EFFECT OF AVIAN BURSA FABERICA EXTRACT ON THE COMPENSATORY CAPACITY OF BONE MARROW, SPLEEN AND THYMUS CELLS IN CYCLOPHOSPHAMIDINE-INDUCED MICE

Abstract

Malignant neoplasms often arise against the background of immunodeficiency. But anticancer chemotherapeutic drugs can also cause the development or aggravate immunodeficiency, affecting the bone marrow function. Previous studies have shown that the bioorganocomplex obtained from the chickens’ Fabricius bursa has an antioxidant and immunotropic effect. The aim of this research was to investigate the protective mechanism of the bioorganocomplex «Bursanatal» against cyclophosphamide-induced immunosuppression in the bone marrow, thymus, spleen of C57Bl/6 mice. Immunodeficiency was induced with single cyclophosphamide injection (200 mg/kg). Histological, morphometric, radiological methods were used, as well as immunohistochemical staining of the spleen and thymus with CD45 and CD3 antibodies. The studies showed that cyclophosphamide injection affects both peripheral blood and bone marrow. Moreover, neutrophilic, basophilic and erythroid precursor cells are less sensitive to the cyclophosphamide. So on the 8th day their compensatory hyperplasia is observed. The use of the bioorganocomplex is accompanied by the leukocytes, erythrocytes and hemoglobin increase in the peripheral blood. The cellularity of the bone marrow increases due to the dividing and maturation of erythrocyte, neutrophil, basophil and lymphocyte lineage cells. Bioorganocomplex administration causes a reliable decrease the area of the red pulp in spleen of mice with cyclophosphamide-induced immunodeficiency. The activation of extramedullary hematopoiesis are found in the spleen of treated mice – the number of colony-forming hematopoietic progenitors increases. Also it is noted that the area of the reactive center in the white pulp decreases with a significant increase the CD3+ cells in the red and white pulp under the «Bursanatal» treatment. At the same time, it does not affect thymus pathomorphology.

1. Kolberg N.A. Tissue preparation “Bursanatal”. Its effect on resistance and immunity in infectious diseases // Innovative Technologies in Agriculture: Proceedings of the III International Scientific Conference (Kazan, 2017). - Kazan: Buk, 2017. - С. 21-34.

2. Kohlberg N.A., Kohlberg M.A., Travnikova D.A., Danilova I.G., Mukhlynina E.A. Method of processing of Fabricia bursa of birds. Patent for invention RU 2782347 C1, 26.10.2022.

3. Kolberg N.A., Mukhlynina E.A., Brilliant S.A., Danilova I.G., Gette I.F., Ulitko M.V. Immunotropic effect of the extract fabricia bursa broiler chickens on C57BL/6 and C57BL/10 mice with experimental immunodeficiency syndrome // APK Russia.- 2023.- Vol. 30, № 2.- С. 275-283. DOI 10.55934/2587-8824-2022-30-2-275-283.

4. Kolberg N.A., Petrova O.G. et al. Immune stimulants in poultry and livestock breeding. - Ekaterinburg: Ural Publishing House, 2012. - 195 с.

5. Nikityuk V.V. Chemotherapy in oncology // Standards of Medical Care, 2017. - С. 673-751.

6. Teles C.A., Medeiros-Souza P., Lima F.C., de Araújo B.G., Lima R.C. Use of cyclophosphamide in routine practice in the treatment of autoimmune rheumatic diseases // Nephrology. - 2018. - Т. 22, №1. - С.104-113. DOI 10.24884/1561-6274-2018-22-1-104-113.

7. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018.- Vol.68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin., 2020 Vol.70(4):313. doi: 10.3322/caac.21609.

8. Huang L., Shen M., Wu T., Yu Y., Yu Q., Chen Y., Xie J. Mesona chinensis Benth polysaccharides protect against oxidative stress and immunosuppression in cyclophosphamide-treated mice via MAPKs signal transduction pathways. Int J Biol Macromol., 2020, Vol.1, no.152, pp.766-774. doi: 10.1016/j.ijbiomac.2020.02.318.

9. Suchitra Ku Panigrahy, Suresh Jatawa, Archana Tiwari Therapeutic use of cyclophosphamide and its cytotoxic action. Journal of Pharmacy Research, 2011, Vol.4, no.8, pp. 2755-2757.

10. Voelcke G. The Mechanism of action of cyclophosphamide and its consequences for the development of a new generation of oxazaphosphorine cytostatics. Sci. Pharm. 2020, Vol. 88, no.4, p. 42; https://doi.org/10.3390/scipharm88040042.

11. Zhu Q., Xu L.H. Analysis of related factors in myelosuppression by antitumor drugs. Pharm. Clin. Res., 2015, Vol. 23, pp. 68–70.