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Keywords = hydrogen inhalation therapy

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13 pages, 1791 KiB  
Article
Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial
by Takafumi Maruyama, Dai Ishikawa, Rina Kurokawa, Hiroaki Masuoka, Kei Nomura, Mayuko Haraikawa, Masayuki Orikasa, Rina Odakura, Masao Koma, Masashi Omori, Hirotaka Ishino, Kentaro Ito, Tomoyoshi Shibuya, Wataru Suda and Akihito Nagahara
Biomedicines 2025, 13(8), 1799; https://doi.org/10.3390/biomedicines13081799 - 23 Jul 2025
Viewed by 314
Abstract
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of [...] Read more.
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article
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23 pages, 3022 KiB  
Review
Neurological Sequelae of Acute Hydrogen Sulfide Poisoning: A Literature Review, Controversies, and Knowledge Gaps
by Wilson K. Rumbeiha and Dong-Suk Kim
Neurol. Int. 2025, 17(5), 71; https://doi.org/10.3390/neurolint17050071 - 6 May 2025
Viewed by 1179
Abstract
Hydrogen sulfide (H2S) is a highly potent toxic gas, and the brain is a primary target organ following acute intoxications. Accidents and misuse of this gas for nefarious purposes, i.e., bioterrorism, are causes for concern regarding acute poisoning. The immediate effects [...] Read more.
Hydrogen sulfide (H2S) is a highly potent toxic gas, and the brain is a primary target organ following acute intoxications. Accidents and misuse of this gas for nefarious purposes, i.e., bioterrorism, are causes for concern regarding acute poisoning. The immediate effects of acute H2S poisoning are well known. Numerous publications have reported neurological sequelae, including insomnia, persistent headaches, ataxia, cognition deficits, hearing impairment, dysarthria, and neuropsychiatric behaviors, among survivors of acute H2S poisoning. However, this subject remains controversial. The goal of this study was to review the literature on acute H2S-poisoning-induced neurological sequelae and on animal models to determine prevalence and knowledge gaps. We also reviewed the literature on cyanide-induced neurological sequelae. The results of large population studies indicate that the majority of victims of acute H2S poisoning survive. There is a lack of patient follow-up and standardized neuropsychological, neurological, and neuroimaging for accurate assessments. We observed flaws in animal models that failed to recapitulate the severe neurotoxicity induced via the inhalation route. We observed a paucity of literature on cyanide-induced neurological sequelae. In contrast to cyanide-induced sequelae, predominantly characterized by Parkinsonian-like motor behavioral deficits, H2S patients exhibit mostly cognition deficits, speech impairment, and neuropsychological effects. This first comprehensive review of neurological sequelae induced by H2S and cyanide poisonings identified knowledge gaps in the prevalence of these sequelae and cellular and molecular mechanisms underlying them. It is unclear whether these sequelae are reversible. There are no FDA-approved drugs for the prevention or treatment of these sequelae. Notably, patients who received life-saving therapy still developed delayed neurological sequelae. Full article
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10 pages, 3203 KiB  
Article
Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model
by Wen-Ling Shih, Tsung-Ming Yeh, Kuang-Den Chen, Steve Leu, Shih-Feng Liu, Ying-Hsien Huang and Ho-Chang Kuo
Life 2024, 14(7), 796; https://doi.org/10.3390/life14070796 - 24 Jun 2024
Viewed by 1645
Abstract
Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels [...] Read more.
Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. Methods: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. Results: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). Conclusion: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model. Full article
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9 pages, 1320 KiB  
Article
The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease
by Shih-Feng Liu, Chin-Ling Li, Hui-Ching Lee, Hui-Chuan Chang, Jui-Fang Liu and Ho-Chang Kuo
Medicina 2024, 60(2), 245; https://doi.org/10.3390/medicina60020245 - 30 Jan 2024
Cited by 2 | Viewed by 10038
Abstract
Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: [...] Read more.
Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5–19.75) vs. 8.5 (3–13.5); p = 0.043] and mMRC scores [2.5 (1–4) vs. 2 (0–3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75–298.75) vs. 260 (232.75–314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count. Full article
(This article belongs to the Special Issue Update on COPD and Cystic Fibrosis)
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18 pages, 798 KiB  
Review
Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review
by Constantin Munteanu, Daniel Andrei Iordan, Mihail Hoteteu, Cristina Popescu, Ruxandra Postoiu, Ilie Onu and Gelu Onose
Int. J. Mol. Sci. 2023, 24(20), 15481; https://doi.org/10.3390/ijms242015481 - 23 Oct 2023
Cited by 15 | Viewed by 3114
Abstract
In the rapidly evolving field of Alzheimer’s Disease (AD) research, the intricate role of Hydrogen Sulfide (H2S) has garnered critical attention for its diverse involvement in both pathological substrates and prospective therapeutic paradigms. While conventional pathophysiological models of AD have primarily [...] Read more.
In the rapidly evolving field of Alzheimer’s Disease (AD) research, the intricate role of Hydrogen Sulfide (H2S) has garnered critical attention for its diverse involvement in both pathological substrates and prospective therapeutic paradigms. While conventional pathophysiological models of AD have primarily emphasized the significance of amyloid-beta (Aβ) deposition and tau protein hyperphosphorylation, this targeted systematic review meticulously aggregates and rigorously appraises seminal contributions from the past year elucidating the complex mechanisms of H2S in AD pathogenesis. Current scholarly literature accentuates H2S’s dual role, delineating its regulatory functions in critical cellular processes—such as neurotransmission, inflammation, and oxidative stress homeostasis—while concurrently highlighting its disruptive impact on quintessential AD biomarkers. Moreover, this review illuminates the nuanced mechanistic intimate interactions of H2S in cerebrovascular and cardiovascular pathology associated with AD, thereby exploring avant-garde therapeutic modalities, including sulfurous mineral water inhalations and mud therapy. By emphasizing the potential for therapeutic modulation of H2S via both donors and inhibitors, this review accentuates the imperative for future research endeavors to deepen our understanding, thereby potentially advancing novel diagnostic and therapeutic strategies in AD. Full article
(This article belongs to the Section Molecular Neurobiology)
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6 pages, 598 KiB  
Opinion
Antitumoral Activity of Molecular Hydrogen and Proton in the Treatment of Glioblastoma: An Atypical Pharmacology?
by Luc Rochette, Geoffrey Dogon, Marianne Zeller, Yves Cottin and Catherine Vergely
Brain Sci. 2023, 13(8), 1168; https://doi.org/10.3390/brainsci13081168 - 5 Aug 2023
Cited by 2 | Viewed by 3234
Abstract
Antioxidants in cancer therapy have been a hot topic in the medical field for 20 years. Antioxidants are able to reduce the risk of cancer formation by neutralizing free radicals. Protons (H+) and molecular hydrogen (H2) interact in the cell and are essential [...] Read more.
Antioxidants in cancer therapy have been a hot topic in the medical field for 20 years. Antioxidants are able to reduce the risk of cancer formation by neutralizing free radicals. Protons (H+) and molecular hydrogen (H2) interact in the cell and are essential in a wide variety of processes. The antioxidant, anti-inflammatory, and antiapoptotic effects of H2 have been studied in numerous experimental and clinical studies. Experimental data indicate that H2 is an antitumor agent in the treatment of glioblastoma (GBM). In vivo H2 inhalation could suppress the growth of GBM tumors, thereby extending the survival of mice with GBM. The sphere-forming ability of glioma cells was suppressed by hydrogen treatment. In addition, H2 treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Proton therapy and proton beam radiotherapy offer some advantages over other modern conformal photon-based therapies when used in the treatment of central nervous system malignancies. Full article
(This article belongs to the Section Neuro-oncology)
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7 pages, 3410 KiB  
Article
Experience with Photodynamic Therapy Using Indocyanine Green Liposomes for Refractory Cancer
by Kensho Yorozu, Masaki Kaibori, Shintarou Kimura, Misa Ichikawa, Kosuke Matsui, Soichiro Kaneshige, Masanori Kobayashi, Daiki Jimbo, Yusuke Torikai, Yoshitaka Fukuzawa and Yoshiharu Okamoto
J. Pers. Med. 2022, 12(7), 1039; https://doi.org/10.3390/jpm12071039 - 24 Jun 2022
Cited by 17 | Viewed by 4770
Abstract
We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg [...] Read more.
We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg of ICG to 50 mL liposomes. Later, 25 mL of ICG liposomes were diluted with 250 mL of 5% glucose solution and administered intravenously to the patient. We selected the multi-laser delivery system (MLDS), a laser irradiator for performing PDT. Further, the patients received a combination of LEM and hydrogen gas inhalation therapy throughout the treatment. We reported two cases of PDT therapy, one with middle intrathoracic esophagus carcinoma and the other with hypopharyngeal cancer. In the first case, the MLDS laser was directly attached to the endoscope and directed to the cancer area with wavelengths of 810 nm. After the treatment, a biopsy demonstrated no tumor recurrence. In the second case, the patient was treated with endovascular PDT using ICG liposomes and MLDS fiber optics. Later, tumor shrinkage was demonstrated after the first round and disappeared after six months. In conclusion, the present findings suggest that the effect of PDT using ICG liposomes with LEM and hydrogen gas may eradicate cancer without burdening patients by enhancing tumor immunity. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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14 pages, 932 KiB  
Article
Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation
by Michal Botek, Jakub Krejčí, Michal Valenta, Andrew McKune, Barbora Sládečková, Petr Konečný, Iva Klimešová and Dalibor Pastucha
Int. J. Environ. Res. Public Health 2022, 19(4), 1992; https://doi.org/10.3390/ijerph19041992 - 10 Feb 2022
Cited by 33 | Viewed by 9319
Abstract
Molecular hydrogen (H2) is potentially a novel therapeutic gas for acute post-coronavirus disease 2019 (COVID-19) patients because it has antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties. The aim of this study was to determine the effect of 14 days of H2 [...] Read more.
Molecular hydrogen (H2) is potentially a novel therapeutic gas for acute post-coronavirus disease 2019 (COVID-19) patients because it has antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties. The aim of this study was to determine the effect of 14 days of H2 inhalation on the respiratory and physical fitness status of acute post-COVID-19 patients. This randomized, single-blind, placebo-controlled study included 26 males (44 ± 17 years) and 24 females (38 ± 12 years), who performed a 6-min walking test (6 MWT) and pulmonary function test, specifically forced vital capacity (FVC) and expiratory volume in the first second (FEV1). Symptomatic participants were recruited between 21 and 33 days after a positive polymerase chain reaction test. The experiment consisted of H2/placebo inhalation, 2 × 60 min/day for 14 days. Results showed that H2 therapy, compared with placebo, significantly increased 6 MWT distance by 64 ± 39 m, FVC by 0.19 ± 0.24 L, and, in FEV1, by 0.11 ± 0.28 L (all p ≤ 0.025). In conclusion, H2 inhalation had beneficial health effects in terms of improved physical and respiratory function in acute post-COVID-19 patients. Therefore, H2 inhalation may represent a safe, effective approach for accelerating early function restoration in post-COVID-19 patients. Full article
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17 pages, 935 KiB  
Review
Molecular Hydrogen as Medicine: An Assessment of Administration Methods
by Grace Russell, Alexander Nenov, Hesham Kisher and John T. Hancock
Hydrogen 2021, 2(4), 444-460; https://doi.org/10.3390/hydrogen2040025 - 25 Nov 2021
Cited by 23 | Viewed by 20691
Abstract
Since the late 18th century, molecular hydrogen (H2) has been shown to be well tolerated, firstly in animals, and then in humans. However, although research into the beneficial effects of molecular hydrogen in both plant and mammalian physiology is gaining momentum, [...] Read more.
Since the late 18th century, molecular hydrogen (H2) has been shown to be well tolerated, firstly in animals, and then in humans. However, although research into the beneficial effects of molecular hydrogen in both plant and mammalian physiology is gaining momentum, the idea of utilising this electrochemically neutral and non-polar diatomic compound for the benefit of health has yet to be widely accepted by regulatory bodies worldwide. Due to the precise mechanisms of H2 activity being as yet undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, long-term effects of treatment, and the patient’s innate antioxidant profile), there is a requirement for H2 research to evidence how it can reasonably and most effectively be incorporated into medical practice. This review collates and assesses the current information regarding the many routes of molecular hydrogen administration in animals and humans, whilst evaluating how targeted delivery methods could be integrated into a modern healthcare system. Full article
(This article belongs to the Special Issue Feature Papers in Hydrogen)
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14 pages, 1925 KiB  
Article
Hydrogen Sulfide Inhibits TMPRSS2 in Human Airway Epithelial Cells: Implications for SARS-CoV-2 Infection
by Giulia Pozzi, Elena Masselli, Giuliana Gobbi, Prisco Mirandola, Luis Taborda-Barata, Luca Ampollini, Paolo Carbognani, Cristina Micheloni, Francesco Corazza, Daniela Galli, Cecilia Carubbi and Marco Vitale
Biomedicines 2021, 9(9), 1273; https://doi.org/10.3390/biomedicines9091273 - 20 Sep 2021
Cited by 34 | Viewed by 4355
Abstract
The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, [...] Read more.
The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, requiring angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) to enter target cells. Therefore, these surface proteins are considered potential druggable targets. Hydrogen sulfide (H2S) is a gasotransmitter produced by several cell types and is also part of natural compounds, such as sulfurous waters that are often inhaled as low-intensity therapy and prevention in different respiratory conditions. H2S is a potent biological mediator, with anti-oxidant, anti-inflammatory, and, as more recently shown, also anti-viral activities. Considering that respiratory epithelial cells can be directly exposed to H2S by inhalation, here we tested the in vitro effects of H2S-donors on TMPRSS2 and ACE2 expression in human upper and lower airway epithelial cells. We showed that H2S significantly reduces the expression of TMPRSS2 without modifying ACE2 expression both in respiratory cell lines and primary human upper and lower airway epithelial cells. Results suggest that inhalational exposure of respiratory epithelial cells to natural H2S sources may hinder SARS-CoV-2 entry into airway epithelial cells and, consequently, potentially prevent the virus from spreading into the lower respiratory tract and the lung. Full article
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10 pages, 745 KiB  
Review
Antitumor Activity of Protons and Molecular Hydrogen: Underlying Mechanisms
by Luc Rochette, Marianne Zeller, Yves Cottin and Catherine Vergely
Cancers 2021, 13(4), 893; https://doi.org/10.3390/cancers13040893 - 20 Feb 2021
Cited by 9 | Viewed by 6019
Abstract
Understanding the structure and dynamics of the various hydrogen forms has been a subject of numerous studies. Protons (H+) and molecular hydrogen (H2) in the cell are critical in a wide variety of processes. A new cancer treatment uses [...] Read more.
Understanding the structure and dynamics of the various hydrogen forms has been a subject of numerous studies. Protons (H+) and molecular hydrogen (H2) in the cell are critical in a wide variety of processes. A new cancer treatment uses H2, a biologically inactive gas. Due to its small molecular weight, H2 can rapidly penetrate cell membranes and reach subcellular components to protect nuclear DNA and mitochondria. H2 reduces oxidative stress, exerts anti-inflammatory effects, and acts as a modulator of apoptosis. Exogenous H2, administered by inhalation, drinking H2-rich water, or injecting H2-rich saline solution, is a protective therapy that can be used in multiple diseases, including cancer. In particle therapy, cyclotrons and synchrotrons are the accelerators currently used to produce protons. Proton beam radiotherapy (PBT) offers great promise for the treatment of a wide variety of cancers due to the sharp decrease in the dose of radiation at a defined point. In these conditions, H2 and different types of H2 donors may represent a novel therapeutic strategy in cancer treatment. Full article
(This article belongs to the Section Cancer Therapy)
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13 pages, 1401 KiB  
Review
Hydrogen Is Promising for Medical Applications
by Shin-ichi Hirano, Yusuke Ichikawa, Bunpei Sato, Fumitake Satoh and Yoshiyasu Takefuji
Clean Technol. 2020, 2(4), 529-541; https://doi.org/10.3390/cleantechnol2040033 - 16 Dec 2020
Cited by 25 | Viewed by 12385
Abstract
Hydrogen (H2) is promising as an energy source for the next generation. Medical applications using H2 gas can be also considered as a clean and economical technology. Since the H2 gas based on electrolysis of water production has potential [...] Read more.
Hydrogen (H2) is promising as an energy source for the next generation. Medical applications using H2 gas can be also considered as a clean and economical technology. Since the H2 gas based on electrolysis of water production has potential to expand the medical applications, the technology has been developed in order to safely dilute it and to supply it to the living body by inhalation, respectively. H2 is an inert molecule which can scavenge the highly active oxidants including hydroxyl radical (·OH) and peroxynitrite (ONOO), and which can convert them into water. H2 is clean and causes no adverse effects in the body. The mechanism of H2 is different from that of traditional drugs because it works on the root of many diseases. Since H2 has extensive and various effects, it may be called a “wide spectrum molecule” on diseases. In this paper, we reviewed the current medical applications of H2 including its initiation and development, and we also proposed its prospective medical applications. Due to its marked efficacy and no adverse effects, H2 will be a next generation therapy candidate for medical applications. Full article
(This article belongs to the Special Issue Hydrogen Economy Technologies)
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