Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 21, Art. 1 (pp. 1-10)    |    2020       

»

Experimental evaluation of radioprotective efficacy of heparin in experiments on mice

Branch of the S.M. Kirov Military Medical Academy, Moscow, Russia
First St. Petersburg State Medical University named after academician I.P. Pavlova of the Ministry of Health of the Russian Federation

Brief summary

The study was aimed at the experimental evaluation of the radioprotective efficacy of heparin and estimation of the possible mechanisms of its radioprotective effect. Experimental studies were performed on male outbred mice, BALB/c mice, and hybrids of the first generation of line mice (CBA x C57Bl), which were subjected to acute total gamma irradiation. Heparin was administered intraperitoneally at a dose of 250 U / kg 3 days before irradiation. The radioprotector cystamine was used as a reference preparation; it was administered intraperitoneally at a dose of 150 mg / kg 20 minutes before irradiation. The estimation of efficacy of heparin and cystamine was based on the 30-day survival rate and average life expectancy of dead animals, as well as calculating the dose modifying factor. To reveal possible mechanisms of radioprotective effects of heparin the thymus mass, number of leukocytes and colony formation units (CFU) in peripheral blood and bone marrow were studied. It was found that cystamine exhibits high and almost identical radioprotective efficacy in all types of mice, while heparin has a lower radioprotective effect, which was manifested by an increase in survival rate only in BALB/c radiosensitive mice and outbred white mice. Heparin has revealed a stimulatory effect on migration of haemopoietic cells: injection of heparin doubles the number of CFU in peripheral blood of BALB/c mice and reliably decreases it in bone marrow. Possible mechanisms of radioprotective action of heparin based on stimulation of hematopoiesis and increase of nonspecific resistance of the organism are discussed.


Key words

irradiation, heparin, cystamine, radioprotector, survival rate, hemopoiesis.

Reference list

1. Argytinskaya S.V., Salganik R.I. Zashitnoe deistvie polianionov v processe rentgenovskogo letalnogo oblycheniya mishei // Radiobiologiya. - 1963. - T. 3, ? 2. - S. 276-279.


2. Grebenuk A.N., Aksenova N.V., Zacepin V.V. i dr. Vliyanie preparata B-190 i interleikina-1β na dinamiky kolichestva kletok perifericheskoi krovi i fynkcionalnii statys neitrofilov oblychennih mishei // Radiacionnaya biologiya. Radioekologiya. - 2013. - T. 53, ? 3. - S. 290-295.


3. Grebenuk A.N., Gladkih V.D. Sovremennoe sostoyanie i perspektivi razrabotki lekarstvennih sredstv dlya profilaktiki i rannei terapii radiacionnih porajenii // Radiacionnaya biologiya. Radioekologiya. - 2019. - T. 59, ? 2. - S. 132-149.


4. Legeza V.I., Grebenuk A.N., Drachev I.S. Radiomitigatori: klassifikaciya, farmakologicheskie svoistva, perspektivi primeneniya // Radiacionnaya biologiya. Radioekologiya. - 2019. - T. 59, ? 2. - S. 161-169.


5. Legeza V.I., Grebenuk A.N., Zacepin V.V. Medicinskaya zashita pri radiacionnih avariyah: nekotorie itogi i yroki Chernobilskoi katastrofi // Radiac. biologiya. Radioekologiya. - 2011. - T. 51, ? 1. - S. 70-75.


6. Lykashin B.P., Grebenuk A.N., Zacepin V.V. Geparin i faktori rosta // Citokini i vospalenie. - 2009. - T. 8, ? 3. - S. 16-21.


7. Lykashin B.P., Grebenuk A.N. Glukozaminglikani: biologicheskaya rol v sisteme mejkletochnih vzaimodeistvii // Yspehi sovremennoi biologii. - 2010. - T. 130, ? 2. - S. 165-179.


8. Halimov U.Sh., Grebenuk A.N., Karamyllin M.A. i dr. Sovremennie vozmojnosti okazaniya terapevticheskoi pomoshi pri vozniknovenii massovih sanitarnih poter radiacionnogo profilya // Voenno-medicinskii jyrnal. - 2012. - T. 333, ? 2. - C. 24-31.


9. Beneš S., Rotreklova E. Rate of synthesis and stability of DNA in bone marrow in heparin // Fol. Biol. - 1970. - Vol. 16. - P. 196-204.


10. Brűckner V. Zum Wirkungsmechanismus des Heparins bei der Strahlenresistenzerhemmung von Mausen // Strahlentherapie. - 1976. - Vol. 151. - P. 347-350.


11. Chaubal K.A., Codbole C.S. Radiobiological effect of heparin in Swiss mice, human omnion cells and E. coli bacteria irradiated with 60Co rays // Radit. Environ. Biophys. - 1983. - Vol. 22. - P. 281-291.


12. Forsberg E., Kjellen L. Heparan sulfate: lessons from knockout mice // J. Clin. Invest. 2001. - Vol. 108, ? 2. - P. 175-180.


13. Grebenyuk A., Zatsepin V., Aksenova N., Timoshevsky A. Effects of early therapeutic administration of interleukin-1β on survival rate and bone marrow haemopoiesis in irradiated mice // Acta Medica (Hradec Kralove). - 2010. - Vol. 53, ? 4. - P. 221-224.


14. Harmer N.S. Insights into the role of heparan sulphate in fibroblast growth factor signaling // Biochem. Soc. Trans. - 2006. - Vol. 34, ? 3. - P. 442-448.


15. Kowaliuk M., Schröder I., Kuess P., Dörr W. Heparin treatment mitigates radiation-induced oral mucositis in mice by interplaying with repopulation processes // Strahlentherapie und Onkologie. - 2019. - Vol. 195, Is. 6. - P. 534-543.


16. Kuna P., Dostál M., Neruda O. et al. Radioprotective effects of amifostine (WR-2721) or cystamine in single whole body fission neutrons irradiated rats // J. Appl. Biomed. - 2004. - Vol. 2, ? 1. - P. 43-49.


17. Lane D.H., Adams L. Non-anticoagulant uses of heparin // N. Engl. J. Med. - 1993. - Vol. 329. - P. 129-130.


18. Micklem H.S., Ogden D.A. Migration of haemopoietic stem cells between bones // Abstracts of 6th International Congress of Radiation Research. - Evian, 1970. - P. 146.


19. Mulloy B., Rider C.C. Cytokines and proteoglycans: an introductory overview // Biochem. Soc. Trans. - 2006. - Vol. 34. - P. 409-413.


20. Oduah E, Linhardt R, Sharfstein S. Heparin: past, present, and future // Pharmaceuticals (Basel). - 2016. - Vol. 9, ? 3. - P. 38.


21. Singh V.K., Hanlon B.K., Santiago P.T., Seed T.M. A review of radiation countermeasures focusing on injury-specific 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, ? 9. - P. 885-906.


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


23. Taylor K.R., Gallo R.L. Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation // JASEB J. - 2006. - Vol. 20. - P. 4-22.


24. Till J.E., McCulloch E.A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells // Rad. Res. - 1961. - Vol. 14, ? 2. - P. 213-222.


25. Wang J., Zheng H., Qui X. et al. Modulation of the intestinal response to ionizing radiation by anticoagulant and non-anticoagulant heparins // Thromb. Haemost. - 2005. - Vol. 94, ? 5. - P. 1054-1059.

Журнал основан 16 ноября 2000г.
Выдано Министерством РФ по делам печати, телерадиовещания и средств массовых коммуникаций

(c) Перепечатка материалов сайта Medline.Ru возможна только с письменного разрешения редакции