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 Table of Contents  
REVIEW
Year : 2020  |  Volume : 10  |  Issue : 1  |  Page : 47-49

A “philosophical molecule,” hydrogen may overcome senescence and intractable diseases


1 MiZ Company Limited, Kamakura, Japan
2 Faculty of Environment and Information Studies, Keio University, Fujisawa, Japan

Date of Submission26-Aug-2019
Date of Decision28-Aug-2019
Date of Acceptance08-Sep-2019
Date of Web Publication13-Mar-2020

Correspondence Address:
DVM, PhD Shin-ichi Hirano
MiZ Company Limited, Kamakura
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2045-9912.279983

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  Abstract 


It has been revealed that the cause of senescence and diseases is associated with the reactive oxygen species “hydroxyl radicals” (·OH). Senescence and diseases may be overcome as long as we can scavenge •OH mostly produced in mitochondria. It is one and only one “molecular hydrogen” (H2) that can both penetrate into the mitochondria and scavenge the •OH. The H2 in the body can function in disease prevention and recovery. H2 gas is explosive so that a safe hydrogen inhaler has to be developed for home use. We would like to advocate the great use of H2.

Keywords: Google; Amazon; Facebook; Apple; hydroxyl radicals; mitochondria; molecular hydrogen; oxidation; reactive oxygen species; reduction; rejuvenation; senescence


How to cite this article:
Hirano Si, Ichikawa Y, Kurokawa R, Takefuji Y, Satoh F. A “philosophical molecule,” hydrogen may overcome senescence and intractable diseases. Med Gas Res 2020;10:47-9

How to cite this URL:
Hirano Si, Ichikawa Y, Kurokawa R, Takefuji Y, Satoh F. A “philosophical molecule,” hydrogen may overcome senescence and intractable diseases. Med Gas Res [serial online] 2020 [cited 2020 May 25];10:47-9. Available from: http://www.medgasres.com/text.asp?2020/10/1/47/279983




  Introduction Top


Although modern medicine has evolved so far with stalling rapidly in the 21st century, large walls hinder the development of medicine. There are many diseases which cannot be cured or healed by treatment based on “element reductionism.” The element reductionism is associated with one treatment. Many diseases are caused not by single factor abnormalities but by multiple factors with various mechanisms. These multiple factors may not have been elucidated in modern medicine. However, we have recently developed how we can break through these challenges. A key solution lies in using molecular hydrogen (H2).

From a scientific standpoint, all activities of the molecules can be called the exchange of electrons: “oxidation” and “reduction.” From the viewpoint of the longevity of the youth, oxidation means “senescence” while reduction does “rejuvenation.” Life activity begins after the birth, and immediately the oxidation proceeds. It means that “electrons are deprived” to be oxidized. H2, supplying electrons, can be said that the reducing agent “rejuvenated material.” Senescence and diseases can be interpreted as oxidative phenomenon, rejuvenation and recovery as reductive one. The substance with oxidizing maximizes the phenomenon. In this paper, we propose the possibility that H2 will overcome the senescence and intractable diseases from the viewpoint of mitochondrial oxidation and reduction.


  Reactive Oxygen Species and Mitochondria Top


What is the most potent oxidizing one? It is hydroxyl radicals (•OH). About 90% of reactive oxygen species (ROS) are generated in the mitochondria in the cells.[1] The •OH have been generated in large quantities almost all within the mitochondria. Mitochondria are the organs that create the energy ATP that is necessary for our life activities.

Mitochondrial functions can be compared to the boiler of a steam locomotive. In the past, the term “boiler” as a word for locomotive originated from the fact that the boiler occupied most of the body of the locomotive. In the same way, mitochondria are energy generating organs for life activities that must be necessary for life. Locomotives run with fuel, but in that case a large amount of soot, imperfect combustion substance is generated. When energy conversion is performed, the combustion efficiency is not perfect without exception. In the mitochondria, when converting the incorporated material into energy, about a few percent of the imperfect combustion substance are produced. The imperfect combustion materials are ROS. There are a variety of ROS that can be used usefully. If they are not necessary for life, metabolic system to scavenge by the use of enzymes has been constructed. However, in the mitochondria of the generated ROS, there is only •OH that cannot be reduced by any means. The •OH is generated in the mitochondria, and can cause oxidation, senescence and diseases. Because •OH has the strongest oxidizing power, and reacts with nucleic acids (DNA), lipids and proteins that make up our bodies and destroy them. This vandalism is an oxidative reaction. We do not know how to handle with •OH. Antioxidants except H2 are not very effective especially because of the impossibility into the cell and mitochondria. We should scavenge the •OH that produces in the mitochondria. Is there any substance that can scavenge it? It is H2 that can solve the vandalism of •OH.


  Development of the Equipment to Deliver H2 to Our Body Top


We have reported that drinking of H2 water produced in our electrolytic cell released a pioneering study to inhibit oxidative disorders in the liver of rats in 2005.[2] This is the first hydrogen medicine paper in Japan. Two years later, a series of papers on H2 began to emerge from other research institutes.[3] We have reported the equipment to deliver H2 to the living body.[4],[5]

H2 is capable to pass through all materials, because H2 is the smallest molecule. Only H2 can pass through the cell membrane and also pass the mitochondrial membrane, while the other antioxidants cannot do that to scavenge the •OH. H2 has been reported to react with two kinds of strong ROS,[3],[6] i.e., •OH and peroxynitrite (ONOO-).[7] However, it is reported that H2 reacts with ONOO- somewhat.[3] The reactivity of H2 with •OH is high and quick. As observed from the production of H2 in the body (gut),[8],[9] it is completely harmless for the body. H2 does not interfere with the metabolic system. Rather, H2 can scavenge the waste, •OH in soot that has occurred in the metabolic reaction, harmless and non-toxic. In conclusion, it is only H2 that can penetrate into the mitochondria and can also scavenge •OH [Figure 1]. Thereby, the H2 in the body can function in disease prevention and recovery.[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26] There is a possibility of longevity of youth.
Figure 1: “Molecular hydrogen” (H2) is the only molecule that can both enter the mitochondria and scavenge the hydroxyl radicals.
Note: Inhalation gas was prepared by mixing of H2 gas and air, where the H2 gas was produced by the electrolysis of water, and the concentration was controlled under the detonation limit of the mixture of H2 gas and air (below 10% H2 concentration in the apparatus “Jobs-α”).·OH: Hydroxyl radicals; PTSD: posttraumatic stress disorder.


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  Gafa and Public Organization in the Us Top


There are many diseases which we cannot treat well. The massive fund-raising of Google, Amazon, Facebook and Apple (GAFA) is continuing to discover the cure for those diseases. Apple CEO Tim Cook said that in the future, if anybody asks what Apple’s greatest contribution to humankind is “health” will be his answer.[27]

The wasteful medical treatment is rampant in the modern therapy. The medical expense increase of the nation is spurred. As a solution, there is a “Choosing Wisely” in the United States. This is a public organization in Philadelphia of United States, the United States Internal Medicine Specialist Certification Organization Foundation (ABIM Foundation) becomes the epicenter, bundling the medical Society of the United States, to announce a wasteful medical treatment. For example, United States Clinical Oncology Society, United States gastroenterological Society, United States Psychiatric Society, United States Cardiology Association, United States Obstetrics and Gynecology Society, United States Pediatrics Association, etc., the world’s first medical Association has presented themselves with “the medical act that seems unnecessary.”

How should we overcome various problems including medical problems and social problems? As mentioned in this paper, we would like to propose a safe H2 medical use with no adverse effects. H2 may be able to solve various problems by combining with modern treatment or alone use in the future. This proposal does not deny the modern medicine indiscriminately. Especially in acute diseases, the modern medical treatments are very effective certainly. However, there are diseases due to chronic diseases and complex factors that cannot be covered by modern medicine. Up to now there are more than 600 papers regarding the use of H2, including about 50 clinical trials papers. The use of H2 is indispensable in the future, and we would like to advocate the promotion of hydrogen medicine.

Acknowledgements

The authors are grateful to Ms. Yoko Satoh and Mr. Masatsugu Saitou of MiZ Company Limited, and Dr. Goh Matsuo for their excellent advices in writing this manuscript.

Author contributions

SH, YT and FS designed and wrote the manuscript. YI and RK supported this study by giving advice and revised the manuscript. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interests to declare.

Financial support

None.

Copyright license agreement

The Copyright License Agreement has been signed by all authors before publication.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.



 
  References Top

1.
Zhang W, Hu X, Shen Q, Xing D. Mitochondria-specific drug release and reactive oxygen species burst induced by polyprodrug nanoreactors can enhance chemotherapy. Nat Commun. 2019;10:1704-1704.  Back to cited text no. 1
    
2.
Yanagihara T, Arai K, Miyamae K, et al. Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: a feeding test with rats. Biosci Biotechnol Biochem. 2005;69:1985-1987.  Back to cited text no. 2
    
3.
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688-694.  Back to cited text no. 3
    
4.
Kurokawa R, Seo T, Sato B, Hirano SI, Sato F. Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation. Med Gas Res. 2015;5:13.  Back to cited text no. 4
    
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Kurokawa R, Hirano SI, Ichikawa Y, Matsuo G, Takefuji Y. Preventing explosions of hydrogen gas inhalers. Med Gas Res. 2019;9:160-162.  Back to cited text no. 5
    
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Sano M, Suzuki M, Homma K, et al. Promising novel therapy with hydrogen gas for emergency and critical care medicine. Acute Med Surg. 2017;5:113-118.  Back to cited text no. 6
    
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Setsukinai Ki, Urano Y, Kakinuma K, Majima HJ, Nagano T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem. 2003;278:3170-3175.  Back to cited text no. 7
    
8.
Levitt MD. Production and excretion of hydrogen gas in man. N Eng J Med. 1969;281:122-127.  Back to cited text no. 8
    
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Shin W. Medical applications of breath hydrogen measurements. Anal Bioanal Chem. 2014;406:3931-3939.  Back to cited text no. 9
    
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Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer. Science. 1975;190:152-154.  Back to cited text no. 10
    
11.
Hirano Si, Aoki Y, Kurokawa R, et al. Hydrogen gas inhalation alleviates radiation-induced bone marrow damage in cancer patients. https://ssrncom/abstract=3349228. Accessed by March 8, 2019. 2019.  Back to cited text no. 11
    
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Fontanari P, Badier M, Guillot C, et al. Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive. Eur J Appl Physiol. 2000;81:325-328.  Back to cited text no. 12
    
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Cai J, Kang Z, Liu WW, et al. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441:167-172.  Back to cited text no. 13
    
14.
Hayashida K, Sano M, Ohsawa I, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373:30-35.  Back to cited text no. 14
    
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Xie K, Yu Y, Pei Y, et al. Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Shock. 2010;34:90-97.  Back to cited text no. 15
    
16.
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010;46:140-149.  Back to cited text no. 16
    
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Nagatani K, Wada K, Takeuchi S, et al. Effect of hydrogen gas on the survival rate of mice following global cerebral ischemia. Shock. 2012;37:645-652.  Back to cited text no. 17
    
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Xiang L, Tan JW, Huang LJ, et al. Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine. World J Gastroenterol. 2012;18:5197-5204.  Back to cited text no. 18
    
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Yoshida A, Asanuma H, Sasaki H, et al. H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther. 2012;26:217-226.  Back to cited text no. 19
    
20.
Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H2 therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013;28:836-839.  Back to cited text no. 20
    
21.
Hayashida K, Sano M, Kamimura N, et al. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation. 2014;130:2173-2180.  Back to cited text no. 21
    
22.
Homma K, Yoshida T, Yamashita M, Hayashida K, Hayashi M, Hori S. Inhalation of hydrogen gas is beneficial for preventing contrast-induced acute kidney injury in rats. Nephron Exp Nephrol. 2015;doi: 10.1159/000369068.  Back to cited text no. 22
    
23.
Tamura T, Hayashida K, Sano M, et al. Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome- first-in-human pilot study. Circ J. 2016;80:1870-1873.  Back to cited text no. 23
    
24.
Matsuoka T, Suzuki M, Sano M, et al. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017;83:469-475.  Back to cited text no. 24
    
25.
Katsumata Y, Sano F, Abe T, et al. The effects of hydrogen gas inhalation on adverse left ventricular remodeling after percutaneous coronary intervention for ST-elevated myocardial infarction- first pilot study in humans. Circ J. 2017;81:940-947.  Back to cited text no. 25
    
26.
Tamaki I, Hata K, Okamura Y, et al. Hydrogen flush after cold storage as a new end-ischemic ex vivo treatment for liver grafts against ischemia/reperfusion injury. Liver Transpl. 2018;24:1589-1602.  Back to cited text no. 26
    
27.
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