https://www.mdpi.com/1422-0067/22/16/8724
Year: 2021
ABSTRACT:
UNDERLYING MECHANISMS:
CHEMOPROTECTIVE MECHANISMS:
H2
https://pubmed.ncbi.nlm.nih.gov/19783965/ [26] – EFFICACY
https://pubmed.ncbi.nlm.nih.gov/21042740/ [27] – EFFICACY
https://www.tandfonline.com/doi/full/10.3109/10715762.2015.1131823 [28] – EFFICACY
https://pubmed.ncbi.nlm.nih.gov/33387361/ [29] – EFFICACY
https://www.scientific.net/MSF.706-709.520 [30] – EFFICACY
https://peerj.com/articles/859/ [31] – EFFICACY
https://www.sciencedirect.com/science/article/abs/pii/S0753332218308667?via%3Dihub [32] – EFFICACY
https://pubmed.ncbi.nlm.nih.gov/31113492/ [34] – EFFICACY
https://pubmed.ncbi.nlm.nih.gov/31924176/ [35] – EFFICACY
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.25782 [37]- EFFICACY
https://www.jstage.jst.go.jp/article/bpb/31/1/31_1_19/_article [38] – EFFICACY
https://www.spandidos-publications.com/10.3892/or.2018.6841 [39] – EFFICACY
https://www.spandidos-publications.com/10.3892/ol.2020.12121 [40] – EFFICACY
https://pubmed.ncbi.nlm.nih.gov/31552873/ [35] – EFFICACY
REDOX CONTROL IN CANCER:
CANCER & CHRONIC INFLAMMATION:
Antitumor Effects of H2
ANIMAL MODELS:
CELLULAR MODELS
The superior bioavailability of molecular hydrogen (H2) when administered through different routes, particularly inhalation compared to oral ingestion or intravenous methods, is a key aspect of its application in therapeutic contexts.
Real-time monitoring of H2 diffusion can be accomplished by measuring H2 concentrations inside various tissues using electrodes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/
INHALATION of H2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/
https://pubmed.ncbi.nlm.nih.gov/24769081/
https://pubmed.ncbi.nlm.nih.gov/28669654/
Protective effects of H2 gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study.
https://doi.org/10.4103/2045-9912.314329
ABSTRACT
H2 gas inhalation therapy alleviated IMRT-induced bone marrow damage without compromising the anti-tumor effects of IMRT.
H2 Gas Inhalation Alleviates Radiation-Induced Bone Marrow Damage in Cancer Patients.
https://doi.org/10.2139/ssrn.3349228
ABSTRACT
H2 gas inhalation therapy significantly alleviates IMRT radiation-induced bone marrow damage without compromising anti-tumor effects. These results suggest that H2 gas treatment would be a strategy for reducing IMRT bone marrow damage in cancer patients..
H2 ameliorates Total Body Irradiation-Induced Hematopoietic Stem Cell Injury by Reducing Hydroxyl Radical.
https://doi.org/10.1155/2017/8241678
ABSTRACT
Collectively, the present results suggest that H2 protects against TBI-induced HSC injury.
Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation.
https://doi.org/10.1186/s13287-019-1241-x
ABSTRACT
The sphere-forming ability of glioma cells was also suppressed by H2. H2 also suppressed the migration, invasion, and colony-forming ability of glioma cells. Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.
Effect of H2 on Radiation-Induced Cognitive Dysfunction in Rats.
https://doi.org/10.1667/RR15464.1
ABSTRACT
H2 has a protective effect on radiation-induced cognitive dysfunction, and that the possible mechanisms mainly involve anti-oxidative and anti-inflammatory reactions, and its protection of newborn neurons by regulating the BDNF-TrkB signaling pathway.
H2 restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis
https://www.spandidos-publications.com/10.3892/or.2018.6841#
H2 can provide an improved prognosis in colorectal cancer
H2 enhances 5-fluorouracil-induced inhibition of colon cancer.
https://peerj.com/articles/859/
H2 can inhibit colon cancer, particularly in combination with 5-fluorouracil
H2 exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model.
https://doi.org/10.4251/wjgo.v14.i1.242
Administration H2, with or without 5-FU, may serve as a therapeutic for treating CRC
Molecular Hydrogen Inhibits Colorectal Cancer Growth via the AKT/SCD1 Signaling Pathway
https://doi.org/10.1155/2022/8024452
hydrogen inhibited colorectal cancer cell survival by reducing pAKT
This study underscores the potential of molecular hydrogen (H2) as a novel therapeutic in oncology, particularly for colorectal cancer (CRC)
By inhibiting the pAKT/SCD1 pathway, H2 treatment significantly reduced tumor proliferation and volume, suggesting a dual function of targeting cancer growth and the associated molecular pathways.
H2 inhibits endometrial cancer growth via ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6491-6
ABSTRACT
Hydrogen exerts a biphasic effect on endometrial cancer by promoting tumor cell death and protecting normal cells.
H2 inhibits endometrial cancer growth via ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6491-6
ABSTRACT
H2 exerts a biphasic effect on endometrial cancer by
promoting tumor cell death and
protecting normal cells.
RNA sequencing analysis reveals apoptosis induction by H2 treatment in endometrial cancer via TNF and NF-κB pathways.
https://doi.org/10.21037/tcr.2020.03.71
ABSTRACT
H2 treatment significantly increased the apoptotic rates of endometrial cancer cells..
Consumption of H2 protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events.
https://www.sciencedirect.com/science/article/abs/pii/S0278691513006790
ABSTRACT
Consumption with H2 decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-exposure. In conclusion, drinking with H2 attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events.
Nephroprotective effect of H2 against cisplatin-induced kidney toxicity and oxidative damage.
https://doi.org/10.1016/j.jcma.2017.08.014
ABSTRACT
H2 exhibits potent nephroprotective effects on cisplatin-induced kidney damage in mice, likely due to both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.
H2 inhibits lung cancer progression through targeting SMC3.
https://doi.org/10.1016/j.biopha.2018.05.055
All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.
H2 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.
https://doi.org/10.1016/j.biopha.2018.05.055
All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.
H2 can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885710/
In combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared with H2 inhalation. H2 inhalation was discovered to be adjunctive in the control of tumor progression and alleviating the adverse events of medications for patients with advanced non-small cell lung cancer.
H2 gas promotes apoptosis of lung adenocarcinoma A549 cells through X-linked inhibitor of apoptosis and baculoviral inhibitor of apoptosis protein repeat-containing 3.
https://doi.org/10.4103/jcrt.jcrt_1137_21
Hydrogen gas promoted apoptosis of A549 cells by reducing the expression of XIAP and BIRC3 protein.
The effects of inhaling H2 gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced (chemotherapy) lung injury.
https://doi.org/10.1186/s12890-021-01712-2
H2 inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.
Two weeks of H2 inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study.
https://doi.org/10.4103/2045-9912.304221
H2 inhalation current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of H2 treatment can significantly improve most of these indexes
Investigating the Effect of H2 on Liver Cell Injury and Liver Cancer by Regulating GP73/ TGF-β Pathway.
H2 has a protective effect on liver cell damage and an inhibitory effect on liver cancer cells, which is effectuated by regulating the GP73/TGF-β signaling pathway.
DEN/ LX-2
HepG2 liver cancer cells
H2 effect on liver cancer
H2 prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis.
https://pubmed.ncbi.nlm.nih.gov/22505328/
ABSTRACT
H2 may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.
Hepatic Tumorigenesis
Protective effect of hydrogen‑rich water on LIVER function of colorectal cancer patients treated with mFOLFOX6 chemotherapy.
https://doi.org/10.3892/mco.2017.1409
ABSTRACT
H2 appeared to alleviate the mFOLFOX6-related liver injury.
The protective effect of hydrogen-rich water on the liver function of colorectal cancer (CRC) patients treated with mFOLFOX6 chemotherapy
H2 Attenuates Cardiac and HEPATIC Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis.
https://doi.org/10.1155/2016/1320365
ABSTRACT
Results revealed a protective effect of H2 on DOX-induced cardiotoxicity and hepatotoxicity in rats by inhibiting inflammation and apoptosis
Safety is a primary concern with respect to H2 transportation, storage, and administration – as with any treatment modality – novel or other.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/
https://www.scientific.net/MSF.706-709.520 [30]
https://www.sciencedirect.com/science/article/pii/S0163725814000941?via%3Dihub [11]
https://www.mdpi.com/2571-8797/2/4/33 [13]
Specific Studies on CHEMOPROTECTION:
https://pubmed.ncbi.nlm.nih.gov/32541132/
https://pubmed.ncbi.nlm.nih.gov/26668628/
https://www.nature.com/articles/nm1577 [9]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666661/
CONCLUSION: Direct Chemoprotective Mechanisms:
The concurrent use of molecular hydrogen (H2) in oncogenic therapy has been investigated in several studies. Molecular hydrogen is noted for its selective antioxidant properties, which can mitigate the adverse effects of treatments like radiotherapy and chemotherapy without compromising their anticancer efficacy. Below are some key studies that illustrate improvements in outcomes when hydrogen is used alongside oncogenic therapy:
Enhancement in Chemotherapy Tolerance
https://pubmed.ncbi.nlm.nih.gov/19148645/
https://www.ajol.info/index.php/tjpr/article/view/164283
Reduction of Chemotherapy-Induced Side Effects
https://pubmed.ncbi.nlm.nih.gov/29142752/
Enhancement of Chemotherapeutic Efficacy
Improvement in Quality of Life for Chemotherapy Patients
Mitigation of Oxidative Stress During Chemotherapy
Reduction of Oxidative Stress in Cancer Treatment
https://pubmed.ncbi.nlm.nih.gov/19249288/
Overall Cancer Treatment Enhancement
https://pubmed.ncbi.nlm.nih.gov/18996093/
These studies collectively suggest that hydrogen has a promising role in oncogenic therapy by improving patient tolerance to treatments, reducing side effects, and potentially enhancing the efficacy of conventional cancer treatments through its antioxidative and anti-inflammatory properties.
These studies contribute to the growing body of evidence supporting the use of molecular hydrogen as a beneficial adjunct in chemotherapy, focusing on both enhancing the efficacy of chemotherapeutic agents and significantly reducing their harmful side effects. This dual benefit could be particularly valuable in improving overall treatment outcomes and patient quality of life during cancer therapy.
https://doi.org/10.3892/or.2018.6841
Junji Akagi et al
STUDY TYPE: HUMAN
YEAR: 2018
INTERPRETATION OF THE PREMISE OF FINDINGS
“Molecular hydrogen (H₂) treatment significantly reinvigorated exhausted CD8+ T cells, enhancing their proliferation and cytokine production, which correlated with a marked improvement in patient prognosis and survival rates.”
QUOTE FROM BODY OF TEXT
“Notably, hydrogen gas decreased the abundance of exhausted terminal PD-1+ CD8+ T cells, increased that of active terminal PD-1- CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1- CD8+ T cells is critical for cancer prognosis.”
Guoqiang Chen et al
STUDY TYPE: IN VITRO YEAR: 2021
INTERPRETATION OF THE PREMISE OF FINDINGS
This study provides valuable insights into the mechanistic effects of molecular hydrogen (H2) on cervical cancer cells. It explores how hydrogen treatment influences key molecular pathways that control cancer cell growth and survival. Understanding these mechanisms is crucial because it adds a new dimension to the strategic management of cervical cancer, offering a basis for developing hydrogen-based therapeutic interventions.
The identification of H2 as a potential therapeutic target is particularly noteworthy. The study’s findings suggest that hydrogen treatment significantly impacts the apoptosis (programmed cell death) and proliferation rates of HeLa cervical cancer cells. Specifically, it reveals that hydrogen treatment leads to decreased expression of hypoxia-inducible factor (HIF)1A and the RELA proto-oncogene, NF-κB p65 subunit, which are critical regulators of cancer cell survival and inflammation, respectively. These proteins are often upregulated in many cancers, including cervical cancer, and are associated with poor prognosis.
QUOTE FROM BODY OF TEXT
“In conclusion, the present study suggests a novel H2-induced tumor suppression target towards HIF-1α and NF-κB. Inhibition of HIF-1α and NF-κB reduces cervical cancer HeLa cell proliferation and oxidative stress level, and decreases tumor growth, which makes H2 therapy a potential target in the treatment of cervical cancer.”
Ye Yang
STUDY TYPE: RODENT
YEAR: 2020
INTERPRETATION OF THE PREMISE OF FINDINGS
“This study supports the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism(s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.”
Their conclusion highlights the potential of hydrogen in activating the pyroptotic pathway to improve outcomes in endometrial cancer treatment.
The study provides foundational knowledge which may be translated into clinical settings, potentially enhancing therapeutic strategies against endometrial cancer by leveraging the cell death pathway of pyroptosis, specifically through the ROS/NLRP3/caspase-1/GSDMD axis.
QUOTE FROM BODY OF TEXT
“In the present study, we explored the effects of hydrogen on endometrial cancer and provided the first evidence that hydrogen induces pyroptosis via ROS-NLRP3-caspase-1 pathways. We demonstrated that drinking hydrogen-enriched water reduced the volume and weight of endometrial tumors in a xenograft mouse model.”
Boyan Liu et al
STUDY TYPE: IN VITRO
YEAR: 2022
INTERPRETATION OF THE PREMISE OF FINDINGS
“This study underscores the potential of molecular hydrogen (H2) as a novel therapeutic in oncology, particularly for colorectal cancer (CRC). By inhibiting the pAKT/SCD1 pathway, H2 treatment significantly reduced tumor proliferation and volume, suggesting a dual function of targeting cancer growth and the associated molecular pathways. Such findings advocate for hydrogen’s integration into cancer treatment protocols, potentially offering a less invasive option that minimizes the severe side effects associated with traditional chemotherapies.”
QUOTE FROM BODY OF TEXT
“In our study, we found that hydrogen did not change the expression of total AKT but significantly decreased pAKT levels, indicating that hydrogen might suppress colorectal cancer cell proliferation by inducing pAKT (Ser473). The inhibition of cell proliferation induced by H2 was reversed by treatment with SC79 in all three cell lines. This result demonstrated that hydrogen inhibited colorectal cancer cell survival by reducing pAKT.”
https://doi.org/10.3892/or.2018.6841
Junji Akagi et al
STUDY TYPE: HUMAN
YEAR: 2018
INTERPRETATION OF THE PREMISE OF FINDINGS
“Molecular hydrogen (H₂) treatment significantly reinvigorated exhausted CD8+ T cells, enhancing their proliferation and cytokine production, which correlated with a marked improvement in patient prognosis and survival rates.”
QUOTE FROM BODY OF TEXT
“Notably, hydrogen gas decreased the abundance of exhausted terminal PD-1+ CD8+ T cells, increased that of active terminal PD-1- CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1- CD8+ T cells is critical for cancer prognosis.”
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