MYELOPROTECTIVE ACTIVITY OF TWO GRANULOCYTE COLONY STIMULATING FACTORS ON MODEL OF CYTOSTATIC MYELOSUPPRESSION

Authors

  • O. O. Shevchuk Ternopil State Medical University, Ternopil
  • I. M. Todor Institute of Experimental Pathology, Oncology and Radiobiology. Kavetsky Sciences of Ukraine, Kyiv
  • K. A. Posokhova Ternopil State Medical University, Ternopil
  • Ye. O. Snezhkova RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv
  • V. G. Nikolaev RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv

DOI:

https://doi.org/10.11603/2415-8798.2017.1.7564

Keywords:

myelosuppression, melphalan, granulocyte colony stimulating factor.

Abstract

Myelosuppression during intensive chemotherapy frequently is a reason of therapy disruption and rising of patients’ lethality. Effective method for prevention and treatment of neutropenia today is granulocyte colony stimulating factor (G-CSF) drugs.

The aim of study – a comparison of myeloprotective activity of original preparation of recombinant G-CSF (rG-CSF), developed by IEPOR stuff, and officinal medication Filgrastim.

Materials and Methods. Experiments were performed on healthy inbred white rats, 200 ±20 g. Melphalan (L-PAM, Alkeran, GlaxoSmithKline) was used to cause the myelosuppression at dose of 4 mg/kg one time intravenously. Filgrastim (Neupogen, Hoffman-La Roche Ltd,Switzerland) was used as a referent-drug. Dose of G-CSF was 50 mcg/kg. Animals were randomly distributed into 4 groups: 1 – intact group; 2 – rats who got L-PAM (L-PAM); rats of group 3 and group 4 except L-PAM got Filgrastim (L-PAM + filgrastim) and rG-CSF (L-PAM + rG-CSF). Cytokine was injected subcutaneously once a day during 4 days after melphalan injection. All data were analyzed using StatSoft STATISTICA 10 software.

Results and Discussion. Melphalan caused prominent myelosuppression and thrombocytopenia: white blood cells count decreased by 75.6 %, erythrocytes count by 10.3 %, platelets count – by 59.9 %, hemoglobin level was without significant changes. Analysis of the ratio of blood cells showed that absolute count of neutrophils decreased by 53.8 % and lymphocytes – by 86.8 %.

Both preparations of G-CSF caused significant rising of white blood cells count by 57.0 % (filgrastim) and by 53.9 % (rG-CSF). Also we observe the increasing of absolute count of neutrophils by 67.0 and 61.1 % at leukocytes formula. There were no changes of the other blood cells sprouts.

Conclusions. Data of our study showed that both preparations of granulocyte colony stimulating factor demonstated significant myeloprotective effect. Ukrainian domestic preparation has the same efficacy as an officinal drug Figrastim. Such results are the base for further investigation of its efficacy and safety parameters and implementation into clinical practice.   

Author Biographies

O. O. Shevchuk, Ternopil State Medical University, Ternopil

Associate Professor of Pharmacology with Clinical Pharmacology candidate. honey. Associate Professor

I. M. Todor, Institute of Experimental Pathology, Oncology and Radiobiology. Kavetsky Sciences of Ukraine, Kyiv

Department mechanisms of anticancer therapy IYEPOR

K. A. Posokhova, Ternopil State Medical University, Ternopil

MD, PhD, DSc, professor, Pharmacology and Clinical Pharmacology Department

Ye. O. Snezhkova, RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv

Department mechanisms of anticancer therapy IYEPOR

V. G. Nikolaev, RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv

Department means and methods of sorption therapy Corr. NAS of Ukraine, Professor, Head of the Department

References

Ferlay, J., Steliarova-Foucher, E., Lortet-Tieulent, J., Rosso, S., Coebergh, J. W. W., Comber, H., … Bray, F. (2013). Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer, 49, 1374-1403. http://doi.org/10.1016/j.ejca.2012.12.027

Kovalchuk, A.Yu. (2014). Kharakterystyka sotsialno-demohrafichnoi sytuatsii ta sotsialno znachushchykh zakhvoryuvan v Ukraini [The characteristic of social-demographic situation and prevalence of the socially significant diseases in Ukraine]. Ukr. Med. Chasopys – Ukrainian Medical Magazine, 99 (1), 29-34. Retrieved from http://www.umj.com.ua/wp/wp-content/uploads/2014/02/4203.pdf?upload=

Voytenko, V.P., Pysaruk, A.V., & Koshel, N.M. (2014). Ukraina v yevropeyskomu konteksti: klasterna model smertnosti vid holovnykh prychyn [Ukraine in European context: cluster model of lethality due to main causes]. Probl. stareniya i dolgoletiya – Problems of Aging and Longevity, 23 (1), 85-95.

Bonadonna, G., Moliterni, A., Zambetti, M., Daidone, M.G., Pilotti, S., Gianni, L., & Valagussa, P. (2005). 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ (Clinical Research Ed.), 330 (7485), 217.

http://doi.org/10.1136/bmj.38314.622095.8F

Denduluri, N., Patt, D. A., Wang, Y., Bhor, M., Li, X., Favret, A. M., … Lyman, G. H. (2015). Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices. Journal of the National Comprehensive Cancer Network: JNCCN, 13 (11), 1383-1393. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26553767

Santolaya, M.E., Alvarez, A.M., Avilés, C.L., Becker, A., Mosso, C., O’Ryan, M., … Zubieta, M. (2007). Admission clinical and laboratory factors associated with death in children with cancer during a febrile neutropenic episode. The Pediatric Infectious Disease Journal, 26 (9), 794-798. http://doi.org/10.1097/INF.0b013e318124aa44

Schwenkglenks, M., Pettengell, R., Jackisch, C., Paridaens, R., Constenla, M., Bosly, A., … Leonard, R. (2011). Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients: data from the INC-EU Prospective Observational European Neutropenia Study. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, 19(4), 483-490. http://doi.org/10.1007/s00520-010-0840-y

Mócsai, A. (2013). Diverse novel functions of neutrophils in immunity, inflammation, and beyond. The Journal of Experimental Medicine, 210 (7), 1283-1299. http://doi.org/10.1084/jem.20122220

Szwajcer, D., Czaykowski, P., & Turner, D. (2011). Assessment and management of febrile neutropenia in emergency departments within a regional health authority-a benchmark analysis. Current Oncology (Toronto, Ont.), 18 (6), 280–4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22184489

Bruslova, K.M. (2013). Zastosuvannya preparatu tevahrastym u ditey z hostrymy leykemiyamy [The application of preparation tevagrastim in children with acute leukemia]. Onkolohiya – Oncology, 15 (1), 51-54.

Aapro, M., Cornes, P., & Abraham, I. (2012). Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. Journal of Oncology Pharmacy Practice, 18 (2), 171-179.

Published

2017-04-27

How to Cite

Shevchuk, O. O., Todor, I. M., Posokhova, K. A., Snezhkova, Y. O., & Nikolaev, V. G. (2017). MYELOPROTECTIVE ACTIVITY OF TWO GRANULOCYTE COLONY STIMULATING FACTORS ON MODEL OF CYTOSTATIC MYELOSUPPRESSION. Bulletin of Scientific Research, (1). https://doi.org/10.11603/2415-8798.2017.1.7564

Issue

Section

REVIEWS AND ORIGINAL RESEARCH