Medical Radiology and Radiation Safety. 2025. Vol. 70. № 4

DOI:10.33266/1024-6177-2025-70-4-21-24

V.Yu. Soloviev, A.Yu. Bushmanov, I.B. Ushakov, O.V. Nikitenko, T.M. Bychkova,
A.A. Ivanov , Yu.A. Fedotov, M.L. Ganzhelyuk, L.Yu. Mershin, A.S. Kretov,
T.I. Gimadova, Dmitrij M. Alekseev, Daniil M. Alekseev, A.N. Osipov

Experimental Study of Radioprotective Efficiency of Indralin
in Outbred Mice icr (cd-1) spf-Category Irradiation
with Pulsed Bremsstrahlung X-Rays in Ultra-High Dose Rate (flash) Mode

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: V.Yu. Soloviev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

Objective: To study the radioprotective efficacy of indralin when mice were irradiated with pulsed X-ray bremsstrahlung in the ultra-high dose rate (FLASH) mode.

Material and methods: Outbred ICR (CD-1) mice of the SPF category were used as the object of the study. All study groups were randomized by body weight at the preparatory stage. During the studies, a setup based on the ILU-14 pulsed linear resonance electron accelerator with a converter was used as a source of X-ray bremsstrahlung. The radiation dose was controlled by thermoluminescent dosimeters in the individual dosimetry mode. The 30-day survival of laboratory animals under conditions without the use of drugs and with the use of indralin, administered 15 minutes before irradiation, was considered as the effect under study. When assessing the dose–effect characteristic, two options were considered: peak dose rate of bremsstrahlung X-rays 12.5 Gy/s (normal mode) and 109–147 Gy/s (FLASH mode). The results of the dose–effect dependence with 80–90 % mortality of mice within 30 days were comparable. The effectiveness of the drug indralin was assessed in the FLASH mode (peak dose rate 147–153 Gy/s, average – 2.2–2.3 Gy/s). Irradiation of the control and study groups of animals was carried out simultaneously. 

Results: The study revealed high protective efficacy of indralin when outbred ICR (CD-1) SPF mice were irradiated with pulsed X-ray bremsstrahlung in the ultra-high dose rate mode (FLASH) at a dose of 8.9 Gy, the 30-day survival rate in the control was 40 %, and when using indralin – 100 %; at a dose of 9.1 Gy, there were no surviving animals in the control, and when using indralin, the survival rate was 70 %. 

Conclusion: Significant protective efficacy of indralin was demonstrated when mice were irradiated with pulsed bremsstrahlung X-rays in the FLASH mode.

Keywords: bremsstrahlung X-rays, ultra-high dose rate (FLASH), mice, 30-day survival, indralin

For citation: Soloviev VYu, Bushmanov AYu, Ushakov IB, Nikitenko OV, Bychkova TM, Ivanov AA, Fedotov YuA, Ganzhelyuk ML, Mershin LYu, Kretov AS, Gimadova TI, Alekseev Dmitrij M, Alekseev Daniil M, Osipov AN. Experimental Study of Radioprotective Efficiency of Indralin in Outbred Mice icr (cd-1) spf-Category Irradiation with Pulsed Bremsstrahlung X-Rays in Ultra-High Dose Rate (flash) Mode. Medical Radiology and Radiation Safety. 2025;70(4):21–24. (In Russian). DOI:10.33266/1024-6177-2025-70-4-21-24

References

1. Ильин Л.А., Рудный Н.М., Суворов Н.Н., Чернов Г.А., Антипов В.В., Васин М.В. Давыдов Б.И., Михайлов П.П. Индралин – радиопротектор экстренного действия. Противолучевые свойства. Фармакология, механизм действия, клиника. М.: Институт биофизики, 1994. 436 с. [Il’in L.A., Rudnyy N.M., Suvorov N.N., Chernov G.A., Antipov V.V., Vasin M.V. Davydov B.I., Mikhaylov P.P. Indralin – eto Ekstrennoye Sredstvo Zashchity ot Radioizlucheniya. Protivoradiatsionnyye Svoystva. Farmakologiya, Mekhanizm Deystviya, Klinika = Indralin – Emergency Radioprotector. Antiradiation Properties. Pharmacology, Mechanism of Action, Clinical Features. Moscow, Institut Biofiziki Publ., 1994. 436 p. (In Russ.)]. 

2. Васин М.В., Ильин Л.А., Ушаков И.Б. Феномен противолучевой защиты индралином крупных животных (собак) и его экстраполяция на человека // Медицинская радиология и радиационная безопасность. 2022. Т.67. №3. С. 5-12 [Vasin M.V., Il’in L.A., Ushakov I.B. Phenomenon of Radiation Protection by Indralin of Large Animals (Dogs) and its Extrapolation to Humans. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2022;67;3:5-12 (In Russ.)]. doi:10.33266/1024-6177-2022-67-3-5-12.

3. Vasin M.V., Ushakov I.B. Comparative Efficacy and the Window of Radioprotection for Adrenergic and Serotoninergic Agents and Aminothiols in Experiments with Small and Large Animals. J Radiat Res. 2015 Jan;56;1:1-10. doi: 10.1093/jrr/rru087. Epub 2014 Oct 13. PMID: 25312329; PMCID: PMC4572585.

4. Bushmanov A.Y., Vorobyeva N.Y., Blokhina T.M., Andrianova I.E., Stavrakova N.M., Bychkova T.M., et al. Effects of Indralin on Immunohematological Parameters and DNA Damage in Irradiated ICR (CD-1) Outbred Mice. Biology Bulletin. 2020;46;11:1564-70. doi: 10.1134/s1062359019110104. 

5. Friedl A.A., Prise K.M., Butterworth K.T., Montay-Gruel P., Favaudon V. Radiobiology of the FLASH Effect. Med Phys. 2022 Mar;49;3:1993-2013. doi: 10.1002/mp.15184. Epub 2021 Sep 20. PMID: 34426981.

6. Babayan N., Grigoryan B., Khondkaryan L., Tadevosyan G., Sarkisyan N., Grigoryan R., et al. Laser-Driven Ultrashort Pulsed Electron Beam Radiation at Doses of 0.5 and 1.0 Gy Induces Apoptosis in Human Fibroblasts. International Journal of Molecular Sciences. 2019;20;20. doi: 10.3390/ijms20205140.

7. Chow J.C.L., Ruda H.E. Mechanisms of Action in FLASH Radiotherapy: a Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells. Cells. 2024;13;10. doi: 10.3390/cells13100835.

8. Favaudon V., Caplier L., Monceau V., Pouzoulet F., Sayarath M., Fouillade C., Poupon M.F., Brito I., Hupé P., Bourhis J., Hall J., Fontaine J.J., Vozenin M.C. Ultrahigh Dose-Rate FLASH Irradiation Increases the Differential Response Between Normal and Tumor Tissue in Mice. Sci Transl Med. 2014 Jul 16;6;245:245ra93. doi: 10.1126/scitranslmed.3008973. Erratum in: Sci Transl Med. 2019 Dec 18;11(523):eaba4525. doi: 10.1126/scitranslmed.aba4525. PMID: 25031268.

9. Inada T., Nishio H., Amino S., Abe K., Saito K. High Dose-Rate Dependence of Early Skin Reaction in Mouse. Int J Radiat Biol Relat Stud Phys Chem Med. 1980 Aug;38;2:139-45. doi: 10.1080/09553008014551031. PMID: 6968733.

10. Acharya S., Bhat N.N., Joseph P., Sanjeev G., Sreedevi B., Narayana Y. Dose Rate Effect on Micronuclei Induction in Human Blood Lymphocytes Exposed to Single Pulse and Multiple Pulses of Electrons. Radiat Environ Biophys. 2011 May;50;2:253-63. doi: 10.1007/s00411-011-0353-1. Epub 2011 Jan 23. PMID: 21259020. 

 PDF (RUS) Full-text article (in Russian)

Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.03.2025. Accepted for publication: 25.04.2025.