A Review Potential Radioprotective Mechanism of Molecular Hydrogen via Regulation of Cellular Signaling Pathways

Authors

  • MD. Sadikuj Jaman Department of BIochemistry and Molecular Biology, University of Rajshahi, Bangladesh

DOI:

https://doi.org/10.56778/rjhs.v3i2.591

Keywords:

Molecular Hydrogen, Radioactivity, Antioxidant, cell Signaling pathway, Radioprotectant.

Abstract

Molecular hydrogen is a biologically significant molecule with diverse applications in the treatment and prevention of diseases in both humans and animals. Exposure to radiation from medical procedures such as CT scans, X-rays, and radiotherapy can disrupt normal cellular functions and cause abnormal cellular behavior. These radiation-induced effects are linked to multiple signaling pathways that contribute to cellular damage. Molecular hydrogen has emerged as a promising therapeutic agent capable of mitigating radiation-related injuries and supporting the recovery of affected cellular pathways. A thorough literature search was carried out using databases including Google Scholar, PubMed, Scopus, and ScienceDirect to obtain detailed information on radiation-related cellular signaling pathways and the possible radioprotective roles of molecular hydrogen. We identified several cellular signaling pathways associated with radiation exposure. Among them are the cell cycle checkpoint pathway, DNA repair pathways, EGFR/tyrosine kinase-mediated pro-survival signaling, Rac1-mediated signaling, ERK1/2 signaling, PI3k/AKT signaling, NF-kB signaling, autophagy signaling, HIF-1α signaling, and YAP signaling pathways. Molecular hydrogen can be administered through various delivery methods and supports the recovery of many of these pathways. It also exhibits multiple beneficial effects in both humans and animals, including antioxidant, anti-apoptotic, anti-inflammatory, and gene regulatory properties. Molecular hydrogen has emerged as one of the most promising radioprotective agents, given that radiation exposure is a major contributor to carcinogenesis and cellular damage. The objective of this review is to elucidate the cellular signaling pathways influenced by radiation and to examine the potential radioprotective mechanisms of molecular hydrogen in mitigating radiation-induced biological effects.

References

oki, M., Jiang, H., & Vogt, P. K. (2004). Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins. Proceedings of the National Academy of Sciences, 101(37), 13613–13617. https://doi.org/10.1073/pnas.0405454101

Asselin, E., Wang, Y., & Tsang, B. K. (2001). X-Linked Inhibitor of Apoptosis Protein Activates the Phosphatidylinositol 3-Kinase/Akt Pathway in Rat Granulosa Cells during Follicular Development1. Endocrinology, 142(6), 2451–2457. https://doi.org/10.1210/endo.142.6.8080

Banfalvi, G. (2017). Methods to detect apoptotic cell death. Apoptosis, 22(2), 306–323. https://doi.org/10.1007/s10495-016-1333-3

Baretic, D., Maia De Oliveira, T., Niess, M., Wan, P., Pollard, H., Johnson, C. M., Truman, C., McCall, E., Fisher, D., Williams, R., & Phillips, C. (2019). Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR. Progress in Biophysics and Molecular Biology, 147, 4–16. https://doi.org/10.1016/j.pbiomolbio.2019.06.003

Bassullu, N., Turkmen, I., Dayangac, M., Yagiz Korkmaz, P., Yasar, R., Akyildiz, M., Yaprak, O., Tokat, Y., Yuzer, Y., & Bulbul Dogusoy, G. (2012). The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma. Hepatitis Monthly, 12(10). https://doi.org/10.5812/hepatmon.7492

Bhuiyan, Md. R. H., Md. Maniruzzaman, Akter, S., Mehjabin, S., Rana, Md. R. R., & Jaman, Md. S. (2022). Drug Promising Effect for Diabetic Mice of CARICA PAPAYA Leaves. European Journal of Pharmaceutical Research, 2(3), 1–5. https://doi.org/10.24018/ejpharma.2022.2.3.47

Bragança, J., Eloranta, J. J., Bamforth, S. D., Ibbitt, J. C., Hurst, H. C., & Bhattacharya, S. (2003). Physical and Functional Interactions among AP-2 Transcription Factors, p300/CREB-binding Protein, and CITED2. Journal of Biological Chemistry, 278(18), 16021–16029. https://doi.org/10.1074/jbc.M208144200

Braithwaite, E., Wu, X., & Wang, Z. (1999). Repair of DNA lesions: Mechanisms and relative repair efficiencies. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 424(1–2), 207–219. https://doi.org/10.1016/S0027-5107(99)00020-2

Brunello, N. (1995). New Insights into the Biology of Schizophrenia through the Mechanism of Action of Clozapine. Neuropsychopharmacology, 13(3), 177–213. https://doi.org/10.1016/0893-133X(95)00068-O

Cader, J., Koneczna, R., & Olczak, P. (2021). The Impact of Economic, Energy, and Environmental Factors on the Development of the Hydrogen Economy. Energies, 14(16), 4811. https://doi.org/10.3390/en14164811

Cao, X., Wu, W., Wang, D., Sun, W., & Lai, S. (2022). Glycogen synthase kinase GSK3α promotes tumorigenesis by activating HIF1/VEGFA signaling pathway in NSCLC tumor. Cell Communication and Signaling, 20(1), 32. https://doi.org/10.1186/s12964-022-00825-3

Cerma, K., Piacentini, F., Moscetti, L., Barbolini, M., Canino, F., Tornincasa, A., Caggia, F., Cerri, S., Molinaro, A., Dominici, M., & Omarini, C. (2023). Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges. Biomedicines, 11(1), 109. https://doi.org/10.3390/biomedicines11010109

Chaudhry, M. A. (2007). Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases. Cancer Cell International, 7(1), 15. https://doi.org/10.1186/1475-2867-7-15

Choi, W.-S., Eom, D.-S., Han, B. S., Kim, W. K., Han, B. H., Choi, E.-J., Oh, T. H., Markelonis, G. J., Cho, J. W., & Oh, Y. J. (2004). Phosphorylation of p38 MAPK Induced by Oxidative Stress Is Linked to Activation of Both Caspase-8- and -9-mediated Apoptotic Pathways in Dopaminergic Neurons. Journal of Biological Chemistry, 279(19), 20451–20460. https://doi.org/10.1074/jbc.M311164200

Coles, L. C., & Shaw, P. E. (2002). PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway. Oncogene, 21(14), 2236–2244. https://doi.org/10.1038/sj.onc.1205302

Crompton, N. E. A. (1998). Programmed Cellular Response to Ionizing Radiation Damage. Acta Oncologica, 37(2), 129–142. https://doi.org/10.1080/028418698429685

De Luca, A., Maiello, M. R., D’Alessio, A., Pergameno, M., & Normanno, N. (2012). The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: Role in cancer pathogenesis and implications for therapeutic approaches. Expert Opinion on Therapeutic Targets, 16(sup2), S17–S27. https://doi.org/10.1517/14728222.2011.639361

Department of Biochemistry and Molecular Biology, University of Rajshahi-6205, Bhuiyan, Md. R. H., Mamun, A. A., Department of Biochemistry and Molecular Biology, Hajee Mohammed Danesh Science and Technology, Dinajpur-5200, Bangladesh., Sharker, B., Department of Biochemistry and Molecular Biology, Hajee Mohammed Danesh Science and Technology, Dinajpur-5200, Bangladesh., Jaman, Md. S., & Department of Biochemistry and Molecular Biology, University of Rajshahi-6205. (2023). Anticancer activity and therapeutic uses of catechins on breast, prostate and lung cancer: Future perspective and clinical proofs. Journal of Clinical Case Reports Medical Images and Health Sciences. https://doi.org/10.55920/JCRMHS.2023.03.001118

Deshmukh, J., Pofahl, R., & Haase, I. (2017). Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis. Cell Death & Disease, 8(3), e2664–e2664. https://doi.org/10.1038/cddis.2017.63

Fu, H., Xu, H., Chen, H., Li, Y., Li, W., Zhu, Q., Zhang, Q., Yuan, H., Liu, F., Wang, Q., Miao, M., & Shi, X. (2014). Inhibition of glycogen synthase kinase 3 ameliorates liver ischemia/reperfusion injury via an energy-dependent mitochondrial mechanism. Journal of Hepatology, 61(4), 816–824. https://doi.org/10.1016/j.jhep.2014.05.017

Fukuda, A., Hikita, A., Wakeyama, H., Akiyama, T., Oda, H., Nakamura, K., & Tanaka, S. (2005). Regulation of Osteoclast Apoptosis and Motility by Small GTPase Binding Protein Rac1. Journal of Bone and Mineral Research, 20(12), 2245–2253. https://doi.org/10.1359/JBMR.050816

Gao, Y., Yang, B., Wang, G., Zhao, P., Xu, J., Cheng, X., Hu, S., Song, Z., Zheng, Q., & Sun, P. (2018). Knockdown of PDGFRL Inhibits Tumor Growth Through the AKT/ GSK-3β/Cyclin D1 Pathway in Hepatocellular Carcinoma. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.3234806

Ge, L., Qi, J., Shao, B., Ruan, Z., Ren, Y., Sui, S., Wu, X., Sun, X., Liu, S., Li, S., Xu, C., & Song, W. (2022). Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier. Gut Microbes, 14(1), 2013764. https://doi.org/10.1080/19490976.2021.2013764

Geng, B., Wang, X., Park, K. H., Lee, K. E., Kim, J., Chen, P., Zhou, X., Tan, T., Yang, C., Zou, X., Janssen, P. M., Cao, L., Ye, L., Wang, X., Cai, C., & Zhu, H. (2022). UCHL1 protects against ischemic heart injury via activating HIF-1α signal pathway. Redox Biology, 52, 102295. https://doi.org/10.1016/j.redox.2022.102295

Giardi, M., Touloupakis, E., Bertolotto, D., & Mascetti, G. (2013). Preventive or Potential Therapeutic Value of Nutraceuticals against Ionizing Radiation-Induced Oxidative Stress in Exposed Subjects and Frequent Fliers. International Journal of Molecular Sciences, 14(8), 17168–17192. https://doi.org/10.3390/ijms140817168

Goldberg, L., & Kloog, Y. (2006). A Ras Inhibitor Tilts the Balance between Rac and Rho and Blocks Phosphatidylinositol 3-Kinase–Dependent Glioblastoma Cell Migration. Cancer Research, 66(24), 11709–11717. https://doi.org/10.1158/0008-5472.CAN-06-1878

González, E. A. P., Fuchs, A. G., & Sánchez, G. S. (2009). Amifostine (WR2721) Confers DNA Protection to in Vivo Cisplatin-Treated Murine Peripheral Blood Leukocytes. Dose-Response, 7(3), dose-response.08-026.Prieto. https://doi.org/10.2203/dose-response.08-026.Prieto

Goodarzi, A. A., Jonnalagadda, J. C., Douglas, P., Young, D., Ye, R., Moorhead, G. B. G., Lees-Miller, S. P., & Khanna, K. K. (2004). Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. The EMBO Journal, 23(22), 4451–4461. https://doi.org/10.1038/sj.emboj.7600455

Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N., & Tarsounas, M. (2023). Targeting DNA damage response pathways in cancer. Nature Reviews Cancer, 23(2), 78–94. https://doi.org/10.1038/s41568-022-00535-5

Gudkov, S. V., Popova, N. R., & Bruskov, V. I. (2015). Radioprotective substances: History, trends and prospects. Biophysics, 60(4), 659–667. https://doi.org/10.1134/S0006350915040120

Guo, J., Zhao, D., Lei, X., Zhao, H., Yang, Y., Zhang, P., Liu, P., Xu, Y., Zhu, M., Liu, H., Chen, Y., Chuai, Y., Li, B., Gao, F., & Cai, J. (2016). Protective Effects of Hydrogen against Low‐Dose Long‐Term Radiation‐Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice. Oxidative Medicine and Cellular Longevity, 2016(1), 1947819. https://doi.org/10.1155/2016/1947819

Halliwell, B. (1999). Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: Measurement, mechanism and the effects of nutrition. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 443(1–2), 37–52. https://doi.org/10.1016/S1383-5742(99)00009-5

He, W., Rahman, Md. H., Bajgai, J., Abdul-Nasir, S., Mo, C., Ma, H., Goh, S. H., Bomi, K., Jung, H., Kim, C.-S., Lee, H., & Lee, K.-J. (2024). Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model. Antioxidants, 13(11), 1328. https://doi.org/10.3390/antiox13111328

Holden, J., & Cunningham, C. (2018). Targeting the Hippo Pathway and Cancer through the TEAD Family of Transcription Factors. Cancers, 10(3), 81. https://doi.org/10.3390/cancers10030081

Hozyen, H. F., Ibrahim, E. S., Khairy, E. A., & El-Dek, S. I. (2019). Enhanced antibacterial activity of capped zinc oxide nanoparticles: A step towards the control of clinical bovine mastitis. Veterinary World, 12(8), 1225–1232. https://doi.org/10.14202/vetworld.2019.1225-1232

Hu, A., Yamaguchi, T., Tabuchi, M., Ikarashi, Y., Mizushima, A., & Kobayashi, H. (2024). A pilot study to evaluate the potential therapeutic effect of hydrogen-water bathing on atopic dermatitis in humans. Advances in Integrative Medicine, 11(1), 2–9. https://doi.org/10.1016/j.aimed.2023.10.003

Huang, C., Zhang, X. M., Tavaluc, R. T., Hart, L. S., Dicker, D. T., Wang, W., & El-Deiry, W. S. (2009). The combination of 5-Fluorouracil plus p53 pathway restoration is associated with depletion of p53-deficient or mutant p53-expressing putative colon cancer stem cells. Cancer Biology & Therapy, 8(22), 2185–2192. https://doi.org/10.4161/cbt.8.22.10446

Hutchinson, F. (1985a). Chemical Changes Induced in DNA by Ionizing Radiation. In Progress in Nucleic Acid Research and Molecular Biology (Vol. 32, pp. 115–154). Elsevier. https://doi.org/10.1016/S0079-6603(08)60347-5

Hutchinson, F. (1985b). Chemical Changes Induced in DNA by Ionizing Radiation. In Progress in Nucleic Acid Research and Molecular Biology (Vol. 32, pp. 115–154). Elsevier. https://doi.org/10.1016/S0079-6603(08)60347-5

Ito, H., Daido, S., Kanzawa, T., Kondo, S., & Kondo, Y. (2005). Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. International Journal of Oncology. https://doi.org/10.3892/ijo.26.5.1401

Jahng, J., Jung, I. S., Choi, E. J., Conklin, J. L., & Park, H. (2012). The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time. Neurogastroenterology & Motility, 24(2), 185. https://doi.org/10.1111/j.1365-2982.2011.01819.x

Jaman, M. S., Alam, M. S., Rezwan, M. S., Islam, M. R., Husna, A. U., & Sayeed, M. A. (2017). Comparison of total antioxidant activity between fresh and commercial mango juices available in Bangladesh. GSC Biological and Pharmaceutical Sciences, 1(2), 026–033. https://doi.org/10.30574/gscbps.2017.1.2.0045

Jaman, Md. S., Al Mamun, A., Sharker, B., Md. Maniruzzaman, Rana, Md. R. R., Hasan, Md. N., & Bhuiyan, Md. R. H. (2023). Curcumin, Diallyl Sulphide, Quercetin and Gallic Acid Uses as Anticancer and Therapeutic Agents for Breast Cancer: Current Strategies and Future Perspectives. European Journal of Medical and Health Sciences, 5(3), 32–48. https://doi.org/10.24018/ejmed.2023.5.3.1699

Jaman, Md. S., Maniruzzaman, Md., Rana, Md. R. R., Bhuyan, Md. R. H., Akter, L., Ahmad, S., Ullah, Md. N., & Saifujjaman, Md. (2024). Overall Summery of Gulf Country Employees from Bangladesh, Preliminary Evaluation for Abnormal Kidney Liver and Virally Infected Individuals Using Low-cost Tests Like CBC Parameters. Chemical Science International Journal, 33(4), 19–33. https://doi.org/10.9734/CSJI/2024/v33i4903

Jaman, Md. S., & Sayeed, Md. A. (2018). Ellagic acid, sulforaphane, and ursolic acid in the prevention and therapy of breast cancer: Current evidence and future perspectives. Breast Cancer, 25(5), 517–528. https://doi.org/10.1007/s12282-018-0866-4

Jamialahmadi, H., Khalili-Tanha, G., Rezaei-Tavirani, M., & Nazari, E. (2024). The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Metabolic Disorders Clinical Trials: A Systematic Review and Meta-analysis. International Journal of Endocrinology and Metabolism, 22(3). https://doi.org/10.5812/ijem-148600

Jeggo, P., & Löbrich, M. (2006). Radiation-induced DNA damage responses. Radiation Protection Dosimetry, 122(1–4), 124–127. https://doi.org/10.1093/rpd/ncl495

Ji, X., Liu, W., Xie, K., Liu, W., Qu, Y., Chao, X., Chen, T., Zhou, J., & Fei, Z. (2010). Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress. Brain Research, 1354, 196–205. https://doi.org/10.1016/j.brainres.2010.07.038

Jit, B. P., Pradhan, B., Dash, R., Bhuyan, P. P., Behera, C., Behera, R. K., Sharma, A., Alcaraz, M., & Jena, M. (2021). Phytochemicals: Potential Therapeutic Modulators of Radiation Induced Signaling Pathways. Antioxidants, 11(1), 49. https://doi.org/10.3390/antiox11010049

Jung, K., Kang, H., & Mehra, R. (2018). Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC). Cancers of the Head & Neck, 3(1), 3. https://doi.org/10.1186/s41199-018-0030-z

Kalman, N. S., Zhao, S. S., Anscher, M. S., & Urdaneta, A. I. (2017). Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature. International Journal of Radiation Oncology*Biology*Physics, 98(3), 662–682. https://doi.org/10.1016/j.ijrobp.2017.02.211

Kato, S., Takada, Y., & Miwa, N. (2021). Heat-retention effects of hydrogen-rich water bath assessed by thermography for humans. Journal of Thermal Biology, 95, 102805. https://doi.org/10.1016/j.jtherbio.2020.102805

Kawabe, T. (2004). G2 checkpoint abrogators as anticancer drugs. Molecular Cancer Therapeutics, 3(4), 513–519. https://doi.org/10.1158/1535-7163.513.3.4

Kemble, D. J., & Sun, G. (2009). Direct and specific inactivation of protein tyrosine kinases in the Src and FGFR families by reversible cysteine oxidation. Proceedings of the National Academy of Sciences, 106(13), 5070–5075. https://doi.org/10.1073/pnas.0806117106

Kempska, J., Oliveira-Ferrer, L., Grottke, A., Qi, M., Alawi, M., Meyer, F., Borgmann, K., Hamester, F., Eylmann, K., Rossberg, M., Smit, D. J., Jücker, M., Laakmann, E., Witzel, I., Schmalfeldt, B., Müller, V., & Legler, K. (2023). Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis. Frontiers in Oncology, 13, 1129682. https://doi.org/10.3389/fonc.2023.1129682

Kloet, D. E. A., & Burgering, B. M. T. (2011). The PKB/FOXO switch in aging and cancer. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1813(11), 1926–1937. https://doi.org/10.1016/j.bbamcr.2011.04.003

Kunte, S., Abraham, J., & Montero, A. J. (2020). Novel HER2–targeted therapies for HER2–positive metastatic breast cancer. Cancer, 126(19), 4278–4288. https://doi.org/10.1002/cncr.33102

Kuo, D.-Y., Wang, Y.-C., Chou, P.-H., Lai, C.-W., Tung, F.-I., & Liu, T.-Y. (2024). Therapeutic Potential of Hydrogen as a Radioprotective Agent for the Prevention of Radiation Dermatitis. Antioxidants, 13(12), 1475. https://doi.org/10.3390/antiox13121475

Le Page, C., Koumakpayi, I. H., Lessard, L., Saad, F., & Mes-Masson, A.-M. (2005). Independent role of phosphoinositol-3-kinase (PI3K) and casein kinase II (CK-2) in EGFR and Her-2-mediated constitutive NF-kappaB activation in prostate cancer cells. The Prostate, 65(4), 306–315. https://doi.org/10.1002/pros.20291

LeBaron, T. W., Sharpe, R., Pyatakovich, F. A., & Artamonov, M. Yu. (2024). Hydrogen: From Stars to Fuel to Medicine. In J. Slezak & B. Kura (Eds.), Molecular Hydrogen in Health and Disease (Vol. 27, pp. 1–20). Springer Nature Switzerland. https://doi.org/10.1007/978-3-031-47375-3_1

Lee, B. J., Egi, Y., Van Leyen, K., Lo, E. H., & Arai, K. (2010). Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro. Brain Research, 1307, 22–27. https://doi.org/10.1016/j.brainres.2009.10.026

Lee, N., Puri, D. R., Blanco, A. I., & Chao, K. S. C. (2007). Intensity‐modulated radiation therapy in head and neck cancers: An update. Head & Neck, 29(4), 387–400. https://doi.org/10.1002/hed.20332

Li, J., Chen, X., Kang, R., Zeh, H., Klionsky, D. J., & Tang, D. (2021). Regulation and function of autophagy in pancreatic cancer. Autophagy, 17(11), 3275–3296. https://doi.org/10.1080/15548627.2020.1847462

Li, J., Ge, Z., Fan, L., & Wang, K. (2017). Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis. BMC Musculoskeletal Disorders, 18(1), 58. https://doi.org/10.1186/s12891-017-1431-6

Li, L., Huang, K., You, Y., Fu, X., Hu, L., Song, L., & Meng, Y. (2014). Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis. International Journal of Oncology, 44(6), 2111–2120. https://doi.org/10.3892/ijo.2014.2368

Li, S.-Y., Xue, R.-Y., Wu, H., Pu, N., Wei, D., Zhao, N., Song, Z.-M., & Tao, Y. (2023). Novel Role of Molecular Hydrogen: The End of Ophthalmic Diseases? Pharmaceuticals, 16(11), 1567. https://doi.org/10.3390/ph16111567

Li, W., & Melton, D. W. (2012). Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance. Oncogene, 31(19), 2412–2422. https://doi.org/10.1038/onc.2011.426

Liu, H., Kang, X., Ren, P., Kuang, X., Yang, X., Yang, H., Shen, X., Yan, H., Kang, Y., Zhang, F., Wang, X., Guo, L., & Fan, W. (2023). Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota. International Immunopharmacology, 120, 110252. https://doi.org/10.1016/j.intimp.2023.110252

Liu, M., Yuan, H., Yin, J., Wang, R., Song, J., Hu, B., Li, J., & Qin, X. (2019). Effect of Hydrogen-Rich Water on Radiation-Induced Cognitive Dysfunction in Rats. Radiation Research, 193(1), 16. https://doi.org/10.1667/RR15464.1

Liu, X., Wang, Q., Liu, B., Zheng, X., Li, P., Zhao, T., Jin, X., Ye, F., Zhang, P., Chen, W., & Li, Q. (2021). Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway. Radiotherapy and Oncology, 155, 93–104. https://doi.org/10.1016/j.radonc.2020.10.026

Lu, X., Nguyen, T.-A., & Donehower, L. A. (2005). Reversal of the ATM/ATR-Mediated DNA Damage Response by the Oncogenic Phosphatase PPM1D. Cell Cycle, 4(8), 4060–4064. https://doi.org/10.4161/cc.4.8.1876

MacVittie, T. J., Farese, A. M., Smith, W. G., Baum, C. M., Burton, E., & McKearn, J. P. (2000). Myelopoietin, an engineered chimeric IL-3 and G-CSF receptor agonist, stimulates multilineage hematopoietic recovery in a nonhuman primate model of radiation-induced myelosuppression. Blood, 95(3), 837–845. https://doi.org/10.1182/blood.V95.3.837.003k08_837_845

Mandal, P. (2010). Anti-inflammatory pathways and alcoholic liver disease: Role of an adiponectin/interleukin-10/heme oxygenase-1 pathway. World Journal of Gastroenterology, 16(11), 1330. https://doi.org/10.3748/wjg.v16.i11.1330

Manolescu, B., Oprea, E., Busu, C., & Cercasov, C. (2009). Natural compounds and the hypoxia-inducible factor (HIF) signalling pathway. Biochimie, 91(11–12), 1347–1358. https://doi.org/10.1016/j.biochi.2009.08.005

Marei, H., & Malliri, A. (2017). Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms. Small GTPases, 8(3), 139–163. https://doi.org/10.1080/21541248.2016.1211398

McBride, W. H., & Schaue, D. (2020). Radiation‐induced tissue damage and response. The Journal of Pathology, 250(5), 647–655. https://doi.org/10.1002/path.5389

McKelvey, K. J., Hudson, A. L., Back, M., Eade, T., & Diakos, C. I. (2018). Radiation, inflammation and the immune response in cancer. Mammalian Genome, 29(11–12), 843–865. https://doi.org/10.1007/s00335-018-9777-0

Mei, K., Zhao, S., Qian, L., Li, B., Ni, J., & Cai, J. (2014). Hydrogen protects rats from dermatitis caused by local radiation. Journal of Dermatological Treatment, 25(2), 182–188. https://doi.org/10.3109/09546634.2012.762639

Meijer, T. W. H., Kaanders, J. H. A. M., Span, P. N., & Bussink, J. (2012). Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy. Clinical Cancer Research, 18(20), 5585–5594. https://doi.org/10.1158/1078-0432.CCR-12-0858

Meredith, L. K., Rao, D., Bosak, T., Klepac‐Ceraj, V., Tada, K. R., Hansel, C. M., Ono, S., & Prinn, R. G. (2014). Consumption of atmospheric hydrogen during the life cycle of soil‐dwelling actinobacteria. Environmental Microbiology Reports, 6(3), 226–238. https://doi.org/10.1111/1758-2229.12116

Minassian, L. M., Cotechini, T., Huitema, E., & Graham, C. H. (2019). Hypoxia-Induced Resistance to Chemotherapy in Cancer. In D. M. Gilkes (Ed.), Hypoxia and Cancer Metastasis (Vol. 1136, pp. 123–139). Springer International Publishing. https://doi.org/10.1007/978-3-030-12734-3_9

Minemoto, Y., Gannon, J., Masutani, M., Nakagama, H., Sasagawa, T., Inoue, M., Masamune, Y., & Yamashita, K. (2001). Characterization of Adriamycin-Induced G2 Arrest and Its Abrogation by Caffeine in FL-Amnion Cells with or without p53. Experimental Cell Research, 262(1), 37–48. https://doi.org/10.1006/excr.2000.5072

Mirzayans, R., Aubin, R., Bosnich, W., Blattner, W., & Paterson, M. (1995). Abnormal pattern of post-γ-ray DNA replication in radioresistant fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome. British Journal of Cancer, 71(6), 1221–1230. https://doi.org/10.1038/bjc.1995.237

Mirzoeva, O. K., Das, D., Heiser, L. M., Bhattacharya, S., Siwak, D., Gendelman, R., Bayani, N., Wang, N. J., Neve, R. M., Guan, Y., Hu, Z., Knight, Z., Feiler, H. S., Gascard, P., Parvin, B., Spellman, P. T., Shokat, K. M., Wyrobek, A. J., Bissell, M. J., … Korn, W. M. (2009). Basal Subtype and MAPK/ERK Kinase (MEK)-Phosphoinositide 3-Kinase Feedback Signaling Determine Susceptibility of Breast Cancer Cells to MEK Inhibition. Cancer Research, 69(2), 565–572. https://doi.org/10.1158/0008-5472.CAN-08-3389

Mokim Ahmed, K., & Li, J. J. (2008). NF-κB-mediated adaptive resistance to ionizing radiation. Free Radical Biology and Medicine, 44(1), 1–13. https://doi.org/10.1016/j.freeradbiomed.2007.09.022

Molinari, M. (2000). Cell cycle checkpoints and their inactivation in human cancer. Cell Proliferation, 33(5), 261–274. https://doi.org/10.1046/j.1365-2184.2000.00191.x

Motta, C., D’Angeli, F., Scalia, M., Satriano, C., Barbagallo, D., Naletova, I., Anfuso, C. D., Lupo, G., & Spina-Purrello, V. (2015). PJ-34 inhibits PARP-1 expression and ERK phosphorylation in glioma-conditioned brain microvascular endothelial cells. European Journal of Pharmacology, 761, 55–64. https://doi.org/10.1016/j.ejphar.2015.04.026

Moulder, J. E., & Cohen, E. P. (2005). Radiation-induced multi-organ involvement and failure: The contribution of radiation effects on the renal system. The British Journal of Radiology, Supplement_27(1), 82–88. https://doi.org/10.1259/bjr/18309193

Munshi, A., & Ramesh, R. (2013). Mitogen-Activated Protein Kinases and Their Role in Radiation Response. Genes & Cancer, 4(9–10), 401–408. https://doi.org/10.1177/1947601913485414

Nakashima, R., Goto, Y., Koyasu, S., Kobayashi, M., Morinibu, A., Yoshimura, M., Hiraoka, M., Hammond, E. M., & Harada, H. (2017). UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization. Scientific Reports, 7(1), 6879. https://doi.org/10.1038/s41598-017-06605-1

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2025-11-24

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JAMAN, M. S. (2025). A Review Potential Radioprotective Mechanism of Molecular Hydrogen via Regulation of Cellular Signaling Pathways . RADINKA JOURNAL OF HEALTH SCIENCE, 3(2), 503–528. https://doi.org/10.56778/rjhs.v3i2.591

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Vol. 3 No. 2 (2025): Radinka Journal of Heatlh Science RJHS)

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A Literature Review

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