Application of Granulocyte Colony-Stimulating Factor in the Form of Pegfilgrastim in Fractionated Irradiation of Mice

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Abstract

The radioprotective efficacy of granulocyte colony-stimulating factor in the form of pegfilgrastim at fractionated irradiation was evaluated on male ICR (CD-1) mice. Mice were exposed to five daily exposures to X-rays at a dose of 2.5 Gy. Three hours after each exposure, pegfilgrastim was injected subcutaneously into mice at a dosage of 0.5 μg/g. The drug was also administered daily 3–7 days after the last irradiation. The efficacy of this therapeutic regimen was evaluated on the basis of the degree of DNA damage in spleen cells 30 min after the last irradiation, hematologic parameters – after 30 min and 3 days, Schiffbases, trieno and oxodiene conjugates in the liver – after 30 min, thymus and spleen weight, the number of karyocytes in the femur, the content of thiobarbiturate-reactive products in the liver – after 3 days, as well as on the basis of 30-day survival. The application of the therapeutic regimen under study contributed to a significant correction of irradiation-induced oxidative stress: according to the criteria of the content of Schiff bases, trieno and oxodieno conjugates, the group receiving pegfilgrastim corresponded to the intact mice, the content of thiobarbiturate-reactive products in the liver decreased relative to the irradiated control, but the parameters of intact mice were not reached. Pegfilgrastim administration did not compensate for the irradiation-induced bone marrow cell death 3 days after the last irradiation and could eventually ensure the survival of only 3 mice out of 14 individuals receiving the drug. Thus, for effective application of pegfilgrastim during fractionated irradiation at a total dose of 12.5 Gy it is necessary to increase the number of irradiation sessions with decreasing dose of each session, or to decrease the total radiation dose. Joint use of pegfilgrastim with other radioprotective drugs with other mechanisms of action is also promising.

About the authors

L. A Romodin

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia

Email: rla2904@mail.ru
Moscow, Russia

A. A Moskovskij

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia; National Research Nuclear University MEPhI

Moscow, Russia

G. O Abelev

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia

Moscow, Russia

O. V Nikitenko

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia; SSC RF Institute of Biomedical Problems, Russian Academy of Sciences

Moscow, Russia

T. M Bychkova

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia; SSC RF Institute of Biomedical Problems, Russian Academy of Sciences

Moscow, Russia

C. C Sodboev

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia

Moscow, Russia

O. S Aldoshina

State Scientific Center of the Russian Federation – Federal Medical Biophysical Center named after A.I. Burnazyan, FMBA of Russia

Moscow, Russia

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