The influence of the impact of biotechnological radioprotective drugs on the antitumor effect of experimental radiation therapy
https://doi.org/10.18699/SSMJ20250211
Abstract
Exposure to ionizing radiation during antitumor radiotherapy can cause undesirable side effects. This is damage to healthy tissues and organs. The use of radioprotective drugs can provide protection for normal cells, but there are risks of their negative impact on the antitumor effect of radiotherapy. The aim of the work is to study the possibility of using promising biotechnological radioprotective drugs to reduce the side effects of antitumor radiotherapy.
Material and methods. The study was performed on model of Ehrlich’s carcinoma in BALB/c mice with experimental radiation treatment (4 Gy X-ray). Biotechnological products, developed by Russian specialists, were administered to mice before irradiation on the 12th day after the tumor was transplanted. Chitin-glucan complex extracted from Pleurotus ostreatus was administered at a dose of 500 mg/kg intragastrically, recombinant flagellin at a dose of 1 mg/kg intraperitoneally. The volume of tumor nodules was assessed at different time points during the experiment, the degree of tumor growth inhibition was calculated, and the spread of the tumor into nearby tissues was recorded.
Results and discussion. The absence of stimulation of tumor growth during the use of drugs has been established. The drugs did not reduce the inhibition of Ehrlich tumor growth in mice caused by experimental X-ray treatment. In some periods of the experiment, mice with combination therapy showed a tendency to increase the effectiveness of radiation treatment by 4–6 %. The use of recombinant flagellin led to a decrease in the number of animals with a total spread of Ehrlich’s carcinoma. When using the mushroom chitin-glucan complex, there was a tendency to decrease the value of the integral dissemination score compared to control.
Conclusions. It was shown that the chitin-glucan complex from the Pleurotus ostreatus and the deimmunized recombinant flagellin did not have a negative effect on the antitumor effect of radiation exposure. The possibility of their use as a means of accompanying radiotherapy of tumors has been experimentally confirmed.
Keywords
About the Authors
E. V. MurzinaRussian Federation
Elena V. Murzina, candidate of biological sciences
194044, Saint-Petersburg, Academika Lebedeva st., 6
E. I. Fedoros
Russian Federation
Elena I. Fedoros, candidate of medical sciences
197758, Saint-Petersburg, vlg. Pesochny, Leningradskaya st., 68
E. D. Ermakova
Russian Federation
Elena D. Ermakova
197758, Saint-Petersburg, vlg. Pesochny, Leningradskaya st., 68
N. V. Aksenova
Russian Federation
Natalia V. Aksenova, candidate of medical sciences
194044, Saint-Petersburg, Academika Lebedeva st., 6
E. V. Vorobeychikov
Russian Federation
Evgeniy V. Vorobeychikov, candidate of medical sciences
197101, Saint-Petersburg, Kronverkskaya st., 23, lit. A, rooms 219-220
A. S. Simbirtsev
Russian Federation
Andrei S. Simbirtsev, doctor of medical sciences, professor, corresponding member of the RAS
197110, Saint-Petersburg, Pudozhskaya st., 7
G. A. Sofronov
Russian Federation
Genrikh A. Sofronov, doctor of medical sciences, professor, academician of the RAS
194044, Saint-Petersburg, Academika Lebedeva st., 6
References
1. Legeza V.I., Drachev I.S., Chepur S.V. Complications of radiation antitumor therapy (clinical presentation, pathogenesis, prevention, treatment). Saint-Petersburg: SpetsLit, 2022. 207 p. [In Russian].
2. de Ruysscher D., Niedermann G., Burnet N.G., Siva S., Lee A.W.M., Hegi-Johnson F. Radiotherapy toxicity. Nat. Rev. Dis. Prim. 2019;5(1):13. doi: 10.1038/s41572-019-0064-5
3. Patyar R.R., Patyar S. Role of drugs in the prevention and amelioration of radiation induced toxic effects. Eur. J. Pharmacol. 2018;819:207–216. doi: 10.1016/j.ejphar.2017.12.011
4. Singh V.K., Seed T.M. The efficacy and safety of amifostine for the acute radiation syndrome. Expert Opin. Drug Saf. 2019;18(11):1077–1090. doi: 10.1080/14740338.2019.1666104
5. Lu Y., Swartz J.R. Functional properties of Flagellin as a stimulator of innate immunity. Sci. Rep. 2016;12(6):18379. doi: 10.1038/srep18379
6. Singh V.K., Seed T.M. Entolimod as a radiation countermeasure for acute radiation syndrome. Drug Discov. Today. 2021;26(1):17–30. doi: 10.1016/j.drudis.2020.10.003
7. Mett V., Kurnasov O.V., Bespalov I.A., Molodtsov I., Brackett C.M., Burdelya L.G., Purmal A.A., Gleiberman A.S., Toshkov I.A., Burkhart C.A., … Osterman A.L. A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications. Commun. Biol. 2021;4(1):466. doi: 10.1038/s42003-021-01978-6
8. Chugh R.M., Mittal P., Mp N., Arora T., Bhattacharya T., Chopra H., Cavalu S., Gautam R.K. Fungal mushrooms: a natural compound with therapeutic applications. Front. Pharmacol. 2022;13:925387. doi: 10.3389/fphar.2022.925387
9. Sharma A., Sharma A., Tripathi A. Biological activities of Pleurotus spp. polysaccharides: A review. J. Food Biochem. 2021;45(6):13748. doi: 10.1111/jfbc.13748
10. Wang W., Xue C., Mao X. Radioprotective effects and mechanisms of animal, plant and microbial polysaccharides. Int. J. Biol. Macromol. 2020;153:373–384. doi: 10.1016/j.ijbiomac.2020.02.203
11. Murzina E.V., Sofronov G.A., Aksenova N.V., Veselova O.M., Grebenyuk A.N., Dukhovlinov I.V., Orlov A.I. Experimental estimation of the radioprotective efficiency of recombinant flagellin. Vestnik Rossiyskoy voyenno-meditsinskoy akademii = Bulletin of the Russian Military Medical Academy. 2017;(3):122–128. [In Russian]. doi: 10.17816/brmma623038
12. Murzina E.V., Sofronov G.A., Simbirtsev A.S., Aksenova N.V., Zagorodnikov G.G., Veselova O.M., Zhirnova N.A., Dmitrieva E.V., Klimov N.A., Vorobeychikov E.V. Impact of beta-D-glucan on survival and hematopoietic parameters of mice after exposure to Xrays. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal. 2023;23(1): 53–66. [In Russian]. doi: 10.17816/MAJ114742
13. Vershinina S.F., Stukov A.N. Handbook of Experimental Tumor Therapy. Saint-Petersburg: Reprint, 2008. 36 p. [In Russian].
14. Koukourakis M.I., Giatromanolaki A., Zois C.E., Kalamida D., Pouliliou S., Karagounis I.V., Yeh T.L., Abboud M.I., Claridge T.D., Schofield C.J., … Harris A.L. Normal tissue radioprotection by amifostine via Warburg-type effects. Sci. Rep. 2016;6:30986. doi: 10.1038/srep30986
15. Rozhdestvensky L.M., Lipengolts A.A., Lisina N.I., Romanova K.Yu. Evaluation of radiomodificator betaleukine influence on exposed Lewis carcinoma growth in mice. Radiatsionnaya biologiya. Radioekologiya = Radiation Biology. Radioecology. 2021;61(6):625–631. [In Russian]. doi: 10.31857/S0869803121060096
16. Filimonova M.V., Samsonova A.S., Korneeva T.S., Shevchenko L.I., Filimonov A.S. Study of the ability of a new nitric oxide synthase inhibitor INOS1 to selectively protect the normal tissue in the Ehrlich carcinoma radiotherapy model. Radiatsiya i risk = Radiation and Risk. 2017;27(2):37–45. [In Russian]. doi: 10.21870/0131-3878-2018-27-2-37-45
17. Malyarenko O.S., Usoltseva R.V., Zvyagintseva T.N., Ermakova S.P. Laminaran from brown alga Dictyota dichotoma and its sulfated derivative as radioprotectors and radiosensitizers in melanoma therapy. Carbohydr. Polym. 2019;206:539–547. doi: 10.1016/j.carbpol.2018.11.008
18. Zhang Z., Zhang Y., Liu H., Wang J., Wang D., Deng Z., Li T., He Y., Yang Y., Zhong S. A water-soluble selenium-enriched polysaccharide produced by Pleurotus ostreatus: Purification, characterization, antioxidant and antitumor activities in vitro. Int. J. Biol. Macromol. 2021;168:356–370. doi: 10.1016/j.ijbiomac.2020.12.070
19. Wisbeck E., Facchini J.M., Alves E.P., Silveira M.L., Gern R.M., Ninow J.L., Furlan S.A. A polysaccharide fraction extracted from Pleurotus ostreatus mycelial biomass inhibit Sarcoma 180 tumor. An. Acad. Bras. Cienc. 2017;89(3 Suppl):2013–2020. doi: 10.1590/0001-3765201720150635
20. Yang E., Choi H., Park J.S., Noh Y.W., Choi C.M., Lee W.J., Ko J.W., Kim J. A first-in-human study of KMRC011, a potential treatment for acute radiation syndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics. Clin. Transl. Sci. 2021;14(6):2161–2170. doi: 10.1111/cts.13073
21. Kokaya G.N., Kokaya A.A., Zatsepin V.V., Mukhina I.V., Mavrenkov E.M. Features of the course of the bone marrow form of acute radiation sickness and acute cytotoxic syndrome in mice. Sovremennaya nauka: aktual'nyye problemy teorii i praktiki. Seriya: Yestestvennyye i tekhnicheskiye nauki = Modern Science: Topical Problems of Theory and Practice. Series: Natural and Technical Sciences. 2023;(4):14–22. [In Russian]. doi: 10.37882/2223–2966.2023.04.17