Disturbances in the functioning of the immune system as a consequence of a prolonged expоsure to low dosages of depleted uranium

Relevance. Depleted uranium (DU) is actively used in many industries. The problems of the safety of personnel employed at industrial facilities of this kind continue to remain relevant. Experimental studies have shown the toxicity of uranium compounds, especially its soluble forms.

Intention.  To identify immunological disorders developing after chronic exposure to low-dose depleted uranium.

Methods. The study involved 30 outbred rats and 60 mice CBA. Uranyl acetate dehydrate was used as a toxicant and administered intragastrically for 120 days. The relative number of T-lymphocytes, apoptotic and necrotic cells, the production of TNF-α, IL-1, -4, -6-β, the level of circulating immune complexes, the phagocytic activity of neutrophils, delayed-type hypersensitivity reactions, and production of immunoglobulins were assessed.

Results and Discussion.  According to the tests on rats, phagocytic-metabolic activity of neutrophils as well as TNF-α production increased, CD4+/CD8+ ratio decreased, and the early stage apoptosis of mononuclear cells was activated after chronic exposure to uranium salts. Most detected changes were dose-dependent. In experiments on mice it was shown that uranyl acetate dehydrate at a dose of 5 mg/kg had no effect on the functional activity of immunocytes, while the index of the delayed-type hypersensitivity reaction and IgG titers increased in animals which were administered DU at a dose of 10 mg/kg.

Conclusion. The results can be used to provide specialized medical care after chronic exposure to depleted uranium.

1. Abdulkadyrov A.M., Bubnova L.N., Glazanova T.V. [et al.]. Vliyanie gemokompetentnoi terapii na immunnyi status razlichnykh kategorii patsientov (meditsinskaya tekhnologiya) [Influence of hemocompetent therapy on the immune status of various categories of patients (medical technology)]. Sankt-Peterburg. 2010. 15 p. URL: www.bloodscience.ru.

2. Kudaeva E.F., Minasyan V.V., Vorontsova Z.A. Adaptivnye vozmozhnosti organov s raznoi skorost’yu obnovleniya posle vozdeistviya obednennogo urana v eksperimente [Adaptive opportunities of organs with different rates of recovery after depleted uranium exposure in the experiment]. Vestnik novykh meditsinskikh tekhnologii : Electronic journal [Journal of New Medical Technologies]. 2017. Vol. 11, N 4. Pp. 172–177. DOI: 10.12737/article_5a3212af059c07.21492129.

3. Okladnikova O.D. Klinicheskie aspekty deistviya urana na organizm cheloveka [Clinical aspects of the action of uranium on the human]. Voprosy radiatsionnoi bezopasnosti [Radiation safety problems]. 2003. Special issue. Pp. 26–35.

4. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv [Guidelines for conducting pre-clinical trials of medicinal products]. A.N. Mironov, N.D. Bunatyan [et al.]. Moskva. 2012. Pt. 1. 944 p.

5. Stosman K.I., Sivak K.V., Savateeva-Ljubimova T.N. Biomarkery khronicheskogo nizkodozovogo vozdeistviya obednennym uranom [Biomarkers of chronic low-dose depleted uranium exposure]. Meditsina truda i promyshlennaya ekologiya [Occupational medicine and industrial ecology]. 2017. N 9. Pp. 179.

6. Bin W., James T.F., Terry W.S., Gary S.S. In vitro immune toxicity of depleted uranium: effects on murine macrophages, CD4+ T Cells, and gene expression profiles. Environmental Health Perspectives. 2006. Vol. 114, N 1. Рр. 85–91.

7. Cerwenka A., Falk C.S., Watzl C. NK cells – from basic research to cancer therapy. Eur. J. Immunol. 2007. Vol. 37, N 5. Pр. 1161–1164. DOI: 10.1002/eji.200790017.

8. Gazin V., Kerdine S., Grillon G. [et al.]. Uranium induces TNF alpha secretion and MAPK activation in a rat alveolar macrophage cell line. Toxicol. Appl. Pharmacol. 2004. Vol. 194, N 1. Pp. 49–59.

9. Gilman A.P., Villeneuve D.C., Secours V.E. [et al.]. Uranyl nitrate: 28-day and 91-day toxicity studies in the Sprague-Dawley rat. Toxicol. Sci. 1998. Vol. 41, N 1. Pp. 117–128.

10. Hao Y., Ren J., Liu J. [et al.]. Immunological changes of chronic oral exposure to depleted uranium in mice. Toxicology. 2013. Vol. 309. Рр. 81–90. DOI: 10.1016/j.tox.2013.04.013

11. Hao Y., Ren J., Liu J. [et al.]. The Protective Role of Zinc against Acute Toxicity of Depleted Uranium in Rats. Basic Clin. Pharmacol. Toxicol. 2012. Vol. 111, N 6. Pp. 402–410. DOI: 10.1111/j.1742-7843.2012.00910.x.

12. Kun L., Yi Shui C., Xiao Liang L. [et al.]. Alteration of cytokine profiles in uranium miners exposed to long-term low dose ionizing radiation [Electronic publication]. The Scientific World Journal. 2014. Vol. 2014. URL: https://dx.doi.org/10.1155/2014/216408.

13. Monleau M., De Meo M., Paquet F. [et al.]. Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats. Toxicol. Sci. 2006. Vol. 89, N 1. Pp. 287–295.

14. Natelson B.H., Haghighi M.H., Ponzio N.M. Evidence for the presence of immune dysfunction in chronic fatigue syndrome. Clin. Diagn. Lab. Immunol. 2002. Vol. 9, N 4. Pр. 747–752.

15. Rafid A. Depleted Uranium Effects on immunophenotyphing of human lymphocytes in Southern Iraq. Iraqi J. Comm. Med. 2009. N 4. Pр. 249–253.

16. Vojdani A., Thrasher J.D. Cellular and humoral immune abnormalities in gulf war veterans. Journal of Toxicology and Environmental Health Perspectives. 2004. Vol. 112, N 8. Рр. 840–846.