Hydrogen therapy may be an effective and specific novel treatment for acute graft-versus-host disease (GVHD)

Liren Qian, Jianliang Shen, Liren Qian, Jianliang Shen

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of haematological malignant and non-malignant haematologic diseases. However, acute graft-versus-host disease (aGVHD) is a kind of severe complication of HSCT limiting its application. Cytokines such as tumour necrosis factor-α (TNF-α), IL-6 play an extremely important role in the formation and development of aGVHD. Besides, the oxidation phenomena and/or the formation of free radicals have been suggested to be causally related to various haematological disorders including aGVHD. Reactive oxygen species (ROS), such as hydroxyl radicals, play an important role in the formation and development of aGVHD. Hydrogen has been reported to have the ability to inhibit levels of cytokines such as TNF, IL-6 in vivo. Our recent studies provided evidence that hydrogen inhalation can selectively reduce cytotoxic oxygen radicals and exert antioxidant effects. Therefore, we suggested that hydrogen may have therapeutic effects on aGVHD. This hypothesis entails many experimentally testable predictions. We propose the experimental study by detecting complete blood counts (CBC) and Clinic signs of aGVHD mice. We also propose to detect the levels of TNF-α, IL-2, IL-1β, IL-6 which play important roles in the pathogenesis of aGVHD. To discover potential mechanisms of the therapeutic effects of hydrogen on the aGVHD model, we will examine gene-expression profiles. This study will open a new therapeutic avenue combining the field of therapeutic medical gases and aGVHD. This theory is original and probably of importance, because therapeutic medical gases have never been used for aGVHD previously.

Keywords: Hydrogen; antioxidant; cytokine; graft-versus-host disease.

© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Figures

Fig. 1
Fig. 1
Cytotoxic oxygen radicals that hydrogen could selectively reduce.
Fig. 2
Fig. 2
Cytokines that hydrogen could down-regulate (→) in the pathogenesis of aGVHD. Adapted from Ferrara [38].

References

    1. Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer. Science. 1975;190:152–4.
    1. Buxton GV, Greenstock CL, Helman WP, et al. Critical review of rate constants for reactions of hydrated electrons, review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals in aqueous solution. J Phys Chem. 1988;17:513–886.
    1. Gharib B, Hanna S, Abdallahi OM, et al. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation. C R Acad Sci III. 2001;324:719–24.
    1. Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688–94.
    1. Sun Q, Kang Z, Cai J, et al. Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats. Exp Biol Med (Maywood) 2009;234:1212–9.
    1. Fukuda K, Asoh S, Ishikawa M, et al. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun. 2007;361:670–4.
    1. Cai J, Kang Z, Liu WW, et al. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441:167–72.
    1. Fu Y, Ito M, Fujita Y, et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease. Neurosci Lett. 2009;453:81–5.
    1. Nagata K, Nakashima-Kamimura N, Mikami T, et al. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009;34:501–8.
    1. Mao YF, Zheng XF, Cai JM, et al. Hydrogen-rich saline reduces lung injury induced by intestinal ischemia/reperfusion in rats. Biochem Biophys Res Commun. 2009;381:602–5.
    1. Chuai Y, Qian L, Sun X, et al. Molecular hydrogen and radiation protection. Free Radic Res. 2012;46:1061–7.
    1. Chuai Y, Shen J, Qian L, et al. Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice. Med Sci Monit. 2012;18:BR89–94.
    1. Chuai Y, Gao F, Li B, et al. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem J. 2012;442:49–56.
    1. Chuai Y, Zhao L, Ni J, et al. A possible prevention strategy of radiation pneumonitis: combine radiotherapy with aerosol inhalation of hydrogen-rich solution. Med Sci Monit. 2011;17:HY1–4.
    1. Qian L, Li B, Cai J, et al. The hypothesis of an effective safe and novel radioprotective agent: hydrogen-rich solution. West Indian Med J. 2010;59:122–4.
    1. Qian L, Cao F, Cui J, et al. The potential cardioprotective effects of hydrogen in irradiated mice. J Radiat Res. 2010;51:741–7.
    1. Qian L, Cao F, Cui J, et al. Radioprotective effect of hydrogen in cultured cells and mice. Free Radic Res. 2010;44:275–82.
    1. 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;373:30–5.
    1. Buchholz BM, Kaczorowski DJ, Sugimoto R, et al. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am J Transplant. 2008;8:2015–24.
    1. Kawamura T, Huang CS, Tochigi N, et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Transplantation. 2010;90:1344–51.
    1. Cardinal JS, Zhan J, Wang Y, et al. Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int. 2010;77:101–9.
    1. Nakao A, Kaczorowski DJ, Wang Y, et al. Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both. J Heart Lung Transplant. 2010;29:544–53.
    1. Kawamura T, Huang CS, Peng X, et al. The effect of donor treatment with hydrogen on lung allograft function in rats. Surgery. 2011;150:240–9.
    1. Vodanovic-Jankovic S, Hari P, Jacobs P, et al. NF-kappaB as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145. Blood. 2006;107:827–34.
    1. Hill GR, Crawford JM, Cooke KR, et al. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90:3204–13.
    1. Hill GR, Teshima T, Gerbitz A, et al. Differential roles of IL-1 and TNF-alpha on graft-versus-host disease and graft versus leukemia. J Clin Invest. 1999;104:459–67.
    1. Ferrara JL, Deeg HJ. Graft-versus-host disease. N Engl J Med. 1991;324:667–74.
    1. Abo-Zena RA, Horwitz ME. Immunomodulation in stem-cell transplantation. Curr Opin Pharmacol. 2002;2:452–7.
    1. 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;81:325–8.
    1. Liu C, Cui J, Sun Q, et al. Hydrogen therapy may be an effective and specific novel treatment for acute radiation syndrome. Med Hypotheses. 2010;74:145–6.
    1. Cooke KR, Kobzik L, Martin TR, et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood. 1996;88:3230–9.
    1. MacDonald KP, Rowe V, Filippich C, et al. Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation. Blood. 2003;101:2033–42.
    1. Wang F, Yu G, Liu SY, et al. Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats. J Surg Res. 2011;167:e339–44.
    1. Sun Q, Cai J, Zhou J, et al. Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity. Crit Care Med. 2011;39:765–9.
    1. Bureau F, Vanderplasschen A, Jaspar F, et al. Constitutive nuclear factor-kappaB activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins. Blood. 2002;99:3683–91.
    1. Dai C, Krantz SB. Interferon gamma induces upregulation and activation of caspases 1, 3, and 8 to produce apoptosis in human erythroid progenitor cells. Blood. 1999;93:3309–16.
    1. Qian L, Mei K, Shen J, et al. Administration of hydrogen-rich saline protects mice from lethal acute graft-versus-host disease (aGVHD) Transplantation. 2013;95:658–62.
    1. Ferrara JLM. Novel strategies for the treatment and diagnosis of graft-versus-host-disease. Best Pract Res Clin Haematol. 2007;20:91–7.

Source: PubMed

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