidation [11], but also indirect, by inducing the expression of antioxidant enzymes. Furthermore, consid- ering that H2 downregulates the expression of inflammatory cytokines [1, 4–8], this may also suppress infiltration of phagocytes into the inflammatory site and subsequent release of reactive species. Possible biological actions of H2 are shown in Figure 1. 3. Exercise-Induced Oxidative Stress Exercise is one of the physiological stimuli that promote the generation of reactive species in the living bodies. The gener- ation of reactive species by exercise depends on exercise intensity, duration, and modality [12, 13]. The living body is equipped with an enzymatic or nonenzymatic antioxidant defense system. However, oxidative stress occurs when the levels of reactive species surpass the antioxidant capacity of the organism [14]. Exercise-induced oxidative stress has been shown to result in transient declines in physical functions through muscle fatigue, muscle damage and inflammation, and delayed-onset muscle soreness (DOMS) [12, 13, 15]. Moreover, there are many previous studies which have verified the effectiveness of taking exogenous antioxidants [12, 13, 15]. On the other hand, it should be mentioned that long- term excessive intake of exogenous antioxidants inhibits redox-sensitive signaling pathways and interferes with phys- iological adaptations to exercise training, such as mitochon- drial biogenesis, cardiac and skeletal muscle hypertrophy, and improvement of insulin sensitivity [13, 16]. The results of previous studies regarding exercise redox biology indicate that the generation of excess levels of reactive species has a negative effect, while the generation of low-to-moderate levels of reactive species has a positive effect on the living body. The dependence of physiological responses or adapta- tions on the level of reactive species is called exercise ? Exercise adaptations

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