Evaluation of the radioprotective potential of fumaric acid, 3-hydroxypyridine fumarate and deanol aceglumate under the action of γ-radiation, protons and ¹²C ions on human cells

The relevance of the research of new radioprotectors is due to the need to protect healthy tissues during radiation therapy. Existing drugs have serious side effects, which requires the search for safer and more effective analogues.

The aim of the work is a comparative analysis of the radioprotective efficacy of three promising compounds – fumaric acid, 3-hydroxypyridine fumarate and deanol aceglumate in vitro. Tasks: to determine non-toxic concentrations of compounds, to evaluate their protective effect under different types of radiation (gamma quanta, protons, ¹²C ions), to compare the effect on normal (fibroblasts Fb-hTERT) and tumor (neuroblastoma SK-N-BE(2)) cells.

Materials and Methods: the study was conducted on cultures of cells under the influence of ionizing radiation of different quality: gamma quanta (60Co), protons and accelerated ¹²C ions. Optimal concentrations have been established: fumaric acid – 400 μmol, 3-hydroxypyridine fumarate – 200 μmol, deanol aceglumate – 1000 μmol. Incubation time is 24 hours.

Results and Discussion: It was shown that all compounds showed a significant radioprotective effect on gamma radiation (1-12 Gy) for fibroblasts; the protective effect was also observed on tumor cells. There was no radioprotective effect when irradiated with protons and ¹²C ions. Deanol aceglumate has demonstrated the greatest effectiveness.

Conclusion: The study confirmed the prospects of deanol aceglumate and other compounds as radioprotectors under gamma irradiation. Their use can reduce damage to healthy tissues during radiation therapy. However, no protective effect has been detected for protons and heavy ions, which requires further study.

1. Kaprin AD, Starinsky VV, Shakhzadova AO. State of cancer care for the population of Russia in 2023. Moscow: P.A. Herzen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; 2024. 262 p. (In Russian).

2. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. International journal of cancer. 2021;149(4): 778789. DOI: 10.1002/ijc.33588.

3. Gardner SJ, Kim J, Chetty IJ. Modern Radiation Therapy Planning and Delivery. Hematology/Oncology Clinics of North America. 2019;33(6): 947-62. DOI: 10.1016/j.hoc.2019.08.005.

4. Johnson D, Chen Y, Ahmad S. Dose and linear energy transfer distributions of primary and secondary particles in carbon ion radiation therapy: A Monte Carlo simulation study in water. Journal of Medical Physics. 2015;40(4): 214-219. DOI: 10.4103/0971-6203.170785.

5. Grebenyuk AN, Legeza VI, Milyaev AV, Starkov AV. Modern strategy of health protection and medical measures in radiation accidents. Radiatsionnaya Gygiena = Radiation Hygiene. 2018;11(4): 80-88. (In Russian).

6. Mun GI, Kim S, Choi M, Kim CS, Lee YS. Pharmacology of natural radioprotectors. Archives of pharmacal research. 2018;41(11): 1033-1050.

7. Abdollahi H, Shiri I, Atashzar M, Sarebani M, Moloudi K, Samadian H. Radiation protection and secondary cancer prevention using biological radioprotectors in radiotherapy. International Journal of Cancer Therapy and Oncology. 2015;3(1). Available from: https://doi.org/10.20935/AcadNano7267 [Accessed 24 Nov 2024].

8. Shivappa P, Bernhardt GV. Natural Radioprotectors on Current and Future Perspectives: A Mini-Review. Journal of pharmacy & bioallied sciences. 2022;14(1): 57-71.

9. Joiner M, van der Kogel A. Basic Clinical Radiobiology. 4th ed. London: Hodder Arnold; 2009. 375 p.

10. Radioprotectors. org: an open database of known and predicted radioprotectors. Available from: https://radioprotectors.org/hom e [Accessed 13 Nov 2024].

11. Ilica RA, Kloetzer L, Galaction AI, Caşcaval D. Fumaric acid: production and separation. Biotechnology Letters. 2019;41(1): 47-57. DOI: 10.1007/s10529-018-2628-y.

12. Wipke BT, Hoepner R, Strassburger-Krogias K, Thomas AM, Gianni D, Szak S, et al. Different Fumaric Acid Esters Elicit Distinct Pharmacologic Responses. Neurology(R) neuroimmunology & neuroinflammation. 2021;8(2): e950. DOI: 10.1212/NXI.0000000000000950.

13. Volc-Platzer B. Fumaric acid esters for paediatric psoriasis. British Journal of Dermatology. 2021;185(1): 5-6. DOI: 10.1111/bjd.20057.

14. Korshunova AB, Kostychev NA, Inchina VI, Chairkin IN. Prospects for pharmacological correction of acute cerebral ischemia. Izvestiya Samarskogo nauchnogo tsentra Rossiyskoy akademii nauk = Bulletin of the Samara Scientific Center of the Russian Academy of Sciences. 2009;11(1): 1287-1290. (In Russian).

15. Salt of 2-ethyl-6-methyl-3-hydroxypyridine with fumaric acid, possessing metabolic and cardioprotective activity, and method for its preparation Available from: https://patents.google.com/patent/RU2365582C1/ru [Accessed 19 Jun 2025]. (In Russian).

16. Vypova ER, Kuptsova PS, Komarova LN, Berseneva AA, Baldov DA, Kotlyarov AA. Study of possible radioprotective properties of deanol aceglumate under the action of ionizing radiation on human cells. Radiatsiya i risk = Radiation and Risk. 2023;32(3): 38-49. (In Russian).

17. Noskov DS, Poroikov VV, Shikh EV, Iasnetsov VV. Deanol aceglumate (Nooclerin): clinical and pharmacological aspects and relevance of use in medical practice. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2013;113: 97-99. (In Russian).

18. Chutko LS, Surushkina SYu, Nikishena IS, Yakovenko EA, Anisimova TI. The use of deanol aceglumate in the treatment of neurasthenia in adolescents with school maladjustment. Voprosy sovremennoy pediatrii = Problems of Modern Pediatrics. 2013;12(5): 99-103. (In Russian).

19. Prilepskiy AYu, Drozdov AS, Bogatyrev VA, Staroverov SA. Methods of working with cell cultures and determining the toxicity of nanomaterials. Saint Petersburg: ITMO University; 2019. 43 p. (In Russian).

20. Khramchenkova OM. Fundamentals of Radiobiology: a textbook for students of biological specialties of higher educational institutions. Gomel: Educational Institution «GSU named after. F. Skorina»; 2003. 238 p. (In Russian).

21. Kuptsova PS, Komarova LN, Vypova ER. Study of radioprotective properties of fumaric acid and 3-oxypyridine fumarate under the action of ionizing radiation on human cells. Radiatsionnaya Gygiena = Radiation Hygiene. 2023;16(1): 32-39. (In Russian).

22. Penabei S, Meesungnoen J, Jay-Gerin JP. Assessment of Cystamine’s Radioprotective Antioxidant Ability under HighDose-Rate Irradiation: A Monte Carlo Multi-Track Chemistry Simulation Study. Antioxidants (Basel). 2023;12(1): 77. DOI: 10.3390/antiox12010077.

23. Thoene J, Gavin RF, Towne A, Wattay L, Ferrari MG, Navarrete J, et al. In vitro activity of cysteamine against SARS-CoV-2 variants. Molecular Genetics and Metabolism. 2022;137(12): 192-200. DOI: 10.1016/j.ymgme.2022.08.005.

24. Baumann M, Krause M, Overgaard J, Debus J, Bentzen SM, Daartz J, et al. Radiation oncology in the era of precision medicine. Nature reviews. Cancer. 2016;16(4): 234-249. DOI: 10.1038/nrc.2016.18.

25. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930): 1029-1033. DOI: 10.1126/science.1160809.