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Radiomitigators: Classification, Pharmacological Properties, and Application Prospects

  • MATERIALS FROM THE INTERNATIONAL CONFERENCE “RADIATION EXPOSURE-RELATED PROBLEMS OF CHEMICAL PROTECTION AND REPAIR” (DUBNA, 30–31 MAY, 2018)
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Abstract—

A classification of radiomitigators, i.e., antiradiation agents for prevention or reduction of the severity of clinical manifestations of acute radiation syndrome and its delayed and long-term clinical consequences, has been proposed. In the classification proposed, radiomitigators used for prophylaxis and treatment of the immediate and remote clinical manifestations of acute radiation syndrome are divided into the following main groups: means (drugs) for treatment of the bone marrow syndrome; means for treatment of the gastrointestinal syndrome; means for treatment of local and subtotal manifestations of radiation injuries; means for prevention and treatment of delayed and long-term effects of irradiation. A list and brief characteristics of the most promising radiomitigators from the groups of cytokines, growth factors, antioxidants, immunomodulators, steroid hormone analogues, and apoptosis blockers are given.

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REFERENCES

  1. Hall, E.J. and Giaccia, A.J., Radiobiology for the Radiologist, Philadelphia: Lippincott Williams and Wilkins, 2006.

    Google Scholar 

  2. Vasin, M.V., Classification of radioprotective agents as a reflection of the current state and prospects of development of radiation pharmacology, Radiats. Biol. Radioekol., 2013, vol. 53, no. 5, pp. 459–467.

    CAS  Google Scholar 

  3. Grebenyuk, A.N., Legeza, V.I., Nazarov, V.B., and Timoshevskii, A.A., Meditsinskie sredstva profilaktiki i terapii radiatsionnykh porazhenii (Health Care Aids of Prevention and Treatment of Radiation Injuries), St. Petersburg: Foliant, 2011.

  4. Grebenyuk, A.N., Legeza, V.I., and Tarumov, R.A., Radiomitigators: prospects for use in the medical radiation protection system, Voen.-Med. Zh., 2014, vol. 335, no. 6, pp. 39–43.

    Google Scholar 

  5. Vasin, M.V., Protivoluchevye svoistva lekarstvennykh sredstv (Antiradiation Properties of Drugs), Moscow: RMAPO, 2010.

  6. Trog, D., Bank, P., Wendt, T.G., and Beleites, E., Daily amifostine given concomitantly to chemoradiation in head and neck cancer, Strahlentherapie Onkologie, 1999, vol. 175, no. 9, pp. 444–449.

    Article  CAS  Google Scholar 

  7. Il’in, L.A., Rudnyi, N.M., Suvorov, N.N., et al., Indralin—radioprotektor ekstrennogo deistviya. Protivoluchevye svoistva, farmakologiya, mekhanizm deistviya, klinika (Indralin—Radioprotectant of Emergency Action: Radioprotective Properties, Pharmacology, Mechanism of Action, and Clinical Use), Moscow: Min. Zdrav. Ross. Fed., 1994.

  8. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., The characteristic of the radioprotective properties of a radioprotectant B-190 at its administration after radiation, Radiats. Biol. Radioekol., 2008, vol. 48, no. 6, pp. 730–733.

    CAS  Google Scholar 

  9. Legeza, V.I. and Chigareva, N.G., Means and methods of early pathogenetic therapy of radiation injuries, Med. Katastrof, 1999, vol. 26, no. 2, pp. 41–45.

    Google Scholar 

  10. Andrushchenko, V.N., Ivanov, A.A., and Mal’tsev, V.N., Radiation-protective action of microbial substances, Radiats. Biol. Radioekol., 1996, vol. 36, no. 2, pp. 195–207.

    CAS  Google Scholar 

  11. Ivanov, A.A., Ivanova, A.S., Ulanova, N.M., et al., Antiradiation effects of vaccine Grippol, Radiats. Biol. Radioekol., 2010, vol. 50, no. 1, pp. 52–57.

    CAS  Google Scholar 

  12. Chertkov, K.S., Treatment and prevention of acute radiation sickness in the conditions of mass destruction (according to experimental data), in Radiatsionnaya meditsina (Radiation Medicine), Il’in, L.A., Ed., Moscow: IzdAT, 2001, vol. 2.

  13. Chertkov, K.S., Davydova, S.A., and Nesterova, T.A., Efficiency of polysaccharide translam for early treatment of acute radiation illness, Radiats. Biol. Radioekol., 1999, vol. 39, no. 5, pp. 572–577.

    CAS  Google Scholar 

  14. Burdelya, L.G., Krivokrysenko, V.I., Tallant, T.C., et al., An agonist of Toll-like receptor 5 has radioprotective activity in mouse and primate models, Science, 2008, vol. 320, no. 5873, pp. 226–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Grebenyuk, A.N., Aksenova, N.V., Petrov, A.V., et al., Obtaining different variants of recombinant flagellin and assessment of their radioprotective efficiency, Vestn. Ross. Voen.-Med. Akad., 2013, no. 3 (43), рр. 75–80.

  16. Ketlinskii, S.A. and Simbirtsev, A.S., Tsitokiny (Cytokines), St. Petersburg: Foliant, 2008.

    Google Scholar 

  17. Simbirtsev, A.S., Tsitokiny v patogeneze i lechenii zabolevanii cheloveka (Cytokines in the Pathogenesis and Treatment of Human Diseases), St. Petersburg: Foliant, 2018.

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

  19. Rozhdestvenskii, L.M., Korovkina, E.P., and Deshevoi, Yu.B., Recombinant human interleukine-1beta (betaleukine) usage for acute radiation sickness of severe degree treatment at canines, Radiats. Biol. Radioekol., vol. 48, no. 2, pp. 185–194.

  20. Wang, C., Zhang, B., Wang, S., et al., Recombinant human thrombopoietin promotes hematopoietic reconstruction after severe whole body irradiation, Sci. Rep., 2015, no. 5, pp. 12–24.

  21. Kuter, D.J., New thrombopoietic growth factors, Blood, 2007, vol. 109, no. 11, pp. 4607–4616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Satyamitra, M., Lombardini, E., Graves, J., et al., A TPO receptor agonist, ALXN4100TPO, mitigates radiation-induced lethality and stimulates hematopoiesis in CD2F1 mice, Radiat. Res., 2011, vol. 175, no. 6, pp. 746–758.

    Article  CAS  PubMed  Google Scholar 

  23. Neelis, K.J., Dubbelman, Y.D., Qingliang, L., et al., Simultaneous administration of TPO and G-CSF after cytoreductive treatment of Rhesus monkeys prevents thrombocytopenia, accelerates platelet and reconstitution, alleviates neutropenia, and promotes the recovery of immature bone marrow cells, Exp. Hematol., 1997, vol. 25, no. 10, pp. 1084–1093.

    CAS  PubMed  Google Scholar 

  24. Neelis, K.J., Hartong, S.C., Egeland, T., et al., The efficacy of single dose administration of thrombopoietin with co-administration of either granulocyte/macrophage or granulocyte colony stimulated factor in myelosuppressed Rhesus monkeys, Blood, 1997, vol. 90, no. 7, pp. 2565–2573.

    Article  CAS  PubMed  Google Scholar 

  25. Herodin, F., Bourin, P., Mayol, J.-F., et al., Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival, Blood, 2003, vol. 101, no. 7, pp. 2609–2616.

    Article  CAS  PubMed  Google Scholar 

  26. Whitnall, M.H., Wilhelmsen, C.L., McKinney, L.-A., et al., Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice, Immunopharmacol. Immunotoxicol., 2002, vol. 24, no. 4, pp. 595–626.

    Article  CAS  PubMed  Google Scholar 

  27. Weiss, J.F. and Landauer, M.R., Radioprotection by antioxidants, Ann. N.Y. Acad. Sci., 2000, vol. 899, pp. 44–60.

    Article  CAS  PubMed  Google Scholar 

  28. Sventitskaya, A.M., Nikiforov, A.S., Ivanov, I.M., et al., Comparative evaluation of therapeutic efficacy of somatotropin, growth hormone-releasing factors, and hematopoietic cytokines in experiments on irradiated mice, Radiats. Biol. Radioekol., 2017, vol. 57, no. 6, pp. 621–629.

    Google Scholar 

  29. Tarumov, R.A., Basharin, V.A., and Grebenyuk, A.N., Radioprotective properties of modern antioxidants, Medline. Ru, 2012, vol. 13, pp. 682–700.

    Google Scholar 

  30. Landauer, M.R., Srinivasan, V., and Seed, T.M., Genistein treatment protects mice from ionizing radiation injury, J. Appl. Toxicol., 2003, vol. 23, no. 6, pp. 379–385.

    Article  CAS  PubMed  Google Scholar 

  31. Bhatia, A.L., Gaur, A., and Sharma, A., Radiation protection by an isoflavone, genistein: a study on the survivability of mice, Nucl. Techn. Radiat. Prot., 2007, vol. 22, no. 1, pp. 34–39.

    Article  CAS  Google Scholar 

  32. Davis, T.A., Clarke, T.K., and Landauer, M.R., Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival, Int. J. Radiat. Biol., 2007, vol. 83, no. 3, pp. 141–151.

    Article  CAS  PubMed  Google Scholar 

  33. Grebenyuk, A.N., Tarumov, R.A., Basharin, V.A., et al., Experimental evaluation of the effect of synthetic genistein on hematologic indices and cytokine status of irradiated rats, Radiats. Biol. Radioekol., 2015, vol. 55, no. 2, pp. 160–168.

    Google Scholar 

  34. Grebenyuk, A.N., Tarumov, R.A., Basharin, V.A., and Kovtun, V.Yu., Experimental evaluation of radioprotective efficacy of synthetic genistein on criteria of glutathione system and lipid peroxidation in erythrocytes of peripheral blood in irradiated rats, Radiats. Biol. Radioekol., 2015, vol. 55, no. 5, pp. 501–506.

    CAS  Google Scholar 

  35. Davis, T.A., Mungunsukh, O., Zins, S., et al., Genistein induces radioprotection by hematopoietic stem cell quiescence, Int. J. Radiat. Biol., 2008, vol. 84, no. 9, pp. 713–726.

    Article  CAS  PubMed  Google Scholar 

  36. Vijayalaxmi, Reiter, R.J., Tan, D.X., et al., Melatonin as a radioprotective agent: a review, Int. J. Radiat. Oncol. Biol. Phys., 2004, vol. 59, no. 3, pp. 639–653.

    Article  CAS  PubMed  Google Scholar 

  37. Pikalova, L.V., Legeza, V.I., and Gorbunov, V.A., The experimental evaluation of influence of exogenous melatonin on the genetic damage induced by radiation exposure, Radiats. Biol. Radioekol., 2013, vol. 53, no. 5, pp. 500–505.

    CAS  Google Scholar 

  38. Mil’, E.M., Albantova, A.A., and Burlakova, E.B., Impact of the antioxidant Phenozan and low dose radiation on the level of p53 and BCL-2 proteins of mice different lines, Radiats. Biol. Radioekol., 2010, vol. 50, no. 1, pp. 58–64.

    Google Scholar 

  39. Jagetia, G.C., Radioprotective potential of plants and herbs against the effects of ionizing radiation, J. Clin. Biochem. Nutr., 2007, vol. 40, no. 2, pp. 74–81.

    Article  CAS  Google Scholar 

  40. Jagetia, G.C. and Baliga, M.S., The evolution of the radioprotective effect of chyavanaprasha (an ayurvedic rasayana drug) in mice exposed to lethal dose of gamma-radiation: a preliminary study, Phytother. Res., 2004, vol. 18, no. 1, pp. 14–18.

    Article  CAS  PubMed  Google Scholar 

  41. Krishna, A. and Kumar, A., Evaluation of radioprotective effects of rajgira (Amaranthus paniculatus) extract in Swiss albino mice, J. Radiat. Res., 2005, vol. 46, no. 2, pp. 233–239.

    Article  PubMed  Google Scholar 

  42. Park, E., Ahn, G., Yun, J.S., et al., Dieckol rescues mice from lethal irradiation by accelerating hemopoiesis and curtailing immunosuppression, Int. J. Radiat. Biol., 2010, vol. 86, no. 10, pp. 848–859.

    CAS  PubMed  Google Scholar 

  43. Maurya, D.K., Salvi, V.P., and Nair, C.K., Radiation protection of DNA by ferulic acid under in vitro and in vivo conditions, Mol. Cell Biochem., 2005, vol. 280, nos. 1–2, pp. 209–217.

    Article  CAS  PubMed  Google Scholar 

  44. Mishra, K., Srivastava, P.S., and Chaudhury, N.K., Sesamol as a potential radioprotective agent: in vitro studies, Radiat. Res., 2011, vol. 176, no. 5, pp. 613–623.

    Article  CAS  PubMed  Google Scholar 

  45. Singh, P.K., Wise, S.Y., Ducey, E.J., et al., α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury, Radiat. Res., 2012, vol. 177, no. 2, pp. 133–145.

    Article  CAS  PubMed  Google Scholar 

  46. Singh, V.K., Beattie, L.A., and Seed, T.M., Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures, J. Radiat. Res., 2013, vol. 54, no. 6, pp. 973–988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gudkov, S.V., Gudkova, O.Y., Chernikov, A.V., and Bruscov, V.I., Protection of mice against X-ray injuries by the post-irradiation administration of guanosine and inosine, Int. J. Radiat. Biol., 2009, vol. 85, no. 2, pp. 116–125.

    Article  CAS  PubMed  Google Scholar 

  48. Soligenix, Inc., OrbeShield® for Gastrointestinal Acute Radiation Syndrome (GI ARS), 2018. www.soligenix.com/pipeline/vaccinesbiodefense/orbeshield-for-gastrointestinal-acute-radiation-syndrome-gi-ars/. Accessed June 28, 2018.

  49. Gluzman-Poltorak, Z., Mendonca, S.R., Vainstein, V., et al., Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation, J. Hematol. Oncol., 2014, vol. 31, p. 7. https://doi.org/10.1186/1756-8722-7-31

    Article  CAS  Google Scholar 

  50. Finch, P.W., Mark, CrossL.J., McAuley, D.F., and Farrell, C.L., Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models, J. Cell. Mol. Med., 2013, vol. 17, no. 9, pp. 1065–1087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Burnett, A.F., Biju, P.G., Lui, H., and Hauer-Jensen, M., Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model, Radiat. Res., 2013, vol. 180, no. 6, pp. 595–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Koukourakis, M.I., Radiation damage and radioprotectants: new concepts in the era of molecular medicine, Br. J. Radiol., 2012, vol. 85, no. 1012, pp. 313–330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Antushevich, A.A., Antonov, V.G., Grebenyuk, A.N., et al., Pathophysiological basis of glutoxim efficiency as an accompanying drug in radiation therapy of oropharyngeal cancer, Vestn. Ross. Voen.-Med. Akad., 2013, no. 3 (43), pp. 32–37.

  54. Yartseva, A.A., Stepanov, A.V., Grebenyuk, A.N., and Antushevich, A.E., Effect of molixan on the oral microbiocenosis after combined chemoradiation exposure, Med.-Biol. Sots.-Psikhol. Probl. Bezop. Chrezv. Situats., 2014, no. 1, pp. 57–63.

  55. Yartseva, A.A., Moroz, B.T., Grebenyuk, A.N., et al., The effectiveness of molixan as a means of correction of chemoradiation therapy negative manifestations in patients with oropharyngeal cancer, Radiats. Biol. Radioekol., 2014, vol. 54, no. 3, pp. 265–272.

    Google Scholar 

  56. Yartseva, A.A., Antushevich, A.E., and Grebenyuk, A.N., Experimental study of the mechanisms of hemostimulating activity of organic salts of glutathione disulfide and inosine under acute radiation exposure, Med.-Biol. Sots.-Psikhol. Probl. Bezop. Chrezv. Situats., 2016, no. 1, pp. 79–84.

  57. Prasanna, P.G.S., Narayanan, D., Hallett, K., et al., Radioprotectors and radiomitigators for improving radiation therapy: the small business innovation research (SBIR) gateway for accelerating clinical translation, Radiat. Res., 2015, vol. 184, no. 3, pp. 235–248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zharikov, A.A., Terekhov, O.V., and Pasov, V.V., Treatment of patients with late radiation damage of pelvic organs with the use of the drug rexod, Onkologiya, 2013, no. 5, pp. 26–30.

  59. Carsten, R.E., Bachand, A.M., Bailey, S.M., and Ullrich, R.L., Resveratrol reduces radiation-induced chromosome aberration frequencies in mouse bone marrow cells, Radiat. Res., 2008, vol. 169, no. 6, pp. 633–638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kulkarni, S.S. and Cantó, C., The molecular targets of resveratrol, Biochim. Biophys. Acta, 2015, vol. 1852, no. 6, pp. 1114–1123.

    Article  CAS  PubMed  Google Scholar 

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  1. State Scientific Research Test Institute of Military Medicine, St. Petersburg, Russia

    V. I. Legeza & I. S. Drachev

  2. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia

    A. N. Grebenyuk

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  1. V. I. Legeza
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Legeza, V.I., Grebenyuk, A.N. & Drachev, I.S. Radiomitigators: Classification, Pharmacological Properties, and Application Prospects. Biol Bull Russ Acad Sci 46, 1625–1632 (2019). https://doi.org/10.1134/S1062359019120045

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