Molecular Hydrogen in Health and Disease (Advances in Biochemistry in Health and Disease, 27)

Preface
Contents
1 Hydrogen: From Stars to Fuel to Medicine
	Introduction
	Historical Overview of Hydrogen Research
	Hydrogen Applications in Humans for Non-medicinal Purposes
		Biodegradable Implants
		Bodily Wound Detection
		Diving
		Blood Flow
		Malabsorption
		Detecting Achlorhydria
	Historical Study of H2 for Its Therapeutic Effects
	Physicochemical Properties and Solubility of Hydrogen
		Saturation
		Concentration
		Units
	Pharmacokinetics of Hydrogen Gas
	Pharmacological Actions of Hydrogen Gas
	Methods of Administration
	Conclusion
	References
2 An Exploration of the Direct Biological Targets of Molecular Hydrogen
	Introduction
	Direct Actions of H2
		Antioxidant and Hydroxyl Radicals
		Redox Action of H2
		H2 Modulating Spin States
		H2 Interacting with Xenon Pockets in Proteins
	Conclusion and the Future
	References
3 Prospects of Hydrogen Medicine Based on Its Protective Effects on Mitochondrial Function
	Introduction
	Oxidative Stress Regulates Health and Disease
		Production and Scavenging Systems of ROS
		ROS-Induced Oxidative Eustress and Distress
	Mitochondrial Dysfunction and Disease
	Effects of H2 on Mitochondrial Function
		Effects in Various Experimental Disease Models
		Effects on Chronic Inflammation
		Effects on “Sequelae” of COVID-19 and Chronic Fatigue
	Prospects for Future Medicine
	Conclusions
	References
4 Molecular Hydrogen: A New Treatment Strategy of Mitochondrial Disorders
	Introduction
	Molecular Hydrogen–A Novel Treatment Strategy
	Characteristics of Mitochondria and Molecular Hydrogen
	Mitochondrial Free Radicals, Antioxidants and H2
	Mitochondrial Dynamics, Sirtuins and H2
	Mitochondrial Circadian Rhythms and H2
	Mitochondrial Ageing and H2
	Mitochondrial Oxidative Phosphorylation and H2 Effect
	Effect of H2 on Mitochondrial Dysfunction in NAFLD Patients
	Molecular Hydrogen–A New Perspective Strategy for Targeted Therapy of Mitochondrial Diseases
	References
5 Autonomic Cardiac Regulation in Response to Exercise and Molecular Hydrogen Administration in Well-Trained Athletes
	Introduction
	Methods of Study A
		Participants
		Experimental Protocol
		HRW and Placebo Characteristics and Administration Schedule
		Basic Anthropometric Measurement
		Maximal Exercise Test
		Heart Rate Variability Analysis
		Statistical Analysis
		Results of Study A
		Discussion of Study A
	Methods of Study B
		Participants
		Experimental Protocol
		HRW and Placebo Characteristics and Administration Schedule
		Repeat Sprint Protocol
		Heart Rate Measurement
		Statistical Analysis
		Results of Study B
		Discussion of Study B
	Conclusions
	References
6 The Clinical Use of Hydrogen as a Medical Treatment
	Introduction
	The Clinical Use of Hydrogen as a Medical Treatment
		The Respiratory System Diseases
		The Digestive System Diseases
		The Hematologic System Diseases
		The Skin Diseases
		The Ophthalmic System Diseases
		The Nervous System Disease
		The Immune System Diseases
		The Circulatory and Endocrine System Diseases
		The Motor System Diseases
	Remaining Issues and Challenges
	Conclusion and Perspectives
	References
7 Homeostatic and Endocrine Response Underlying Protective Effects by Molecular Hydrogen
	Introduction
	Concentration of H2 in the Brain After Inhalation of H2 or Drinking H2-Containing Water
	H2 and Gastrointestinal Hormone
	H2 and Hypothalamic–Pituitary–Adrenal (HPA) Axis
	H2 and Hypothalamic–Pituitary–Gonadal (HPG) Axis
	Homeostatic Action of H2
	References
8 Radiation-Induced Heart Disease: Potential Role for Molecular Hydrogen
	Introduction
	Pathophysiology of RIHD
		Oxidative Stress
		Endothelial Cell Injury and Inflammation
		Cell Death
		Fibrosis and Hypertrophy
	Beneficial Effects of H2 Application to Prevent RIHD
		Antioxidant Activity
		Anti-inflammatory Effect
		Cytoprotective Action
		Anti-fibrotic and Anti-hypertrophic Action
	Evidence for H2 Action to Mitigate Radiation-Induced Injury
	Future Perspectives
	Conclusion
	References
9 Short-Lasting Supplementation with Molecular Hydrogen and Vitamin E Upregulates Myocardial Connexin-43 in Irradiated and Non-irradiated Rat Heart
	Introduction
	Material and Methods
		Statistical Evaluation
	Results
	Discussion
	References
10 Molecular Hydrogen: A New Protective Tool Against Radiation-Induced Toxicity
	Introduction
	Materials and Methods
		Experimental Animals
		Experimental Model
		Treatment
		Materials
	Results
	Discussion
	Conclusion
	References
11 Role of Matrix Metalloproteinases in Effects of Molecular Hydrogen
	Introduction
	Molecular Hydrogen as Modulator of Cellular Functions
	Physiological Functions of Matrix Metalloproteinases
	Role of Matrix Metalloproteinases in Responses to Pathological Stress Conditions
	Effects of Molecular Hydrogen on Modulation of Matrix Metalloproteinases
	Conclusion
	References
12 Perioperative Mitigation of Oxidative Stress with Molecular Hydrogen During Simulated Heart Transplantation in Pigs
	Introduction
	Effects of Molecular Hydrogen
	Material and Methods
	Statistical Analysis
	Results
		Hydrogen Measurement
		Tissue Damage and Inflammation Markers
		Oxidative Stress
		Matrix Metalloproteinases 2 and 9
		Histochemistry Results
		Electron Microscopy
	Discussion
	References
13 Application of Hydrogen in Hemodialysis: A Brief Review with Emphasis on the Quantification of Dissolved H2
	Hydrogen as Antioxidant and Anti-inflammatory Agent
	Calibration of the HWMS Device
	Hydrogen Mass Transfer During Dialysis
		Low-Flux Dialyzer
		Purely Diffusive Dialyzer
	Epilogue
	References
14 Hydrogen as a Potential Therapeutic Approach in the Treatment of Cancer: From Bench to Bedside
	Introduction
	Hydrogen: As a New Treatment Option for Human Disease
	Potential Mechanisms of Hydrogen
		Reactive Oxygen Species (ROS)
		Regulation of Mitochondria
		Anti-inflammatory Effect
		Apoptosis
		Autophagy
		Pyrolysis
		Impacts of Hydrogen on the Immune System
	Hydrogen Therapy in Cancer
		Preclinical Studies on Cancer
		Clinical Studies
	Side Effects of Hydrogen Therapy
		Gastrointestinal Side Effects
		Hypoglycemia
		Heartburn
		Heart Failure
		Headache
	Conclusion
	References
15 The Role of the Smallest Molecule Hydrogen Overcoming Ageing-Related Disease
	Introduction
	The Source of ROS
	ROS and Regulation of Aging
	Hydrogen and Aging
	Signal Pathway on Hydrogen and Aging
	Molecule Hydrogen and Aging-Related Disease
		Cancer
		Alzheimer’s Disease
		Gastrointestinal Diseases
	Conclusion
	References
16 Dihydrogen and Hepatic Function: Systematic Review and Meta-analysis
	Introduction
	Methods
		Eligibility Criteria
		Information Sources and Search Strategy
		Selection Process
		Data Extraction and Study Coding
		Study Risk of Bias Assessment
		Statistical Analysis
	Results
		Literature Search
		Study Characteristics
		Level of Quality of the Studies
		Meta-analysis
	Discussion
	Conclusion
	References
17 Hydrogen-Rich Water Using as a Modulator of Gut Microbiota and Managing the Inflammatory Bowel Disease
	Introduction
	Molecular Hydrogen
		Physiology
		Biological Activities
	Hydrogen-Rich Water (HRW) and Gut Microbiota
	HRW Mechanisms of Action on Gut Microbiota
	HRW Be Used as a Therapy (Hydrobiotic)
	Administration Routes for H2
	HRW as IBD Therapy
	Conclusion Remarks
	References
18 Effects of Molecular Hydrogen in the Pathophysiology and Management of Metabolic and Non-communicable Diseases
	Introduction
	Oxidative Stress and Antioxidants in the Pathogenesis of Chronic Diseases
	Physiology of Molecular Hydrogen and the Gut Microbiota
	Molecular Hydrogen; A New Therapeutic Agent
	Effects of Hydrogen Therapy on Blood Lipids
	Effects of Hydrogen Therapy on Blood Pressures
	Effects of Hydrogen Therapy on Endothelial Function
	Effects of Molecular Hydrogen in Stroke
	Effects of Molecular Hydrogen on Ischemia and Reperfusion Injury
	Effects of Hydrogen Therapy in Neurodegenerative Diseases
	Effects of Molecular Hydrogen on Bone and Joint Diseases
	Effects of Hydrogen on Cancer
	Effects of Hydrogen Therapy in Kidney Diseases
	Effects of Hydrogen in Chronic Lung Diseases
	Conclusions
	Competing Interests
	References
19 Consumption of Hydrogen-Treated Foods Provides Nutritional and Health Benefits
	Introduction
	Properties of Hydrogen
	Use of Hydrogen in Food Processing
		Hydrogen-Rich Water (HRW)
		Hydrogen-Rich Beverages
		HRW-Washed Butter
		HRW-Washed Olive Oil
		Hydrogen Atmosphere Packaged Foods
		Hydrogen-Rich Water-Prepared Pickle
	Use of Hydrogen in Crop Production and Protection
		HRW Increases the Phytochemical Concentration of Crops
		Hydrogen Extends the Shelf Life of Crops
	Health and Nutritional Benefits of Intaking Hydrogen-Treated Foods
		Potential Health and Medicinal Benefits of Intaking Hydrogen-Included Product
		Potential Increase of Phytochemical Bioavailability When Intaking HRW
	Conclusions
	References
20 Differential Effects of Carbohydrates on the Generation of Hydrogen and Methane in Low- and High-Methane-Producing Rats
	Introduction
	Materials and Methods
		Laboratory Animals
		Intragastric Administration of Substances
		Dietary Compounds Used for Hydrogen/methane Breath Tests
		Experimental Setup for Exhaled Air Samples Collection
		Sample Analysis
		Collection of Feces Samples
		Analysis of Microbial Community Composition
		Statistical Analysis
	Results
		The Effect of a Single Carbohydrate of Various Structures Load (Lactulose, Inulin, PHGG) on the Content of Gaseous Markers (H2 and CH4) in the Rat’s Exhaled Air
		Analysis of the Gut Microbiota Composition
		Correlation Analysis Between Taxonomic Composition and the Level of Gaseous Metabolites (H2 and CH4) of Gut Microbiota
	Discussion
	Conclusion
	References
21 Natural Biomolecules, Plant Extracts and Molecular Hydrogen—New Antioxidant Alternatives in the Management of Male Infertility
	Introduction
	Alternative Plant-Derived Bioactive Molecules
		Resveratrol
		Quercetin
		Lycopene
		Curcumin
		Plant Extracts
		Molecular Hydrogen
	Conclusions
	References
22 Comparison of Free-Radical Scavenging Activity of Various Sources of Molecular Hydrogen
	Introduction
	Materials and Methods
		Materials
		DPPH Assay
		Rotational Viscometry
	Results and Discussion
	Conclusion
	References
23 Development of a Preclinical Tool for Measuring Percutaneous Transfer of Dihydrogen, with a View to Optimizing Medical Devices Adapted to Focal Therapies in Dermatology
	Introduction
	Methods
		Skin Sampling
		H2 Preparation
		Experimental Set-Up
		Modeling H2 Concentrations in the Two Compartments in Egn Experiments (Gas/Skin/Air)
		Fitting the Model with the Measurements in Egn Experiments (Gas/Skin/Air)
		Estimation of the H2 Flows Jij in Egn Experiments (Gas/Skin/Air)
		Estimation of Flow J12 in the Ebn Experiments (Gas/Skin/Buffer/Air)
	Results
		Estimation of the Flow Across the Skin with Egn Experiments (Gas/Skin/Air)
		Estimation of the Flow Across the Skin with Ebn Experiments (Gas/Skin/Buffer/Air)
	Discussion
	Conclusion
	References
24 Intraosseous Administration of Molecular Hydrogen: A Novel Technique—From Molecular Effects to Tissue Regeneration
	Introduction: Features of Bone Tissue Metabolism and Its Role in the Pathogenesis of Disease
	Characteristics of Molecular and Cellular Aspects of the Biological Action of H2
		Antioxidant Effects
		Anti-inflammatory Effects
		Anti-apoptotic Effects
		Modulation of Autophagy
		Regulation of Pyroptosis
	Routes of Introducing Molecular Hydrogen into the Body
	The Effect of Molecular Hydrogen on Various Cell Pools and Regeneration Processes
	Hypothesis: Intraosseous Administration of Molecular Hydrogen
	Method of Intraosseous Hydrogen Administration
	Conclusion
	References
25 Perspective of Nanomaterials and Nanomedicine Procedures in Molecular Hydrogen Therapy
	Introduction
	Therapy with Local Generation and Controlled Release of Hydrogen
	Safe Solid-State Storage of Hydrogen
	Monitoring Hydrogen in the Environment Using Nanosensors
		Metal Oxides-Based Hydrogen Sensors
		Graphene-Based Hydrogen Sensors
		Cross Sensitivity
	History and Perspectives
	Conclusion
	References
26 The Emergence, Development, and Future Mission of Hydrogen Medicine and Biology
	The Initiation of the Hydrogen Medicine and Biology
	From Mitochondrial Medicine to Hydrogen Medicine
	Selective Reduction of Oxidative Stress by Molecular Hydrogen
	Pharmacokinetics of Molecular Hydrogen Ingested by Various Ways
	Discovery of the Target of H2 that Resolves the Unresolved Discrepancy
	Porphyrin-Involved Multiple Functions of Molecular Hydrogen
	Safety of Molecular Hydrogen Compared to Other Medical Gasses
	Indirect Hormonal Regulation by Molecular Hydrogen
	Subsequent Signaling Involving Lipid Peroxides
	Future Mission of Hydrogen Medicine
		Post-cardiac Arrest Syndrome
		Alzheimer’s Disease
		Advanced Stage of Cancer
		Metabolic Syndrome
		Cytokine Storm Involved in Infection
		Improving the Quality of Life and Beauty of Healthy People
	Conclusion
	References