Advancements in pharmacological effects and administration routes of hydrogen gas: A comprehensive research overview

doi:10.5246/jcps.2024.06.042

Abstract

Abstract:

Hydrogen, the simplest element in the universe. Hydrogen gas is colorless, odorless, and tasteless. As a reducing agent composed of two atoms. It exhibits strong reducing power and possesses numerous pharmacological effects, including anti-oxidation, antifatigue, anti-radiation, anti-inflammation, hypoglycemic, and hypolipidemic effects. Various methods exist for supplying hydrogen, but inhaling the gas is dangerous, drinking hydrogen-rich water is ineffective, and injecting hydrogen-rich saline is inconvenient. The most viable approach for clinical use is oral medicine, which produces hydrogen in vivo. Hydrogen gas holds promising potential as a clinical medicine in the future.

Key words: Hydrogen gas, Pharmacological effects, Administration route, Research progress

Supporting:

Hui Zhang, Hongmei Zhang, Jun Peng, Yun Ling. Advancements in pharmacological effects and administration routes of hydrogen gas: A comprehensive research overview[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(6): 571-578.

References 35

[1]	Liu, B.Y.; Jia, X.B.; Xue, J.L.; Qin, S.C. Headspace gas chromatography and hydrogen microelectrode methods are used for the detection of hydrogen content in hydrogen rich water. Food Indus. Tech. 2023, 44, 352–357.
[2]	Ohsawa, I.; Ishikawa, M.; Takahashi, K.; Watanabe, M.; Nishimaki, K.; Yamagata, K.; Katsura, K.I.; Katayama, Y.; Asoh, S.; Ohta, S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007, 13, 688–694.
[3]	Tang, H.; Wang, Y.; Li, M.L.; Fen, N.H. Research progress of antioxidant hydrogen molecules in improving renal pathological damage in diabetes. Chin. J. Pathol. 2022, 51, 788–791.
[4]	Wang, Z.; Wang, G.L.; Xie, K. Prospects of molecular hydrogen in perioperative neuroprotection from basic research to clinical application. Curr. Opin. Anaesthesiol. 2020, 33, 655–660.
[5]	Guan, W.J.; Wei, C.H.; Chen, A.L.; Sun, X.C.; Guo, G.Y.; Zou, X.; Shi, J.D.; Lai, P.Z.; Zheng, Z.G.; Zhong, N.S. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J. Thorac. Dis. 2020, 12, 3448–3452.
[6]	Jin, L.; Fan, K.; Liu, S.X.; Zhang, X.L.; Ge, Q.; Wang, Y.; Qiu, Y.R.; Yu, S.Q. Clinical exploration of hydrogen inhalation in the treatment of acute primary tinnitus. Chin. J. Otolaryn. 2022, 29, 500–503.
[7]	Li, H.; Luo, Y.; Yang, P.F.; Liu, J.M. Hydrogen as a complementary therapy against ischemic stroke: a review of the evidence. J. Neurol. Sci. 2019, 396, 240–246.
[8]	Su, J.K.; Li, P.; Liu, Y.; Deng, L.X.; Wen, C.H.; Zhang, M.Q. Preparation methods of exogenous hydrogen in different route of administration. Med. Equip. 2017, 30, 25–26
[9]	Li, T.T.; Yang, W.C.; Wang, Y.Z.; Sun, T.; Cao, H.L.; Chen, J.F.; Li, W.Z. Effects of a high concentration of hydrogen on neurological function after traumatic brain injury in diabetic rats. Brain Res. 2020, 1730, 146651.
[10]	Hirano, S.I.; Ichikawa, Y.; Sato, B.; Yamamoto, H.; Takefuji, Y.; Satoh, F. Molecular hydrogen as a potential clinically applicable radioprotective agent. Int. J. Mol. Sci. 2021, 22, 4566.
[11]	Mu, F.; Chen, J.B.; Kong, X.F. High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study. Med. Gas Res. 2021, 11, 12–17.
[12]	Wang, C.; Li, J.A.; Liu, Q.A.; Yang, R.; Zhang, J.H.; Cao, Y.P.; Sun, X.J. Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer’s disease. Neurosci. Lett. 2011, 491, 127–132.
[13]	Wang, J.L.; Zhang, Q.S.; Zhu, K.D.; Sun, J.F.; Zhang, Z.P.; Sun, J.W.; Zhang, K.X. Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury. Neural Regen. Res. 2015, 10, 958–964.
[14]	Zou, R.; Wang, M.H.; Chen, Y.; Fan, X.; Yang, B.; Du, J.; Wang, X.B.; Liu, K.X.; Zhou, J. Hydrogen-rich saline attenuates acute lung injury induced by limb ischemia/reperfusion via down-regulating chemerin and NLRP3 in rats. Shock. 2019, 52, 134–141.
[15]	Yu, M.D.; Li, P.; Lu, Y.C.; Chen, H.M.; Wang, X.; Xie, K.L. Effect of hydrogen inhalation on DNA methylation in hippocampus of septic mice. Tianjin Pharm. 2020, 48, 177–181.
[16]	Kang, K.M.; Kang, Y.N.; Choi, I.B.; Gu, Y.; Kawamura, T.; Toyoda, Y.; Nakao, A. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res. 2011, 1, 11.
[17]	Li, L.T.; Liu, T.T.; Liu, L.; Zhang, Z.; Li, S.C.; Zhang, Z.L.; Zhou, Y.J.; Liu, F.L. Metabolomics analysis of the effect of hydrogen-rich water on myocardial ischemia-reperfusion injury in rats. J. Bioenerg. Biomembr. 2020, 52, 257–268.
[18]	Lucas, K.; Rosch, M.; Langguth, P. Molecular hydrogen (H₂) as a potential treatment for acute and chronic fatigue. Arch. Pharm. 2021, 354, 378–382.
[19]	Nogueira, J.E.; Passaglia, P.; Mota, C.M.D.; Santos, B.M.; Batalhão, M.E.; Carnio, E.C.; Branco, L.G.S. Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status. Free. Radic. Biol. Med. 2018, 129, 186–193.
[20]	Kawamura, T.; Higashida, K.; Muraoka, I. Application of molecular hydrogen as a novel antioxidant in sports science. Oxidative Med. Cell Longev. 2020, 2020, 1–7.
[21]	Uto, K.; Sakamoto, S.; Que, W.T.; Shimata, K.; Hashimoto, S.; Sakisaka, M.; Narita, Y.; Yoshii, D.; Zhong, L.; Komohara, Y.; Li, X.K.; Inomata, Y.; Hibi, T. Hydrogen-rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation. BMC Gastroenterol. 2019, 19, 1–9.
[22]	Zhang, Y.G.; Sheng, Q.S.; Wang, Z.J.; Lv, L.I.; Zhao, W.; Chen, J.M.; Xu, H. Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats. Exp. Ther. Med. 2015, 10, 727–732.
[23]	Zhao, S.H.; Yang, Y.Y.; Liu, W.; Xuan, Z.Q.; Wu, S.M.; Yu, S.F.; Mei, K.; Huang, Y.J.; Zhang, P.; Cai, J.M.; Ni, J.; Zhao, Y.X. Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction. J. Cell Mol. Med. 2014, 18, 938–946.
[24]	Meng, J.H.; Liu, L.Y.; Wang, D.C.; Yan, Z.F.; Chen, G. Hydrogen gas represses the progression of lung cancer via down-regulating CD47. Biosci. Rep. 2020, 40, BSR20192761.
[25]	Kato, S.; Saitoh, Y.; Miwa, N. Hydrogen-bubbled platinum-colloid suppresses human esophagus- or tongue-carcinoma cells with intracellular platinum-uptake and the diminished normal-cell mortality. Hum. Cell. 2020, 33, 1294–1301.
[26]	Saitoh, Y.; Kawasaki, N.; Eguchi, N.; Ikeshima, M. Combined treatment with dissolved hydrogen molecule and platinum nanocolloid exerts carcinostatic/carcinocidal effects by increasing hydrogen peroxide generation and cell death in the human gastric cancer cell line NUGC-4. Free Radic. Res. 2021, 55, 211–220.
[27]	Hirano, S.I.; Aoki, Y.; Li, X.K.; Ichimaru, N.; Takahara, S.; Takefuji, Y. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study. Med. Gas Res. 2021, 11, 104–109.
[28]	Li, Q.A.; Hu, L.A.; Li, J.A.; Yu, P.; Hu, F.; Wan, B.; Xu, M.M.; Cheng, H.X.; Yu, W.Y.; Jiang, L.P.; Shi, Y.D.; Li, J.C.; Duan, M.L.; Long, Y.; Liu, W.T. Hydrogen attenuates endotoxin-induced lung injury by activating thioredoxin 1 and decreasing tissue factor expression. Front. Immunol. 2021, 12, 625957.
[29]	Akagi, J.; Baba, H. Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD‑1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer. Oncol. Lett. 2020, 20, 1.
[30]	Saito, M.; Chen-Yoshikawa, T.F.; Takahashi, M.; Kayawake, H.; Yokoyama, Y.; Kurokawa, R.; Hirano, S.I.; Date, H. Protective effects of a hydrogen-rich solution during cold ischemia in rat lung transplantation. J. Thorac. Cardiovasc. Surg. 2020, 159, 2110–2118.
[31]	Kamimura, N.; Nishimaki, K.; Ohsawa, I.; Ohta, S. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity. 2011, 19, 1396–1403.
[32]	Zhang, G.M.; Gao, S.; Li, X.Y.; Zhang, L.L.; Tan, H.; Xu, L.; Chen, Y.Y.; Geng, Y.J.; Lin, Y.L.; Aertker, B.; Sun, Y.Y. Pharmacological postconditioning with lactic acid and hydrogen rich saline alleviates myocardial reperfusion injury in rats. Sci. Rep. 2015, 5, 9858.
[33]	Yang, Y.Y.; Li, B.L.; Liu, C.; Chuai, Y.H.; Lei, J.X.; Gao, F.; Cui, J.G.; Sun, D.; Cheng, Y.; Zhou, C.F.; Cai, J.M. Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis. Med. Sci. Monit. 2012, 18, BR144–BR148.
[34]	Zhang, B.Y.; Wang, F.; Zhou, H.; Gao, D.Y.; Yuan, Z.; Wu, C.F.; Zhang, X.J. Polymer dots compartmentalized in liposomes as a photocatalyst for in situ hydrogen therapy. Angew. Chem. Int. Ed Engl. 2019, 58, 2744–2748.
[35]	Cao, Y.J.; Yin, W.Z.; Yoshikawa, Y.; Cong, X.S. The effect of hydrogenated coral calcium on antioxidant activity in aging mice. Chin. J. Geront. 2014, 34, 982–984.