THE ROLE OF MOLECULAR HYDROGEN AND NITROGEN OXIDE IN THE PATHOGENESIS OF COVID-19
DOI:
https://doi.org/10.11603/mcch.2410-681X.2021.i1.12119Keywords:
COVID-19, molecular hydrogen, hydrogen water, nitric oxide, oxidative stressAbstract
Introduction. The article presents a review of the scientific literature about the biochemical role of two molecules – molecular hydrogen and nitric oxide, primarily in COVID-19 – a viral infection that can be fatal for people with weakened immune systems. Numerous preclinical and clinical studies have shown that gaseous molecules such as molecular hydrogen and nitric oxide have antioxidant, anti-inflammatory and immunomodulatory benefits. Nitric oxide can directly kill pathogens and this is a key role in immune function because it can inhibit viral replication, it can also cause fatal cell damage under stress, particularly in COVID-19. Unlike nitric oxide, molecular hydrogen has a very high degree of safety and helps to regulate the production of nitric oxide, its metabolism and reduce its harmful effects. To date, not all the exact molecular mechanisms of H2 have been discovered, but it is already known that it provides a number of protective effects, modulates signal transduction, affects gene expression and alters the cascades of protein phosphorylation. Because of these proven effects of molecular hydrogen, it can be unambiguously qualified as the optimal therapy against COVID-19 and similar diseases. Both of these molecules (nitric oxide, molecular hydrogen) are used in preclinical and clinical trials to reveal the biochemical and pathogenetic mechanisms of interaction in various pathological processes, including COVID-19.
The aim of the study – to analyze modern literature sources on the effect of molecular hydrogen and nitric oxide on the prevention of multiorgan failure in COVID-19.
Conclusion. The growing number of studies gives reason to hope that in the future the results of the presented studies will have practical application in clinical medicine. Thus, today there are still a number of questions to explain the mechanisms of the positive effect of molecular hydrogen in various pathological conditions, including COVID-19. Therefore, the research is relevant and will be continued.
References
Hui, D.S. (2020). The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis., 91, 264-266.
Suzuki, Y. (2009). Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract? FEBS Letters, 583, 2157-2159.
Dole, M., Wilson, F.R., Fife, W.P. (1975). Hyperbaric hydrogen therapy: a possible treatment for cancer. Science, 190, 152-154.
Ohsawa, I. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med., 13, 688-694.
LeBaron, T.W. (2019). A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules, 24.
Tamura, T. (2017). Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial. Trials, 18, 488.
Yang, M. (2017). Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases? SOJ Microbiology & Infectious Diseases, 5, 1-6.
Hu, Z. (2017). Impact of molecular hydrogen treatments on the innate immune activity and survival of zebrafish (Danio rerio) challenged with Aeromonas hydrophila. Fish Shellfish Immunol, 67, 554-560.
Saramago, E.A. (2019). Molecular hydrogen potentiates hypothermia and prevents hypotension and fever in LPS-induced systemic inflammation. Brain Behav. Immun., 75, 119-128.
Spulber, S. (2012). Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLoS One, 7, e42078.
Zhao, S. (2014). Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction. J. Cell Mol. Med., 18, 938-946.
Akagi, J., & Baba, H. (2019). Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncol. Rep., 41, 301-311.
Appay, V., Douek, D.C., & Price, D.A. (2008). CD8+ T cell efficacy in vaccination and disease. Nat. Med., 14, 623-628.
Xia, C. (2013). Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin. Transl. Sci., 6, 372-375.
Itoh, T. (2009). Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. Biochem. Biophys. Res. Commun., 389, 651-656.
Itoh, T. (2011). Molecular hydrogen inhibits lipopolysaccharide/interferon gammainduced nitric oxide production through modulation of signal transduction in macrophages. Biochemical and Biophysical Research Communication, 411, 143-149.
Ren, J.D. (2016). Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species. Biochim. Biophys. Acta., 1863, 50-55.
Chen, H.G. (2013). Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages. Int. J. Surg., 11, 1060-1066.
Bogdan, C. (2001). Nitric oxide and the immune response. Nat. Immunol., 2, 907-916.
Akerstrom, S. (2005). Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J. Virol., 79, 1966-1969.
Wijnands, K.A. (2015). Arginine and citrulline and the immune response in sepsis. Nutrients, 27, 1426-1463.
Torregrossa, A.C., Aranke, M., Bryan, N.S. (2011). Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. J. Geriatr. Cardiol., 8, 230-242.
Schwedhelm, E. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br. J. Clin. Pharmacol., 65, 51-59.
Ware, L.B. (2013). Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis. Crit. Care., 17, R10.
Pacher, P., Beckman, J.S., Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiol. Rev., 87, 315-424.
Liu, H. (2015). Combination therapy with nitric oxide and molecular hydrogen in a murine model of acute lung injury. Shock, 43, 504-511.
Zhang, N. (2018). Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma. Res. Pract., 4, 3.
Arnold, R.J. (2018). A Review of the Utility and Cost Effectiveness of Monitoring Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management. Manag. Care, 27, 34-41.
Khan, A.S. (2001). Growth hormone increases regional coronary blood flow and capillary density in aged rats. J. Gerontol. A. Biol. Sci. Med. Sci. 56, B364-B371.
Panthi, S., Gautam, K. (2017). Roles of nitric oxide and ethyl pyruvate after peripheral nerve injury. Inflamm. Regener., 37, 20. Retrieved from: https://doi.org/10.1186/s41232-017-0051-831.
Khaddaj, Mallat, R. (2017). The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit. Rev. Clin. Lab. Sci., 54, 458-470.
Sakai, T. (2014). Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vasc. Health. Risk. Manag., 10, 591-597.
Li, Q. (2013). Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Med. Gas. Res. 3, 20.
Ref A: https://www.cebm.net/oxford-covid-19__trashed/covid-19-registered-trialsand-analysis/? fbclid= IwAR2TnDJspDYcrF-yeq3cv2wtLTfd7vbgIo4VIT340tjz9- AN5BiRJJnp-z0.
Ref C: Perspectives of the management of COVID-19 infection in China (EWS webinar serious).
Ref D: New Coronavirus Pneumonia Diagnosis and Treatment Scheme (Trial Ver7: Mar 3, 2020).
Ito, M. (2012). Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats. Med. Gas. Res., 2, 15.
Ref B: NCT04290871: Nitric Oxide Gas Inhalation for SARS in COVID-19. (NOSARSCOVID).
Pokotylo, O., Zakharchuk, I., & Vykhovanets, B. (2020). Stan i perspektyvy vykorystannia molekuliarnoho vodniu dlia sportsmeniv [Status and prospects of using molecular hydrogen for athletes]. Sportyvnyi visnyk Prydniprovia – Sport Bulletin of Prydniprovia, [in Ukrainian].
Pokotylo, O.S., Holovach, P.I., & Pokotylo, S.O. (2019). Doslidzhennia zakonomirnostei utvorennia elektronodonornoi vody na osnovi zmin rN i OVP vod v termosakh-ionizatorakh-heneratorakh “Living Water” [Research of regularities of electron-donor water formation on the basis of changes of pH and ORP of waters in thermoses-ionizers-generators “Living Water”]. Naukovi zapysky Ternopilskoho natsionalnoho pedahohichnoho universytetu imeni Volodymyra Hnatiuka. Ser. Biolohiia – Scien. Notes of Ternopil Nat. Ped. By Volodymyr Hnatiuk University. Biology Series. Ternopil: TNPU by V. Hnatiuk [in Ukrainian].
LeBaron, T.W., McCullough, M.L., & Ruppman, Sr.K.H. (2019). A novel functional beverage for COVID-19 and other conditions: Hypothesis and preliminary data, increased blood flow, and wound healing. J. Transl. Sci., 6, DOI: 10.15761/JTS.1000380.
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