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Biomedicines
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Therapeutic Potential of Molecular Hydrogen in Human Diseases
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Therapeutic Potential of Molecular Hydrogen in Human Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 13325

Special Issue Editors

Dr. Shin-Ichi Hirano

E-Mail Website
Guest Editor
Department of Research and Development, MiZ Company Limited, Kanagawa, Japan
Interests: Molecular Hydrogen; Oxidative Stress; Reactive Oxygen Species; Mitochondria; Inflammation; Nitric Oxide
Prof. Dr. Yoshiyasu Takefuji

E-Mail Website
Guest Editor
1. Faculty of Data Science, Musashino University, Tokyo, Japan
2. Professor Emeritus, Faculty of Environmental Information, Keio University, Tokyo, Japan
Interests: data science; science and health policy; artificial intelligence; molecular hydrogen
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Molecular hydrogen (H2) was identified as an antioxidant that directly reduces hydroxyl radicals (·OH) and peroxynitrite. H2 also exerts indirect antioxidant, anti-inflammatory, and antiapoptotic effects via the regulation of gene expression. Other indirect mechanisms through which H2 exerts its effects have been reported, such as nuclear factor erythroid-related factor 2 and various signaling pathways in cells. The total number of studies on the biological effects of H2 now exceeds 2000. Among them, the total number of studies on human clinical trials is more than 130. A target molecule of H2 was recently identified that indicates that an oxidized form of porphyrin catalyzes the reaction of H2 with ∙OH to reduce oxidative stress; however, the details of the mechanistic actions of H2, including its target molecules, true clinical viability, and the appropriate doses as well as dosages for individual human diseases, are still in the initial stages.

This Special Issue is seeking contributions that will further elucidate the potential therapeutic use of H2 in human diseases. Both in vitro cellular and in vivo animal studies are of interest; however, studies that only contain human clinical trials or data are not suitable. Authors are invited to submit original research articles and reviews that advance our understanding of the therapeutic potential of H2 in the treatment of various human diseases.

Dr. Shin-Ichi Hirano
Prof. Dr. Yoshiyasu Takefuji
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular hydrogen
  • reactive oxygen species
  • oxidative stress, mitochondria
  • inflammation
  • nitric oxide
  • cell death
  • cellular and animal models
  • signal transduction
  • human disease

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Published Papers (4 papers)

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Research

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12 pages, 2152 KiB  
Article
Molecular Hydrogen and Extracorporeal Gas Exchange: A Match Made in Heaven? An In Vitro Pilot Study
by Foivos Leonidas Mouzakis, Flutura Hima, Ali Kashefi, Johannes Greven, Lothar Rink, Emiel P. C. van der Vorst, Joachim Jankowski, Khosrow Mottaghy and Jan Spillner
Biomedicines 2024, 12(8), 1883; https://doi.org/10.3390/biomedicines12081883 - 18 Aug 2024
Viewed by 1348
Abstract
Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC [...] Read more.
Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC treatments themselves are also responsible for sustaining or promoting inflammation. On these grounds, an in vitro study was designed to investigate the therapeutic potential of molecular hydrogen (H2) against pro-inflammatory agents in ECC settings. Five miniature ECMO circuits and a small vial (Control) were primed with heparinized blood from healthy adult donors (n = 7). Three of the ECMO systems were injected with lipopolysaccharide (LPS), out of which one was additionally treated with an H2 gas mixture. After 6 h, samples were drawn for the assessment of specific biomarkers (MCP-1, MPO, MDA-a, TRX1, and IL-6). Preliminary results indicate a progressive oxidative and inflammatory response between the six systems. Circulation has triggered inflammation and blood trauma, but the staggering influence of LPS in this outcome is indisputable. Accordingly, hydrogen’s remedial potential becomes immediately apparent as biomarker concentrations tend to be lower in the H2-handled circuit. Future research should have distinct objectives (e.g., dosage/duration/cycle of hydrogen administration) in order to ascertain the optimal protocol for patient treatment. Full article
(This article belongs to the Special Issue Therapeutic Potential of Molecular Hydrogen in Human Diseases)
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13 pages, 3400 KiB  
Article
Hydrogen Inhalation Reduces Lung Inflammation and Blood Pressure in the Experimental Model of Pulmonary Hypertension in Rats
by Tatyana Kuropatkina, Dmitrii Atiakshin, Fedor Sychev, Marina Artemieva, Tatyana Samoilenko, Olga Gerasimova, Viktoriya Shishkina, Khaydar Gufranov, Natalia Medvedeva, Tyler W. LeBaron and Oleg Medvedev
Biomedicines 2023, 11(12), 3141; https://doi.org/10.3390/biomedicines11123141 - 25 Nov 2023
Cited by 4 | Viewed by 3229
Abstract
Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male [...] Read more.
Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male Wistar rats were subcutaneously injected with a water–alcohol solution of monocrotaline or a control with an only water–alcohol solution. One group of monocrotaline-injected animals was placed in a plastic box that was constantly ventilated with atmospheric air containing 4% of molecular hydrogen, and the two groups of rats, injected with monocrotaline or vehicle, were placed in boxes ventilated with atmospheric air. After 21 days, hemodynamic parameters were measured under urethane narcosis. The results showed that, although hydrogen inhalation had no effect on the main markers of pulmonary hypertension induced by monocrotaline injection, there was a reduction in systemic blood pressure due to its systolic component, and a decrease in TGF-β expression, as well as a reduction in tryptase-containing mast cells. Full article
(This article belongs to the Special Issue Therapeutic Potential of Molecular Hydrogen in Human Diseases)
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Review

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14 pages, 1039 KiB  
Review
Hydrogen in Transplantation: Potential Applications and Therapeutic Implications
by Takafumi Obara, Hiromichi Naito, Tsuyoshi Nojima, Takahiro Hirayama, Takashi Hongo, Kohei Ageta, Toshiyuki Aokage, Masaki Hisamura, Tetsuya Yumoto and Atsunori Nakao
Biomedicines 2024, 12(1), 118; https://doi.org/10.3390/biomedicines12010118 - 6 Jan 2024
Viewed by 2626
Abstract
Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and [...] Read more.
Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen’s capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation. Full article
(This article belongs to the Special Issue Therapeutic Potential of Molecular Hydrogen in Human Diseases)
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24 pages, 3051 KiB  
Review
Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease
by Shin-ichi Hirano, Yusuke Ichikawa, Bunpei Sato, Yoshiyasu Takefuji and Fumitake Satoh
Biomedicines 2023, 11(10), 2817; https://doi.org/10.3390/biomedicines11102817 - 17 Oct 2023
Cited by 5 | Viewed by 4676
Abstract
As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the [...] Read more.
As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the effectiveness of current medical treatments for DKD leaves much to be desired. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. Recent studies have demonstrated that H2 not only possesses antioxidant properties but also exhibits anti-inflammatory effects, regulates cell lethality, and modulates signal transduction. Consequently, it is now being utilized in clinical applications. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Hence, we undertook a comprehensive review of the literature focusing on animal models and human clinical trials where H2 demonstrated effectiveness against a variety of renal diseases. The collective evidence from this literature review, along with our previous findings, suggests that H2 may have therapeutic benefits for patients with DKD by enhancing mitochondrial function. To substantiate these findings, future large-scale clinical studies are needed. Full article
(This article belongs to the Special Issue Therapeutic Potential of Molecular Hydrogen in Human Diseases)
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