ksmaКубанский научный медицинский вестникKuban Scientific Medical Bulletin1608-62282541-9544Kuban State Medical University10.25207/1608-6228-2018-25-4-124-131ksma-1312Research ArticleОБЗОРЫREVIEWЭНДОТЕЛИАЛЬНАЯ ДИСФУНКЦИЯ ПРИ ВОЗДЕЙСТВ ИИ ИОНИЗИРУЮЩЕГО ИЗЛУЧЕНИЯ: ПАТОГЕНЕТИЧЕСКИЕ ОСНОВЫ И В ОЗМОЖНОСТИ ФАРМАКОЛОГИЧЕСКОЙ КОРРЕКЦИИENDOTHELIAL DYSFUNCTION UNDER INFLUENCE OF IONIZING RADIATION: PATHOGENETIC BASIS AND OPPORTUNITIES OF PHARMACOLOGICAL CORRECTIONСАРОЯНК. В.SAROYANK. V.

ул. Победы, д. 85, г. Белгород, Россия, 308015

тел.: +7 (910) 325-84-96

Россия, Курск, 305021, ул. Школьная, д. 48А, кв. 88.

85 Pobedy str., Belgorod, Russia, 308015

tel.: +7 (910) 325-84-96

saroyan_1981@mail.ruСЫТНИКИ. Н.SYTNIKI. N.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

СОЛДАТОВВ. О.SOLDATOVV. O.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

ПЕРШИНАМ. А.PERSHINAM. A.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

ЖЕРНАКОВАН. И.ZHERNAKOVAN. I.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

ПОВЕТКИНС. В.POVETKINS. V.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

СЕРНОВЛ. Н.SERNOVL. N.

ул. Победы, д. 85, г. Белгород, Россия, 308015

85 Pobedy str., Belgorod, Russia, 308015

Белгородский национальный исследовательский университетРоссияBelgorod National Research UniversityRussian Federation201803102018254124131Copyright © САРОЯН К.В., СЫТНИК И.Н., СОЛДАТОВ В.О., ПЕРШИНА М.А., ЖЕРНАКОВА Н.И., ПОВЕТКИН С.В., СЕРНОВ Л.Н., 20182018САРОЯН К.В., СЫТНИК И.Н., СОЛДАТОВ В.О., ПЕРШИНА М.А., ЖЕРНАКОВА Н.И., ПОВЕТКИН С.В., СЕРНОВ Л.Н.SAROYAN K.V., SYTNIK I.N., SOLDATOV V.O., PERSHINA M.A., ZHERNAKOVA N.I., POVETKIN S.V., SERNOV L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ksma.elpub.ru/jour/article/view/1312

Проблема радиационно-индуцированных поражений становится все более актуальной. Исследования последних лет показывают, что одной из наиболее уязвимых тканей при  воздействии высоких доз ионизирующего излучения является эндотелий. Изучение  патогенетических основ данного явления показало, что повреждение эндотелиоцитов  происходит как за счет прямого воздействия радиации, так и за счет системного нарушения  гомеостаза, приводящего к дезадаптации исполнительных и регуляторных систем организма. В  данном обзоре рассмотрены механизмы развития эндотелиальной дисфункции при воздействии  радиоактивного излучения и возможные способы фармакологической коррекции данного состояния.

The problem of radiation-induced lesions is becoming increasingly urgent. Studies in recent years show that one of the most vulnerable  tissues is the endothelium when exposed to high doses of ionizing  radiation. The study of the pathogenetic bases of this phenomenon has  shown that damage to endotheliocytes occurs both at the expense of  the direct exposure to radiation and due to the systemic disturbance of  homeostasis which leads to the disadaptation of the executive and  regulatory systems of the organism. In this review we considered the  mechanisms of the development of endothelial dysfunction under the influence of radioactive radiation and possible methods of pharmacological correction of this condition.

эндотелиальная дисфункциярадиациярадиопротекторыэндотелиопротекторыendothelial dysfunctionradiationradioprotectorsendothelioprotectorsReferencesAzizova T., Grigoryeva E., Haylock R., Pikulina M., Moseeva M. Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948– 1982. The British Journal of Radiology. 2015; 88(1054): 20150169. DOI: 10.1259/bjr.20150169.Azizova T., Grigoryeva E., Haylock R., Pikulina M., Moseeva M. Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948– 1982. The British Journal of Radiology. 2015; 88(1054): 20150169. DOI: 10.1259/bjr.20150169.Moseeva M., Azizova T., Grigoryeva E., Haylock R. Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008. Radiation and Environmental Biophysics. 2014; 53: 469-477. DOI: 10.1007/s00411-014-0517-x.Moseeva M., Azizova T., Grigoryeva E., Haylock R. Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008. Radiation and Environmental Biophysics. 2014; 53: 469-477. DOI: 10.1007/s00411-014-0517-x.Adams M., Hardenbergh P., Constine L., Lipshultz S. Radiation- associated cardiovascular disease. Critical Reviews In Oncology Hematology. 2003; 45(1): 55-75.Adams M., Hardenbergh P., Constine L., Lipshultz S. Radiation- associated cardiovascular disease. Critical Reviews In Oncology Hematology. 2003; 45(1): 55-75.Little M., Tawn E., Tzoulaki I. A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms. Journal of Radiation Research. 2008; 169: 99-109. DOI: 10.1667/RR1070.1.Little M., Tawn E., Tzoulaki I. A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms. Journal of Radiation Research. 2008; 169: 99-109. DOI: 10.1667/RR1070.1.Gimbrone M., García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research. 2016; 118: 620-636. DOI: 10.1161/CIRCRESAHA.115.306301.Gimbrone M., García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research. 2016; 118: 620-636. DOI: 10.1161/CIRCRESAHA.115.306301.Kumarathasan P., Vincent R., Blais E., Saravanamuthu A., Gupta P., Wyatt H., Mitchel R., Hannan M., Trivedi A., Whitman S. Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation. PLoS One. 2013; 8(6): e65486. DOI: 10.1371/journal.pone.0065486.Kumarathasan P., Vincent R., Blais E., Saravanamuthu A., Gupta P., Wyatt H., Mitchel R., Hannan M., Trivedi A., Whitman S. Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation. PLoS One. 2013; 8(6): e65486. DOI: 10.1371/journal.pone.0065486.Rom O., Reznick A. The stress reaction: a historical perspective. Advances in Experimental Medicine and Biology. 2016; 905: 1-4. DOI: 10.1007/5584_2015_195.Rom O., Reznick A. The stress reaction: a historical perspective. Advances in Experimental Medicine and Biology. 2016; 905: 1-4. DOI: 10.1007/5584_2015_195.Coppe J., Patil C., Rodier F. Senescence-associated secretory phenotypes reveal cell- nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology. 2016; 6: 2853- 68. DOI: 10.1371/journal.pbio.0060301.Coppe J., Patil C., Rodier F. Senescence-associated secretory phenotypes reveal cell- nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology. 2016; 6: 2853- 68. DOI: 10.1371/journal.pbio.0060301.Heckmann M., Douwes K., Peter R., Degitz K. Vascular activation of adhesion molecule mRNA and cell surface expression by ionizing radiation. Experimental Cell Research. 1998; 238(1): 148-54. DOI: 10.1006/excr.1997.3826.Heckmann M., Douwes K., Peter R., Degitz K. Vascular activation of adhesion molecule mRNA and cell surface expression by ionizing radiation. Experimental Cell Research. 1998; 238(1): 148-54. DOI: 10.1006/excr.1997.3826.Adams G., Jameson D. Time effects in molecular radiation biology. Radiation and Environmental Biophysics. 1980; 17(2): 95- 11310.Adams G., Jameson D. Time effects in molecular radiation biology. Radiation and Environmental Biophysics. 1980; 17(2): 95- 11310.Childs B., Durik M., Baker D., van Deursen J. Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nature Medicine. 2015; 21:1424-1435. DOI: 10.1038/nm.4000.Childs B., Durik M., Baker D., van Deursen J. Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nature Medicine. 2015; 21:1424-1435. DOI: 10.1038/nm.4000.Wang Y., Boerma M., Zhou D. Ionizing radiation-induced endothelial cell senescence and cardiovascular diseases. Journal of Radiation Research. 2016; 186(2): 153-161. DOI: 10.1667/RR14445.1.Wang Y., Boerma M., Zhou D. Ionizing radiation-induced endothelial cell senescence and cardiovascular diseases. Journal of Radiation Research. 2016; 186(2): 153-161. DOI: 10.1667/RR14445.1.Schultz-Hector S., Balz K. Radiation-induced loss of endothelial alkaline phosphatase activity and development of myocardial degeneration. An ultrastructural study. Laboratory Investigation; a Journal of Technical Methods and Pathology. 1994; 71(2): 252-260.Schultz-Hector S., Balz K. Radiation-induced loss of endothelial alkaline phosphatase activity and development of myocardial degeneration. An ultrastructural study. Laboratory Investigation; a Journal of Technical Methods and Pathology. 1994; 71(2): 252-260.Vieira D., Gloaguen C., Kereselidze D., Manens L., Tack K., Ebrahimian T. Gamma Low- Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner. Dose Response 2018; 16(1): 1559325818755238. DOI: 10.1177/1559325818755238.Vieira D., Gloaguen C., Kereselidze D., Manens L., Tack K., Ebrahimian T. Gamma Low- Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner. Dose Response 2018; 16(1): 1559325818755238. DOI: 10.1177/1559325818755238.Langley R., Bump E., Quartuccio S., Medeiros D., Braunhut S. Radiation-induced apoptosis in microvascular endothelial cells. The British Journal of Cancer 1997; 75: 666.Langley R., Bump E., Quartuccio S., Medeiros D., Braunhut S. Radiation-induced apoptosis in microvascular endothelial cells. The British Journal of Cancer 1997; 75: 666.Zhong G., Chen F., Bu D., Wang S., Pang Y., Tang C. Cobalt-60 gamma radiation increased the nitric oxide generation in cultured rat vascular smooth muscle cells. Life Science Journal 2004; 74(25): 3055-3063. DOI: 10.1016/j.lfs.2003.08.049.Zhong G., Chen F., Bu D., Wang S., Pang Y., Tang C. Cobalt-60 gamma radiation increased the nitric oxide generation in cultured rat vascular smooth muscle cells. Life Science Journal 2004; 74(25): 3055-3063. DOI: 10.1016/j.lfs.2003.08.049.Donato A., Morgan R., Walker A., Lesniewski L. Cellular and molecular biology of aging endothelial cells. Journal of Molecular and Cellular Cardiology. 2015; 89: 122-35. DOI: 10.1016/j.yjmcc.2015.01.021.Donato A., Morgan R., Walker A., Lesniewski L. Cellular and molecular biology of aging endothelial cells. Journal of Molecular and Cellular Cardiology. 2015; 89: 122-35. DOI: 10.1016/j.yjmcc.2015.01.021.Higashi Y., Kihara Y., Noma K. Endothelial dysfunction and hypertension in aging. Hypertension Research. 2012; 35:1039-47. DOI: 10.1038/hr.2012.138.Higashi Y., Kihara Y., Noma K. Endothelial dysfunction and hypertension in aging. Hypertension Research. 2012; 35:1039-47. DOI: 10.1038/hr.2012.138.Beausejour C., Krtolica A., Galimi F., Narita M., Lowe S., Yaswen P. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO Journal 2003; 22:4212-22. DOI: 10.1093/emboj/cdg417.Beausejour C., Krtolica A., Galimi F., Narita M., Lowe S., Yaswen P. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO Journal 2003; 22:4212-22. DOI: 10.1093/emboj/cdg417.Leach J., Black S., Schmidt-Ullrich R., Аikkelsen R. Activation of constitutive nitric-oxide synthase activity is an early signaling event induced by ionizing radiation. Journal of Biological Chemistry 2002; 277(18): 15400-15406. DOI: 10.1074/jbc.M110309200.Leach J., Black S., Schmidt-Ullrich R., Аikkelsen R. Activation of constitutive nitric-oxide synthase activity is an early signaling event induced by ionizing radiation. Journal of Biological Chemistry 2002; 277(18): 15400-15406. DOI: 10.1074/jbc.M110309200.Oesterle A., Laufs U., Liao J.K. Pleiotropic effects of statins on the cardiovascular system. Circulation Research. 2017; 120: 229-43. DOI: 10.1161/CIRCRESAHA.116.308537.Oesterle A., Laufs U., Liao J.K. Pleiotropic effects of statins on the cardiovascular system. Circulation Research. 2017; 120: 229-43. DOI: 10.1161/CIRCRESAHA.116.308537.Di Micco R., Fumagalli M., Cicalese A., Piccinin S., Gasparini P., Luise C., Schurra C., Garre M., Nuciforo P., Bensimon A., Maestro R., Pelicci P., d'Adda di Fagagna F. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 2006; 444: 638-642. DOI: 10.1038/nature05327.Di Micco R., Fumagalli M., Cicalese A., Piccinin S., Gasparini P., Luise C., Schurra C., Garre M., Nuciforo P., Bensimon A., Maestro R., Pelicci P., d'Adda di Fagagna F. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 2006; 444: 638-642. DOI: 10.1038/nature05327.Epperly M., Gretton J., DeFilippi S., Greenberger J., Sikora C., Liggitt D., Koe, G., Greenberger J. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutaseplasmid/liposome (SOD2-PL) gene therapy. Journal of Radiation Research. 2001; 155:2-14.Epperly M., Gretton J., DeFilippi S., Greenberger J., Sikora C., Liggitt D., Koe, G., Greenberger J. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutaseplasmid/liposome (SOD2-PL) gene therapy. Journal of Radiation Research. 2001; 155:2-14.Epperly M., Kagan V., Sikora C., Gretton J., Defilippi S., Bar-Sagi D. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. International Journal of Cancer. 2001; 96(4): 221-31.Epperly M., Kagan V., Sikora C., Gretton J., Defilippi S., Bar-Sagi D. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. International Journal of Cancer. 2001; 96(4): 221-31.Pitt B. Effects of ACE inhibitors on endothelial dysfunction: unanswered questions and implications for further investigation and therapy. Cardiovasc Drugs Ther. 1996; 10(4): 469-73.Pitt B. Effects of ACE inhibitors on endothelial dysfunction: unanswered questions and implications for further investigation and therapy. Cardiovasc Drugs Ther. 1996; 10(4): 469-73.Patarroyo Aponte M.M., Francis G.S. Effect of angiotensinconverting enzyme inhibitors and angiotensin receptor antagonists in atherosclerosis prevention. Curr Cardiol Rep. 2012; 14(4): 433- 442.Patarroyo Aponte M.M., Francis G.S. Effect of angiotensinconverting enzyme inhibitors and angiotensin receptor antagonists in atherosclerosis prevention. Curr Cardiol Rep. 2012; 14(4): 433- 442.Robbins M., Diz D. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. International Journal of Radiation Oncology Biology Physics. 2006; 64(1): 6-1210. DOI: 10.1016/j.ijrobp.2005.08.033.Robbins M., Diz D. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. International Journal of Radiation Oncology Biology Physics. 2006; 64(1): 6-1210. DOI: 10.1016/j.ijrobp.2005.08.033.Robbins M., Hopewell J. Physiological factors effecting renal radiation tolerance: a guide to the treatment of late effects. The British Journal of Cancer. 1986; 7: 265-7.Robbins M., Hopewell J. Physiological factors effecting renal radiation tolerance: a guide to the treatment of late effects. The British Journal of Cancer. 1986; 7: 265-7.Davis T., Landauer M., Mog S., Barshishat-Kupper M., Zins S., Amare M. Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation. Experimental Hematology. 2010; 38(4): 270-81. DOI: 10.1016/j.exphem.2011.02.006.Davis T., Landauer M., Mog S., Barshishat-Kupper M., Zins S., Amare M. Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation. Experimental Hematology. 2010; 38(4): 270-81. DOI: 10.1016/j.exphem.2011.02.006.Kma L., Gao F., Fish B., Moulder J., Jacobs E., Medhora M. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. Journal of Radiation Research. 2012; 53(1):10-7.Kma L., Gao F., Fish B., Moulder J., Jacobs E., Medhora M. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. Journal of Radiation Research. 2012; 53(1):10-7.Medhora M., Gao F., Jacobs E., Moulder J. Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology. 2012; 17(1): 66-71. DOI: 10.1111/j.1440-1843.2011.02092.x.Medhora M., Gao F., Jacobs E., Moulder J. Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology. 2012; 17(1): 66-71. DOI: 10.1111/j.1440-1843.2011.02092.x.Ward W., Kim Y., Molteni A., Solliday N. Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme. International Journal of Radiation Oncology Biology Physics. 1988; 15(1): 135-40.Ward W., Kim Y., Molteni A., Solliday N. Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme. International Journal of Radiation Oncology Biology Physics. 1988; 15(1): 135-40.Ward W., Molteni A., Ts’ao C., Hinz J. The effect of captopril on benign and malignant reactions in irradiated rat skin. The British Journal of Radiology. 1990; 63(749): 349-54. DOI: 10.1259/0007-1285-63-749-349.Ward W., Molteni A., Ts’ao C., Hinz J. The effect of captopril on benign and malignant reactions in irradiated rat skin. The British Journal of Radiology. 1990; 63(749): 349-54. DOI: 10.1259/0007-1285-63-749-349.Cohen E., Fish B., Moulder J. Treatment of radiation nephropathy with ACE inhibitors. Journal of Radiation Research. 1992; 132(3): 346-50.Cohen E., Fish B., Moulder J. Treatment of radiation nephropathy with ACE inhibitors. Journal of Radiation Research. 1992; 132(3): 346-50.Cohen E., Irving A., Drobyski W., Klein J., Passweg J., Talano J. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. International Journal of Radiation Oncology Biology Physics. 2008; 70(5): 1546-51. DOI: 10.1016/j.ijrobp.2007.08.041.Cohen E., Irving A., Drobyski W., Klein J., Passweg J., Talano J. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. International Journal of Radiation Oncology Biology Physics. 2008; 70(5): 1546-51. DOI: 10.1016/j.ijrobp.2007.08.041.Charrier S., Michaud A., Badaoui S., Giroux S., Ezan E., Sainteny F. Inhibition of angiotensin I-converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells. Blood. 2004; 104(4): 978-85. DOI: 10.1182/blood-2003-11-3828.Charrier S., Michaud A., Badaoui S., Giroux S., Ezan E., Sainteny F. Inhibition of angiotensin I-converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells. Blood. 2004; 104(4): 978-85. DOI: 10.1182/blood-2003-11-3828.Hu P., Li B., Zhang W., Li Y., Li G., Jiang X. AcSDKP regulates cell proliferation through the PI3KCA/Akt signaling pathway. PLoS ONE. 2013; 8(11): e79321. DOI: 10.1371/journal.pone.0079321.Hu P., Li B., Zhang W., Li Y., Li G., Jiang X. AcSDKP regulates cell proliferation through the PI3KCA/Akt signaling pathway. PLoS ONE. 2013; 8(11): e79321. DOI: 10.1371/journal.pone.0079321.Chisi J., Briscoe C., Ezan E., Genet R., Riches A., Wdzieczak-Bakala J. Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation. British Journal of Haematology. 2000; 109(3): 563-70.Chisi J., Briscoe C., Ezan E., Genet R., Riches A., Wdzieczak-Bakala J. Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation. British Journal of Haematology. 2000; 109(3): 563-70.Day R., Davis T., Barshishat-Kupper M., McCart E., Tipton A., Landauer M. Enhanced hematopoietic protection from radiation by the combination of genistein and captopril. International Journal of Pharmacology. 2013; 15(2): 348-56. DOI: 10.1016/j.intimp.2012.12.029.Day R., Davis T., Barshishat-Kupper M., McCart E., Tipton A., Landauer M. Enhanced hematopoietic protection from radiation by the combination of genistein and captopril. International Journal of Pharmacology. 2013; 15(2): 348-56. DOI: 10.1016/j.intimp.2012.12.029.Moon C., Krawczyk M., Paik D., Coleman T., Brines M., Juhaszova M. Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. Journal of Pharmacology and Experimental Therapeutics. 2006; 316: 999-1005. DOI: 10.1124/jpet.105.094854.Moon C., Krawczyk M., Paik D., Coleman T., Brines M., Juhaszova M. Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. Journal of Pharmacology and Experimental Therapeutics. 2006; 316: 999-1005. DOI: 10.1124/jpet.105.094854.Um M., Gross A., Lodish H. A “Classical” homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells. Cellular Signalling. 2007; 19: 634- 45. DOI: 10.1016/j.cellsig.2006.08.014.Um M., Gross A., Lodish H. A “Classical” homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells. Cellular Signalling. 2007; 19: 634- 45. DOI: 10.1016/j.cellsig.2006.08.014.Assaraf M., Diaz Z., Liberman A., Miller W., Jr., Arvanitakis Z., Li Y. Brain erythropoietin receptor expression in Alzheimer disease and mild cognitive impairment. Journal of Neuropathology & Experimental Neurology. 2007; 66: 389-98. DOI: 10.1097/nen.0b013e3180517b28.Assaraf M., Diaz Z., Liberman A., Miller W., Jr., Arvanitakis Z., Li Y. Brain erythropoietin receptor expression in Alzheimer disease and mild cognitive impairment. Journal of Neuropathology & Experimental Neurology. 2007; 66: 389-98. DOI: 10.1097/nen.0b013e3180517b28.Palazzuoli A., Silverberg D., Iovine F., Capobianco S., Giannotti G., Calabro A. Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. American Heart Journal. 2006; 152:1096-15. DOI: 10.1016/j.ahj.2006.08.005.Palazzuoli A., Silverberg D., Iovine F., Capobianco S., Giannotti G., Calabro A. Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. American Heart Journal. 2006; 152:1096-15. DOI: 10.1016/j.ahj.2006.08.005.Anagnostou A., Lee E., Kessimian N., Levinson R., Steiner M. Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proceedings of the National Academy of Sciences. 1990; 87: 5978-82.Anagnostou A., Lee E., Kessimian N., Levinson R., Steiner M. Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proceedings of the National Academy of Sciences. 1990; 87: 5978-82.Catlin D., Breidbach A., Elliott S., Glaspy J. Comparison of the isoelectric focusing patterns of darbepoetin alfa, recombinant human erythropoietin, and endogenous erythropoietin from human urine. Clinical Chemistry. 2002; 48: 2057-9.Catlin D., Breidbach A., Elliott S., Glaspy J. Comparison of the isoelectric focusing patterns of darbepoetin alfa, recombinant human erythropoietin, and endogenous erythropoietin from human urine. Clinical Chemistry. 2002; 48: 2057-9.Shabelnikova A.S. Correction of ischemic damage to the retina on application of pharmacological preconditioning of recombinant erythropoietin. Research result: pharmacology and clinical pharmacology. 2016; 2(2): 67-90.Shabelnikova A.S. Correction of ischemic damage to the retina on application of pharmacological preconditioning of recombinant erythropoietin. Research result: pharmacology and clinical pharmacology. 2016; 2(2): 67-90.Denisiuk T.A. Pharmacotherapeutic strategies for endothelial dysfunction correction with use of statines in syndrome of systemic inflammatory response. Research Result: Pharmacology and Clinical Pharmacology. 2017; 3(4): 35-77. DOI: 10.18413/2313-8971-2017-3-4-35-77.Denisiuk T.A. Pharmacotherapeutic strategies for endothelial dysfunction correction with use of statines in syndrome of systemic inflammatory response. Research Result: Pharmacology and Clinical Pharmacology. 2017; 3(4): 35-77. DOI: 10.18413/2313-8971-2017-3-4-35-77.Brunner S., Winogradow J., Huber B., Zaruba M.M., Fischer R., David R. Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR- 4/SDF-1 axis. FASEB Journal. 2009; 23: 351-61. DOI: 10.1096/fj.08-109462.Brunner S., Winogradow J., Huber B., Zaruba M.M., Fischer R., David R. Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR- 4/SDF-1 axis. FASEB Journal. 2009; 23: 351-61. DOI: 10.1096/fj.08-109462.Lin J., Chen Y., Chiang H., Ma M. Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: role of erythropoietin on progenitor cell mobilization. The Journal of Physiology. 2008; 586: 5757-69. DOI: 10.1113/jphysiol.2008.160887.Lin J., Chen Y., Chiang H., Ma M. Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: role of erythropoietin on progenitor cell mobilization. The Journal of Physiology. 2008; 586: 5757-69. DOI: 10.1113/jphysiol.2008.160887.Ribeiro M., Silva A., Rodrigues J., Naia L., Rego A. Oxidizing effects of exogenous stressors in Huntington's disease knock-in striatal cells-protective effect of cystamine and creatine. Toxicological Sciences. 2013; 136: 487-499. DOI 10.1093/toxsci/kft199.Ribeiro M., Silva A., Rodrigues J., Naia L., Rego A. Oxidizing effects of exogenous stressors in Huntington's disease knock-in striatal cells-protective effect of cystamine and creatine. Toxicological Sciences. 2013; 136: 487-499. DOI 10.1093/toxsci/kft199.Borrell-Pages M., Canals J., Cordelieres F., Parker J., Pineda J., Grange G. Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase. The Journal of Clinical Investigation. 2006; 116: 1410-1424. DOI 10.1172/JCI27607.Borrell-Pages M., Canals J., Cordelieres F., Parker J., Pineda J., Grange G. Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase. The Journal of Clinical Investigation. 2006; 116: 1410-1424. DOI 10.1172/JCI27607.Aleman M., Holle L., Stember K., Devette C., Monroe D., Wolberg A. Cystamine preparations exhibit anticoagulant activity. PLoS One. 2015; 10(4): e0124448. DOI 10.1371/journal.pone.0124448.Aleman M., Holle L., Stember K., Devette C., Monroe D., Wolberg A. Cystamine preparations exhibit anticoagulant activity. PLoS One. 2015; 10(4): e0124448. DOI 10.1371/journal.pone.0124448.Lee F., Sun C., Sung P., Chen K., Chua S., Sheu J., Chung S., Chai H., Chen Y., Huang T., Huang C., Li Y., Luo C., Yip H. Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice. Journal of Pineal Research. 2018; 127: 201- 1440. DOI 10.1111/jpi.12489.Lee F., Sun C., Sung P., Chen K., Chua S., Sheu J., Chung S., Chai H., Chen Y., Huang T., Huang C., Li Y., Luo C., Yip H. Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice. Journal of Pineal Research. 2018; 127: 201- 1440. DOI 10.1111/jpi.12489.Carrillo-Vico A, Lardone P. J, Alvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero J. Melatonin: buffering the immune system. International Journal of Molecular Sciences. 2013; 14: 8638-8683. DOI 10.3390/ijms14048638.Carrillo-Vico A, Lardone P. J, Alvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero J. Melatonin: buffering the immune system. International Journal of Molecular Sciences. 2013; 14: 8638-8683. DOI 10.3390/ijms14048638.Baker J., Kimpinski K. Role of melatonin in blood pressure regulation: An adjunct anti- hypertensive agent. Clinical and Experimental Pharmacology and Physiology. 2018; 10: 1440-1681. DOI 10.1111/1440-1681.12942.Baker J., Kimpinski K. Role of melatonin in blood pressure regulation: An adjunct anti- hypertensive agent. Clinical and Experimental Pharmacology and Physiology. 2018; 10: 1440-1681. DOI 10.1111/1440-1681.12942.Leach J., Van Tuyle G., Lin P., Schmidt-Ullrich R., Mikkelsen R. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Research. 2001; 61(10): 3894-3901.Leach J., Van Tuyle G., Lin P., Schmidt-Ullrich R., Mikkelsen R. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Research. 2001; 61(10): 3894-3901.Mihandoost E., Shirazi A. Can melatonin help us in radiation oncology treatments? Biomed Res Int. 2014: 578137. DOI 10.1155/2014/578137.Mihandoost E., Shirazi A. Can melatonin help us in radiation oncology treatments? Biomed Res Int. 2014: 578137. DOI 10.1155/2014/578137.Khan S., Adhikari J., Rizvi M., Chaudhury N. Radioprotective potential of melatonin against Co γ-ray-induced testicular injury in male C57BL/6 mice. Journal of Biomedical Science. 2015; 22: 1-15. DOI 10.1186/s12929-015-0156-9.Khan S., Adhikari J., Rizvi M., Chaudhury N. Radioprotective potential of melatonin against Co γ-ray-induced testicular injury in male C57BL/6 mice. Journal of Biomedical Science. 2015; 22: 1-15. DOI 10.1186/s12929-015-0156-9.Ma Z., Yang Y., Fan C., Han J., Wang D., Di S. Melatonin as a potential anticarcinogen for non-small-cell lung cancer. Oncotarget. 2016; 7(29): 46768-46784. DOI 10.18632/oncotarget.8776.Ma Z., Yang Y., Fan C., Han J., Wang D., Di S. Melatonin as a potential anticarcinogen for non-small-cell lung cancer. Oncotarget. 2016; 7(29): 46768-46784. DOI 10.18632/oncotarget.8776.Chakrabarti S., Morton J.S., Davidge S.T. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol. 2014; 30(7): 705-12. DOI 10.1016/j.cjca.2013.08.006.Chakrabarti S., Morton J.S., Davidge S.T. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol. 2014; 30(7): 705-12. DOI 10.1016/j.cjca.2013.08.006.

The authors declare that there are no conflicts of interest present.