БИОМЕДИЦИНСКИЙ ЖУРНАЛ МЕДЛАЙН.РУ
Содержание журнала

Архив

Редакция
Учредители

Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"


Федеральное государственное бюджетное учреждение науки
Институт теоретической и экспериментальной биофизики
Российской академии наук


ООО "ИЦ КОМКОН"

Адрес редакции и реквизиты

199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314


Том: 21
Статья: « 22 »
Страницы:. 246-270
Опубликована в журнале: 17 мая 2020 г.

English version

Перспективные направления фармакологической профилактики и ранней терапии радиационных поражений (обзор зарубежной литературы)

Гладких В.Д.

Федеральное государственное унитарное предприятие Научно-производственный центр «Фармзащита» Федерального медико-биологического агентства


Резюме
На основании анализа литературных данных рассмотрены зарубежные направления разработки медикаментозных средств профилактики и ранней терапии лучевых поражений. Дана общая характеристика семи радиомитигаторам, получивших статус IND (investigational new drug - новый лекарственный препарат) Управления по санитарному надзору за качеством пищевых продуктов и медикаментов США: 5-андростендиол (Neumune?), беклометазон (OrbeShield?), генистеин (BIO 300?), гранулоцитарный колониестимулирующий фактор Филграстим (Neupogen?), ингибитор киназы ON01210 (Ex-RAD?), рекомбинантный человеческий интерлейкин-12 (HemaMax?), флагеллин (Entolimod ?). Дальнейшая экспериментально-клиническая оценка их эффективности и безопасности, лицензирование в качестве противолучевых лекарственных средств, а также поиск перспективных радиомитигаторов среди ингибиторов радиационно-индуцированного апоптоза и лигандов для модуляции внутриклеточных сигнальных путей определяет стратегию разработки фармакологической профилактики и ранней терапии радиационных поражений.


Ключевые слова
ионизирующее излучение, противолучевые средства, радиационные поражения, радиомитигаторы.



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Список литературы

1. Гребенюк А.Н., Гладких В.Д. Современное состояние и перспективы разработки лекарственных средств для профилактики и ранней терапии радиационных поражений / Радиационная биология. Радиоэкология. 2019. том 59. N 2. С. 132-149.


2. Состояние и перспективы развития средств профилактики и лечения радиационных поражений. Ред. В.Д. Гладких. М.: Комментарий, 2016. 304 с.


3. Тарумов Р.А., Гребенюк А.Н., Башарин В.А. Биологические свойства фитоэстрогена генистеина (обзор литературы) / Мед. экстрем. ситуаций. 2014. N 2. С. 55-68.


4. Финашов Л.В., Рафиков У.М. Анализ литературных данных о перспективных радиопротекторах, разработанных в Соединенных Штатах Америки / Вопр. радиац. безопасности. 2017. N 2 (86). С. 75-81.


5. Ahmad I.U., Forman J.D., Sarkar F.H. Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer / Nutr. Cancer. 2010. Vol. 62, N 7. P. 996-1000.


6. Ariyasu S., Sawa A., Morita A. Design and synthesis of 8-hydroxyquinoline-based radioprotective agents / Bioorg. Med. Chem. 2014. Vol. 22, N 1. P. 3891-3905.


7. Basile L.A., Ellefson D., Gluzman-Poltorak Z. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates / PLoS One. 2012. Vol. 7, N 2. doi: .10.1371/journal.pone.0030434


8. Burdelya L.G., Brackett C.M., Kojouharov B. Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist / Proc. Natl. Acad. Sci. USA. 2013. Vol. 110, N 20. P. 1857-1866


9. Burdelya L.G., Krivokrysenko V.I., Tallant T.C. Anagonist of toll-like receptor 5 has radioprotective activity in mouse and primate models / Science. 2008. Vol. 320, N 5873. P. 226-230.


10. Casey-Sawicki К. Zhang M, Kim S. et al. А basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes / Health Phys. 2014. Vol. 106, N 6. Р. 704-712.


11. Chen J.K., Li Z.P., Liu Y.Z. Activation of alpha 7 nicotinic acetylcholine receptor protects mice from radiation-induced intestinal injury and mortality / Radiat. Res. 2014. Vol. 181, N 6. P. 666-671.


12. Compadre C.M., Singh A., Thakkar S. Molecular dynamics guided design of tocof1exol: a new radioprotectant tocotrienol with enhanced bioavailability / Drug Dev. Res. 2014. Vol. 75, N 1. P. 10-22.


13. Davis T.A., Clarke T.K., Mog S.R., 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, N 3. P. 141-151.


14. Davis T.A., Mungunsukh O., Zins S. Genistein induces radioprotection by hematopoietic stem cell quiescence / Int. J. Radiat. Biol. 2008. Vol. 84, N 9. P. 713-726.


15. Fuccio L., Guido A., Laterza L. et al. Randomised clinical trial: preventive treatment with topical rectal beclomethasone dipropionate reduces post-radiation risk of bleeding in patients irradiated for prostate cancer / Aliment. Pharm. Ther. 2011. Vol. 34, N 6. P. 628-637.


16. Ganai A.A., Farooqi H. Bioactivity of genistein: A review of in vitro and in vivo studies / Biomed. Pharmacother. 2015. Vol. 76. P. 30-38.


17. Georges G.E., Kuver R.P., Jordan R. Post-exposure oral 17,21-beclomethasone dipropionate (BDP) improves survival in a canine gastrointestinal acute radiation syndrome (GI-ARS) model / 58th Annual Meeting of the Radiation Research Society. San Juan: Lawrence, KS: Radiation Research Society, 2012.


18. Gerber S. А., Cummings R.J, Judge J.L. et al. Il-12 preserves the cutaneous physical and immunological ваrrier after radiation exposure / Radiat. Res. 2015. Vol. 183, Р.72-81.


19. Ghosh S.P., Kulkarni S., Perkins M.W. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice / J. Radiat. Res. 2012. Vol. 53, N 4. P. 526-536.


20. Ghosh S.P., Perkins M.W., Hieber K. Radiation protection by a new chemical entity, Ex-Rad: efficacy and mechanisms / Radiat. Res. 2009. Vol. 171, N 2. P. 173-179.


21. Gluzman-Poltorak Z., Mendonca S.R., Vainstein V. 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. 7. P. 31.


22. Gluzman-Poltorak Z., Vainstein V., Basile L.A. Association of hematological nadirs and survival in a nonhumanprimate model of hematopoietic syndrome of acute radiation syndrome / Radiat. Res. 2015. Vol. 184. P. 226-230.


23. Gluzman-Poltorak Z., Vainstein V., Basile L.A. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure / Am. J. Hematol. 2014. Vol. 89. P. 868-873.


24. Grace M.B., Blakely W.F., Landauer M.R. Genisteininduced alterations of radiation-responsive gene expression / Radiat. Meas. 2007. V. 42. Is. 6-7. P. 1152-1157.


25. Grace M.B., Singh V.K., Rhee J.G. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis / J. Radiat. Res. 2012. Vol. 53, N 6. P. 840-853.


26. Grebenyuk A.N., Gladkikh V.D. Modern condition and prospects for the development of medicines towards prevention and early treatment of radiation damage / Biol. Bull. 2019. Vol. 46, N. 11. Р. 1540-1555.


27. Goldman D.C., Alexeev V., Lash E., Guha C., Rodeck U., Fleming W.H. The Triterpenoid RTA 408 is а Robust Mitigator of Hematopoietic Acute Radiation Syndrome in Mice / Radiat. Res. 2015. Vol. 183, N 3. Р. 338-44.


28. Hauer-Jensen М. Toward development of interleukin-11 as а medical countermeasure for use in radiological/nuclear emergencies / Dig. Dis. Sci. 2014. Vol. 59, N7. Р.1349-1351.


29. Herodin F., Bourin P., Mayol J.-F. Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival / Blood. 2003. Vol. 101, N 7. P. 2609-2616.


30. Hofer M., Hoferova Z., Falk M. Pharmacological modulation of radiation damage. Does it exist a chance for other substances than hematopoietic growth factors and cytokines? / Int. J. Mol. Sci. 2017. Vol. 18, N 7. doi: 10.3390/ijms18071385


31. Kang A.D., Cosenza S.C., Bonagura M. et al. ON01210.Na (Ex-RAD?) mitigates radiation damage through activation of the AKT pathway / PLoS One. 2013. Vol. 8, N 3. doi: 10.1371/journal. pone.0058355


32. Kim J.S., Jang W.S., Lee S. A study of the effect of sequential injection of 5-androstenediol on irradiationinduced myelosuppression in mice / Arch. Pharm. Res. 2015. Vol. 38, N 6. P. 1213-1222.


33. Kim J., Thimmulappa R.K., Kumar V. et al. NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation / J. Clin. Invest. 2014. Vol. 124, N 2. P. 730-741.


34. Krivokrysenko V.I., Toshkov I.A., Gleiberman A.S. The Toll-like receptor 5 agonist Entolimod mitigates lethal acute radiation syndrome in non-human primates / PLoS One. 2015. Vol. 10, N 9. doi: 10.1371/journal.pone.0135388


35. Krivokrysenko V.I., Shakhov A.N., Singh V.K. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure / J. Pharmacol. Exp. Ther. 2012. Vol. 343, N 2. P. 497-508.


36. Landauer M.R., Srinivasan V., Seed T.M. Genistein treatment protects mice from ionizing radiation injury / J. Appl. Toxicol. 2003. Vol. 23, N 6. P. 379-385.


37. Lee C.L., Lento W.E., Castle K.D. Inhibiting glycogen synthase kinase-3 mitigates the hematopoietic acute radiation syndrome in mice / Radiat. Res. 2014. Vol. 181, N 5. P. 445-451.


38. Li Х.Н., Ha C.T., Fu D., Landauer M.R., Ghosh S.P., Xiao M. Delta-tocotrienol suppresses radiation-induced microRNA-30 and protects mice and human CD34+ cells from radiation injury// PLoS Оnе. 2015. Vol. 10, N 3.


39. Miller R.C., Murley J.S, Grdina D. J. Metformin Exhibits Radiation Countermeasures Efficacy When Used Alone оr in Combination with Sulfhydryl Containing Drugs / Radiat. Res. 2014. V. 181. Р. 464-470.


40. Mirzoeva S. Paunesku T., Wanzer M.B., Shirvan A., Kaempfer R., Woloschak G.E., Small W. Single administration of р2ТА (АВ103), а CD28 antagonist peptide, prevents inflammatory and thrombotic reactions and protects against gastrointestinal injury in total-body irrаdiаtеd mice / PLoS One. 2014. Vol. 9, N 7.


41. Morita A., Ariyasu S., Wang B. AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation / Biochem. Biophys. Res. Commun. 2014. Vol. 450, N 4. P. 1498-1504.


42. NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats / U.S. Department of Health and Human Services. NIH Publication No. 05-5608, 2005.


43. Neelis K.J., Dubbelman Y.D., Qingliang L. 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, N 10. P. 1084-1093.


44. Neelis K.J., Hartong S.C., Egeland T. 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, N 7. P. 2565-2573.


45. Pathak R. Shao L., Hauer-Jensen M. Thrombomodulin contributes to gamma tocotrienol-mediated lethality protection and hematopoietic сеll recovery in irrаdiаtеd mice / PLoS Оnе. 2015. Vol. 10. N 4.


46. Rosen Е.М., Day R., Singh V.К. New approaches to radiation protection / Front. Oncol. 2015. Vol. 4. Article 381. 15 р.


47. Satyamitra M., Lombardini E., Graves J. A TPO receptor agonist, ALXN4100TPO, mitigates radiation-induced lethality and stimulates hematopoiesis in CD2F1 mice / Radiat. Res. 2011. V. 175, N 6. P. 746-758.


48. Shukla P.N., Gairola M., Mohanti B.K., Rath G.K. Prophylactic beclomethasone spray to the skin during postoperative radiotherapy of carcinoma breast: a prospective randomized study / Indian J. Cancer. 2006. Vol. 43, N 4. P. 180-184.


49. Singh V.K., Beattie L.A., Seed T.M. Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures / J. Radiat. Res. 2013. Vol. 54, N 6. P. 973-988.


50. Singh V.K., Grace M.B., Jacobsen K.O. Administration of 5-androstenediol to mice: pharmacokinetics and cytokine gene expression / Exp. Mol. Pathol. 2008. Vol. 84, N 2. P. 178-188.


51. Singh P.K., Wise S.Y., Ducey E.J. α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury / Radiat. Res. 2012. Vol. 177, N 2. P. 133-145


52. Singh V.K., Newman V.L., Romaine P.L. Radiation countermeasure agents: an update (2011-2014) / Expert. Opin. Ther. Pat. 2014. Vol. 24, N 11. P. 1229-1255.


53. Singh V.K., Newman V.L., Seed T.M. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review / Cytokine. 2014. Vol. 71, N 1. P. 22-37.


54.Singh V. К., Romaine P.L., Newman V.L., Seed T.M. Tocols induce G-CSF and mobilise progenitors that mitigate radiation injury / Radiat. Prot. Dosimetry. 2014. Vol. 162, N. 1-2. Р.83-87.


55. Singh V.K., Romaine P.L., Newman V.L. Biologics as countermeasures for acute radiation syndrome: where are we now? / Expert. Opin. Biol. Ther. 2015. Vol. 15, N 4. P. 465-471.


56. Singh V.K., Romaine P.L., Seed T.M. Medical countermeasures for radiation exposure and related injuries: characterization of medicines, FDA-approval status and inclusion into the Strategic National Stockpile / Health Phys. 2015. Vol. 108, N 6. P. 607-630.


57. Singh V.K., Romaine P.L., Newman V.L., Seed T.M. Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents / Expert. Opin. Ther. Pat. 2016. Vol. 26, N 12. P. 1399-1408.


58. Singh V.K., Hanlon B.K., Santiago P.T., Seed T.M. A review of radiation countermeasures focusing on injuryspecific medicinals and regulatory approval status: part III. Countermeasures under early stages of development along with 'standard of care' medicinal and procedures not requiring regulatory approval for use / Int. J. Radiat. Biol. 2017. Vol. 93, N 9. P. 885-906.


59. Singh V.K., 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 counter measures / Int. J. Radiat. Biol. 2017. Vol. 93, N 9. P. 851-869.


60.Sridharan V,. Tripathi P., Aykin-Burns N., Krager K.J., Sharma S.K., Moros E.G. Tocotrienol-Enriched Formulation Рrotects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure / Rad. Res. 2015. Vol.183, N 3. Р. 357-366.


61. Stickney D.R., Dowding C., Garsd A. 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression / Int. Immunopharmacol. 2006. Vol. 6, N 11. P. 1706-1713.


62. Suman S., Datta K., Doiron K. Radioprotective effects of ON 01210.Na upon oral administration / J. Radiat. Res. 2012. Vol. 3, N 3. P. 368-376.


63. Suman S., Maniar M., Fornace A.J., Datta K. Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response / Radiat. Oncol. 2012. Vol. 7. P. 6. doi: 10.1186/1748-717X-7-6


64. Tacyildiz N., Ozyoruk D., Yavuz G. Soy isoflavones ameliorate the adverse effects of chemotherapy in children // Nutr. Cancer. 2010. Vol. 62, N 7. P. 1001-1005.


65. Wang C., Zhang B., Wang S. Recombinant human thrombopoietin promotes hematopoietic reconstruction after severe whole body irradiation / Sci. Rep. 2015. N 5. P. 12-24.


66. Weiss J.F., Landauer M.R. Protection against ionizing radiation by antioxidant nutrients and phytochemicals / Toxicol. 2003. Vol. 189, N 1-2. P. 1-20.


67. Weiss J.F., Landauer M.R. History and development of radiation-protective agents / Int. J. Radiat. Biol. 2009. Vol. 85, N 7. P. 539-573.


68. Whitnall M.H., Elliott T.B., Harding R.A. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice / Int. J. Immunopharmacol. 2000. Vol. 22, N 1. P. 1-14.


69. Whitnall M.H., Villa V., Seed T.M. Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice / Immunopharmacol. Immunotoxicol. 2005. Vol. 27, N 1. P. 15-32.


70. Whitnall M.H., Wilhelmsen C.L., McKinney L.-A. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice / Immunopharmacol. Immunotoxicol. 2002. Vol. 24, N 4. P. 596-626.


71. Xiao M., Inal C.E., Parekh V.I. 5-Androstenediol promotes survival of gamma-irradiated human hematopoietic progenitors through induction of nuclear factor kappaB activation and granulocyte colony-stimulating factor expression / Mol. Pharmacol. 2007. Vol. 72, N 2. P. 370-379.


72. Yoon S.I., Kurnasov O., Natarajan V. Structural basis of TLR5-flagellin recognition and signaling / Science. 2012. Vol. 335, N 6070. P. 859-864.


73. Zhou Y., Mi M.T. Genistein stimulates hematopoiesis and increases survival in irradiated mice / J. Radiat. Res. 2005. Vol. 46, N 4. P. 425-433.