THE EFFECT OF MOLECULAR HYDROGEN ON OXIDATIVE MODIFICATION OF PROTEINS IN COLORECTAL CANCER IN THE EXPERIMENT
DOI:
https://doi.org/10.11603/mcch.2410-681X.2024.i1.14592Keywords:
molecular hydrogen, hydrogen water, oxidative stress, colorectal cancer, antioxidantsAbstract
Introduction. An important role in the pathogenesis of the development of colorectal cancer is played by oxidative stress or imbalance of prooxidant/antioxidant homeostasis, which leads to oxidative modification of proteins and enhanced formation of protein carbonyl groups. The presence of oxidative stress in colorectal cancer requires effective antioxidant therapy. In recent years, there has been a growing interest in the study of molecular hydrogen as an inert gas that effectively exhibits an antioxidant effect.
The aim of the study – to investigate the effect of water saturated with molecular hydrogen on the content of carbonyl derivatives of oxidatively modified proteins in the blood serum of white rats with colorectal cancer.
Research Methods. Experiments were conducted on 50 male Wistar white rats. Colorectal cancer (CRC) was simulated in animals by subcutaneous injection of 1,2-dimethylhydrazine at a dose of 7.2 mg/kg of body weight once a week for 30 weeks. Rats consumed water saturated with molecular hydrogen at a concentration of 0.6 ppm ad libitum. Animals were euthanized under thiopental anesthesia. Blood serum was used for the study, in which the content of carbonyl groups was determined by the colorimetric method. Statistical data processing was performed using the SPSS22 software package.
Results and Discussion. It was established that the modeling of colorectal cancer led to an increase in the content of carbonyl groups in the blood serum of rats by 1.93 times compared to intact animals. The content of carbonyl groups in the blood serum of rats with colorectal cancer that consumed water saturated with molecular hydrogen for 30 weeks in parallel with the administration of 1,2-dimethylhydrazine was 1.29 times lower than in animals with colorectal cancer that consumed ordinary water . Consumption of water saturated with molecular hydrogen for 30 days after modeling colorectal cancer in white rats also led to a decrease in the content of carbonyl groups in their blood serum.
Conclusions. The use of water saturated with molecular hydrogen is an effective method of reducing oxidative stress in rats with colorectal cancer.
References
Siegel R.L, Miller K.D., Goding Sauer A. (2020). Colorectal cancer statistics, CA: Cancer Journal for Clinicians., 70(3), 145-164. DOI: 10.3322/caac.21601
Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. (2021). Global Cancer Statistics: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin., 71, 209-249.
Ayla O., Metin O. (2015). Biochemistry of Reactive Oxygen and Nitrogen Species. Basic Principles and Clinical Significance of Oxidative Stress; Sivakumar Joghi Thatha. Intech Open: Rijeka – Croatia.
Basak D., Uddin M.N., Hancock J. (2020). The Role of Oxidative Stress and Its Counteractive Utility in Colorectal Cancer (CRC). Cancers., 12.
Boakye D., Jansen L., Schottker B. (2020). Blood markers of oxidative stress are strongly associated with poorer prognosis in colorectal cancer patients. Int. J. Cancer, 147, 2373-2386.
Liou G.Y., Storz P. (2010). Reactive oxygen species in cancer. Free Radic. Res., 44, 479-496. DOI: 10. 3109/10715761003667554
Sreevalsan, S., Safe, S. (2013). Reactive oxygen species and colorectal cancer .Current Colorectal Cancer Reports, 9 (4), 350-357. DOI: 10.1007/s11888-013-0190-5
Isabella Dalle-Donne, Ranieri Rossi, Daniela Giustarini, Aldo Milzani, Roberto Colombo. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Clinica Chimica Acta. – 329. – Iss. 1–2, 23-38. DOI: 10.1016/S0009-8981(03)00003-2
Kachur, O., Fira, L., Lykhatskyі, P., Fira, D., Stechyshyn, I. (2021). The state of pro- and antioxidant systems in rats with DMH-induced colon carcinogenesis on the background of extracorporeal detoxification. Pharmacia, 68(4), 941-946.
Mitsugu Akagawa. (2021). Protein carbonylation: molecular mechanisms, biological implications, and analytical approaches. Free Radical Research, 55 (4), 307-320. DOI: 10.1080/10715762.2020.1851027
Slezák, J., Kura, B., Frimmel, K. (2016). Preventive and therapeutic application of molecular hydrogen in situations with excessive production of free radicals. Physiol. Res., 65 (Suppl.1), 11-28. DOI: 10.33549/physiolres.933414
Ram B. Singh, Zuzana Sumbalova, Ghizal Fatima, Viliam Mojto, Jan Fedacko, Alex Tarnava, Oleg Pokotylo, Anna Gvozdjakova, Kristina Ferenczyova, Jana Vlkovicova, Branislav Kura, Barbora Kalocayova, Pavol Zenuch, Jan Slezak. (2024). Effects of Molecular Hydrogen in the Pathophysiology and Management of Cardiovascular and Metabolic Diseases. Rev. Cardiovasc. Med. 25(1), 33. DOI: 10.31083/j.rcm2501033
Xiao L., Miwa N. (2017). Hydrogen-rich water achieves cytoprotection from oxidative stress injury in human gingival fibroblasts in culture or 3D-tissue equivalents, and wound-healing promotion, together with ROS-scavenging and relief from glutathione diminishment. Hum. Cell, 30 (2), 72-87. DOI: 10.1007/s13577-016-0150-x
Pokotylo, O.S., Pokotylo, O.O., Korda, M.M. (2023). Effects of biological action of molecular hydrogen. Medychna ta klinichna khimiia, 25, No. 2,102-121.
Pokotylo O. S., Korda M. M., Kravchuk Yu. S. (2021). The role of molecular hydrogen and nitric oxide in the pathogenesis of COVID-19. Medychna ta klinichna khimiia, (1), 93-100. DOI: 10.11603/mcch.2410-681X. 2021.i1.12119
Ohsawa, I., Ishikawa, M., Takahashi, K. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med., 13, 688-694.
Runtuwene J., Amitani H., Amitani M., Asakawa A., Cheng K.C., Inui A. (2015). Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer. Peer J., 3 e859. DOI: 10.7717/peerj.859
Yang Q., Ji G., Pan R., Zhao Y., Yan P. (2017). Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Mol. Clin. Oncol., 7, 891-896. DOI: 10. 3892/mco.2017.1409
Perse, M., Cerar, A. (2011). Morphological and molecular alterations in 1,2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J. Biomed. Biotechnol. Article ID 473964 – 14 pages. DOI: 10.1155/2011/473964
(1986). European convention for the protection of vertebrate animals used for experimental and other scientific purposes. – Council of Europe, Strasbourg.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem.,193, 265-275.
De-Souza, A.S.C., Costa-Casagrande, T.A. (2018). Animal models for colorectal cancer. Arq. Bras. Cir. Dig., 31, 1369.
Shen Luo, Nancy B. Wehr. (2009). Protein carbonylation: avoiding pitfalls in the 2,4-dinitrophenylhydrazine assay. Redox Report., 14 (4), 159-166 DOI: 10.1179/135100009X392601
Okeh, U. (2009). Statistical problems in medical research. East Afr. J. Public Health. 6 (1), 1-7.
Corpet, D.E., Pierre, F. (2005). How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men. Eur. J. Cancer. 41, 1911-1922.
Hennie Marie Johnsen, Marianne Hiorth, Jo Klaveness. (2023). Molecular Hydrogen Therapy – A Review on Clinical Studies and Outcomes. Molecules 28(23),7785. DOI: 10.3390/molecules28237785
Sun Q., Han W., Nakao A. (2015). Biological safety of hydrogen. Hydrogen Molecular Biology and Medicine; Springer: Dordrecht, The Netherlands, 35-48.
Wang D., Wang L., Zhang Y., Zhao Y., Chen G. (2018). Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomed. Pharmacother., 104, 788-797.
Zhang, J.H., Matei, N., Camara, R. (2018). Emerging mechanisms and novel applications of hydrogen gas therapy. Med. Gas Res., 8, 98-102.
Mitsugu Akagawa. (2021). Protein carbonylation: molecular mechanisms, biological implications, and analytical approaches. Free Radical Research, 55(4), 307-320. DOI: 10.1080/10715762.2020.1851027
Thomas Nyström. (2005). Role of oxidative carbonylation in protein quality control and senescence. The EMBO Journal, 24, 1311-1317. DOI: 10.1038/sj.emboj.7600599
Young Rim Song, Jwa-Kyung Kim, Hyung-Seok Lee, Sung Gyun Kim, Eun-Kyoung Choi. (2020). Serum levels of protein carbonyl, a marker of oxidative stress, are associated with overhydration, sarcopenia and mortality in hemodialysis patients. BMC Nephrology. 21(21), 281, 2-11.
Rodney L. Levine, Joy A. Williams, Earl P. Stadtman, Emily Shacter. (1994). Carbonyl assays for determination of oxidatively modified proteins. Methods in Enzymology. 233, 346-357. DOI: 10.1016/S0076-6879(94)33040-9
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Medical and Clinical Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
