Breathing hydrogen, patients with asthmaScientific Research
Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice
https://asthmarp.biomedcentral.com/articles/10.1186/s40733-018-0040-y
Abstract
Asthma is a global chronic respiratory disease that has no cure and imposes a huge burden on public health. Oxidative stress has been recognized as an important mechanism in the pathogenesis of asthma. Hydrogen has been shown to act as a novel antioxidant and exert therapeutic antioxidant activity in a range of diseases, while the role of this nontoxic gas in asthma is unknown. The aim of this study was to investigate the effect of inhaled hydrogen gas on the pathophysiology of a mouse model of asthma.
Methods
In this study, a mouse model of ovalbumin (OVA)-induced allergic airway inflammation was used. Briefly, mice were sensitized to ovalbumin and inhaled a high concentration of 67% hydrogen gas for 60 minutes once a day for 7 consecutive days following OVA or PBS challenge. Lung function was assessed in a device with 4 biosignaling system channels. Morphology and goblet cell hyperplasia were stained with H/E and periodic acid Schiff staining. Cytological classification in bronchoalveolar lavage fluid (BALF) was analyzed by Wright-Giemsa staining. Serum, BALF and lung tissue were collected for biochemical assays. Statistical significance between groups was determined using one-way analysis of variance (ANOVA). Bonferroni’s multiple comparisons test was used for several comparisons using GraphPad Prism 5 software.
Results
Hydrogen inhalation abolished the increase in pulmonary resistance caused by ovalbumin. Meanwhile, asthmatic mice exhibited severe inflammatory infiltration and goblet cell hyperplasia, which was reversible after hydrogen inhalation. Hydrogen inhalation significantly reduced the numbers of total cells, eosinophils and lymphocytes in BALF. Elevated BALF IL-4, IL-13, TNF-α and CXCL15 and serum IL-4 levels were significantly reduced after inhalation. Hydrogen inhalation significantly upregulated the activity of decreased superoxide dismutase and significantly attenuated the elevation of malondialdehyde and myeloperoxidase levels.
Conclusions
Hydrogen gas inhalation improves lung function and protects established airway inflammation in the allergic asthmatic mice model which may be associated with the inhibition of oxidative stress process. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma.
References
Andreadis AA, Hazen SL, Comhair SA, Erzurum SC. Oxidative and nitrosative events in asthma. Free Radic Biol Med. 2003;35(3):213–25.
Gardette B, Delauze HG. Techniques of underwater intervention: means, methods, research and outlook. Bull Acad Natl Med. 1996;180(5):975–83.
Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun. 2007;361(3):670–4.
Ji X, Liu W, Xie K, Liu W, Qu Y, Chao X, Chen T, Zhou J, Fei Z. Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress. Brain Res. 2010;1354:196–205.
Kajiya M, Silva MJ, Sato K, Ouhara K, Kawai T. Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochem Biophys Res Commun. 2009;386(1):11–5.
Cai J, Kang Z, Liu WW, Luo X, Qiang S, Zhang JH, Ohta S, Sun X, Xu W, Tao H, Li R. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441(2):167–72.
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30–5.
Cui J, Chen X, Zhai X, Shi D, Zhang R, Zhi X, Li X, Gu Z, Cao L, Weng W, Zhang J, Wang L, Sun X, Ji F, Hou J, Su J. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats – a possible new hydrogen resource for clinical use. Neuroscience. 2016;335:232–41.
Kohama K, Yamashita H, Aoyama-Ishikawa M, Takahashi T, Billiar TR, Nishimura T, Kotani J, Nakao A. Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation. Surgery. 2015;158(2):399–407.
Amdur MO, Mead J. Mechanics of respiration in unanesthetized Guinea pigs. Am J Phys. 1958;192(2):364–8.
Khakzad MR, Mirsadraee M, Mohammadpour A, Ghafarzadegan K, Hadi R, Saghari M, Meshkat M. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. Pulm Pharmacol Ther. 2012;25(2):163–8.
Riedl MA, Nel AE. Importance of oxidative stress in the pathogenesis and treatment of asthma. Curr Opin Allergy Clin Immunol. 2008;8(1):49–56.
Nadeem A, Masood A, Siddiqui N. Oxidant–antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options. Ther Adv Respir Dis. 2008;2(4):215–35.
Sugiura H, Ichinose M. Oxidative and nitrative stress in bronchial asthma. Antioxid Redox Signal. 2008;10(4):785–97.
Ben Anes A, Ben Nasr H, Fetoui H, Bchir S, Chahdoura H, Yacoub S, Garrouch A, Benzarti M, Tabka Z, Chahed K. Alteration in systemic markers of oxidative and antioxidative status in Tunisian patients with asthma: relationships with clinical severity and airflow limitation. J Asthma. 2016;53(3):227–37.
Fatani SH. Biomarkers of oxidative stress in acute and chronic bronchial asthma. J Asthma. 2014;51(6):578–84.
Schulze J, Biedebach S, Christmann M, Herrmann E, Voss S, Zielen S. Impulse Oscillometry as a predictor of asthma exacerbations in young children. Respiration. 2016;91(2):107–14.
Iketani M, Ohsawa I. Molecular hydrogen as a neuroprotective agent. Curr Neuropharmacol. 2017;15(2):324–31.
Kurokawa R, Seo T, Sato B, Hirano S, Sato F. Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation. Med Gas Res. 2015;5:13.
Zheng J, Liu K, Kang Z, Cai J, Liu W, Xu W, Li R, Tao H, Zhang JH, Sun X. Saturated hydrogen saline protects the lung against oxygen toxicity. Undersea Hyperb Med. 2010;37(3):185–92.
Kawamura T, Huang CS, Tochigi N, Lee S, Shigemura N, Billiar TR, Okumura M, Nakao A, Toyoda Y. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Transplantation. 2010;90(12):1344–51.
Ning Y, Shang Y, Huang H, Zhang J, Dong Y, Xu W, Li Q. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats. PLoS One. 2013;8(12):e83429.
Yu S, Zhao C, Che N, Jing L, Ge R. Hydrogen-rich saline attenuates eosinophil activation in a Guinea pig model of allergic rhinitis via reducing oxidative stress. J Inflamm (Lond). 2017;14:1.
Rayaman P, Rayaman E, Cevikbas A, Demirtunc R, Sehirli AO, Alagoz SG, Gurer US. Effect of antibiotics on Polymorphonuclear leukocyte functions and myeloperoxidase activity, glutathione and malondialdehyde levels in allergic asthma. Pol J Microbiol. 2015;64(1):69–72.
Seys SF, Daenen M, Dilissen E, Van Thienen R, Bullens DM, Hespel P, Dupont LJ. Effects of high altitude and cold air exposure on airway inflammation in patients with asthma. Thorax. 2013;68(10):906–13.
Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA. Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. J Allergy Clin Immunol. 2009;123(1):146–52. e8
Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2010;12(1):93–124.
Ahmad A, Shameem M, Husain Q. Relation of oxidant-antioxidant imbalance with disease progression in patients with asthma. Ann Thorac Med. 2012;7(4):226–32.
El-Sherbeeny NA, Hassan ZA, Ateyya H. Tiron ameliorates oxidative stress and inflammation in a murine model of airway remodeling. Int Immunopharmacol. 2016;39:172–80.
DOI: 10.1186
Published on: 15/03/2018
Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice
https://asthmarp.biomedcentral.com/articles/10.1186/s40733-018-0040-y
Abstract
Asthma is a global chronic respiratory disease that has no cure and imposes a huge burden on public health. Oxidative stress has been recognized as an important mechanism in the pathogenesis of asthma. Hydrogen has been shown to act as a novel antioxidant and exert therapeutic antioxidant activity in a range of diseases, while the role of this nontoxic gas in asthma is unknown. The aim of this study was to investigate the effect of inhaled hydrogen gas on the pathophysiology of a mouse model of asthma.
Methods
In this study, a mouse model of ovalbumin (OVA)-induced allergic airway inflammation was used. Briefly, mice were sensitized to ovalbumin and inhaled a high concentration of 67% hydrogen gas for 60 minutes once a day for 7 consecutive days following OVA or PBS challenge. Lung function was assessed in a device with 4 biosignaling system channels. Morphology and goblet cell hyperplasia were stained with H/E and periodic acid Schiff staining. Cytological classification in bronchoalveolar lavage fluid (BALF) was analyzed by Wright-Giemsa staining. Serum, BALF and lung tissue were collected for biochemical assays. Statistical significance between groups was determined using one-way analysis of variance (ANOVA). Bonferroni’s multiple comparisons test was used for several comparisons using GraphPad Prism 5 software.
Results
Hydrogen inhalation abolished the increase in pulmonary resistance caused by ovalbumin. Meanwhile, asthmatic mice exhibited severe inflammatory infiltration and goblet cell hyperplasia, which was reversible after hydrogen inhalation. Hydrogen inhalation significantly reduced the numbers of total cells, eosinophils and lymphocytes in BALF. Elevated BALF IL-4, IL-13, TNF-α and CXCL15 and serum IL-4 levels were significantly reduced after inhalation. Hydrogen inhalation significantly upregulated the activity of decreased superoxide dismutase and significantly attenuated the elevation of malondialdehyde and myeloperoxidase levels.
Conclusions
Hydrogen gas inhalation improves lung function and protects established airway inflammation in the allergic asthmatic mice model which may be associated with the inhibition of oxidative stress process. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma.
References
Andreadis AA, Hazen SL, Comhair SA, Erzurum SC. Oxidative and nitrosative events in asthma. Free Radic Biol Med. 2003;35(3):213–25.
Gardette B, Delauze HG. Techniques of underwater intervention: means, methods, research and outlook. Bull Acad Natl Med. 1996;180(5):975–83.
Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun. 2007;361(3):670–4.
Ji X, Liu W, Xie K, Liu W, Qu Y, Chao X, Chen T, Zhou J, Fei Z. Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress. Brain Res. 2010;1354:196–205.
Kajiya M, Silva MJ, Sato K, Ouhara K, Kawai T. Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochem Biophys Res Commun. 2009;386(1):11–5.
Cai J, Kang Z, Liu WW, Luo X, Qiang S, Zhang JH, Ohta S, Sun X, Xu W, Tao H, Li R. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441(2):167–72.
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30–5.
Cui J, Chen X, Zhai X, Shi D, Zhang R, Zhi X, Li X, Gu Z, Cao L, Weng W, Zhang J, Wang L, Sun X, Ji F, Hou J, Su J. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats – a possible new hydrogen resource for clinical use. Neuroscience. 2016;335:232–41.
Kohama K, Yamashita H, Aoyama-Ishikawa M, Takahashi T, Billiar TR, Nishimura T, Kotani J, Nakao A. Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation. Surgery. 2015;158(2):399–407.
Amdur MO, Mead J. Mechanics of respiration in unanesthetized Guinea pigs. Am J Phys. 1958;192(2):364–8.
Khakzad MR, Mirsadraee M, Mohammadpour A, Ghafarzadegan K, Hadi R, Saghari M, Meshkat M. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. Pulm Pharmacol Ther. 2012;25(2):163–8.
Riedl MA, Nel AE. Importance of oxidative stress in the pathogenesis and treatment of asthma. Curr Opin Allergy Clin Immunol. 2008;8(1):49–56.
Nadeem A, Masood A, Siddiqui N. Oxidant–antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options. Ther Adv Respir Dis. 2008;2(4):215–35.
Sugiura H, Ichinose M. Oxidative and nitrative stress in bronchial asthma. Antioxid Redox Signal. 2008;10(4):785–97.
Ben Anes A, Ben Nasr H, Fetoui H, Bchir S, Chahdoura H, Yacoub S, Garrouch A, Benzarti M, Tabka Z, Chahed K. Alteration in systemic markers of oxidative and antioxidative status in Tunisian patients with asthma: relationships with clinical severity and airflow limitation. J Asthma. 2016;53(3):227–37.
Fatani SH. Biomarkers of oxidative stress in acute and chronic bronchial asthma. J Asthma. 2014;51(6):578–84.
Schulze J, Biedebach S, Christmann M, Herrmann E, Voss S, Zielen S. Impulse Oscillometry as a predictor of asthma exacerbations in young children. Respiration. 2016;91(2):107–14.
Iketani M, Ohsawa I. Molecular hydrogen as a neuroprotective agent. Curr Neuropharmacol. 2017;15(2):324–31.
Kurokawa R, Seo T, Sato B, Hirano S, Sato F. Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation. Med Gas Res. 2015;5:13.
Zheng J, Liu K, Kang Z, Cai J, Liu W, Xu W, Li R, Tao H, Zhang JH, Sun X. Saturated hydrogen saline protects the lung against oxygen toxicity. Undersea Hyperb Med. 2010;37(3):185–92.
Kawamura T, Huang CS, Tochigi N, Lee S, Shigemura N, Billiar TR, Okumura M, Nakao A, Toyoda Y. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Transplantation. 2010;90(12):1344–51.
Ning Y, Shang Y, Huang H, Zhang J, Dong Y, Xu W, Li Q. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats. PLoS One. 2013;8(12):e83429.
Yu S, Zhao C, Che N, Jing L, Ge R. Hydrogen-rich saline attenuates eosinophil activation in a Guinea pig model of allergic rhinitis via reducing oxidative stress. J Inflamm (Lond). 2017;14:1.
Rayaman P, Rayaman E, Cevikbas A, Demirtunc R, Sehirli AO, Alagoz SG, Gurer US. Effect of antibiotics on Polymorphonuclear leukocyte functions and myeloperoxidase activity, glutathione and malondialdehyde levels in allergic asthma. Pol J Microbiol. 2015;64(1):69–72.
Seys SF, Daenen M, Dilissen E, Van Thienen R, Bullens DM, Hespel P, Dupont LJ. Effects of high altitude and cold air exposure on airway inflammation in patients with asthma. Thorax. 2013;68(10):906–13.
Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA. Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. J Allergy Clin Immunol. 2009;123(1):146–52. e8
Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2010;12(1):93–124.
Ahmad A, Shameem M, Husain Q. Relation of oxidant-antioxidant imbalance with disease progression in patients with asthma. Ann Thorac Med. 2012;7(4):226–32.
El-Sherbeeny NA, Hassan ZA, Ateyya H. Tiron ameliorates oxidative stress and inflammation in a murine model of airway remodeling. Int Immunopharmacol. 2016;39:172–80.
