RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2019 : vol. 28, No. 3 : Radioprotective effect of creatine on DNA damage in peripheral blood mononuclear cells and adaptive properties of brain and liver creatine-creatine

Radioprotective effect of creatine on DNA damage in peripheral blood mononuclear cells and adaptive properties of brain and liver creatine-creatine

«Radiation and Risk», 2019, vol. 28, No. 3, pp.119-131

DOI: 10.21870/0131-3878-2019-28-3-119-131

Authors

Nersesova L.S. – Lead. Researcher, C. Sc., Biol. Contacts: 7 Hasratyan str., Yerevan, Republic of Armenia, 0014. Tel.: +37410 287506; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Petrosyan M.S. – Research Assistant, Lead. Specialist of the Committee on Nuclear Safety Regulation of the Republic of Armenia.
Babayan N.S. – Researcher, C. Sc., Biol.
Tadevosyan G.L. – Research Assistant.
Khondkaryan L.G. – Research Assistant.
Akopian J.I. – Head of Lab., D.Sc., Biol., Prof., Corr. member of NAS RA, Honoured Worker of Science of NAS RA. IMB of NAS RA.

Institute of Molecular Biology of NAS RA, Yerevan, Armenia.

Abstract

A substantial body of research data demonstrate nueroprotective effect of creatine (Cr), it exerts beneficial effect in nuerodegenerative and myopathic diseases, aging and UV-induced injuries due to its antiapoptotic and antioxidant properties. The previous research data demonstrate that oxidative stress plays the main role in a pathophysiology of the disorders. Because oxidative stress is one of the main mechanisms underlying cellular response to ionizing radiation, featuring the DNA and enzyme proteins as its primary targets, exogenous creatine, dietary supplement, may exert radioprotective effect. The purpose of the study is to evaluate radioprotective efficacy of exogenous Cr on DNA damage in peripheral blood mononuclear cells and adaptive properties Cr/CK system in the brain and liver of rats, exposed to the single whole-body X-ray irradiation at dose of 4.5 Gy. Cr is shown to exert protective effect, Cr/CK system in the brain and liver and stimulate adaptive properties of the system. The amount of Cr and CK in the brain is higher than in the liver. The brain is more susceptible to radiation injury than the liver, a the same time it easier adapts to radiation stress. During the first 24 hours after irradiation the nearly twofold decrease in the number of radiation-induced injuries to DNA is registered. To the 7th day after irradiation the number of injuries to DNA in irradiated animals come up to the number in control rats, this level has remained unchanged to the 15th days after the exposure. The study results demonstrate efficacy of Cr as radioprotector and its capacity to improve adaptability of the rats to X-ray irradiation.

Key words
X-ray irradiation, radioprotective effect, creatine, creatine kinase, DNA damage, mononuclear cells of peripheral blood cells, brain, liver, adaptation, rats.

References

1. Sweeney T.R. A survey of compounds from the antiradiation drug development program of the U.S. Army Medical Research and development command. Washington, Government Printing office, 1979, pp. 308-318.

2. Little J.B. Cellular, molecular and carcinogenic effects of radiation. Hematol. Oncol. Clin., 1993, vol. 7, no. 2, pp. 337-352.

3. Wallimann T., Tokarska-Schlattner M., Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids, 2011, vol. 40, no. 5, pp. 1271-1296.

4. Nersesova L.S. Role of creatine kinase and its substrates in the central nervous system in norm and in various pathologies. J. Evol. Biochem. Physiol., 2011, vol. 47, no. 2, pp. 140-150.

5. Lawler J.M., Barnes W.S., Wu G., Song W., Demaree S. Direct antioxidant properties of creatine. Biochem. Biophys. Res. Commun., 2002, vol. 290, no. 2, pp. 47-52.

6. Sestili P., Martinelli C., Bravi G., Picolli G., Curci R. Creatine supplementation affords cytoprotection in oxidatively injured cultured mammalian cells via direct antioxidiant activity. Free Radic. Biol. Med., 2006, vol. 40, no. 5, pp. 837-849.

7. Alcaide P., Merinero B., Ruiz-Sala P. Defining the pathogenicity of creatine deficiency syndrome. Hum. Mutat., 2011, vol. 32, no. 3, pp. 282-291.

8. Nersesova L.C., Gazaryants M.G., Mkrtshyan Z.C. Vliyaniye ioniziruyushchey radiatsii na fermentnyye aktivnosti i sostoyaniye yaderno-yadryshkovogo apparata gepatotsitov krys [Influence of Ionizing Radiation on Enzymatic Activity and State of Nucleus – Nucleolar Apparatus in Rat Hepatocytes]. Radiatsionnaya. biologiya. Radioekologiya – Radiation Biology. Radioecology, 2013, vol. 53, no. 1, pp. 55-62.

9. Petrova T.A., Lyzlova S.N. Optimizatsiya usloviy opredeleniya aktivnosti kreatinkinazy kolorimetricheskim metodom [Optimization of the conditions for determining the activity of creatine kinase by the colorimetric method]. Vestnik LGU – Bulletin of Leningrad State University, 1985, no. 24, pp. 88-90.

10. Field A. Discovering statistics using IBM SPSS statistics. Los Angeles, SAGE Publications Ltd., 2013. 2617 p.

11. Tice R.R., Andrews P., Hirai O., Singh N.P. The single cell gel (SCG) assay: an electrophoretic technique for the detection of DNA damage in individual cells. Adv. Exp. Med. Biol., 1991, vol. 283, pp. 157-164.

12. Malone J., Ullrich R. Novel radiation response genes identified in gene trapped MCF10A mammary epithelial cells. Radiat. Res., 2007, vol. 167, no. 2, pp. 176-184.

13. Aksenov M., Aksenova M., Butterfield D.A., Markesbery W.R. Protein oxidation in the brain in Alzheimer’s disease. Neuroscience, 2001, vol. 103, no. 2, pp. 373-383.

14. Qasim N., Mahmood R. Diminution of oxidative damage to human erythrocytes and lymphocytes by crea-tine: possible role of creatine in blood. Plos One, 2015, vol. 10, no. 15, pp. 1-21.

15. Shevtsov V.I., Ir’yanov Yu.M., Petrovskaya N.V., Ir’yanova T.Yu., Migalkin N.S., Ocheretina R.Yu. Metodika modelirovaniya ostroy luchevoy bolezni u krys linii Avgust [Methods of modeling acute radiation sickness in August rats]. Sovremennyye naukoyemkiye tekhnologii – Modern High Technologies, 2004, no. 1, p. 95.

16. Hatano E., Tanaka A., Iwata S., Satoh S., Kitai T., Tsunekawa S., Inomoto T., Shinohara H., Chance B., Yamaoka Y. Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase. Hepatology, 1996, vol. 24, no. 3, pp. 663-669.

17. Satoh S., Tanaka A., Hatano E., Inomoto T., Iwata S., Kitai T., Shinohara H., Tsunekawa S., Chance B., Yamaoka Y. Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy. Gastroenterology, 1996, vol. 110, no. 4, pp. 1166-1174.

18. Garau M.M., Calduch A.L., Lopez E.C. Radiobiology of the acute radiation syndrome. Rep. Pract. Oncol. Radiother., 2011, vol.16, no. 4, pp. 123-130.

19. Nouspikel T. DNA repair in differentiated cells: some new answers to old questions. Neuroscience, 2007, vol. 145, no. 4, pp. 1213-1221.

20. Petrosyan M.S., Nersesova L.S., Gazaryants M.G., Malakyan M.H., Akopian J.I. Creatine kinase effects of ionizing radiation and radioprotective potential of creatine. Proceedings of the “The BRITE (Biomarkers of Radiation In The Environment): Robust tools for risk assessment", Advanced Research Workshop. Yerevan, 2017, p. 37.

Full-text article (in Russian)