DOSE-DEPENDENT CHARACTER OF DISTURBANCE OF HEMATOPOIETIC AND IMMUNE SYSTEMS FUNCTION, PRODUCTION OF SOME HORMONES IN EXPERIMENTAL URANIUM ACETATE DIHYDRATE EXPOSURE

The paper presents the results of an experimental study of the dose-dependent nature of functional changes in the body systems under chronic administration of uranyl acetate dihydrate in doses of 0.5 and 5.0 mg/kg per element for 18 weeks. The study was performed on 45 male outbred rats. It has been shown that uranyl acetate dihydrate in a dose of 0.5 mg/kg had no significant effect on hematological parameters. At the same time, activation of bactericidal activity of neutrophils, a decrease in the immunoregulatory index, and an increase in the blood concentration of tumor necrosis factor (TNF-α) have been revealed. The toxicant administered to rats in a dose of 5 mg/kg led to a decrease in the absolute number of erythrocytes, hemoglobin, hematocrit, platelets, the release of myelocytes into the blood, basophilia, monocytosis, the appearance of leukolysis cells and plasmatization of lymphocytes. On the part of the immune system, an increase in the biocidal capacity of neutrophilic granulocytes, TNF-α production, an increase in the number of CD8+ cells, and a reduction in the CD4+/CD8+ ratio have been found. Uranyl acetate dihydrate had a dose-dependent effect only on the number of cytotoxic T-lymphocytes, T-cells with the CD4+CD8+ phenotype, on the immunoregulatory index, and on the level of TNF-α. Hyperglycemia and glucosuria were also dose-dependent. An increase in glucose in the blood and urine indicated a violation of carbohydrate metabolism and kidney function. There was a decrease in the concentration of thyroxine, testosterone and an increase in the level of insulin. Uranyl acetate dihydrate led to the development of insulin resistance. The level of hormones did not depend on the dose of the toxicant administered to the animals.

uranyl acetate dihydrate, hematopoiesis, hormones, immune system

1. On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2019: State report. - M.: Federal Service for Supervision of Consumer Rights Protection and Human Welfare. 299 ;2020 (in Russian).

2. Official website of Russian statistics.URL: https://gks.ru/folder/13721 (in Russian).

3. Antonenko O.M. Toxic liver damage: ways of pharmacological correction. Polyclinic MC. 51-45 :(2):6 ;2013 (in Russian).

4. Stravitz R.T., Lee W.M. Acute liver failure.Lancet. 881-869 :394 ;2019.

5. Esquer F., Esquer M., Parrau D., Carpio D., Yañez A., Cong P. Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type I diabetic mice. Biol. Blood Marrow Transplant. ;2008 40-631 :14.

6. Wang J., Wan H. Mesenchymal stromal cells as a therapeutic treatment for ischemic stroke. Neuroscience bull. ;2014 35-524 :30.

7. Protasova G.A., Shabasheva L.V., Popov V.B. Stem cell correction of toxic liver lesions. Toxicological Review. :(4) ;2020 26-21. https://doi.org/-0869/10.36946 26-21-4-2020-7922 (in Russian).

8. Airapetov G.A., Zagorodiy N.V., Vorotnikov A.A. An experimental method for the replacement of osteochondral defects of the joints (early results). Medical Bulletin of the South of Russia.76-71 :(2)10 ;2019 (in Russian).

9. Ball L.M., Bernardo M.E., Roelofs H., Lankester A., Cometa A., Egeler M.R., et al. Co-transplantation of ex vivo-expanded mesenchymal stem cells accelerates lymphocytes recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem cell transplantation.Blood. 2767-2764 :10 ;2007.

10. Le Blanc K., Samuelsson H., Gustafsson B., Remberger M., Sundberg B., Arvidson J., et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 1738-1733 :(8)21 ;2007.

11. Wyse R.D. Use of genetically modified mesenchymal stem cells tо treat neurodegeneration diseases. Int. J. Mol.Sci. 1745-1719 :15 ;2014.

12. Jo C.H., Lee Y.G., Shin W.H., Kim H., Chai J.W., Jeong E.C., et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 1266–1254 :32 ;2014.

13. Huebner K., Frank R.M., Getgood A. Ortho-Biologics for Osteoarthritis. Clinics in Sports Medicine. 141-123 :(1)38 ;2019.

14. Golchin A., Tahereh Z. F., Khojasteh A., Soleimanifar F., Ardeshirylajimi A. The Clinical Trials of Mesenchymal Stem Cell Therapy in Skin Diseases: An Update and Concise Review. Current Stem Cell Research & Therapy.33-22:(1)14 ;2019.

15. Li M., Ma J., Gao Y., Yang L. Cell sheet technology: a promising strategy in regenerative medicine. Cytotherapy. ;2019 16–3:(1)21.

16. Konno T., Akito K., Kurita K., Ito Y. Formation of embryoid bodies by mouse embryonic stem cells on plastic surfaces. Journal of Bioscience and Bioengineering. 93 - 88 :(1)100 ;2005.

17. Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini Fc., Krause Ds., et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 317-315 :(4)8 ;2006.

18. Muzhikyan A.A., Makarova M.N., Gushchin Ya.A. Features of histological processing of organs and tissues of laboratory animals. SPb: International Veterinary Bulletin. 9-103 :2 ;2014 (in Russian).

19. Kinnaird T., Stabile E., Burnett M.S., Lee C.W., Barr S., Fuchs S., Epstein S.E. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. ;2004 685–678 :94.

20. Stagg J., Galipeau J. Mechanisms of Immune Modulation by Mesenchymal Stromal Cells and Clinical Translation. Curr. Mol. Med. 867-856 :(5)13 ;2013.

21. Praveen K.L., Kandoi S., Misra R., Vijayalakshmi S., Rajagopal K., Verma R.S. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine & Growth Factor Reviews. 9-1 :46 ;2019. DOI: 10.1016/j.cytogfr.2019.04.002.