Myeloprotective activity of granulocyte-colony stimulating factor drugs and enterosorption in rats grafted with Guerin carcinoma

Authors

  • O. O. Shevchuk Ivan Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine,
  • I. M. Todor Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Science of Ukraine, Kyiv,
  • N. K. Rodionova Institute for Nuclear Research of National Academy of Sciences of Ukraine, Kyiv,
  • K. A. Posokhova Ivan Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine,
  • V. H. Nikolaiev R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Science of Ukraine, Kyiv,

DOI:

https://doi.org/10.14739/2310-1210.2020.1.194645

Keywords:

melphalan, granulocyte colony stimulating factor, enterosorption, rats, Guerin carcinoma

Abstract

 

The aim of this work is the study of granulocyte-colony stimulating factor (G-CSF) (officinal drug filgrastim and analogue, synthesized by IEPOR, r-GCSF) and enterosorption impact on the bone marrow of Guerin carcinoma-grafted rats with melphalan administration.

Materials and methods. The study was performed in rats grafted with Guerin carcinoma. On the 10th day after Guerin carcinoma cells implantation, melphalan was injected at a dose of 5.5 mg/kg. Drugs of G-CSF and granular carbon oral adsorbent С2 (bulk density of 0.18 g/cm3, granules 0.15–0.25 mm in diameter, total specific surface by BET of 2162 m2/g) were used for correction. Rats were sacrificed on the 17th day after Guerin carcinoma grafting, the indices of peripheral blood and myelograms were examined.

Results. It was found that single injection of alkylating cytostatic agent caused a profound destruction (hypoplasia and aplasia) of bone marrow in rats as well as a drop in leukocytes (by 95.7 %) and granulocytes (by 73.9 %) in peripheral blood. Officinal drug of G-CSF – filgrastim and enterosorbent C2 with bulk density of 0.18 g/cm3, used alone for the pathological condition correction, slightly improved indices (leukocyte count increased by 2.3 and 1.5 times, respectively), but there was only a tendency to improve the granulocyte count. Bone-marrow cellularity increased and there were some differentiating cells. The use of these drugs in combination was the most efficient compared to their separate administration. The granulocyte count in peripheral blood was almost normalized in the groups of rats received the combination of C2 enterosorbent with G-CSF (L-PAM + filgrastim + С2) and (L-PAM + r-GCSF + С2) as it was 3.5 and 3.0 times increased, respectively. The same tendency was observed in the bone marrow.

Conclusions. The results obtained indicate benefits from further study and implementation into clinics the combination of hemostimulating cytokines and enterosorption.

References

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492

Denduluri, N., Patt, D. A., Wang, Y., Bhor, M., Li, X., Favret, A. M., Morrow, P. K., Barron, R. L., Asmar, L., Saravanan, S., Li, Y., Garcia, J., & 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, 13(11), 1383–1393. https://doi.org/10.6004/jnccn.2015.0166

Taylor, S. J., Duyvestyn, J. M., Dagger, S. A., Dishington, E. J., Rinaldi, C. A., Dovey, O. M., Vassiliou, G. S., Grove, C. S., & Langdon, W. Y. (2017). Preventing chemotherapy-induced myelosuppression by repurposing the FLT3 inhibitor quizartinib. Science Translational Medicine, 9(402), Article eaam8060. https://doi.org/10.1126/scitranslmed.aam8060

Tao, J. J., Visvanathan, K., & Wolff, A. C. (2015). Long term side effects of adjuvant chemotherapy in patients with early breast cancer. The Breast, 24(Suppl. 2), S149–S153. https://doi.org/10.1016/j.breast.2015.07.035

Al-Ansari, S., Zecha, J. A. E. M., Barasch, A., de Lange, J., Rozema, F. R., & Raber-Durlacher, J. E. (2015). Oral Mucositis Induced By Anticancer Therapies. Current Oral Health Reports, 2(4), 202–211. https://doi.org/10.1007/s40496-015-0069-4

Lyman, G. H., Abella, E., & Pettengell, R. (2014). Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review. Critical Reviews in Oncology/Hematology, 90(3), 190–199. https://doi.org/10.1016/j.critrevonc.2013.12.006

Liu, W., Zhang, C. C., & Li, K. (2013). Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer. Cancer Biology & Medicine, 10(2), 92 98. https://doi.org/10.7497/j.issn.2095-3941.2013.02.005

Parkhill, A. L. (2013). Oral Mucositis and Stomatitis Associated with Conventional and Targeted Anticancer Therapy. Journal of Pharmacovigilance, 1(4), Article 1000112. https://doi.org/10.4172/2329-6887.1000112

Diamond, O. M., Turgeman, O., & Blumenfeld, Z. (2015). Minimizing the doxorubicin-Induced gonadotoxicity by sphingosine-1-phosphate analogue FTY720. American Journal of Clinical and Experimental Obstetrics and Gynecology, 2(1), 24–33. https://pdfs.semanticscholar.org/2c33/96b0a4f12d6c5952f8e602a654ffbb2f7d55.pdf

Kostakou, P. M., Kouris, N. T., Kostopoulos, V. S., Damaskos, D. S., & Olympios, C. D. (2018). Cardio-oncology: a new and developing sector of research and therapy in the field of cardiology. Heart Failure Reviews, 24, 91–100. https://doi.org/10.1007/s10741-018-9731-y

Su, Z., Mao, Y.-P., OuYang, P.-Y., Tang, J., Lan, X.-W., & Xie, F.-Y. (2015). Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma. BMC Cancer, 15, Article 429. https://doi.org/10.1186/s12885-015-1442-3

Nikolaev, V. G. (2017). Sorption Therapy with the Use of Activated Carbons: Effects on Regeneration of Organs and Tissues. In T. M. S. Chang, Y. Endo, V. G. Nikolaev, T. Tani, Y. Yu, & W.-H. Zheng (Eds.), Hemoperfusion, Plasmaperfusion and Other Clinical Uses of General, Biospecific, Immuno and Leucocyte Adsorbents (pp. 221–243). World Scientific Publishing Co. Pte. Ltd. https://doi.org/10.1142/9789814749084_0007

Andreychyn, M. A., Nikolaev, V. G., Yosyk, Ya. I., & Bidovanets, O. Yu. (2011). Kliniko-patohenetychne obgruntuvannia enterosorbtsiinoi terapii infektsiinykh khvorob [Enterosorbtion Therapy Сliniс Nosotropic Ground of Infectious Diseases]. Liky Ukrainy, (5), 46–50 [in Ukrainian].

Hryh, N. I. (2015). Obgruntuvannia zastosuvannia eferentnoi terapii u terapevtychnii stomatolohii [Substantiation of Application of Efferent Therapy in Therapeutic]. Novyny stomatolohii, (4), 61–67 [in Ukrainian].

Shevchuk, O. O., Posokhova, K. A., Sidorenko, A. S., Bardakhivskaya, K. I., Maslenny, V. M., Yushko, L. A., Chekhun, V. F., & Nikolaev, V. G. (2014). The influence of enterosorption on some haematological and biochemical indices of the normal rats after single injection of melphalan. Experimental oncology, 36(2), 94 100.

Shevchuk, O. O., Posokhova, K. A., Todor, I. N., Lukianova, N. Yu., Nikolaev, V. G., & Chekhun, V. F. (2015). Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor. Experimental Oncology, 37(2), 135–138.

Shevhuk, О. О. (2015). Vplyv vuhletsevoho enterosorbentu i hranulotsytarnoho koloniiestymuliuiuchoho faktora na proksydantno-antyoksydatnyi homeostaz na tli zastosuvannia melfalanu [The influence of carbonic enterosorbent and granulocyte colony stimulating factor on prooxidant-antioxidant homeostasis impaired by alkylating cytostatic melphalan]. Farmakolohiia ta likarska toksykolohiia, (4–5), 97–102. [in Ukrainian].

Shevhuk, О. О., Todor, І. М., Posokhova, К. А., Snezhkova, E. O., & Nikolaev, V. G. (2017). Doslidzhennia miieloprotektornoi aktyvnosti dvokh preparativ hranulotsytarnoho koloniiestymuliuiuchoho faktora na modeli tsytostatychnoi miielosupresii (ohliad literatury i rezultaty vlasnykh doslidzhen) [Myeloprotective activity of two granulocyte colony stimulating factors on model of cytostatic myelosuppression (literature review and results of our own researchers)]. Visnyk naukovykh doslidzhen, (1), 16–20. https://doi.org/10.11603/2415-8798.2017.1.7564 [in Ukrainian].

Marinelli, A., van Dierendonck, J., van Brakel, G., Irth, H., Kuppen, P., Tjaden, U., & van de Velde, C. (1991). Increasing the effective concentration of melphalan in experimental rat liver tumours: comparison of isolated liver perfusion and hepatic artery infusion. British Journal of Cancer, 64, 1069–1075. https://doi.org/10.1038/bjc.1991.466

Gerashchenko, B. I., Todor, I. M., Shevchuk, O. O., & Nikolaev, V. G. (2018). Melphalan-induced cytotoxicity in the bone marrow of rats by flow cytometry measurements. International Journal of Medicine and Medical Research, 4(2), 72–78. https://doi.org/10.11603/ijmmr.2413-6077.2018.2.9836

Jain, T., Alahdab, F., Firwana, B., Sonbol, M. B., Almader-Douglas, D., & Palmer, J. (2019). Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis. Biology of Blood and Marrow Transplantation, 25(4), 728–733. https://doi.org/10.1016/j.bbmt.2018.11.016

Aapro, M. S., Bohlius, J., Cameron, D. A., Lago, L. D., Donnelly, J. P., Kearney, N., Lyman, G. H., Pettengell, R., Tjan-Heijnen, V. C., Walewski, J., Weber, D. C., & Zielinski, C. (2011). 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. European Journal of Cancer, 47(1), 8–32. https://doi.org/10.1016/j.ejca.2010.10.013

Xie, J., Cao, J., Wang, J., Zhang, B., Zeng, X., Zheng, H., Zhang, Y., Cai, L., Wu, Y., Yao, Q., Zhao, X., Mao, W., Jiang, A.-M., Chen, S., Yang, S., Wang, S., Wang, J., Pan, Y., Ren, B., … Hu, X. (2018). Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study. Breast Cancer Research and Treatment, 168(2), 389–399. https://doi.org/10.1007/s10549-017-4609-6

Hoffman, K. E., Pugh, S. L., James, J. L., Scarantino, C., Movsas, B., Valicenti, R. K., Fortin, A., Pollock, J., Kim, H., Brachman, D. G., Berk, L. B., Bruner, D. W., & Kachnic, L. A. (2014). The impact of concurrent granulocyte–macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of the randomized, placebo-controlled Radiation Therapy Oncology Group 9901 trial. Quality of Life Research, 23(6), 1841–1858. https://doi.org/10.1007/s11136-014-0628-5

Barnes, G., Pathak, A., & Schwartzberg, L. (2014). Pharmacoeconomics of Granulocyte Colony-Stimulating Factor: A Critical Review. Advances in Therapy, 31(7), 683–695. https://doi.org/10.1007/s12325-014-0133-9

Shevchuk, O. O., Snezhkova, E. A., Bilous, A. G., Sarnatskaya, V. V., Badakhivska, K. I., Sakhno, L. A., Chekhun, V. F., & Nikolaev V. G. (2019). Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia. In O. Fuchs (Ed.), Cells of the Immune System (pp. 1 20). IntechOpen, https://doi.org/10.5772/intechopen.85690

Muravskaya, G. V., Nikolaev, V. G., Sergeev, V. P., Krutilina, N. I., Bonatskaya, L. V., Klevtsov, V. N., Surovikina, V. V., & Sinajko, V. V. (1991). Enterosorption in Oncotherapy. Biomaterials, Artificial Cells and Immobilization Biotechnology, 19(1), 167–174. https://doi.org/10.3109/10731199109117823

Bonatskaya, L. V., Plotnikov, V. M., & Nikolaev, V. G. (1989). Snizhenie gematotoksichnosti protivoopukholevykh preparatov pri enterosorbtsii [Reduction of hematotoxicity of anticancer drugs during enterosorption]. Eksperimental'naya onkologiya, 23(11), 71–73. [in Russian].

Shevchuk, O. O., Todor, I. M., Lukianova, N. Y., Rodionova, N. K., Nikolaev, V. G., & Chekhun, V. F. (2019). Efficacy of granulocyte colony-stimulating factor and enterosorption in melphalan-induced bone marrow suppression in guerin carcinoma grafted rats. International Journal of Medicine and Medical Research, 5(1), 66–74. https://doi.org/10.11603/ijmmr.2413-6077.2019.1.10307

How to Cite

1.
Shevchuk OO, Todor IM, Rodionova NK, Posokhova KA, Nikolaiev VH. Myeloprotective activity of granulocyte-colony stimulating factor drugs and enterosorption in rats grafted with Guerin carcinoma. Zaporozhye Medical Journal [Internet]. 2020Feb.10 [cited 2024Nov.23];22(1). Available from: http://zmj.zsmu.edu.ua/article/view/194645

Issue

Section

Original research