Molecular Hydrogen: Redox Reactions and Possible Biological Interactions

Molecular hydrogen (H2), either as a gas or as hydrogen-rich water (HRW), is suggested to be a useful treatment for a range of human diseases and also to improve agricultural output. It is often posited that H2 accomplishes its biological action, in part, through its antioxidant effects, including reacting with hydroxyl radicals (OH˙) and peroxynitrite (ONOOˉ); however, this direct reaction has been questioned. The antioxidant effects of H2 are also often mediated by heme oxygenase-1 (HO-1), although the exact mechanism remains elusive. Alternatively, it has been proposed that H2 can propagate its effects through the reduction of Fe3+ in various redox-active proteins, which is the focus of this review. It is suggested that a systematic experimental analysis of proteins containing heme prosthetic groups would help elucidate the biological mechanisms of H2 and its development as a medical and restorative therapeutic. (First online: May 10, 2021)

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Hydrogenases and the Role of Molecular Hydrogen in Plants

Plants ◽

10.3390/plants9091136 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1136 ◽

Cited By ~ 1

Author(s):

Grace Russell ◽

Faisal Zulfiqar ◽

John T. Hancock

Keyword(s):

Stress Responses ◽

Molecular Hydrogen ◽

Molecular Mechanisms ◽

Covalent Modification ◽

Cellular Effects ◽

Oxidation Of H2 ◽

Redox Active ◽

Future Work ◽

Prosthetic Groups

Molecular hydrogen (H2) has been suggested to be a beneficial treatment for a range of species, from humans to plants. Hydrogenases catalyze the reversible oxidation of H2, and are found in many organisms, including plants. One of the cellular effects of H2 is the selective removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS), specifically hydroxyl radicals and peroxynitrite. Therefore, the function of hydrogenases and the action of H2 needs to be reviewed in the context of the signalling roles of a range of redox active compounds. Enzymes can be controlled by the covalent modification of thiol groups, and although motifs targeted by nitric oxide (NO) can be predicted in hydrogenases sequences it is likely that the metal prosthetic groups are the target of inhibition. Here, a selection of hydrogenases, and the possibility of their control by molecules involved in redox signalling are investigated using a bioinformatics approach. Methods of treating plants with H2 along with the role of H2 in plants is also briefly reviewed. It is clear that studies report significant effects of H2 on plants, improving growth and stress responses, and therefore future work needs to focus on the molecular mechanisms involved.

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Beyond Antioxidant Effects: Nature-Based Templates Unveil New Strategies for Neurodegenerative Diseases

Antioxidants ◽

10.3390/antiox10030367 ◽

2021 ◽

Vol 10 (3) ◽

pp. 367

Author(s):

Andrea Bacci ◽

Massimiliano Runfola ◽

Simona Sestito ◽

Simona Rapposelli

Keyword(s):

Drug Discovery ◽

Neurodegenerative Diseases ◽

Redox Reactions ◽

Identification Process ◽

Defense Systems ◽

Natural Defense ◽

Effective Drugs ◽

Antioxidant Effects ◽

Neuronal Disorders ◽

New Strategies

The complex network of malfunctioning pathways occurring in the pathogenesis of neurodegenerative diseases (NDDs) represents a huge hurdle in the development of new effective drugs to be used in therapy. In this context, redox reactions act as crucial regulators in the maintenance of neuronal microenvironment homeostasis. Particularly, their imbalance results in the severe compromising of organism’s natural defense systems and subsequently, in the instauration of deleterious OS, that plays a fundamental role in the insurgence and progress of NDDs. Despite the huge efforts in drug discovery programs, the identification process of new therapeutic agents able to counteract the relentless progress of neurodegenerative processes has produced low or no effective therapies. Consequently, a paradigm-shift in the drug discovery approach for these diseases is gradually occurring, paving the way for innovative therapeutical approaches, such as polypharmacology. The aim of this review is to provide an overview of the main pharmacological features of most promising nature-based scaffolds for a possible application in drug discovery, especially for NDDs, highlighting their multifaceted effects against OS and neuronal disorders.

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Anti-Inflammatory and Antioxidant Effects of Soroseris hirsuta Extract by regulating iNOS/NF-κB and NRF2/HO-1 Pathways in Murine Macrophage RAW 264.7 Cells

Applied Sciences ◽

10.3390/app11104711 ◽

2021 ◽

Vol 11 (10) ◽

pp. 4711

Author(s):

Woo Jin Lee ◽

Wan Yi Li ◽

Sang Woo Lee ◽

Sung Keun Jung

Keyword(s):

Nitric Oxide ◽

Nuclear Translocation ◽

Antioxidant Properties ◽

Raw 264.7 Cells ◽

Heme Oxygenase 1 ◽

Raw 264.7 ◽

Related Factor ◽

Iκb Kinase ◽

Anti Inflammatory ◽

Antioxidant Effects

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.

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Redox‐Active Phenolic Compounds Mediate the Cytotoxic and Antioxidant Effects of Carpodesmia tamariscifolia (= Cystoseira tamariscifolia )

Chemistry & Biodiversity ◽

10.1002/cbdv.202000121 ◽

2020 ◽

Vol 17 (7) ◽

Author(s):

Hanaa Moussa ◽

Elías Quezada ◽

Dolores Viña ◽

Hassane Riadi ◽

José Gil‐Longo

Keyword(s):

Phenolic Compounds ◽

Redox Active ◽

Cystoseira Tamariscifolia ◽

Antioxidant Effects

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Photocatalytic redox reactions with metalloporphyrins

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424619300131 ◽

2020 ◽

Vol 24 (01n03) ◽

pp. 21-32 ◽

Cited By ~ 3

Author(s):

Shunichi Fukuzumi ◽

Yong-Min Lee ◽

Wonwoo Nam

Keyword(s):

Hydrogen Evolution ◽

Redox Reactions ◽

Bond Formation ◽

Visible Region ◽

Photosynthetic Reaction Center ◽

Structure And Function ◽

Free Base ◽

Redox Catalyst ◽

Redox Active ◽

And Function

Metalloporphyrinoids are utilized as efficient sensitizers and catalysts in photosynthesis and the reverse reaction that is respiration. Because metalloporphyrinoids show strong absorption in the visible region and redox active, metalloporphyrinoids are also suited as photoredox catalysts for photo-driven redox reactions using solar energy. In particular, metalloporphyrins are utilized as pivotal components to mimic the structure and function of the photosynthetic reaction center. Metalloporphyrins are used as photoredox catalysts for hydrogen evolution from electron and proton sources combining hydrogen evolution catalysts. Metalloporphyrins also act as thermal redox catalysts for photocatalytic reduction of CO2 with photoredox catalysts. Metalloporphyrins are also used as dual catalysts for a photoredox catalyst for oxygenation of substrates with H2O and a redox catalyst for O2 reduction when dioxygen is used as a two-electron oxidant and H2O as an oxygen source, both of which are the greenest reactants. Free base porphyrins can also be employed as promising photoredox catalysts for C–C bond formation reactions.

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Molecular hydrogen potentiates beneficial anti-infarct effect of hypoxic postconditioning in isolated rat hearts: a novel cardioprotective intervention

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0693 ◽

2017 ◽

Vol 95 (8) ◽

pp. 888-893 ◽

Cited By ~ 4

Author(s):

Marek Zálešák ◽

Branislav Kura ◽

Ján Graban ◽

Veronika Farkašová ◽

Ján Slezák ◽

...

Keyword(s):

Molecular Hydrogen ◽

Redox Reactions ◽

Heart Function ◽

Ischemia Reperfusion ◽

Area At Risk ◽

Rat Hearts ◽

Hypoxic Postconditioning ◽

Cardioprotective Effects ◽

Krebs Henseleit Buffer ◽

Isolated Rat

Generation of free radicals through incomplete reduction of oxygen during ischemia–reperfusion (I/R) is well described. On the other hand, molecular hydrogen (H2) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against I/R (30 min global I – 120 min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB). Furthermore, the possibility to potentiate the effect of HpostC by H2using oxygen-free KHB saturated with H2(H2+ HpostC) was tested. HPostC was induced by 4 cycles of 1-minute perfusion with oxygen-free KHB intercepted by 1-minute perfusion with normal KHB, at the onset of reperfusion. H2+ HPostC was applied in a similar manner using H2-enriched oxygen-free KHB. Cardioprotective effects were evaluated on the basis of infarct size (IS, in % of area at risk, AR) reduction, post-I/R recovery of heart function, and occurrence of reperfusion arrhythmias. HPostC significantly reduced IS/AR compared with non-conditioned controls. H2present in KHB during HPostC further decreased IS/AR compared with the effect of HPostC, attenuated severe arrhythmias, and significantly restored heart function (vs. controls). Cardioprotection by HpostC can be augmented by molecular hydrogen infusion.

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1-Aminocyclopropanecarboxylic Acid, an Antagonist of N-Methyl-D-Aspartate Receptors, Causes Hypotensive and Antioxidant Effects with Upregulation of Heme Oxygenase-1 in Stroke-Prone Spontaneously Hypertensive Rats

Hypertension Research ◽

10.1291/hypres.30.249 ◽

2007 ◽

Vol 30 (3) ◽

pp. 249-257 ◽

Cited By ~ 7

Author(s):

Ming GAO ◽

Fumio KONDO ◽

Takayasu MURAKAMI ◽

Jin-Wen XU ◽

Ning MA ◽

...

Keyword(s):

Heme Oxygenase ◽

Spontaneously Hypertensive Rats ◽

Heme Oxygenase 1 ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Antioxidant Effects

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Interaction of iron ions with melanin

Acta Biochimica Polonica ◽

10.18388/abp.2019_2889 ◽

2019 ◽

Cited By ~ 1

Author(s):

Andrzej Czesław Żądło ◽

Tadeusz Sarna

Keyword(s):

Redox Reactions ◽

Transition Metal Ions ◽

Iron Binding ◽

Iron Ions ◽

Paramagnetic Resonance ◽

Redox Active ◽

Active Transition ◽

Electron Paramagnetic ◽

Aerobic And Anaerobic ◽

Anaerobic System

One of the antioxidant roles of melanin is binding redox-active transition metal ions. The aim of this study was to examine the redox reactions accompanying iron binding by melanin. Two kinds of synthetic eumelanin were mixed with iron (II) and iron (III) in the presence and absence of citrate and ADP in the aerobic and anaerobic system. The iron binding was examined by electron paramagnetic resonance (EPR) spectroscopy and thiocyanate assay. Obtained results indicate that although melanin reduces iron (III) that is unbound to this polymer, binding of iron (II) is accompanied by its oxidation by melanin.

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Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.658662 ◽

2021 ◽

Vol 15 ◽

Author(s):

Anette Elisabeth Fransson ◽

Pernilla Videhult Pierre ◽

Mårten Risling ◽

Göran Frans Emanuel Laurell

Keyword(s):

Hearing Loss ◽

Molecular Hydrogen ◽

Noise Exposure ◽

Real Life ◽

Outer Hair Cells ◽

Broadband Noise ◽

Hydrogen Gas ◽

Rescue Treatment ◽

Brainstem Response ◽

Antioxidant Effects

Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2-treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.

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