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The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.

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Medical Radiology and Radiation Safety. 2022. Vol. 67. № 3

M.V. Vasin1, L.A. Ilyin2, I.B. Ushakov2

The Phenomenon of Radiation Protection of Large Animals (Dogs) with Indralin
and its Extapolation to Humans

1Russian Medical Academy of Continuous Professional Education, Moscow, Russia

2A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia

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

CONTENT

Testing the effectiveness of radioprotectors in large animals is an important stage in the introduction of drugs into the practice of medicine. Unique in scale and world practice, comprehensive studies of the radioprotector of emergency action of the drug B-190 (indralin) in experiments on dogs were carried out. Its high radioprotective efficiency was established with gamma, gamma-neutron and proton high energy irradiation. Under gamma irradiation of dogs indralin at an optimal dose of 30 mg/kg had DRF equel 3, the result of which was not recorded in large animals by any of known radioprotectors. It is important that under non-uniform radiation (shielding of abdomen, head or pelvis), protective effect of indralin doubles. The drug is also active in peroral use. Analysis of extrapolation of experimental data on radioprotective properties of indralin from large animals (dogs) to humans on measurement of succinate dehydrogenase (SDH) activity in lymphocytes of peripheral blood is carried out. Activation of SDH during stress response to acute hypoxia, including under the influence of indralin, is associated with the release of adrenaline and noradrenaline. Catecholamines realize their effect through beta-adrenoceptors on lymphocytes. A close correlation was established between the dose and radioprotective effect of indralin and the growth of SDH lymphocyte activity
(r = 0.99 p < 0.01). Extrapolation of expected radioprotective effect of indralin per person was carried out according to the formula:
DRF = 0.3988e0.009181x[r = 0.995 (0.78–0.9999) p < 0.01], where x is the activity of SDH. DRF of indralin (100 mg intramuscularly) for humans was 1.6. When orally administered indralin at a dose of 450 mg DRF was 1.3.

Keywords: gamma-, gamma-neutron-, proton radiation, indralin, dogs, DRF, SDH, extrapolation

For citation: Vasin MV, Ilyin LA, Ushakov IB. The Phenomenon of Radiation Protection of Large Animals (Dogs) with Indralin and its Extapolation to Humans. Medical Radiology and Radiation Safety. 2022;67(3):5–12. (In Russian). DOI:10.33266/1024-6177-2022-67-3-5-12

References

1. Ilin L.A., Ushakov I.B., Vasin M.V. Radioprotective Drugs in the System of Radiation Protection of Exposed Radiation Workers and Population in the Case of Radiation Accidents // Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2012;57;3:26–31. (In Russian).

2. Ushakov I.B., Vasin M.V. The Drugs and Natural Antioxidants as the Components of Anti-Radiation Countermeasures During Space Flights. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2017;62;4:66-78. (In Russian).

3. Ilin L.A., Rudnyy N.M., Suvorov N.N. Indralin is an Emergency Radioprotector. Protivoluchevyye Svoystva, Farmakologiya, Mekhanizm Deystviya, Klinika = Anti-Radiation Properties, Pharmacology, Mechanism of Action, Clinic. Moscow, Minzdrav RF Publ., 1994. 435 p. (In Russian).

4. Crouch B.G., Overman R.R. Chemical Protection Against X-Irradiation Death in Primates: a Preliminary Report. Science. 1957;125:1092–1093.

5. Jacobus D.P. Protection of the Dog Against Ionizing Radiation. Fed. Proc. 1959;18:74.

6. Jacobus D.P., Dacquisto M.D. Anti-Radiation Drug Development. Military Med. 1961;126:698.

7. Razorenova V.A. Protective Action of Mercamine in Experimental Acute Radiation Injury. Voprosy Patogeneza, Eksperimentalnoy Terapii i Profilaktiki Luchevoy Bolezni = Issues of Pathogenesis, Experimental Therapy and Prevention of Radiation Sickness. Moscow, Medgiz Publ., 1960. P. 351–359. (In Russian).

8. Razorenova V.A., Shcherbova Ye.N. On the Prophylactic Use of Cysteinamine and Cystamine in Acute Radiation Sickness. Meditsinskaya Radiologiya = Medical Radiology. 1961;6;3:266–269. (In Russian).

9. Benson R.E., Michaelson S.M., Downs W. Toxicological and Radioprotection Studies on S-Beta-Aminoethyl Isothiouronium Bromide (AET). Radiat. Res. 1961;15;5:561–567.

10. Mozzhukhin A.S., Rachinskiy F.Yu. Khimicheskaya Profilaktika Radiatsionnykh Porazheniy = Chemical Prophylaxis of Radiation Injuries. Moscow, Atomizdat Publ., 1964. 244 p. (In Russian). 

11. Semenov L.F. Profilaktika Ostroy Luchevoy Bolezni = Prevention of Acute Radiation Sickness. Leningrad, Meditsina, 1967. 215 p. (In Russian).

12. Zherebchenko P.G. Protivoluchevyye Svoystva Indolilalkilaminov = Antiradiation Properties of Indolylalkylamines. Moscow, Atomizdat Publ., 1971. 200 p. (In Russian).

13. Chernov G.A., Trushina M.N., Suvorov N.N. Radioprotective Efficacy of Oral Mexamine in Dogs Radiobiologiya. 1973;13;3:464-468. (In Russian).

14. Trushina M.N., Znamenskiy V.V., Chernov G.A., Lemberg V.K. Radioprotective Effect of Oral Mexamine in Monkeys. Radiobiologiya. 1973;13;5:719-722. (In Russian).

15. Semenov L.F., Lapin B.A., Strelkov R.B., et al. Comparative Study of the Anti-Radiation Efficacy of Mexamine and Gaseous Hypoxic Mixture in Experiments on Rhesus Monkeys. Vestnik AMN SSSR. 1978;8:83–88.
(In Russian).

16. Akerfeldt S., Ronnback C., Nelson A. Radioprotective Agents: Results with S-(3-amino-2-Hydroxypropyl) Phosphorothioate, Amidophosphorothioate and Owe Related Compounds. Radiat. Res. 1967;31;4:850–855.

17. Piper J., Stringfellow C., Elliot R., Johnston T. S-2(Omegaa-
minoalkylamino)-Ethyldihydrogen Phosphorothioates and Related Compounds as Potential Antiradiation Agents. J. Med. Chem. 1969;12;2:236–243.

18. Piper J.R., Rose L.M., Johnson T.P. et al. S-2-Omega-Diaminoalkyl Dihydrogen Phosphorothioates as Antiradiation Agents. J. Med. Chem. 1979;22;6:613–639.

19. Yuhas J.M., Storer J.B. Chemoprotection Against Threemodes of Radiation Death in the Mice. Int. J. Radiat. Biol. 1969;15;3:233–237.

20. Yuhas J.M. Biological Factors Affecting the Radioprotective Efficiency of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR-2721) LD50/30 Doses. Radiat. Res. 1970;44;3:621–628.

21. Yuhas J.M. Biological Factors Affecting the Radioprotective Efficiency of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR-2721) LD50/7 Doses. Radiat. Res. 1971;47;2:226–229.

22. Yuhas J.M., Proctor J.O., Smith L.H. Some Pharmacologic Effects of WR-2721: Their Role in Toxicity and Radioprotection. Radiat. Res. 1973;54;2:222–233.

23. Lu Z. Optimization of Amifostine Administration for Radioprotection. Doctor’s thesis (Ph.). University of Michigan, 2007, 143 p. 

24. Wagner M., Sedlmeier H., Metzger E. et al. Untersuchungen zu Toxizität und Strahlenschutz Effect der Chemischen Strahlenschutzsubstanz WR-2721 bei Beagle-Hunden. Teil II: Strahlenschutzeffekt des WR-2721. Strahlentherapie 1980;156:655–662.

25. Stork E.J., Melville G.S.J., Gass A.E. S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid Hydrate as a Radioprotectant in Rodents and Primates. SAM-TR-68-120. Tech Rep SAM, 1968.

26. Vasin M.V., Chernov G.A., Antipov V.V. The Breadth of the Radioprotective Action of Indralin in Comparative Studies on Various Animal Species. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 1997;37;6:896–904. (In Russian).

27. Vasin M.V., Ushakov I.B. Comparative Efficiency and the Window of Radioprotection for Adrenergic and Serotoninergic Agents and Aminothiols in Experiments with Small and Large Animals. J. Radiat. Res. 2015;56;1:1–10. https://doi.org/10.1093/jrr/rru087

28. Vasin M.V. Protivoluchevyye Lekarstvennyye Sredstva = Anti-Radiation Medicines. Moscow, Kniga-Memuar Publ., 2020. 239 p. (In Russian).

29. Vasin M.V. Comparative Characteristics of Modification of Radiosensitivity of Mice and rats by Hypoxic Hypoxia. Radiobiologiya. 1986;26;4:563–565. (In Russian).

30. Antipov V.V., Vasin M.V., Gaydamakin A.N. Specific Features of the Response of SDH Lymphocytes in Animals to Acute Hypoxic Hypoxia and Its Relationship with Radioresistance of the Organism. Kosmicheskaya Biologiya i Aviakosmicheskaya Meditsina = Space Biology and Aerospace Medicine. 1989;23;2:63-66. (In Russian). 

31. Ovakimov V.G., Yarmonenko S.P. Modification of the Anti-Radiation Effect of Hypoxic Hypoxia During Artificial Hibernation of the Body. Radiobiologiya. 1975;15;1:69–73. (In Russian).

32. Norris W.P., Fritz T.E., Rehfeld C.E., Poole G.M. Response of Beagle Dog to Cobalt-60 Gamma-radiation. Determination of the LD50 and Description of Associated Changes. Radiat. Res. 1968;35:681-708.

33. MacVittie T.J., Monroy R., Vigmeulle R.M. et al. The Relative Biological Effectiveness of Fission-Neutron-Gamma Radiation on Hematopoietic Syndrome in the Canine: Effect of Therapy on Survival. Radiat. Res. 1991;128;1:S29-S36. 

34. MacVittie T.J., Jackson W. Acute Radiation-Induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study. Health Phys. 2020;119;3;351-357. doi: 10.1097/HP.0000000000001215.

35. Vasin M.V. Poisk i Issledovaniye Novykh Effektivnykh Sredstv Farmakokhimicheskoĭ Zashchity Organizma ot Porazhayushchego Deĭstviya Ioniziruyushchego Izlucheniya v Ryadu Indolilalkilaminov = Search and Study of New Effective Means of Pharmacochemical Protection of the Body from the Damaging Effects of Ionizing Radiation in the Series of Indolylalkylamines, Doctor’s Thesis in Medicine. Moscow, GNIII AiKM MO Publ., 1977. 510 p. (In Russian).

36. Shashkov V.S., Yefimov V.I., Vasin M.V., et al. Indralin - a Novel Effective Radioprotector During Irradiation by High-Energy Protons. Aviakosmicheskaya i Ekologicheskaya Meditsina = Aerospace and Environmental Medicine. 2010;44;1:15-20 (In Russian).

37. Vasin M.V., Ushakov I.B., Koroleva L V. Antipov V.V. The Role of Cellular Hypoxia in the Anti-Radiation Effect of Radioprotectors. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 1999;39;2-3:238-248 (In Russian).

38. Vasin M.V., Ushakov I.B. Activation of Respiratory Chain Complex II as a Hypoxia Tolerance Indicator During Acute Hypoxia. Biofizika = Biophysics. 2018;63;2:329–333 (In Russian).

39. Vasin M.V. B-190 (Indralin) in the Light of History of Formation of Ideasof the Mechanism of Action of Radioprotectors. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2020;60;4:378–395. (In Russian).

40. Nartsissov R.P. Application of p-Nitrotetrazolium Violet for Quantitative Cytochemistry of Human Lymphocyte Dehydrogenases. Arkhiv Anatomii, Gistologii i Embriologii. 1969;56;5:85-92. (In Russian).

41. Koroleva L.V. Radiochuvstvitelnost Organizma i Protivoluchevaya Effektivnost Radioprotektorov v Usloviyakh Sochetannogo Vozdeystviya Ioniziruyushchego Izlucheniya i Normobaricheskoy Giperoksii = Radiosensitivity of The Body and Anti-Radiation Efficiency of Radioprotectors under Conditions of Combined Exposure to Ionizing Radiation and Normobaric Hyperoxia. Diss. Candidate’s Thesis in Medicine. Moscow Publ., 1990. 134 p. (In Russian).

42. Kondrashova M., Zakharchenko M., Khunderyakova N. Preservation of the in Vivo State of Mitochondrial Network for ex Vivo Physiological Study of Mitochondria. Int. J. Biochem. Cell Biol. 2009;41;10:2036-2050. doi: 10.1016/j.biocel.2009.04.020.

43. Kondrashova M.N., Mayevskiy Ye.I., Babayan G.V., et al. Adaptation to Hypoxia by Switching Metabolism to the Transformation of Succinic Acid. Mitokhondrii. Biokhimiya i Ultrastruktura = Mitochondria. Biochemistry and Ultrastructure. Pushchino, Nauka Publ., 1973. P. 112-129 (In Russian). 

44. Dhingra R., Kirshenbaum L.A. Succinate Dehydrogenase/Complex II Activity Obligatorily Links Mitochondrial Reserve Respiratory Capacity to Cell Survival in Cardiac Myocytes. Cell. Death Dis. 2015;6;10:e1956. doi: 10.1038/cddis.2015.310.

45. Rustin P., Munnich A., Rötig A. Succinate Dehydrogenase and Human Diseases: New Insights into a Well-Known Enzyme. Europ. J. Hum. Genet. 2002;10;5:289–291. doi: 10.1038/sj.ejhg.5200793.

46. Kondrashova M., Zakharchenko M., Zakharchenko A., et al. Study of Succinate Dehydrogenase and α-Ketoglutarate Dehydrogenase in Mitochondria Inside Glass-Adhered Lymphocytes under Physiological Conditions – the Two Dehydrogenases as Counterparts of Adrenaline and Acetylcholine Regulation. Dehydrogenases. Ed. Canuto R.A. InTech, 2012. P. 235-264. doi: 10.5772/50059. https://www.intechopen.com/chapters/40939.

47. Vetrenko L.M. The Effect of Some Neurotransmitters on the Activity of Succinate Dehydrogenase. Biokhimiya = Biochemistry. 1973;38;1:22-27 (In Russian).

48. Sivaramakrishnan S., Panini S.R., Ramasarma T. Indian J. Biochem. Biophys. 1983;20;1:23-28.

49. Sivaramakrishnan S., Ramasarma T. Noradrenaline Stimulates Succinate Dehydrogenase Through Beta-Adrenergic Receptors. Indian J. Biochem. Biophys. 1983;20;1:16-22.

50. Sanders V.M. The Beta2-Adrenergic Receptor on T and B Lymphocytes: Do We Understand it yet? Brain Behav. Immun. 2012;26;2:195-200. doi: 10.1016/j.bbi.2011.08.001.

51. Vasin M.V., Petrova T.V., Koroleva L.V. Effect of Adrenaline on Cyclic Nucleotides and Succinate Dehydrogenase Activity. Fiziolog. Zhurnal SSSR im. I.M. Sechenova. 1991;77;4:106-108 (In Russian).

52. Vasin M.V., Ushakov I.B., Koroleva L.V., et al. Reaction of the Succinate Oxidase System of Mitochondria of Human Blood Lymphocytes to Adrenaline in Vitro in Healthy People and Patients with Neurovascular Dystonia. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2002. Т.134, № 4. С. 393-396. (In Russian).

53. Vasin M.V., Ushakov I.B. Activation of Respiratory Chain Complex II as a Hypoxia Tolerance Indicator During Acute Hypoxia. Biofizika = Biophysics. 2018;63;2:329–333 (In Russian).

54. Hernansanz-Agustín P., Enríquez J.A. Generation of Reactive Oxygen Species by Mitochondria. Antioxidants. 2021;10;3:415. doi: 10.3390/antiox10030415.

55. Holzer P. Acid-Sensitive Ion Channels and Receptors. Handb. Exp. Pharmacol. 2009;194:283-332. doi: 10.1007/978-3-540-79090-7_9.

56. Picard M., McEwen B.S., Epel E.S., Sandi C. An Energetic View of Stress: Focus on Mitochondria. Front. Neuroendocrinol. 2018;49:72–85. doi: 10.1016/j.yfrne.2018.01.001.

57. Sharma D., Farrar J.D. Adrenergic Regulation of Immune Cell Function and Inflammation. Seminars Immunopathol. 2020;42:709–717.

58. Vasin M.V., Chernov G.A., Koroleva L.V., et al. On the Mechanism of Anti-Radiation Action of Indralin. Radiatsionnaya biologiya. Radioekologiya = Radiation biology. Radioecology. 1996;36;1:36-46 (In Russian).

59. Vasin M.V., Ushakov I.B., Semenova L.A., Kovtun V.Yu. On the Pharmacological Analysis of the Antiradiation Action of Indralin. Radiatsionnaya biologiya. Radioekologiya = Radiation biology. Radioecology. 2001;41;3:307–309 (In Russian).

60. Vasin M.V., Ganshina T.S., Mirzoyan R.S., et al. Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2018;165;3:340-343 (In Russian).

61. Lee Y.-J., Kim H.S., Seo H.S., et al. Stimulation of Alpha1-Adrenergic Receptor Ameliorates Cellular Functions of Multiorgans Beyond Vasomotion Through PPARδ. PPAR Res. 2020;2020:3785137. doi:10.1155/2020/3785137.

62. O’Connell T.D., Jensen B.C., Baker A.J., Simpson P.C.  Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance. Pharmacol. Rev. 2013;66;1:308-333. doi: 10.1124/pr.112.007203.

63. Vasin M.V., Ushakov I.B., Antipov V.V. Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2015;159;5:549–552 (In Russian).

64. Ricci A., Bronzetti E., Conterno A. et al. α1-Adrenergic Receptor Subtypes in Human Peripheral Blood Lymphocytes. Hypertension. 1999;33;2:708–712.

65. Bao J.-Y., Huang Y., Wang F. et al. Expression of α-AR subtypes in T-lymphocytes and role of the α-ARs in mediating modulation of T-cell function. Neuroimmunomodul. 2007;14:344–353.

 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: 17.01.2022. Accepted for publication: 15.03.2022. 

 

 

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