EXPERIMENTAL EVALUATION OF THE CARDIOPROTECTIVE POTENTIAL OF MOLECULAR HYDROGEN

Authors

  • N. V. Zyhrii I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • O. O. Shevchuk I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY

DOI:

https://doi.org/10.11603/mcch.2410-681X.2025.i2.15523

Keywords:

molecular hydrogen; doxorubicin; cardiotoxicity; biomarkers; structural changes; heart planimetry.

Abstract

Introduction. The search for effective agents to mitigate the adverse effects of anticancer drugs remains highly relevant, given the growing number of patients with oncological diseases. Anthracycline antibiotics are among the most effective chemotherapeutic agents; however, their clinical use is often limited due to their known cardiotoxicity. Aim of the study. To investigate the cardioprotective potential of molecular hydrogen in a model of subchronic doxorubicin (DOX) toxicity. Materials and Methods. The study was conducted on rats divided into four groups: a control group; groups 2 and 3 received DOX (5 mg/kg once weekly, cumulative dose of 20 mg/kg); and groups 3 and 4 consumed molecular hydrogen-enriched water ad libitum. Parameters assessed included mortality rate, cardiac structural alterations, and serum biomarkers such as lactate dehydrogenase (LDH), creatine phosphokinase-MB (CPK-MB), and cardiac troponin I (cTnI). Results and Discussion. Doxorubicin administration led to marked cardiac remodelling, including a 43.7% (p<0.001) increase in left ventricular wall dilation and a 40.7% rise in planimetric index. Histologically, significant cardiomyocyte alterations were observed, including myocytolysis, contraction band necrosis, and fibre fragmentation. These changes were accompanied by elevated serum levels of LDH (1.55-fold, p<0.001), CPK-MB (1.76-fold, p<0.001), and cTnI (8.3-fold, p<0.001). Hydrogen-rich water intake reduced animal mortality from 32% to 20%, significantly decreased biochemical markers of cardiac injury, partially restored myocardial morphology, and stimulated regenerative processes. These effects included reduced interstitial oedema, fewer zones of myocytolysis and contraction, and improved vascular integrity. Conclusions. The results demonstrate that molecular hydrogen exhibits cardioprotective properties and reduces mortality in animals exposed to doxorubicin.

References

Bray F., Laversanne M., Sung H., Ferlay J., Siegel R. L., Soerjomataram I., Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2024. Vol. 74. Issue 3. P. 229–263. DOI: https://doi.org/10.3322/CAAC.21834.

Рак в Україні, 2022–2023 : захворюваність, смертність, показники діяльності онкологічної служби : бюлетень № 25 / за ред. О. В. Єфіменка ; ДНП «Національний інститут раку». Київ, 2024. 84 с.

Mattioli R., Ilari A., Colotti B., Mosca L., Fazi F., Colotti G. Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming. Molecular Aspects of Medicine. 2023. Vol. 93. P. 101205. DOI: https://doi.org/10.1016/J.MAM.2023.101205.

Kciuk M., Gielecińska A., Mujwar S., Kołat D., Kałuzińska-Kołat Ż., Celik I., Kontek R. Doxorubicin – an Agent with Multiple Mechanisms of Anticancer Activity. Cells. 2023. Vol. 12. Issue 4. P. 659. DOI: https:// doi.org/10.3390/CELLS12040659.

Espírito Santo S. G., Monte M. G., Polegato B. F., Barbisan L. F., Romualdo G. R. Protective Effects of Omega-3 Supplementation against Doxorubicin- Induced Deleterious Effects on the Liver and Kidneys of Rats. Molecules. 2023. Vol. 28, issue 7. P. 3004. DOI: https://doi.org/10.3390/molecules28073004.

Moazeni S., Cadeiras M., Yang E. H., Deng M. C., Nguyen K.-L. Anthracycline induced cardiotoxicity: biomarkers and Omics technology in the era of patient specific care. Clinical and Translational Medicine. 2017. Vol. 6, issue 1. P. 17. DOI: https://doi.org/10.1186/ s40169-017-0148-3.

Weintraub R. G., Semsarian C., Macdonald P. Dilated cardiomyopathy. The Lancet. 2017. Vol. 390. Issue 10092. P. 400–414. DOI: https://doi.org/10.1016/ S0140-6736(16)31713-5.

Tanwar S. S., Dwivedi S., Khan S., Sharma, S. Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy. Egyptian Heart Journal. 2025. Vol. 77. Issue 1. P. 29. DOI: https://doi.org/10.1186/ S43044-025-00628-0.

Vitale R., Marzocco S., Popolo A. Role of Oxidative Stress and Inflammation in Doxorubicin-Induced Cardiotoxicity: A Brief Account. International Journal of Molecular Sciences, 2024. Vol. 25. Issue 13. P. 7477. DOI: https://doi.org/10.3390/IJMS25137477.

Li Y., Yan J., Yang P. The mechanism and therapeutic strategies in doxorubicin-induced cardiotoxicity: Role of programmed cell death. Cell Stress & Chaperones. 2024. Vol. 29. Isuue 5. P. 666. DOI: https:// doi.org/10.1016/J.CSTRES.2024.09.001.

Szponar J., Ciechanski E., Ciechanska M., Dudka J., Mandziuk S. Evolution of Theories on Doxorubicin- Induced Late Cardiotoxicity-Role of Topoisomerase. International Journal of Molecular Sciences. 2024. Vol. 25. Issue 24. P. 13567. DOI: https:// doi.org/10.3390/IJMS252413567.

Kong C. Y., Guo Z., Song P., Zhang X., Yuan Y. P., Tengm T., Yan L., Tang, Q. Z. Underlying the Mechanisms of Doxorubicin-Induced Acute Cardiotoxicity: Oxidative Stress and Cell Death. International Journal of Biological Sciences. 2022. Vol. 18. Issue 2. P. 760. DOI: https:// doi.org/10.7150/IJBS.65258.

Kitakata H., Endo J., Ikura H., Moriyama H., Shirakawa K., Katsumata Y., Sano M. Therapeutic Targets for DOX-Induced Cardiomyopathy: Role of Apoptosis vs. Ferroptosis. International Journal of Molecular Sciences, 2022. Vol. 23. Issue 3. P. 1414. DOI: https:// doi.org/10.3390/IJMS23031414.

Nakashima-Kamimura N., Mori T., Ohsawa I., Asoh S., Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemotherapy and Pharmacology, 2009. Vol. 64. Issue 4. P. 753–761. DOI: https://doi.org/10.1007/S00280-008- 0924-2.

Kitamura A., Kobayashi S., Matsushita T., Fujinawa H., Murase K. Experimental verification of protective effect of hydrogen-rich water against cisplatin- induced nephrotoxicity in rats using dynamic contrast- enhanced CT. British Journal of Radiology. 2010. Vol. 83. Issue 990. P. 509–514. DOI: https://doi.org/10.1259/ bjr/25604811.

Стефанов О. В. Доклінічні дослідження лікарських засобів : методичні рекомендації. Вінниця : Авіценна, 2001. 528 с. URL: https:// www.twirpx.com/file/537410/

Li M., Zhang Y., Wu B., Qiu R., Zhao C., Chen B., Shang H. Optimizing dose selection for doxorubicin-induced cardiotoxicity in mice: A comprehensive analysis of single and multiple-dose regimens. European Journal of Pharmacology. 2025. Vol. 1003. P. 77883. DOI: https:// doi.org/10.1016/J.EJPHAR.2025.177883.

Шевчук О. О. Ефекти ентеросорбції та філграстиму при субхронічній доксорубіциновій токсичності. Здобутки клінічної та експериментальної медицини. 2019. № 3. С. 146–156. DOI: https://doi.org/ 10.11603/1811-2471.2019.v.i3.10510

Слабий О. Б. Кількісна морфологія гіпертрофованого серця. Вісник наукових досліджень. 2017. № 4. С. 6–9. URL: https://ojs.tdmu.edu.ua/index. php/visnyk-nauk-dos/article/view/8169/7799.

Jain D., Russell R. R., Schwartz R. G., Panjrath G. S., Aronow W. Cardiac Complications of Cancer Therapy: Pathophysiology, Identification, Prevention, Treatment, and Future Directions. Current Cardiology Reports. 2017. Vol. 19. Issue 5. P. 36. DOI: https://doi.org/10.1007/ s11886-017-0846-x

Dhingra R., Rabinovich-Nikitin I., Rothman S., Guberman M., Gang H., Margulets V., Jassal D. S., Alagarsamy K. N., Dhingra S., Valenzuela Ripoll C., Billia F., Diwan A., Javaheri A., Kirshenbaum L. A. Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy. Circulation. 2022. Vol. 146. Issue 12. P. 934. DOI: https:// doi.org/10.1161/CIRCULATIONAHA.121.058411.

Balough E., Ariza A., Asnani A., Hoeger C. W. Cardiotoxicity of Anthracyclines. Cardiology Clinics. 2025. Vol. 43, Issue 1. P. 111–127. DOI: https:// doi.org/10.1016/J.CCL.2024.08.002.

Published

2025-03-25

How to Cite

Zyhrii, N. V., & Shevchuk, O. O. (2025). EXPERIMENTAL EVALUATION OF THE CARDIOPROTECTIVE POTENTIAL OF MOLECULAR HYDROGEN. Medical and Clinical Chemistry, (2), 35–43. https://doi.org/10.11603/mcch.2410-681X.2025.i2.15523

Issue

Section

ORIGINAL INVESTIGATIONS