Comparison of the effects of copper chlorophyllin, riboxin, indralin and the combined use of glutathione and ascorbic acid on the survival of mice during fractionated X-ray irradiation
https://doi.org/10.33380/2305-2066-2025-14-1-1957
Abstract
Introduction. The problem of effectiveness and safe pharmacological means of reducing the consequences of exposure to the ionizing effect is becoming increasingly urgent. This solution is difficult due to the high chemical toxicity of all known modern effective radioprotectors. Nowadays, much attention is paid to the study of the radioprotective properties of the so-called effects. But in most of these works, the experimental model was subjected to a one-time acute irradiation. At the same time, a safe and effective radioprotective drug under conditions of fractionated irradiation will be useful in radiation therapy for oncological diseases and during space missions, as well as in conditions of radiation contamination of territories.
Aim. Comparison of the radioprotective effect of copper chlorophyllin, riboxin, also called inosine, and the combined use of glutathione and ascorbic acid with that of the reference Russian radioprotector indralin during fractionated exposure to X-ray radiation.
Materials and methods. Male ICR (CD-1) mice were exposed to five daily irradiations of 2.5 Gy. On the days of each irradiation, experimental animals were administered chlorophyllin (20 μg/g), indralin (50 μg/g) in a solution of tartaric acid or glutathione (250 μg/g) and ascorbic acid (150 μg/g) before irradiation or riboxin (200 μg/g) after irradiation. The survival of mice was assessed within 30 days after the last irradiation.
Result and discussion. Only the use of Riboxin ensured the survival of 10 % of irradiated animals, but without a statistically significant increase in the average life expectancy of dead animals relative to the group of intact mice. A significant increase in this parameter was provided only by the use of indralin. Copper chlorophyllin had no radioprotective effect. Perhaps the use of metal-free chlorophyll derivatives in the future will be able to have a radioprotective effect under these conditions. The combined use of glutathione and ascorbic acid led to the death of 2 out of 10 mice during the period of irradiation and drug administration, without providing an increase in survival during the observation period.
Conclusion. The use of copper chlorophyllin and glutathione with ascorbic acid did not increase the survival rate and average life expectancy of deceased mice irradiated at a dose of 12.5 Gy, distributed into 5 fractions of 2.5 Gy. The use of indralin only increased the life expectancy of dead animals. Riboxin contributed to the survival of 10 % of the corresponding group.
Keywords
About the Authors
L. A. RomodinRussian Federation
46/8, Zhivopisnaya str., Moscow, 123098
A. A. Moskovskij
Russian Federation
46/8, Zhivopisnaya str., Moscow, 123098
O. V. Nikitenko
Russian Federation
46/8, Zhivopisnaya str., Moscow, 123098
T. M. Bychkova
Russian Federation
46/8, Zhivopisnaya str., Moscow, 123098
E. D. Rodionova
Russian Federation
46/8, Zhivopisnaya str., Moscow, 123098
References
1. Rozhdestvensky L. M. Difficulties in radiation counter measure preparations development in russiain crysis period: actual approaches searching. Radiation biology. Radioecology. 2020;60(3):279–290. (In Russ.) DOI: 10.31857/S086980312003011X.
2. Mun G.-I., Kim S., Choi E., Kim C. S., Lee Y.-S. Pharmacology of natural radioprotectors. Archives of pharmacal research. 2018;41(11):1033–1050. DOI: 10.1007/s12272-018-1083-6.
3. Vasin M. V. The Classification of Radiation Protective Agents as the Reflection of the Present State and Development Perspective of Current Radiation Pharmacology. Radiation biology. Radioecology. 2013;53(5):459–467. (In Russ.) DOI: 10.7868/S0869803113050160.
4. Legeza V. I., Ushakov I. B., Grebenyuk A. N., Antushevich A. E. Radiobiology, radiation physiology and medicine. Saint-Petersburg: Foliant; 2017. 176 p. (In Russ.).
5. Raj S., Manchanda R., Bhandari M., Alam M. S. Review on Natural Bioactive Products as Radioprotective Therapeutics: Present and Past Perspective. Current Pharmaceutical Biotechnology. 2022;23(14):1721–1738. DOI: 10.2174/1389201023666220110104645.
6. Shivappa P., Bernhardt G. V. Natural Radioprotectors on Current and Future Perspectives: A Mini-Review. Journal of Pharmacy and Bioallied Sciences. 2022;14(2):57–71. DOI: 10.4103/jpbs.jpbs_502_21.
7. Stasiłowicz-Krzemień A., Gościniak A., Formanowicz D., Cielecka-Piontek J. Natural Guardians: Natural Compounds as Radioprotectors in Cancer Therapy. International Journal of Molecular Sciences. 2024;25(13):6937. DOI: 10.3390/ijms25136937.
8. Burlakova E. B., Alesenko A. V., Molochkina E. M., Palmina N. P., Khrapova N. G. Bioantioxidants in radiation damage and malignant growth. Moscow: Nauka; 1975. 213 p. (In Russ.)
9. Lysenko N. P., Pak V. V., Rogozhina L. V., Kusurova Z. G. Radiobiology. Saint-Petersburg: Lan; 2023. 572 p. (In Russ.)
10. Lin Y., Chen X., Yu C., Xu G., Nie X., Cheng Y., Luan Y., Song Q. Radiotherapy-mediated redox homeostasis-controllable nanomedicine for enhanced ferroptosis sensitivity in tumor therapy. Acta Biomaterialia. 2023;159:300–311. DOI: 10.1016/j.actbio.2023.01.022.
11. González E., Cruces M. P., Pimentel E., Sánchez P. Evidence that the radioprotector effect of ascorbic acid depends on the radiation dose rate. Environmental Toxicology and Pharmacology. 2018;62:210–214. DOI: 10.1016/j.etap.2018.07.015.
12. Inal M. E., Akgun A., Kahraman A. Radioprotective effects of exogenous glutathione against whole-body gamma-ray irradiation: age- and gender-related changes in malondialdehyde levels, superoxide dismutase and catalase activities in rat liver. Methods and findings in experimental and clinical pharmacology. 2002;24(4):209–212. DOI: 10.1358/mf.2002.24.4.678452.
13. Averill-Bates D. A. The antioxidant glutathione. Vitamins and hormones. 2023;121:109–141. DOI: 10.1016/bs.vh.2022.09.002.
14. Yemelyanov V. V., Prikaziuk E. G., Lastochkin V. V., Aresheva O. M., Chirkova T. V. Ascorbate-glutathione cycle in wheat and rice seedlings under anoxia and subsequent reaeration. Vavilov Journal of Genetics and Breeding. 2024;28(1):44–54. DOI: 10.18699/vjgb-24-06.
15. Foyer C. H., Kunert K. The ascorbate-glutathione cycle coming of age. Journal of Experimental Botany. 2024;75(9):2682–2699. DOI: 10.1093/jxb/erae023.
16. Vernigorova L. A., Zhorova E. S., Popov B. A., Parfenova I. M. Joint prophylactic use of riboxin and algisorb upon entry into the gastrointestinal tract of rats 239Рu. Radiation biology. Radioecology. 2005;45(2):201–206. (In Russ.)
17. Popova N. R., Gudkov S. V., Bruskov V. I. Natural purine compounds as radioprotective agents. Radiation biology. Radioecology. 2014;54(1):38–49. (In Russ.) DOI: 10.7868/S0869803114010135.
18. Pospísil M., Netíková J., Pipalová I., Volenec K. Radioprotective effect of inosine and its enhancement by magnesium and global hypoxia. Physiological Research. 1991;40(4):445–452.
19. Hou B., Xu Z.-W., Yang C.-W., Gao Y., Zhao S.-F., Zhang C.-G. Protective effects of inosine on mice subjected to lethal total-body ionizing irradiation. Journal of Radiation Research. 2007;48(1):57–62. DOI: 10.1269/jrr.06067.
20. Sycheva L. P., Rozhdestvenskii L. M., Lisina N. I., Shliakova T. G., Zorin V. V. Antimutagenic activity and hepatoprotective effect of anti-radiation drugs. Medical Genetics. 2020;19(9):81–82. (In Russ.) DOI: 10.25557/2073-7998.2020.09.81-82.
21. Vasin M. V., Ushakov I. B. Potential ways of increase in bogy resistance to damaging actionof ionizing radiation with the aids of radiomitigators. Biology Bulletin Reviews. 2019;139(3):235–253. (In Russ.) DOI: 10.1134/S0042132419030098.
22. Pozdeev A. V., Lysenko N. P. Increasing the radiation resistance of the mammalian body when using chlorophyll preparations in conditions of radioactive environmental pollution. Izvestija Mezhdunarodnoj akademii agrarnogo obrazovanija. 2018;2(42):60–62. (In Russ.)
23. Geric M., Gajski G., Mihaljevic B., Miljanic S., Domijan A.-M., Garaj-Vrhovac V. Radioprotective properties of food colorant sodium copper chlorophyllin on human peripheral blood cells in vitro. Mutation research/Genetic Toxicology and Environmental Mutagenesis. 2019;845:403027. DOI: 10.1016/j.mrgentox.2019.02.008.
24. Kumar S. S., Shankar B., Sainis K. B. Effect of chlorophyllin against oxidative stress in splenic lymphocytes in vitro and in vivo. Biochimica et Biophysica Acta (BBA) – General Subjects. 2004;1672(2):100–111. DOI: 10.1016/j.bbagen.2004.03.002.
25. Zimmering S., Olvera O., Hernández M. E., Cruces M. P., Arceo C., Pimental E. Evidence for a radioprotective effect of chlorophyllin in Drosophila. Mutation Research Letters. 1990;245(1):47–49. DOI: 10.1016/0165-7992(90)90024-e.
26. Romodin L. A., Nikitenko O. V., Bychkova T. M., Zrilova Yu. A., Rodionova E. D., Bocharov D. A. Comparative Evaluation of the Radioprotective Properties of Copper Chlorophyllin, Trolox, and Indralin in an Experiment on Mice. Bulletin of Experimental Biology and Medicine. 2024;177(3):328–332. DOI: 10.1007/s10517-024-06183-z.
27. Romodin L. A., Nikitenko O. V., Bychkova T. M., Zrilova Yu. A., Rodionova E. D., Bocharov D. A. Comparison of the Radioprotective Properties of Riboxin (Inosine) and Indralin with Prophylactic Administration at Dosages of 100 mg/кg According to the Survival Criterion of Irradiated Mice. Medical Radiology and Radiation Safety. 2024;69(2):18–23. (In Russ.) DOI: 10.33266/1024-6177-2024-69-2-18-23.
28. Kaplan E. L., Meier P. Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association. 1958;53(282):457–481. DOI: 10.1080/01621459.1958.10501452.
29. Sycheva L. P., Lisina N. I., Shchegoleva R. A., Rozhdestvenskiy L. M. Antimutagenic effect of anti-radiation drugs in an experiment on mice. Radiation biology. Radioecology. 2019;59(4):388–393. (In Russ.) DOI: 10.1134/S086980311904012X.
30. Srinivasan S., Torres A.G., Ribas de Pouplana L. Inosine in Biology and Disease. Genes. 2021;12(4):600. DOI: 10.3390/genes12040600.
31. Gudkov S. V., Gudkova O. Yu., Shtarkman I. N., Gapeev A. B., Chemeris N. K., Bruskov V. I. Guanosine and inosine as natural geroprotectors for mouse blood cells when exposed to X-rays. Radiation biology. Radioecology. 2006;46(6):713–718. (In Russ.)
32. Il’in L. A., Rudny N. M., Suvorov N. N., Chernov G. A., Antipov V. V., Vasin M. V., Davydov B. I., Mihailov P. P. Indralin – an emergency radioprotector. Anti-radiation properties, pharmacology, mechanism of action, clinic. Moscow: Minzdrav Rossiyskoy Federacii; 1994. 435 p. (In Russ.)
33. Vasin M. V., Ushakov I. B., Chernov Yu. N., Semenova L. A., Afanasyev R. V. Radioprotective properties of indralin and essentiale h for separate and combined application under fractionated γ-irradiation. Radiation biology. Radioecology. 2021;61(6):645–651. (In Russ.) DOI: 10.31857/S0869803121060126.
34. Singh V. K., Seed T. M. The efficacy and safety of amifostine for the acute radiation syndrome. Expert Opinion on Drug Safety. 2019;18(11):1077–1090. DOI: 10.1080/14740338.2019.1666104.
35. Kouvaris J. R., Kouloulias V. E., Vlahos L. J. Amifostine: the first selective-target and broad-spectrum radioprotector. The Oncologist. 2007;12(6):738–747. DOI: 10.1634/theoncologist.12-6-738.
36. Kuna P., Dostal M., Neruda O., Volenec K., Vodicka I., Navratil L., Petyrek P., Svoboda V., Simsa J., Vavrova J., Hermanska J., Prouza Z., Pitterman P., Listik E., Spurny F., Knajfl J., Podzimek F., Spelda S., Osterreicher J., Konrad F., Havrankova R. Radioprotective effects of amifostine (WR-2721) or cystamine on radiation damage and its repair in rats whole body exposed to fission neutrons. Acta medica. 2004;47(1):19–23.
37. Kuna P., Dostal M., Neruda O., Knajfl J., Petyrek P., Podzimek P., Severa J., Svoboda V., Šimša J., Špelda S., Vavrova J., Heřmanska J., Prouza Z., Pitterman P., Listík E., Navrátil L., Spurny F., Konrad F., Vilasova Z., Havrankova R. Acute toxicity and radioprotective effects of amifostine (WR-2721) or cystamine in single whole body fission neutrons irradiated rats. Journal of Applied Biomedicine. 2004;2:43–49.
Supplementary files
|
1. Графический абстракт | |
Subject | ||
Type | Исследовательские инструменты | |
View
(1020KB)
|
Indexing metadata ▾ |
Review
For citations:
Romodin L.A., Moskovskij A.A., Nikitenko O.V., Bychkova T.M., Rodionova E.D. Comparison of the effects of copper chlorophyllin, riboxin, indralin and the combined use of glutathione and ascorbic acid on the survival of mice during fractionated X-ray irradiation. Drug development & registration. 2025;14(1):365-374. (In Russ.) https://doi.org/10.33380/2305-2066-2025-14-1-1957