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B-190 (Indralin) in Light of the History of the Formation of Ideas about the Mechanism of Action of Radioprotectors

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Abstract

The history of the discovery of radioprotectors from the group of aminothiols and biogenic amines and of the formation of an idea about the mechanism of their action is presented. An analysis of the achievements of domestic scientists, radiation pharmacologists, and chemists is conducted. The role of the Institute of Aviation and Space Medicine, the Institute of Biophysics of the Ministry of Health, and Mendeleev Moscow Institute of Chemical Technology in the synthesis and development of an emergency radioprotector, B‑190 (indralin), is noted. The mechanism of pharmacological, radioprotective, and radiomitigative effect of indralin and its advantages over known radioprotectors are presented. The critical role of tissue hypoxia due to increased oxygen consumption against circulatory hypoxia under the action of α1-adrenomimetic radioprotector indralin in the implementation of its radioprotective properties in large animals (dogs and monkeys) is discussed. Radiomitigative effect of indralin occurs mainly through 5-H2 cherotonin receptors.

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REFERENCES

  1. Il’in, L.A., Ushakov, I.B., and Vasin, M.V., Radioprotective agents in radiation protection system of personnel and population in case of radiation accidents, Med. Radiol. Radiats. Bezop., 2012, vol. 57, no. 3, pp. 26–31.

    Google Scholar 

  2. Il’in, L.A., Rudnyi, N.N., Suvorov, N.N., et al., Indralin—radioprotektor ekstrennogo deistviya. Protivoluchevye svoistva, farmakologiya, mekhanizm deistviya, klinika (Indralin as Emergent Radioprotector: Radioprotective Properties, Pharmacology, Mechanism of Action, and Clinic), Moscow: Minist. Zdravookhr. Ross. Fed., 1994.

  3. Vasin, M.V., Lekarstvennye protivoluchevye sredstva (Radioprotective Medical Agents), Moscow: Ross. Med. Akad. Postdiplomnogo Obraz., 2010.

  4. Weiss, J.F. and Landauer, M.R., History and development of radiation-protective agents, Int. J. Radiat. Biol., 2009, vol. 85, no. 7, pp. 539–573.

    Article  CAS  PubMed  Google Scholar 

  5. Grebenyuk, A.N. and Legeza, V.I., Protivoluchevye svoistva interleikina-1 (Radioprotective Properties of Interleukin-1), St. Petersburg: Foliant, 2012.

  6. Gibrat, C. and Cicchetti, F., Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases, Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, vol. 35, no. 2, pp. 380–389.

    Article  CAS  PubMed  Google Scholar 

  7. Kawabe, K., Takano, K., Moriyama, M., and Nakamura, Y., Transglutaminases derived from astrocytes accelerate amyloid β aggregation, Neurochem. Res., 2017, vol. 42, no. 8, pp. 2384–2391.

    Article  CAS  PubMed  Google Scholar 

  8. Barnett, M. and Hegarty, R., Cysteamine hydrochloride increases bodyweight and wool fibre length, improves feed conversion ratio and reduces methane yield in sheep, Anim. Prod. Sci., 2014, vol. 54, no. 9, pp. 1288–1293.

    Article  CAS  Google Scholar 

  9. Lissoni, P., Malugani, F., Bukovec, R., et al., Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients, Neuro Endocrinol. Lett., 2003, vol. 24, nos. 1–2, pp. 83–85.

    CAS  PubMed  Google Scholar 

  10. Vasin, M.V., Meditsinskie aspekty radiatsionnykh katastrof (Medical Aspects of Radiation Disasters), Moscow: Ross. Med. Akad. Postdiplomnogo Obraz., 2008.

  11. Kamran, M.Z., Ranjan, A., Kaur, N., et al., Radioprotective agents: strategies and translational advances, Med. Res. Rev., 2016, vol. 36, no. 3, pp. 461–493. https://doi.org/10.1002/med.21386

    Article  PubMed  Google Scholar 

  12. Saaya, F.M., Katsube, T., Xie, Y., et al., Research and development of radioprotective agents: a mini-review, Int. J. Radiol., 2017, vol. 4, nos. 2–3, pp. 128–138.

    Article  Google Scholar 

  13. Smith, T.A., Kirkpatrick, D.R., Smith, S., et al., Radioprotective agents to prevent cellular damage due to ionizing radiation, J. Transl. Med., 2017, vol. 15, p. 232. https://doi.org/10.1186/s12967-017-1338-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh, V.K. and Seed, T.M., A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures, Int. J. Radiat. Biol., 2017, vol. 93, no. 9, pp. 1–19. https://doi.org/10.1080/09553002.2017.1332438

    Article  CAS  Google Scholar 

  15. Gudkov, S.V., Popova, N.R., and Bruskov, V.I., Radioprotective substances: history, trends and prospects, Biophysics (Moscow), 2015, vol. 60, no. 4, pp. 659–667.

    Article  CAS  Google Scholar 

  16. Patt, H.M., Tyree, E.B., Straube, R.L., and Smith, D.E., Cysteine protection against X-irradiation, Science, 1949, vol. 110, no. 2852, pp. 213–214.

    Article  CAS  PubMed  Google Scholar 

  17. Chapman, W.H. and Cronkite, E.P., Further studies of beneficial effect of glutathione on X-irradiation mice, Proc. Soc. Exp. Biol. Med., 1950, vol. 75, no. 2, pp. 318–322.

    Article  CAS  PubMed  Google Scholar 

  18. Bacq, Z.M., Herve, A., Lecomte, J., et al., Protection contre le rayonnement X par la beta-mercaptoethylamine, Arch. Int. Physiol., 1951, vol. 59, no. 4, pp. 442–447.

    CAS  PubMed  Google Scholar 

  19. Bacq, Z.M., The amines and particularly cystamine as protectors against roentgen rays, Acta Radiol., 1954, vol. 41, no. 2, pp. 47–55.

    Article  CAS  PubMed  Google Scholar 

  20. Gray, J.L., Tew, J.T., and Jensen, H., Protective effect of serotonin and para-aminopropiophenon against lethal doses of X-irradiation, Proc. Soc. Exp. Biol. Med., 1952, vol. 80, no. 4, pp. 604–607.

    Article  CAS  PubMed  Google Scholar 

  21. Krasnykh, I.G., Zherebchenko, P.G., Murashova, V.S., et al., Radioprotective effect of 5-methoxytryptamine and other alkoxytryptamines, Radiobiologiya, 1962, vol. 2, no. 1, pp. 156–160.

    CAS  Google Scholar 

  22. Zherebchenko, P.G., Protivoluchevye svoistva indolilalkilaminov (Radioprotective Properties of Indolylalkylamines), Moscow: Atomizdat, 1971.

  23. Gray, J.L., Moulden, E.J., Tew, J.T., and Jensen, H., Protective effect of pitressin and of epinephrine against total body X-irradiation, Proc. Soc. Exp. Biol. Med., 1952, vol. 79, no. 3, pp. 384–387.

    Article  CAS  PubMed  Google Scholar 

  24. Gray, L.H., Conger, A.D., Ebert, M., et al., The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy, Br. J. Radiol., 1953, vol. 26, pp. 638–648.

    Article  CAS  PubMed  Google Scholar 

  25. Alper, T. and Howard-Flanders, P., The role of oxygen in modifying the radiosensitivity of E. coli B., Nature, 1956, vol. 178, no. 4540, pp. 978–979.

    Article  CAS  PubMed  Google Scholar 

  26. Barron, E., Dickman, S., Muntz, I., and Singer, T.R., Studies on the mechanism of action of ionizing radiations, J. Gen. Physiol., 1949, vol. 32, no. 4, pp. 537–552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Weiss, J., Radiochemistry of aqueus solutions, Nature, 1944, vol. 153, pp. 748–750.

    Article  CAS  Google Scholar 

  28. Lea, D.E., Action of Radiation on Living Cells, Cambridge: Cambridge Univ. Press, 1956, 2nd ed.

    Google Scholar 

  29. Bacq, Z.M. and Alexander, P., Fundamentals of Radiobiology, London: Butterworth, 1955, 1st ed.

    Google Scholar 

  30. Alexander, P. and Charlesby, A., Physico-chemical methods of protection against ionizing radiations, Proc. Radiobiology Symp., Liege, 1954, London: Butterworth, 1955, pp. 49–59.

  31. Howard-Flanders, P., Effect of oxygen on the radiosensitivity of bacteriophage in the presence of sulphydryl compounds, Nature, 1960, vol. 186, no. 4723, pp. 485–487.

    Article  CAS  PubMed  Google Scholar 

  32. Howard-Flanders, P., Levin, J., and Theriot, L., Reactions of deoxyribonucleic acid radicals with sulphydryl compounds in X-irradiated bacteriophage systems, Radiat. Res., 1963, vol. 18, no. 4, pp. 593–606.

    Article  CAS  PubMed  Google Scholar 

  33. Eidus, L.H. and Korystov, Yu.N., Kislorod v radiobiologii (Oxygen in Radiobiology), Moscow: Energoatomizdat, 1984.

  34. Jellum, E., Interaction of cysteamine and cystamine derivatives with nucleic acids and nucleoproteins, Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1965, vol. 9, pp. 185–200.

    Article  CAS  Google Scholar 

  35. Brown, P.E., Mechanism of action of aminothiol radioprotectors, Nature, 1967, vol. 213, no. 5074, pp. 363–364.

    Article  CAS  PubMed  Google Scholar 

  36. van der Meer, C. and van Bekkum, D.W., The mechanism of radiation protection by histamine and other biological amines, Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1959, vol. 1, no. 1, pp. 5–12.

    Article  CAS  Google Scholar 

  37. Ovakimov, V.G., Ayrapetyan, G.M., Ivanov, V.N., et al., Protective effect of biogenic amines in radiation intestinal syndrome, Radiobiologiya, 1970, vol. 10, no. 4, pp. 551–555.

    Google Scholar 

  38. Vasin, M.V., Search and research of new effective means of pharmacochemical protection of the body against damaging effect of ionizing radiation, Doctoral (Med.) Dissertation, Moscow: State Sci. Res. Test. Inst. Aviat. Space Med., Minist. Defense USSR, 1977.

  39. Kulinskii, V.I., Receptor-action radioprotectors, Radiats. Biol., Radioekol., 1993, vol. 33, no. 6, pp. 831–847.

    CAS  Google Scholar 

  40. Hasegawa, A.T. and Landahl, H.D., Studies on spleen oxygen tension and radioprotection in mice with hypoxia, serotonin and p-aminopropiophenone, Radiat. Res., 1967, vol. 31, no. 3, pp. 389–399.

    Article  CAS  Google Scholar 

  41. Yarmonenko, S.P., Rampan, Yu.I., Karochkin, B.B., et al., Kinetics of oxygen consumption in critical organs under the influence of mexamine in comparison with its radioprotective effect, Radiobiologiya, 1970, vol. 10, no. 5, pp. 700–705.

    CAS  Google Scholar 

  42. Zherebchenko, P.G. and Suvorov, N.N., The relationship between radioprotective and vasoconstrictive action of indolylalkylamines, Radiobiologiya, 1963, vol. 3, no. 4, pp. 595–599.

    CAS  Google Scholar 

  43. Abramov, M.M. and Vasin, M.V., Radioprotective properties of serotonin and its acyl and alkyl derivatives and their ability to change local blood flow in body tissues, Radiobiologiya, 1978, vol. 18, no. 2, pp. 204–209.

    CAS  Google Scholar 

  44. Vasin, M.V., Antipov, V.V., Suvorov, N.N., et al., The role of hydroxyl group of serotonin in pharmacological and radioprotective effect of serotonin, Radiobiologiya, 1984, vol. 24, no. 3, pp. 411–414.

    CAS  Google Scholar 

  45. Vasin, M.V., Suvorov, N.N., Abramov, M.M., and Gordeev, E.N., Change of therapeutic window of action on pharmacological and radioprotective effect in O-alkylation of serotonin and 5(2-oxyethoxytryptamine), Radiobiologiya, 1987, vol. 27, no. 5, pp. 700–703.

    CAS  Google Scholar 

  46. Dowdy, A., Bennett, L.R., and Chastain, S.M., Protective action of anoxia against total body roentgen irradiation of mammals, Radiology, 1950, vol. 55, no. 6, pp. 879–885.

    Article  CAS  PubMed  Google Scholar 

  47. Limperos, G., Effects of varying oxygen tension on mortality of X-rayed mice, J. Frankl. Inst., 1950, vol. 249, pp. 513–514.

    Article  CAS  Google Scholar 

  48. van den Brenk, H. and Jamieson, D., Studies of mechanisms of chemical radiation protection in vivo. II. Effect of pressure oxygen on radioprotection in vivo and its relation to “Oxygen poisoning,” Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1962, vol. 4, no. 4, pp. 379–402.

    Article  CAS  Google Scholar 

  49. van den Brenk, H. and Moore, R., Effect of high oxygen pressure on the protective action of cystamine and 5-hydroxytryptamine in irradiated rats, Nature, 1959, vol. 183, no. 4674, pp. 1530–1531.

    Article  CAS  PubMed  Google Scholar 

  50. van den Brenk, H. and Haas, M., Studies of mechanisms of chemical radiation protection in vivo. I. 5‑Hydroxytryptamine in relation to effect of antimetabolites, antagonists and releasing agents, Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1961, vol. 3, no. 1, pp. 73–94.

    Article  CAS  Google Scholar 

  51. van der Meer, C. and Bekkum, D., A study on the mechanism of radiation protection by 5-hydroxytryptamine and tryptamine, Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1961, vol. 4, pp. 105–110.

    Article  CAS  Google Scholar 

  52. Devik, F. and Lothe, F., The effect of cysteamine, cystamine and hypoxia on mortality and bone-marrow chromosome aberrations in mice after total bogy roentgen irradiation, Acta Radiol., 1955, vol. 44, pp. 243–248.

    Article  CAS  PubMed  Google Scholar 

  53. Duplan, J.F. and Fuhrer, J., Estimation de l’ffect radioprotecteur de l’aminoethylisothiouronium (AET) par le denombrement des nodules spleniques, C. R. Soc. Biol., 1966, vol. 160, no. 6, pp. 1142–1145.

    CAS  Google Scholar 

  54. Feher, I., Gidali, J., and Sztanyik, L., Study of the radioprotective effect of 5-methoxytryptamine on hemopoietic stem cells, Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med., 1968, vol. 14, no. 3, pp. 257–263.

    Article  CAS  Google Scholar 

  55. Crouch, B.G. and Overman, R.R., Chemical protection against X-irradiation dearth in primates: a preliminary report, Science, 1957, vol. 125, pp. 1092–1093.

    Article  CAS  PubMed  Google Scholar 

  56. Jacobus, D.P., Preprotection of the dog against ionizing radiation, Fed. Proc., 1959, vol. 18, p. 74.

    Google Scholar 

  57. Jacobus, D.P. and Dacquisto, M.D., Anti-radiation drug development, Military Med., 1961, vol. 126, p. 698.

    Article  Google Scholar 

  58. Razorenova, V.A., Protective action of mercamine in experimental acute radiation damage, in Voprosy patogeneza, eksperimental’noi terapii i profilaktiki luchevoi bolezni) (The Pathogenesis, Experimental Therapy, and Prevention of Radiation Disease), Moscow: Medgiz, 1960, pp. 351–359.

  59. Razorenova, V.A. and Scherbova, E.N., Preventive use of cysteinamine and cystamine in acute radiation disease, Med. Radiol., 1961, vol. 6, no. 3, pp. 266–269.

    Google Scholar 

  60. Benson, R.E., Michaelson, S.M., and Downs, W., Toxicological and radioprotection studies on S,beta-aminoethyl isothiouronium bromide (AET), Radiat. Res., 1961, vol. 15, no. 5, pp. 561–567.

    Article  CAS  PubMed  Google Scholar 

  61. Mozzhukhin, A.S. and Rachinskii, F.Yu., Khimicheskaya profilaktika radiatsionnykh porazhenii (Chemical Prevention of Radiation Leisure), Moscow: Atomizdat, 1964.

  62. Semenov, L.F., Profilaktika ostroi luchevoi bolezni (Prevention of Acute Radiation Disease), Leningrad: Meditsina, 1967.

  63. Akerfeldt, S., Ronnback, C., and Nelson, A., Radioprotective agents: results with S-(3-amino-2-hydroxypropyl)phosphorothioate, amidophosphorothioate and some related compounds, Radiat. Res., 1967, vol. 31, no. 4, pp. 850–855

    Article  CAS  Google Scholar 

  64. Piper, J., Stringfellow, C., Elliot, R., and Johnston, T., S-2-(omega-aminoalkylamino)ethyl dihydrogenphosphorothioates and related compounds as potential antiradiation agents, J. Med. Chem., 1969, vol. 12, no. 2, pp. 236–243.

    Article  CAS  PubMed  Google Scholar 

  65. Piper, J.R., Rose, L.M., Johnnson, T.P., et al., S-2‑omega-diaminoalkyl dihydrogen phosphorothioates as antiradiation agents, J. Med. Chem., 1979, vol. 22, no. 6, pp. 613–639.

    Article  Google Scholar 

  66. Yuhas, J.M. and Storer, J.B., Chemoprotection against three modes of radiation death in the mice, Int. J. Radiat. Biol., 1969, vol. 15, no. 3, pp. 233–237.

    CAS  Google Scholar 

  67. Yuhas, J.M., Biological factors affecting the radioprotective efficiency of S-2-[2-aminopropylamino] ethylphosphorothioic acid (WR-2721). LD50(3)) doses, Radiat. Res., 1970, vol. 44, no. 3, pp. 621–628.

    Article  CAS  PubMed  Google Scholar 

  68. Yuhas, J.M., Biological factors affecting the radioprotective efficiency of S,2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) LD50/7 doses, Radiat. Res., 1971, vol. 47, no. 2, pp. 226–229.

    Article  Google Scholar 

  69. Yuhas, J.M., Proctor, J.O., and Smith, L.H., Some pharmacologic effects of WR-2721: their role in toxicity and radioprotection, Radiat. Res., 1973, vol. 54, no. 2, pp. 222–233.

    Article  CAS  PubMed  Google Scholar 

  70. Gu, J., Zhu, S., and Li, X., Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials, PLoS One, 2014, vol. 9, no. 5, p. e95968. https://doi.org/10.1371/journal.pone.0095968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Devine, A. and Marignol, L., Potential of amifostine for chemoradiotherapy and radiotherapy-associated toxicity reduction in advanced NSCLC: a meta-analysis, Anticancer Res., 2016, vol. 36, no. 1, pp. 5–12.

    CAS  PubMed  Google Scholar 

  72. Suvorov, N.N. and Shashkov, V.S., Khimiya i farmakologiya sredstv profilaktiki radiatsionnykh porazhenii (Chemistry and Pharmacology of Means of Prevention of Radiation Lesions), Moscow: Atomizdat, 1975.

  73. Gorelova, N.V., Shashkov, V.S., Vasin, M.V., et al., Radioprotective properties of O-acyl derivatives of serotonin, Radiobiologiya, 1970, vol. 10, no. 5, pp. 758–762.

    CAS  Google Scholar 

  74. Vasin, M.V., Antipov, V.V., Suvorov, N.N., et al., Radioprotective properties of indolylalkylaminoethanols, Radiobiologiya, 1971, vol. 11, no. 5, pp. 779–781.

    CAS  Google Scholar 

  75. Starostina, Z.G., Suvorov, N.N., Vasin, M.V., et al., Synthesis of 3-dialkylamino 3-deoxyanalogs 1-(indolyl-3) glycerol, Khim.-Farm. Zh., 1972, vol. 6, no. 11, pp. 14–18.

    CAS  Google Scholar 

  76. Suvorov, N.N., Gulyaev, V.A., Kostyuchenko, N.N., et al., Indole derivatives: synthesis of some O (-oxyalkoxypropyl) derivatives of serotonin, Khim. Geterotsikl. Soedin., 1973, no. 11, pp. 1515–1518.

  77. Suvorov, N.N., Vinograd, L.Kh., Minaeva, V.S., et al., Indole derivatives: aminothiols and aminothiosulfates of indole series, Khim. Geterotsikl. Soedin., 1973, no. 11, pp. 1505–1511.

  78. Vasin, M.V., Antipov, V.V., Suvorov, N.N., et al., Radioprotective properties of diserotonin esters of dicarboxylic acids, Radiobiologiya, 1974, vol. 14, no. 2, pp. 242–246.

    CAS  Google Scholar 

  79. Vasin, M.V., Antipov, V.V., Suvorov, N.N., et al., Radioprotective properties of -oxy and -mercaptotriptamines and their derivatives, Radiobiologiya, 1974, vol. 14, no. 4, pp. 610–612.

    CAS  Google Scholar 

  80. Rusinova, V.N., Suvorov, N.N., Smushkevich, Yu.A., et al., Indole derivatives; Indolyl-3-phenylacetic acid, Khim. Geterotsikl. Soedin., 1974, no. 2, pp. 211–213.

  81. Suvorov, N.N., Gordeev, E.N., and Vasin, M.V., Indole derivatives; Synthesis and biological activity of certain tryptamines, Khim. Geterotsikl. Soedin., 1974, no. 11, pp. 1496–1501.

  82. Balabushevich, A.B., Yaros’ko, N.S., Suvorov, N.N., et al., Synthesis and radioprotective properties of certain isotriptamines, Tr. Mosk. Khim.-Tekhnol. Inst., 1977, no. 94, pp. 20–22.

  83. Suvorov, N.N., Vinograd, L.H., Lavrischeva, L.N., et al., Sulfur-containing indolylalkylamine derivatives, Tr. Mosk. Khim.-Tekhnol. Inst., 1977, no. 94, pp. 9–19.

  84. Il’in, L.A., Mify i realii Chernobylya (Myths and Realities of Chernobyl), Moscow: ALARA, 1994.

  85. Vasin, M.V., Chernov, G.A., and Antipov, V.V., The radioprotective action of indralin in comparative studies on different species of animals, Radiats. Biol., Radioekol., 1997, vol. 37, no. 6, pp. 896–904.

    CAS  Google Scholar 

  86. Vasin, M.V., Semenov, L.F., Suvorov, N.N., et al., Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys, J. Radiat. Res., 2014, vol. 55, no. 6, pp. 1048–1055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sukhinina, G.P., Pharmacology of 1-(indolyl-3)-2-alkylaminoalkanols, Extended Abstract of Cand. Sci. (Biol.) Dissertation, Moscow: Ordzhonikidze Sci. Res. Chem.-Pharm. Inst., 1972.

  88. Vasin, M.V., Gan’shina, T.S., Mirzoyan, R.S., et al., Mitigating effect of nitrates (monizol) on pharmacodynamic shifts in the cardiovascular system caused by radioprotector indralin, Bull. Exp. Biol. Med., 2018, vol. 165, no. 3, pp. 364–367.

    Article  CAS  PubMed  Google Scholar 

  89. Vasin, M.V., Antipov, V.V., Chernov, G.A., et al., The role of vasoconstrictor effect in the realization of radioprotectiveproperties of indralin in dog experiments, Radiats. Biol., Radioekol., 1997, vol. 37, no. 1, pp. 46–55.

    CAS  Google Scholar 

  90. Vasin, M.V. and Gavrilyuk, D.N., Effect of mexamine on artery tone in dogs, Farmakol. Toksikol., 1979, vol. 42, no. 4, pp. 376–378.

    CAS  PubMed  Google Scholar 

  91. Vasin, M.V., Chernov, G.A., Koroleva, L.V., et al., The mechanism of radioprotective action of indraline, Radiats. Biol., Radioekol., 1996, vol. 36, no. 1, pp. 36–46.

    CAS  Google Scholar 

  92. Vasin, M.V., Ushakov, I.B., Semenova, L.A., and Kovtun, V.Yu., Pharmacological analysis of radioprotective action of indralin, Radiats. Biol., Radioekol., 2001, vol. 41, no. 3, pp. 307–309.

    CAS  Google Scholar 

  93. Chen, Z.J. and Minneman, K.P., Recent progress in alpha1-adrenergic receptor research, Acta Pharmacol. Sin., 2005, vol. 26, no. 11, pp. 1281–1287.

    Article  CAS  PubMed  Google Scholar 

  94. Hu, Z.W., Shi, X.Y., Lin, R.Z., and Hoffman, B.B., Alpha1 adrenergic receptors activate phosphatidylinositol 3-kinase in human vascular smooth muscle cells. Role in mitogenesis, J. Biol. Chem., 1996, vol. 271, no. 15, pp. 8977–8982.

    Article  CAS  PubMed  Google Scholar 

  95. Rameh, L.E., Rhee, S.G., Spokes, K., et al., Phosphoinositide 3-kinase regulates phospholipase C γ‑mediated calcium signaling, J. Biol. Chem., 1998, vol. 273, no. 37, pp. 23750–23757.

    Article  CAS  PubMed  Google Scholar 

  96. Barrière, E., Tazi, K.A., Pessione, F., et al., Role of small-conductance Ca2+-dependent K+ channels in in vitro nitric oxide-mediated aortic hyporeactivity to alpha-adrenergic vasoconstriction in rats with cirrhosis, J. Hepatol., 2001, vol. 35, no. 3, pp. 350–357.

    Article  PubMed  Google Scholar 

  97. Tuttle, J.L. and Falcone, J.C., Nitric oxide release during α1-adrenoceptor-mediated constriction of arterioles, Am. J. Physiol.: Heart Circ. Physiol., 2001, vol. 281, no. 2, pp. H873–H881.

    CAS  Google Scholar 

  98. Chitaley, K. and Webb, R.C., Nitric oxide induces dilation of rat aorta via inhibition of rho-kinase signaling, Hypertension, 2002, vol. 39, no. 2, pp. 438–442.

    Article  CAS  PubMed  Google Scholar 

  99. Sampson, L.J., Plane, F., and Garland, C.J., Involvement of cyclic GMP and potassium channels in relaxation evoked by the nitric oxide donor, diethylamine NONOate, in the rat small isolated mesenteric artery, Naunyn-Schmiedeberg’s Arch. Pharmacol., 2001, vol. 364, no. 3, pp. 220–225.

    Article  CAS  Google Scholar 

  100. Dora, K.A., Richards, S.M., Rattigan, S., et al., Serotonin and norepinephrine vasoconstriction in rat hind limb have different oxygen requirements, Am. J. Physiol.: Heart Circ. Physiol., 1992, vol. 262, no. 3, pp. H698–H703.

    CAS  Google Scholar 

  101. Hall, J.L., Ye, J.M., Clark, M.G., and Colquhoun, E.Q., Sympathetic stimulation elicits increased or decreased VO2 in the perfused rat hindlimb via alpha 1-adrenoceptors, Am. J. Physiol.: Heart Circ. Physiol., 1997, vol. 272, no. 2, pp. H2146–H2153.

    CAS  Google Scholar 

  102. Bartlett, I.S. and Marshall, J.M., Analysis of the effects of graded levels of hypoxia on noradrenaline-evoked contraction in the rat iliac artery in vitro, Exp. Physiol., 2002, vol. 87, no. 2, pp. 171–184.

    Article  CAS  PubMed  Google Scholar 

  103. Kulinskii, V.I., Klimova, A.D., Yashunskii, V.G., and Alpatova, T.G., Mechanism of radioprotective action of catecholamine receptor agonists. Incorporation of both subtypes of alpha adrenoreceptors into the radioprotective effect, Radiobiologiya, 1986, vol. 26, no. 1, pp. 11–16.

    CAS  Google Scholar 

  104. Lo, Y.C., Tsou, H.H., Lin, R.J., et al., Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition, Life Sci., 2005, vol. 76, no. 8, pp. 931–944.

    Article  CAS  PubMed  Google Scholar 

  105. Vasin, M.V., Ushakov, I.B., Koroleva, L.V., and Antipov, V.V., The role of cellular hypoxia in radioprotective effect of radioprotectors, Radiats. Biol., Radioekol., 1999, vol. 39, no. 2–3, pp. 238–248.

    CAS  Google Scholar 

  106. Vasin, M.V. and 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, vol. 56, no. 1, pp. 1–10. https://doi.org/10.1093/jrr/rru087

    Article  CAS  PubMed  Google Scholar 

  107. Kulinskii, V.I. and Zolochevskaya, L.I., There is no correlation between the effects of sympathomimetics on the blood flow of internal organs, oxygen consumption and survival of irradiated animals, Radiobiologiya, 1973, vol. 13, no. 3, pp. 373–376.

    CAS  Google Scholar 

  108. Chance, B., The energy-linked reaction of calcium with mitochondria, J. Biol. Chem., 1965, vol. 240, pp. 2729–2748.

    Article  CAS  PubMed  Google Scholar 

  109. Rizzuto, R., Pinton, P., Brini, M., et al., Mitochondria as biosensors of calcium microdomains, Cell Calcium, 1999, vol. 26, no. 5, pp. 193–199.

    Article  CAS  PubMed  Google Scholar 

  110. Breton, L., Clot, J.P., Bouriannes, J., and Baudry, M., Adrenaline activates oxidative phosphorylation of rat liver mitochondria through alpha 1-receptors, C. R. Seances Soc. Biol. Ses Fil., 1987, vol. 181, no. 3, pp. 242–248.

    CAS  PubMed  Google Scholar 

  111. Gesek, F.A. and Strandhoy, J.W., Alpha adrenoceptor agonist stimulation of oxygen consumption in rat proximal and distal nephrons, J. Pharmacol. Exp. Ther., 1989, vol. 249, no. 2, pp. 529–534.

    CAS  PubMed  Google Scholar 

  112. Vasin, M.V., Ushakov, I.B., Korovkina, E.P., and Kovtun, V.Iu., Effect of α1-adrenomimetic indralin on oxygen consumption by bone marrow cells in vitro, Bull. Exp. Biol. Med., 2013, vol. 155, no. 3, pp. 360–362.

    Article  CAS  PubMed  Google Scholar 

  113. Praslicka, M., Hill, M., and Novak, L., Protective action of 2,4-dinitrophenol against X-radiation injury. Radioprotective effect of 2,4-dinitrophenol, Int. J. Radiat. Biol., 1962, vol. 4, pp. 567–579.

    CAS  Google Scholar 

  114. Vacek, A. and Rotkovska, D., On protective effect of 2,4-dinitrophenol, Int. J. Radiat. Biol., 1964, vol. 8, no. 3, pp. 285–289.

    CAS  Google Scholar 

  115. Krasnykh, I.G., Zherebchenko, P.G., Semenov, L.F., et al., Prevention of radiation injuries on monkeys with 5-ietoxytryptamine, Radiobiologiya, 1963, vol. 3, no. 1, pp. 259–261.

    CAS  Google Scholar 

  116. Semenov, L.F., Lapin, B.A., Strelkov, R.B., et al., Comparative study of radioprotective effectiveness of mexamine and gas hypoxic mixture in experiments on rhesus monkeys, Vestn. Akad. Med. Nauk SSSR, 1978, no. 8, pp. 83–88.

  117. Vasin, M.V., Comparative characteristic of modification of radiosensitivity of mice and rats by hypoxic hypoxia, Radiobiologiya, 1986, vol. 26, no. 4, pp. 563–565.

    CAS  Google Scholar 

  118. Antipov, V.V., Vasin, M.V., and Gaidamakin, A.N., Species features of the response of lymphocyte SDG in animals to acute hypoxic hypoxia and its association with body radioresistance, Kosm. Biol. Aviakosm. Med., 1989, vol. 23, no. 2, pp. 63–66.

    CAS  PubMed  Google Scholar 

  119. Ovakimov, V.G. and Yarmonenko, S.P., Modification of radioprotective effect of hypoxic hypoxia in artificial body hibernation, Radiobiologiya, 1975, vol. 15, no. 1, pp. 69–73.

    CAS  Google Scholar 

  120. Voitkevich, N.D. and Palyga, G.F., Radioprotective effect of mexamine, Med. Radiol., 1974, vol. 19, no. 1, pp. 74–86.

  121. Vasin, M.V., Ushakov, I.B., and Antipov, V.V., Potential role of catecholamine response to acute hypoxia in the modification of the effects of radioprotectors, Bull. Exp. Biol. Med., 2015, vol. 159, no. 5, pp. 597–600.

    Article  CAS  PubMed  Google Scholar 

  122. Vasin, M.V. and Ushakov, I.B., Activation of respiratory chain complex II during acute hypoxia, Biophysics (Moscow), 2018, vol. 63, no. 2, pp. 237–240.

    Article  CAS  Google Scholar 

  123. Vasin, M.V., Ushakov, I.B., and Bukhtiyarov, I.V., Stress reaction and biochemical shock as interrelated and unavoidable components in the formation of high radioresistance of the body in acute hypoxia, Biol. Bull. (Moscow), 2018, vol. 45, no. 1, pp. 73–81. https://doi.org/10.1134/S1062359017060115

    Article  Google Scholar 

  124. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., The targets for radioprotective and mitigatory action of radioprotector Indralin, J. Radiat. Res., 2014, vol. 2, no. 2, pp. 3–9.

    Google Scholar 

  125. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Radioprotective properties of indralin in combination with monizol in the treatment of local acute and delayed radiation injuries caused by local skin γ-irradiation, Bull. Exp. Biol. Med., 2015, vol. 159, no. 6, pp. 747–749.

    Article  CAS  PubMed  Google Scholar 

  126. Konoplyannikov, A.G., Konoplyannikova, O.A., and Proskurikov, S.Ya., The reaction “ischemia/reperfusion” for stem cells of two “critical” systems of cellular renewal of the organism, Radiats. Biol., Radioekol., 2005, vol. 45, no. 5, pp. 605–609.

    Google Scholar 

  127. Rixon, E.H. and Baird, K.M., The therapeutic effect of serotonin on the survival of X-irradiated rats, Radiat. Res., 1968, vol. 33, no. 2, pp. 395–402.

    Article  CAS  PubMed  Google Scholar 

  128. Shashkov, V.S., Anashkin, O.D., Suvorov, N.N., and Manaeva, I.A., Efficiency of serotonin, mexamine, AET and cystamine at repeated administration after γ‑irradiation, Radiobiologiya, 1971, vol. 11, no. 4, pp. 621–623.

    CAS  Google Scholar 

  129. Smirnova, I.B., Dontsova, G.V., Konstantinova, M.M., and Rakhmanina, O.N., Radiomodifying effect of serotonin on cells of hematopoetic system, Radiobiologiya, 1984, vol. 24, no. 2, pp. 236–240.

    CAS  Google Scholar 

  130. Kolesnickenko, I.S., Mikhailov, L.S., Boyarinov, A.S., and Grishin, A.V., Anti-radiation schemes of prevention and treatment of service dogs, Veterinarya, 2005, no. 12, pp. 52–54.

  131. Rozhdestvenskii, L.M., Korovkina, E.P., and Deshovoi, Yu.B., Use of recombinant human interleukin-1beta (betaleikin) for the treatment of severe acute radiation disease in dogs, Radiats. Biol., Radioekol., 2008, vol. 48, no. 2, pp. 185–184.

    CAS  Google Scholar 

  132. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Characteristics of radioprotective properties radioprotector B-190 at its application after irradiation, Radiats. Biol., Radioekol., 2008, vol. 48, no. 6, pp. 730–733.

    CAS  Google Scholar 

  133. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Radioprotective properties of indralin emergency action radioprotector in its application after irradiation under conditions of partial shielding of rat abdomen, Radiats. Biol., Radioekol., 2008, vol. 48, no. 2, pp. 199–202.

    CAS  Google Scholar 

  134. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Pharmacological analysis of the therapeutic effect of radioprotectors cystamine and indralin in the capacity of radiomitigators, Bull. Exp. Biol. Med., 2017, vol. 162, no. 4, pp. 466–469.

    Article  CAS  PubMed  Google Scholar 

  135. Graevskii, E.J., Yanushevskii, M.I., Bueverova, E.I., et al., Study of radioprotective activity and certain aspects of the mechanism of action of biogenic amines on mammalian cells cultured in vitro, Radiobiologiya, 1981, vol. 21, no. 5, pp. 683–687.

    CAS  Google Scholar 

  136. Fossier, P., Blanchard, B., Ducrocq, C., et al., Nitric oxide transforms serotonin into an inactive form and this affects neuromodulation, Neuroscience, 1999, vol. 93, no. 2, pp. 597–603.

    Article  CAS  PubMed  Google Scholar 

  137. Nefedova, V.V., Inzhevatkin, E.V., and Nefedov, V.P., Role of S2 receptors in the stimulatory effect of serotonin on hemopoietic bone marrow stem cells, Bull. Exp. Biol. Med., 2002, vol. 133, no. 5, pp. 419–420.

    Article  CAS  PubMed  Google Scholar 

  138. Yang, M., Li, K., Ng, P.C., et al., Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis, Stem Cells, 2007, vol. 25, no. 7, pp. 1800–1806.

    Article  CAS  PubMed  Google Scholar 

  139. Spiegel, A., Kalinkovich, A., Shivtiel, S., et al., Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment, Cell Stem Cell., 2008, vol. 3, pp. 484–492.

    Article  CAS  PubMed  Google Scholar 

  140. Fouquet, G., Coman, T., Hermine, O., and Côté, F., Serotonin, hematopoiesis and stem cells, Pharmacol. Res., 2019, vol. 140, pp. 67–74. https://doi.org/10.1016/j.phrs.2018.08.005

    Article  CAS  PubMed  Google Scholar 

  141. Skurikhin, E.G., Khmelevskaya, E.S., Pershina, O.V., et al., Effect of adrenomimetics and serotonin on polypotent stromal and hemopoietic precursors in cytostatic myelosuppression, Bull. Exp. Biol. Med., 2010, vol. 150, no. 1, pp. 113–116.

    Article  CAS  PubMed  Google Scholar 

  142. Meuleman, N., Tondreau, T., Ahmad, I., et al., Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study, Stem Cells Dev., 2009, vol. 18, pp. 1247–1252.

    Article  PubMed  Google Scholar 

  143. Mo Y., Li, S., Liang E., et al., The expression of functional dopamine and serotonin receptors on megakaryocytes, Blood, 2014, vol. 124, no. 21, p. 4205.

    Article  Google Scholar 

  144. Cosentino, M., Marino, F., and Maestroni, G.J., Sympathoadrenergic modulation of hematopoiesis: a review of available evidence and of therapeutic perspectives, Front. Cell Neurosci., 2015, vol. 9, p. 302.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Waldrop, B.A., Mastalerz, D., Piascik, M.T., and Post, G.R., α1B- and α1D-Adrenergic receptors exhibit different requirements for agonist and mitogen-activated protein kinase activation to regulate growth responses in rat 1 fibroblasts, J. Pharmacol. Exp. Ther., 2002, vol. 300, no. 1, pp. 83–90.

    Article  CAS  PubMed  Google Scholar 

  146. Xiang, B., Han, L., Wang, X., et al., Nicotinamide phosphoribosyltransferase upregulation by phenylephrine reduces radiation injury in submandibular gland, Int. J. Radiat. Oncol. Biol. Phys., 2016, vol. 96, no. 3, pp. 538–546. https://doi.org/10.1016/j.ijrobp.2016.06.2442

    Article  CAS  PubMed  Google Scholar 

  147. Li, L. and Bhatia, R., Role of SIRT1 in the growth and regulation of normal hematopoietic and leukemia stem cells, Curr. Opin. Hematol., 2015, vol. 22, no. 4, pp. 324–329. https://doi.org/10.1097/MOH.0000000000000152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Effect of combined application of quercetin and indralin on postradiation recovery, Radiats. Biol., Radioekol., 2011, vol. 51, no. 2, pp. 247–251

    CAS  Google Scholar 

  149. Li, P., Liu, Y., and Burns, N., SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells, Int. J. Mol. Med., 2017, vol. 39, no. 5, pp. 1127–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Vasin, M.V., Potential role of the non-uniformity of absorption of ionizing radiation energy in the body in the effectiveness of radioprotective preparations, Med. Radiol. Radiats. Bezop., 2011, vol. 56, no. 4, pp. 60–70.

    Google Scholar 

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  1. Research Testing Center of Aerospace Medicine and Military Ergonomics, Central Research Institute of the Air Force of the Ministry of Defense of the Russian Federation, Moscow, Russia

    M. V. Vasin

  2. Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, Moscow, Russia

    M. V. Vasin

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Vasin, M.V. B-190 (Indralin) in Light of the History of the Formation of Ideas about the Mechanism of Action of Radioprotectors. Biol Bull Russ Acad Sci 48, 2045–2059 (2021). https://doi.org/10.1134/S1062359021110091

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