RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2016 : vol. 25, No. 1 : Hematopoietic parameters in acute irradiated mice treated with copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine

Hematopoietic parameters in acute irradiated mice treated with copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine

«Radiation and Risk», 2016, vol. 25, No. 1, pp.65-75

Authors

Panov A.V.1 – Director of Science Dep., C. Sc., Chem. JSC «Institute of Pharmaceutical Technology», Moscow, Russia.
Kedik S.A.1 – General Manager, D.Sc., Tech., Prof. JSC «Institute of Pharmaceutical Technology», Moscow, Russia.
Yakovleva T.A.1 – Researcher. JSC «Institute of Pharmaceutical Technology», Moscow, Russia.
Izmestieva O.S. – Lead. Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.
Selivanova E.I. – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: (484) 399-71-88; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Zhavoronkov L.P. – Deputy Director, D.Sc., Med. A. Tsyb MRRC, Obninsk, Russia.

Abstract

In framework of this work we obtained the experimental data on hematopoiesis and viability of mice after acute irradiation with 7 and 8.5 Gy and measured the morphofunctional readings for peripheral blood cells and bone marrow under this condition. We investigated anti-radiation properties of Nvinylpyrrolidone and 2-methyl-5-vinylpyridine copolymer using the intramuscular injection (dose 500 mg/kg) in two experimental scenarios: 20 minutes before and 20 minutes after irradiation with different intensity. We demonstrated anti-radiation effectiveness of copolymer compound using 280 C57B1/6j line male mice. The average life expectancy was increased by 40% for mice irradiated with absolutely lethal dose (8.5 Gy) .Copolymer increases bone marrow cellularity and absolute number of hematopoietic stem cells (7 Gy) in 5-6 time and leads to a significant release of mature and proliferating cells into blood stream. This study shows that the N-vinylpyrrolidone and 2-methyl- 5-vinylpyridine copolymer is radiomitigator, which acts via the activation of a number of proinflammatory signaling pathways and stimulates the secretion of hematopoietic growth factors.

Key words
Acute irradiation, copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine, automatic Hematology analyzer, flow cytometer, mouse lines C57Bl/6j, leukocytes, granulocytes, hematopoietic stem cells, catalase, superoxide dismutase.

References

1. Plateh N.A., Vasil'ev A.E. Fiziologicheski aktivnye polimery [Physiologically active polymers]. Moscow, Himiya, 1986. 296 p.

2. Sidel'kovskaya F.P. Himiya N-vinilpirrolidona i ego polimerov [N-vinylpyrrolidone сhemicals and зolymers]. Moscow, Nauka, 1970. 150 p.

3. Shtil'man M.I. Polimery mediko-biologicheskogo naznacheniya [Polymers medical and biological applications]. Moscow, IKC Akademkniga, 2006. 400 p.

4. Alekseev K.V., Grickova I.A., Kedik S.A. Polimery dlya farmacevticheskoj tekhnologii [Polymers for pharmaceutical technology]. Moscow, ZAO IFT, 2011. 512 p.

5. Zhavoronkov L.P. Vliyanie na sistemu krovi i radiozashchitnaya ehffektivnost' sinteticheskih ionogennyh polimerov. Diss. kand. med. nauk [Effects on the blood system and radioprotective efficacy of synthetic ionic polymers. Can. med. sci. diss.]. Moscow, 1979. 105 p.

6. Kalistratov V.G., Kedik S.A., Svergun V.I. Protivoluchevye i drugie biologicheskie svojstva sopolimera 2- metil-5-vinilpiridina i N-vinilpirrolidona [Antiradiation and other biological properties of the copolymer of 2- methyl-5-vinylpyridine and N-vinylpyrrolidone]. Medicinskaya radiologiya – Medical Radiology, 1993, vol. 38, no. 10, pp. 21-25.

7. Zhavoronkov L.P. Osnovy prikladnoj mediko-biologicheskoj statistiki [Fundamentals of applied biomedical statistics]. Obninsk, FGBU MRNC Minzdravsocrazvitiya Rossii, 2012. 60 p.

8. Kedik S.A., Panov A.V., Zajcev M.A., Cherta Yu.V. Sopolimery 2-metil-5-vinilpiridina i N-vinilpirrolidona, obladayushchie svojstvami aktivatorov fagocitoza [Copolymers of 2-methyl-5-vinylpyridine and Nvinylpyrrolidone having properties activators phagocytosis]. Patent RF, no. 2430933, 2011.

9. Kedik S.A., Svergun V.I., Cherta Yu.V., Yarcev E.I., Panov A.V. Sopolimery na osnove N-vinilpirrolidona [Copolymers of N-vinylpyrrolidone]. Patent RF, no. 2415876, 2011.

10. Kedik S.A., Vorozhcova S.V., Yarcev E.I., Sakaeva I.V., Kochkina (Cherta) Yu.V., Panov A.V. Vliyanie Sovidona na citogeneticheskie izmeneniya v kletkah ehpiteliya rogovicy. povrezhdennyh radiacionnym vozdejstviem [Influence Sovidona on cytogenetic changes in corneal epithelium cells damaged by radiation exposure]. Voprosy biologicheskoi medicinskoi i farmacevticheskoi khimii – Problems of Biological Medical and Pharmaceutical Chemistry, 2012, no. 8, pp. 32-35.

11. Kedik S.A., Panov A.V., Sakaeva I.V., Kochkina (Cherta) Yu.V., Eremin D.V., Suslov V.V. Sintez i radioprotektornaya aktivnost' sopolimerov N-vinilpirrolidona i 2-metil-5-viniltetrazola [Synthesis and radioprotective activity of copolymers of vinylpyrrolidone and N-2-methyl-5-vinyltetrazole]. Khimikofarmacevticheskij zhurnal – Pharmaceutical Chemistry Journal, 2012, vol. 46, no. 12, pp. 30-33.

12. Kedik S.A., Panov A.V., Sakaeva I.V., Kochkina (Cherta) Yu.V., Eremin D.V., Suslov V.V. Sintez i molekulyarno-massovye harakteristiki sopolimerov N-vinilpirrolidona i 2-metil-5-vinilpiridina [Synthesis and molecular weight characteristics of the copolymers of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine]. Khimiko-farmacevticheskij zhurnal – Pharmaceutical Chemistry Journal, 2012, vol. 46, no. 8, pp. 110-113.

13. Kalistratova V.S., Ivanov A.A., Nisimov P.G. K probleme profilaktiki pri pomoshchi immunomodulyatorov otdalennyh posledstvai, vyzvannyh vnutrennim oblucheniem [By preventing the problem of using immunomodulators long-term effects caused by internal exposure]. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2001, vol. 41, no. 1, pp. 104-112.

14. Zapadnyuk I.A., Zapadnyuk V.I., Zahariya E.A., Zapadnyuk B.V. Laboratornye zhivotnye. Razvedenie, soderzhanie, ispol'zovanie v ehksperimente [Laboratory animals. Breeding, maintenance, use in the experiment]. Kiev, Vishcha shkola, 1983. 383 p.

15. Kostyuk V.A., Potapovich A.I., Kovaleva Zh.V. Prostoj i chuvstvitel'niy metod opredeleniya aktivnosti superoksiddismutazy. osnovannyj na reakcii okisleniya kvercetina [A simple and sensitive method for determining the activity of superoxide dismutase. based on the reaction of oxidation of quercetin]. Voprosy meditsinskoy khimii – Problems of Medical Chemistry, 1990, vol. 36, no. 2, pp. 88-91.

16. Korolyuk M.A., Ivanova L.I., Majorova I.G., Tokarev V.E. Metod opredeleniya aktivnosti katalazy [The method for determining the activity of catalase]. Laboratornoe delo – Laboratory Case, 1988, no. 1, pp. 16-19.

17. Semina O.V., Semenets T.N., Zamulaeva I.A., Selivanova E.I., Iljina T.P., Maliutina Y.V., Deigin V.I., Saenko A.S. Dipeptide thymodepressin inhibits migration of CD34+ cells from the bone marrow into peripheral blood during tumor growth. Bulletin of Experimental Biology and Medicine, 2008, vol. 146, no. 1, pp. 96-99.

18. Kedik S.A., Fedorov E.K., Svergun V.I., Gavrilov V.A., Zubairov M.M. Sopolimery 2-metil-5-vinilpiridina i N-vinilpirrolidona, obladayushchie immunostimuliruyushchim dejstviem [Copolymers of 2-methyl-5- vinylpyridine and N-vinylpyrrolidone having immunostimulating activity]. Copyright certificate RF, no. 2000004, 1993.

19. Vasin M.V. Klassifikaciya protivoluchevyh sredstv kak otrazhenie sovremennogo sostoyaniya i perspektivy razvitiya radiacionnoj farmakologii [Classification of radioprotective agents as a reflection of the current state and prospects of development of radiation pharmacology]. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2013, vol. 53, no. 5, pp. 459-467.

20. Shannon M.F., Coles L.S., Vadas M.A., Cockerill P.N. Signals for activation of the GM-CSF promoter and enhancer in T cell. Critical Review of Immunology, 1997, vol. 17, pp. 301-323.

21. Bogomazov S.D. Antikomplementarnye svojstva poliehlektrolitov i ih zashchitnaya ehffektivnost' pri radiacionnom porazhenii immuniteta. Diss. kand. med. nauk [Anti complementary properties of polyelectrolyte and protective efficacy in radiation injury immunity. Can. med. sci. diss.]. Moscow, 1978. 198 p.

Full-text article (in Russian)