Progress in the Use of Molecular Hydrogen for Cancer Treatment

Abstract

Molecular hydrogen is an effective antioxidant. Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases. The possibility of using hydrogen in the treatment of cancer was first discovered in 1975, and in recent studies, researchers have reported numerous positive effects of hydrogen in cancer therapy, including: 1) the alleviation of complications caused by chemotherapy; 2) a reduction of complications caused by radiotherapy; 3) delays in the progression of cancer; and 4) enhanced efficacy of conventional therapy when used in combination with hydrogen. This article reviews the research progress in the use of hydrogen in the treatment of cancer, and proposes future directions for research in this field.

Full text

Progress in the Use of Molecular Hydrogen for Cancer Treatment
Dong Yue Du, Yun Hua Peng, Jian Kang Liu, Jian Gang Long
Center for Mitochondrial Biology and Medicine, Biomedical Information Engineering Laboratory of State Ministry of Education,
School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Corresponding author: Jian Gang Long, PhD, Center for Mitochondrial
Biology and Medicine, School of Life Science and Technology, Xi’an
Jiaotong University, 28 West Xianning Road, Xi’an 710049, China; Tel:
+86 199 2907 2355; Email: jglong@mail.xjtu.edu.cn
Introduction
Hydrogen is the smallest molecule, and is a colorless,
tasteless, odorless, and nontoxic gas at ambient tempera-
tures [1]. Over the past few decades, there has been ex-
tensive researches on the benecial effects of hydrogen in
the clinical setting, including studies of its anti-oxidative,
anti-inammatory and potential anti-cancer activity [2].
The possibility of using hydrogen in the treatment of
cancer was rst described by Dore M et al. in 1975. They
reported that hyperbaric hydrogen treatment for 2 weeks
could lead to significant regression of skin carcinomas
in mice [3]. However, concerns about the safety of trans-
porting, storing and administering hyperbaric hydrogen
limited the application of this therapy. However, in 2007,
Ohsawa I et al. suggested that inhaling small amounts of
hydrogen gas could selectively reduce the level of oxygen
radicals, and could protect neurons from injury caused by
ischemia-reperfusion or inflammation [4]. Since then, the
potential therapeutic effects of molecular hydrogen have at-
tracted increasing attention. Several studies have shown that
hydrogen has positive effects against metabolic syndrome,
inammation, injury, and cancer [5].
The application of hydrogen for cancer treatment is now
a hot research topic. Clinical and experimental research
has indicated that hydrogen could reduce complications
associated with treatment using conventional anti-cancer
drugs, could prevent cancer progression and could improve
the quality of life of cancer patients. In this article, we re-
view the progress made in the application of hydrogen for
the prevention and treatment of cancer, and propose future
directions for research on the potential use of molecular hy-
drogen for cancer therapy.
Hydrogen Reduces the Complications Associ-
ated with Chemotherapy
Chemotherapy is commonly used for most types of
cancer, as has been the mainstay of treatment for decades.
However, these antitumor drugs are often cytotoxic, and
also cause damage to normal cells and organs [6], poten-
tially leading to complications such as nephrotoxicity, car-
diotoxicity and hepatotoxicity. These side effects strongly
decrease the life quality of cancer patients.
Studies have found that human tumor cells produce
more reactive oxygen species (ROS) than normal cells, thus
promoting the proliferation, angiogenesis, and DNA synthe-
sis of cancer cells [7]. Nakashima-Kamimura N et al. found
that inhaling hydrogen or drinking hydrogen-rich water,
which is water contains a high concentration of dissolved
hydrogen, could alleviate the nephrotoxicity caused by
cisplatin, an anti-cancer drug, without affecting the drug’s
anti-tumor activity [8].
Doxorubicin (DOX) is widely used as an anticancer
drug, but its cardiotoxicity and hepatotoxicity limit its
application [9]. It was reported that hydrogen-rich saline
treatment could effectively inhibit the heart and liver injury,
as well as the inammation caused by DOX [9]. Getinib is
an epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitor, which is an effective drug used in the treatment of
non-small cell lung cancer. However, it can cause acute lung
injury [10]. Terasaki Y et al. recently reported that hydro-
gen water intake could effectively protect the lungs of mice
from severe damage caused by getinib without interfering
with the anti-tumor activity of the drug [10]. Hydrogen wa-
ter also alleviated the liver injury caused by mFOLFOX6
chemotherapy in colorectal cancer patients [6].
Abstract: Molecular hydrogen is an effective antioxidant. Numerous studies have demonstrated the therapeutic
effects of hydrogen in the treatment of various human diseases. The possibility of using hydrogen in the treatment
of cancer was rst discovered in 1975, and in recent studies, researchers have reported numerous positive effects of
hydrogen in cancer therapy, including: 1) the alleviation of complications caused by chemotherapy; 2) a reduction of
complications caused by radiotherapy; 3) delays in the progression of cancer; and 4) enhanced efcacy of conventional
therapy when used in combination with hydrogen. This article reviews the research progress in the use of hydrogen in
the treatment of cancer, and proposes future directions for research in this eld.
Key words: Molecular hydrogen; Cancer; Chemotherapy; Radiotherapy; Anticancer drug; Complications; Quality
of life
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Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3

The above studies suggest that hydrogen can improve
the life quality of cancer patients during chemotherapy by
mitigating the side effects of anti-cancer drugs. However,
most of these studies were based on animal and cell models,
and little has been reported regarding the possible molecular
mechanisms. Therefore, more clinical evidence and molecu-
lar experiments are needed to verify the impact of hydrogen
on chemotherapy-associated complications.
Hydrogen Reduces Radiotherapy-related
Complications
Radiation therapy is also frequently used in treating can-
cer, but the radiation-induced complications limit the doses
that can be administrated and reduce the quality of life of
patients. During treatment with ionizing radiation treatment,
oxidative injuries which produce ROS are the major medi-
ators of radiation-induced complications [11]. It has been
reported that hydrogen could ameliorate radiation-induced
complications during cancer treatment by selectively reduc-
ing the level of free radicals [12]. In 2011, Chuai Y et al.
rst proposed that a hydrogen-rich solution could be used
during radiotherapy to prevent the development of radiation
pneumonitis [12].
Radiation therapy also causes gastrointestinal toxicity.
Xiao HW et al. found that hydrogen water ameliorated the
radiation-induced intestinal injury, and increased the surviv-
al rate and body weight of experimental mice [13]. Clinical
research has shown similar results. For example, Kang KM
et al. found that drinking hydrogen-rich water could im-
prove the life quality of liver tumor patients receiving radio-
therapy by reducing the biological reaction to radiation-in-
duced oxidative stress without compromising the anti-tumor
effects of treatment [14].
In 2014, Mei K et al. [15] found that injecting hydro-
gen water could significantly reduce the development of
radiation-induced dermatitis after single and divided irra-
diation of the neck and head in rats. They also found that
hydrogen-rich medium could protect human immortalized
epidermal (HaCaT) cells from radiation-induced injury by
signicantly reducing the oxygen level and increasing the
antioxidative capacity of the cells. In 2018, it was reported
that hydrogen may protect HaCaT cells from UVB radia-
tion-induced oxidative stress by inhibiting the activation of
Nrf2/HO-1 through the PI3K/Akt pathway [16].
Another hydrogen-producing nanomaterial, PdH0.2
nanocrystals, have been reported to release hydrogen and
heat in a controlled manner, with tumor-targeted delivery.
These nanocrystals could produce hydrogen locally and
have been found to reduce side effects and enhance the
positive effects of hyperthermia in different cancer cell lines
[17].
It was also found that hydrogen-rich water was effective
in preventing osteoradionecrosis of the jaw, which is a se-
rious complication of radiotherapy during the treatment of
· 104 · Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3
head and neck cancer patients [18].
The above studies indicate that hydrogen has signicant
effects that can mitigate different complications caused by
radiotherapy. Different methods of hydrogen intake have
been demonstrated to be effective, and clinical results have
shown that hydrogen could improve the quality of in cancer.
Although researchers have demonstrated the effectiveness
of hydrogen and its ability to reduce the ROS level, only
one study so far has discussed the possible mechanism
by which hydrogen protects cells from radiation-induced
oxidative stress [16]. Therefore, the molecular mechanisms
should be a focus of further investigation.
Hydrogen Delays the Progression of Cancer
Besides reducing complications during cancer treatment,
hydrogen was also found to have benecial effects against
cancer progression. In 2008, Saitoh Y et al. rst proposed
that hydrogen water may inhibit tumor growth based on
observations in human tongue carcinoma cells and brosar-
coma cells [19].
Oxidative stress is considered to be a strong contributor
to the progression from fatty liver to nonalcoholic steato-
hepatitis (NASH), and even hepatocarcinogenesis. It was
reported that hydrogen water was effective in the treatment
of NASH in mice, and may prevent the progression of he-
patocarcinogenesis [20].
In 2017, Li Q et al. reported hydrogen-occluding-silica
(H2-silica), a novel hydrogen-generating material which
could release hydrogen into the medium. The H2-silica
could effectively inhibit the proliferation and migration of
human esophageal squamous cell carcinoma (KYSE-70)
cells. They suggested that the H2-silica may selectively in-
crease cell apoptosis by triggering the non-caspase pathway,
because the Bax/Bcl-2 ratios were increased specically in
cancer cell lines [21].
Loss of immunological activity of differentiation
cluster CD8+ T cells is associated with the inactivation
of peroxisome proliferator-activated receptor gamma
coactivator 1 alpha (PGC-1α), which causes mitochondrial
dysfunction, and is widely found in patients with advanced
cancer [22]. In 2018, Akagi J et al. found that hydrogen gas
could activate PGC-1α and restore the exhausted CD8+ T
cells in stage IV colorectal carcinoma patients, suggesting
that hydrogen could improve the prognosis of patients with
advanced cancer [22].
Recently, Wang D et al. found that hydrogen gas
inhibited the viability, migration and invasion of lung
cancer cells in vitro; and inhibited tumor growth in vivo
[23]. They also discovered that hydrogen inhibits lung
cancer progression by down-regulating the expression
and structural stability of structural maintenance of
chromosomes 3 (SMC3). Their study showed that hydrogen
could down-regulate the expression of SMC3, structural
maintenance of chromosomes 5 (SMC5), structural

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Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3
maintenance of chromosomes 6 (SMC6) and Nipped-B
homolog (Drosophila) (NIBPL). They found that hydrogen
translocated SMC3 during cell division, resulting in
decreased cell stability and enhanced SMC3 ubiquitination
in A549 and H1975 lung cancer cell lines [23]. This study
suggested that hydrogen gas may inhibit the progression of
lung cancer by down-regulating SMC3.
These research studies showed that hydrogen may de-
lay cancer progression by inhibiting the growth of tumor
cells and triggering tumor cell apoptosis. Some possible
pathways have been identified, including the non-caspase
apoptosis pathway, and key proteins such as PGC-1α and
SMC3. Some of these studies suggested hydrogen may in-
terfere with different proteins located in the nucleus and cy-
toplasm, indicating that hydrogen may participate in the ac-
tivation or inhibition of multiple pathways. However, more
experiments are needed to support the role of hydrogen in
delaying cancer progression, and to determine whether this
nding translates to the clinic.
Combination Treatment with Hydrogen and
Anti-Cancer Drugs
It was also reported that using hydrogen in combination
with other anti-cancer drugs appeared to be useful in en-
hancing the therapeutic effects of the drugs.
For example, Runtuwene J et al. found that hydrogen
water could signicantly increase the survival rate, improve
the anti-oxidative effects and enhance the pro-apoptotic ef-
fects of 5-FU in a mouse model of colon cancer [2].
The PI3K/AKT signaling pathway has proven to be a
viable target for novel antitumor drugs [16]. Researchers
recently found that the combination of hydrogen-rich saline
with a PI3K inhibitor, LY294002, could reduce proliferation
and promote apoptosis in A549 non-small cell lung cancer
cells [24]. Although these findings are preliminary, they
suggest that combining hydrogen with other treatments may
have additive or synergistic effects, in addition to decreasing
treatment-related toxicity.
Conclusion
Molecular hydrogen has anti-oxidative, anti-inflam-
matory and anti-allergic effects mediated by its selective
removal of free radicals. Since 2007, when safer and more
convenient methods of hydrogen intake were proven to be
effective in the treatment of disease [4], numerous studies
have examined the potential of using hydrogen for a variety
of diseases and conditions.
The biological effects of hydrogen in disease models
and the potential mechanisms of action of hydrogen in these
diseases have also been investigated in our lab. In 2016, we
Colon Cancer
• Decrease cancel progression with 5-FU
• Inhibit liver injury caused by chemotherapy
• Restore exhausted CD8+ T cells
Non-small Cell Lung Cancer
• Decrease cancer progression
• Improve effects of anti-cancer drugs
• Ameliorate lung damage caused by
chemotherapy
Skin Cancer
• Decrease tumor growth
Liver Cancer
• Decrease cancer progression from fatty
liver disease
• Ameliorate radiation-induced oxidative
stress
Tongue Cancer
• Inhibit tumor growth
Head and Neck Cancer
• Ameliorate osteoradionecrosis of the jaw
caused by radiotherapy
• Reduce radiation-inducecl dermatitis
Radiotherapy
• Mitigate radiation-induced oxidative stress
• Mitigate osteoradionecrosis of jaw
• Mitigate gastrointestinal toxicity
• Mitigate radiation-induced dermatitis
Chemotherapy
• Mitigate nephrotoxicity
• Mitigate heart and liver injury
• Mitigate lung damage
Possible Mechanisms
• Decrease the ROS level of cancer cells
• Increase cancer cell apoptosis
• Decrease cancer cell stability
Possible Pathways & Proteins
• Inhibit the activation of Nrf2/HO-1 through
the PI3K/Akt pathway
• Triggering the non-caspase pathway
• Activate PGC-lα
• Down-regulate SMC3
Cancer
Types
Therapies
Possible
Mechanisms
Molecular
Hydrogen
Figure 1 Current progress on the use of hydrogen in the treatment of cancer.

· 106 · Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3
found that inhalation of a small amount of hydrogen could
improve the cardiac function and neurological outcomes in
the asphyxia rat model of cardiac arrest, and the therapeutic
benets were superior to traditional hypothermia methods
[25]. It was also noted that coral calcium hydride (CCH), an
efcient hydrogen-releasing agent, could effectively prevent
high fat diet-induced nonalcoholic fatty liver disease by im-
proving the mitochondrial function and activating phase II
enzymes [26]. Recently, we discovered that hydrogen may
gender-dependently improve the cognitive function of APP/
PSI mice (a model of Alzheimer’s disease) by interfering
with the estrogen receptor-β and brain-derived neurotrophic
factor (ERβ-BDNF) signaling pathways [27]. The medical
effects of hydrogen are gaining increasing interest, and nu-
merous investigators are evaluating the effects of hydrogen
in various disease states and are working to determine the
associated mechanisms of action.
Because cancer cells produce more ROS than normal
cells, and since hydrogen can act as an anti-oxidative mole-
cule, hydrogen may be useful for cancer treatment. In fact,
several studies have already indicated that hydrogen has
anti-tumor effects that are at least partially mediated through
reductions of the ROS in tumor cells to suppress cell growth
[28,29].
Nevertheless, there is only limited information available
about the optimal doses and timing of hydrogen therapy,
as well as the safety of this treatment [30]. Moreover, there
have been only a few studies of the possible molecular
mechanisms underlying the effects of hydrogen. Therefore,
further studies are needed to elucidate the mechanism(s)
of action when hydrogen is used alone and in combination
with other agents; and more clinical research is also needed
to conrm the safety and efcacy of the treatment.
In conclusion, recent studies have found that hydrogen
treatment could alleviate the adverse effects induced by
chemotherapy and radiotherapy to improve the quality of
life of cancer patients. Hydrogen treatment may also slow
down the progression of cancer; and the combined use of
hydrogen with other anti-cancer drugs may enhance the
anti-cancer effects of the treatment. Some possible molecular
mechanisms by which hydrogen induces these effects have
been described. In Figure 1, we summarize the current
progress that has been made in the use of hydrogen in the
treatment of cancer. Although the eld is still relatively new,
molecular hydrogen appears to have promise as an adjuvant
treatment for cancer patients, and may also have a role in
prevention medicine for high risk populations.
Conict of Interests
The authors declare that they have no conflicts of
interest.
Funding
This study was supported by the Major State Basic
Research Development Program (2015CB856302,
2015CB553602), the National Natural Science Foundation
of China (31870848, 81741110, 81802787), and the Natural
Science Foundation of Shaanxi (2018JZ3005).
References
1. Ohta S. Recent progress toward hydrogen medicine: Potential of
molecular hydrogen for preventive and therapeutic applications. Curr
Pharm Des 2011;17(22):2241-52.
2. Runtuwene J, Amitani H, Amitani M, Asakawa A, Cheng KC, Inui
A. Hydrogen-water enhances 5-uorouracil-induced inhibition of colon
cancer. Peer J 2015;3:e859.
3. Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: A possi-
ble treatment for cancer. Science 1975;190(4210):152-4.
4. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K,
Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts
as a therapeutic antioxidant by selectively reducing cytotoxic oxygen
radicals. Nat Med 2007;13(6):688-94.
5. Ge L, Yang M, Yang NN, Yin XX, Song WG. Molecular hydrogen: a
preventive and therapeutic medical gas for various diseases. Oncotarget
2017;8(60):102653-73.
6. Yang Q, Ji G, Pan R, Zhao Y, Yan P. Protective effect of hydro-
gen-rich water on liver function of colorectal cancer patients treated
with mFOLFOX6 chemotherapy. Mol Clin Oncol 2017;7(5):891-6.
7. Nonaka Y, Iwagaki H, Kimura T, Fuchimoto S, Orita K. Effect of
reactive oxygen intermediates on the in vitro invasive capacity of tumor
cells and liver metastasis in mice. Int J Cancer 1993;54(6):983-6.
8. Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molec-
ular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug
cisplatin without compromising anti-tumor activity in mice. Cancer
Chemother Pharmacol 2009;64(4):753-61.
9. Gao Y, Yang H, Fan Y, Li L, Fang J, Yang W. Corrigendum to “Hy-
drogen-rich saline attenuates cardiac and hepatic injury in doxorubicin
rat model by inhibiting inflammation and apoptosis”. Mediators In-
amm 2017;2017:3675910.
10. Terasaki Y, Suzuki T, Tonaki K, Terasaki M, Kuwahara N, Ohsiro
J, Iketani M, Takahashi M, Hamanoue M, Kajimoto Y, Hattori S,
Kawaguchi H, Shimizu A, Ohsawa I. Molecular hydrogen attenuates
getinib-induced exacerbation of naphthalene-evoked acute lung injury
through a reduction in oxidative stress and inammation. Lab Invest
2019;99(6):793-806.
11. Mihailovic M, Milosevic V, Grigorov I, Poznanovic G, Iva-
novic-Matic S, Grdovic N, Bogojevic D. The radioprotective effect
of alpha2-macroglobulin: a morphological study of rat liver. Med Sci
Monit 2009;15(7):BR188-93.
12. Chuai Y, Zhao L, Ni J, Sun D, Cui J, Li B, Qian L, Gao F, Cai J.
A possible prevention strategy of radiation pneumonitis: combine ra-
diotherapy with aerosol inhalation of hydrogen-rich solution. Med Sci
Monit 2011;17(4):HY1-4.
13. Xiao HW, Li Y, Luo D, Dong JL, Zhou LX, Zhao SY, Zheng QS,
Wang HC, Cui M, Fan SJ. Hydrogen-water ameliorates radiation-in-
duced gastrointestinal toxicity via MyD88’s effects on the gut microbi-
ota. Exp Mol Med 2018;50:e433.
14. Kang KM, Kang YN, Choi IB, Gu Y, Kawamura T, Toyoda Y, Na-
kao A. Effects of drinking hydrogen-rich water on the quality of life

· 107 ·
Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3
of patients treated with radiotherapy for liver tumors. Med Gas Res
2011;1(1):11.
15. Mei K, Zhao S, Qian L, Li B, Ni J, Cai J. Hydrogen protects
rats from dermatitis caused by local radiation. J Dermatolog Treat
2014;25(2):182-8.
16. Zhang B, Zhao Z, Meng X, Chen H, Fu G, Xie K. Hydrogen ame-
liorates oxidative stress via PI3K-Akt signaling pathway in UVB-in-
duced HaCaT cells. Int J Mol Med 2018;41(6):3653-61.
17. Zhao P, Jin Z, Chen Q, Yang T, Chen D, Meng J, Lu X, Gu Z, He Q.
Local generation of hydrogen for enhanced photothermal therapy. Nat
Commun 2018;9(1):4241.
18. Chen Y, Zong C, Guo Y, Tian L. Hydrogen-rich saline may be an
effective and specic novel treatment for osteoradionecrosis of the jaw.
Ther Clin Risk Manag 2015;11:1581-5.
19. Saitoh Y, Okayasu H, Xiao L, Harata Y, Miwa N. Neutral pH
hydrogen-enriched electrolyzed water achieves tumor-preferential
clonal growth inhibition over normal cells and tumor invasion inhi-
bition concurrently with intracellular oxidant repression. Oncol Res
2008;17(6):247-55.
20. Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T,
Koike K, Tsuzaki R, Matsumoto K, Miyake Y, Shiraha H, Morita M,
Makino H, Yamamoto K. Hydrogen-rich water prevents progression of
nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in
mice. Hepatology 2012;56(3):912-21.
21. Li Q, Tanaka Y, Miwa N. Inuence of hydrogen-occluding-silica on
migration and apoptosis in human esophageal cells in vitro. Med Gas
Res 2017;7(2):76-85.
22. Akagi J, Baba H. Hydrogen gas restores exhausted CD8+ T cells in
patients with advanced colorectal cancer to improve prognosis. Oncol
Rep 2018;41(1):301-11.
23. Wang D, Wang L, Zhang Y, Zhao Y, Chen G. Hydrogen gas inhibits
lung cancer progression through targeting SMC3. Biomed Pharmacoth-
er 2018;104:788-97.
24. Jiang Y, Liu G, Zhang L, Cheng S, Luo C, Liao Y, Guo S. Ther-
apeutic efficacy of hydrogen-rich saline alone and in combination
with PI3Kinhibitor in nonsmall cell lung cancer. Mol Med Rep
2018;18(2):2182-90.
25. Wang P, Jia L, Chen B, Zhang L, Liu J, Long J, Li Y. Hydrogen in-
halation is superior to mild hypothermia in improving cardiac function
and neurological outcome in an asphyxial cardiac arrest model of rats.
Shock 2016;46(3):312-8.
26. Hou C, Wang Y, Zhu E, Yan C, Zhao L, Wang X, Qiu Y, Shen H,
Sun X, Feng Z, Liu J, Long J. Coral calcium hydride prevents hepatic
steatosis in high fat diet-induced obese rats: A potent mitochondrial nu-
trient and phase II enzyme inducer. Biochem Pharmacol 2016;103:85-
97.
27. Hou C, Peng Y, Qin C, Fan F, Liu J, Long J. Hydrogen-rich water
improves cognitive impairment gender-dependently in APP/PS1 mice
without affecting Aβ clearance. Free Radic Res 2018;52(11-12):1311-
22.
28. Asada R, Kageyama K, Tanaka H, Matsui H, Kimura M, Saitoh Y,
Miwa N. Antitumor effects of nano-bubble hydrogen-dissolved water
are enhanced by coexistent platinum colloid and the combined hyper-
thermia with apoptosis-like cell death. Oncol Rep 2010;24(6):1463-70.
29. Yang Y, Zhu Y, Xi X. Anti-inammatory and antitumor action of
hydrogen via reactive oxygen species. Oncol Lett 2018;16(3):2771-6.
30. Ostojic SM. Molecular hydrogen: an inert gas turns clinically effec-
tive. Ann Med 2015;47(4):301-4.
Received: April 22, 2019 Revised: May 22, 2019 Accepted: May 28, 2019