Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury

Kura, Branislav; Bagchi, Ashim K.; Singal, Pawan K.; Barančı́k, Miroslav; LeBaron, Tyler W.; Valachová, Katarína; Šoltés, Ladislav; Slezák, J

doi:10.1139/cjpp-2018-0604

Cited by 65 publications

(44 citation statements)

References 67 publications

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“…We reported similar changes in rats, where H 2 prevented irradiationinduced increases in TNF-α and MDA. But when H 2 was administered alone, TNF-α initially increased above control, and then decreased and remained below both the irradiated group and the non-irradiated control, whereas MDA tended to initially decrease then increase (Kura et al 2018).…”

Section: )mentioning

confidence: 82%

“…Furthermore, pretreatment of SH-SY5Y cells with H 2 protected them from subsequent oxidative stress induced by H 2 O 2 (Murakami et al 2017). In this case, H 2 acted as a mitohormetic effector by transiently increasing mitochondrial superoxide production, followed by an upregulation of Nrf2 transcription D r a f t and induction of other cytoprotective phase II proteins (Murakami et al 2017;Kura et al 2018).…”

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confidence: 95%

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Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes

LeBaron

Laher

Kura

et al. 2019

Can. J. Physiol. Pharmacol.

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H2 has been clinically demonstrated to provide antioxidant and anti-inflammatory effects, which makes it an attractive agent in exercise medicine. Although exercise provides a multiplicity of benefits including decreased risk of disease, it can also have detrimental effects. For example, chronic high-intensity exercise in elite athletes, or sporadic bouts of exercise (i.e., noxious exercise) in untrained individuals, result in similar pathological factors such as inflammation, oxidation, and cellular damage that arise from and result in disease. Paradoxically, exercise-induced pro-inflammatory cytokines and reactive oxygen species largely mediate the benefits of exercise. Ingestion of conventional antioxidants and anti-inflammatories often impairs exercise-induced training adaptations. Disease and noxious forms of exercise promote redox dysregulation and chronic inflammation, changes that are mitigated by H2 administration. Beneficial exercise and H2 administration promote cytoprotective hormesis, mitochondrial biogenesis, ATP production, increased NAD+/NADH ratio, cytoprotective phase II enzymes, heat-shock proteins, sirtuins, etc. We review the biomedical effects of exercise and those of H2, and we propose that hydrogen may act as an exercise mimetic and redox adaptogen, potentiate the benefits from beneficial exercise, and reduce the harm from noxious exercise. However, more research is warranted to elucidate the potential ergogenic and therapeutic effects of H2 in exercise medicine.

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confidence: 82%

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confidence: 95%

Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes

LeBaron

Laher

Kura

et al. 2019

Can. J. Physiol. Pharmacol.

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“…1 Molecular hydrogen modulates signal transduction, protein phosphorylation cascades, gene expression, autophagy, miRNA expression, as well as has important metabolic effects. 5,6 H 2 can induce the Keap1/Nrf2 signaling pathway, 7 promote mitochondrial biogenesis, 8 and the cytoprotective mitochondrial unfolded protein response. 9 H 2 has been proposed to act as an exercise mimetic and redox adaptogen via activating hormetic pathways.…”

Section: Introductionmentioning

confidence: 99%

<p>The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial</p>

LeBaron¹,

Singh²,

Fatima³

et al. 2020

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Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H 2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Preclinical and clinical studies have shown promising effects of H 2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. Methods: We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H 2 per day) for 24 weeks. Results: Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H 2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. Conclusion: Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.

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“…Molecular hydrogen (H 2 ) has been regarded as a novel therapeutic medical gas since the 2007-Nature Medicine publication [7]. Its potential benefits has been reported in various disease models, including cardiovascular and metabolic diseases [8], brain injury [9], inflammatory disease [10], ocular disease [11], radiation injury [12], cancer [13], and so on. We previously showed that hydrogen inhalation could effectively suppress GBM tumor growth via induction of GSCs differentiation [14].…”

Section: Introductionmentioning

confidence: 99%

Molecular hydrogen induces metabolic reprogramming to promote differentiation of glioma stem cells

Xie

Zhang

et al. 2020

Preprint

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Background: Our previous study showed that molecular hydrogen could effectively suppress glioblastoma multiforme (GBM) tumor growth via induction of glioblastoma stem cells (GSCs) differentiation. Metabolic reprogramming has been demonstrated to delicately regulate the stemness of cancer stem cells. In the present study, we explored whether metabolic reprogramming is involved in the hydrogen-induced GSCs differentiation. Methods: Immunofluorescence staining was conducted to determine the expression of cell surface markers. Glucose uptake and lactate secretion was determined by spectrophotometric method. Untargeted metabolomics analyses were conducted to investigate the metabolic alteration in GSCs after hydrogen treatment. 13 C-labeled metabolic flux analysis was performed to explore the regulatory effects of molecular hydrogen on the glucose metabolism of GSCs. Results: Immunofluorescence staining showed the up-regulated expression of oligodendroglial markers in hydrogen-treated GSCs. Both glucose uptake and lactate production in GSCs were significantly inhibited by hydrogen treatment. Untargeted metabolomics analyses showed hydrogen-induced promotion of de novo synthesis of nucleotides in GSCs. Metabolic flux analysis showed decreased glucose metabolism in GSCs induced by hydrogen. Conversely, the content of glycerol 3-phosphate, glutamate and glutamine were increased by hydrogen treatment. Conclusions: Results from this study demonstrated that molecular hydrogen could inhibit glucose metabolism and promote de novo synthesis of nucleotides in GSCs, suggesting the involvement of metabolic reprogramming in the hydrogen-induced GSCs differentiation. Our study also provides important new clues to seek the target of molecular hydrogen.

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Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury

Cited by 65 publications

References 67 publications

Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes

Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes

<p>The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial</p>

Molecular hydrogen induces metabolic reprogramming to promote differentiation of glioma stem cells

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