UDC: 599.323.4-114.44.044:[577.118:549.232]
BBC: Е623.362.432.2*692.32-641.2/641.9:Г126.2
Samakina E.S., Struchko G.Yu., Merkulova L.M., Kostrova O.Yu., Nyuganen A.O.
Assessment of Rat Spleen Structure under an Isolated and Combined Action of Selenium and Ethyl Carbamat
Keywords: spleen, morphology, morphometry, selenium exposure, ethyl carbamate exposure
The immune system, having a complex structural organization, performs the main functions in providing an anti-inflammatory and antitumor immune response. The spleen, as a peripheral organ of the immune system, plays an important role in realization of these functions and contains a significant number of immune cells. Ethylcarbamate, being a group 2A carcinogen, can provoke the development of neoplastic processes through activation of Kras gene mutation and stimulation of oncogenic signals. Alongside with that, selenium affects the immune response, reducing the proliferation of tumor cells and producing an anti-inflammatory effect. Despite the existence of several studies on the effect of ethyl carbamate and selenium on the animal body, there is no data on the combined effect of these substances on the rat spleen under experimental conditions in the scientific literature. The aim of the study was to evaluate morphological and morphometric changes in the structure of the spleen in male rats with oral administration of selenium into their body and intraperitoneal injection of ethyl carbamate. Materials and methods of the study. The body mass of male rats and their spleen were studied, morphological and morphometric parameters of the spleen were evaluated, the lymphoid coefficient and the Kernoghan index were calculated. The animals were divided into four groups: N1 – control group; N2 – animals receiving selenium with drinking water; N3 – animals injected intraperitoneally with ethyl carbamate; N4 – animals receiving selenium with drinking water followed by injection of ethyl carbamate. Results. It was found that in the group 2, the area of lymphoid nodules was reduced, the Kernoghan index was reduced and the lymphoid coefficient was increased, while the body weight of rats and their spleen remained unchanged. In a month after an isolated intake of ethyl carbamate, both the body weight and the spleen weight in rats were significantly decreased. At this, in group 3, the area and the diameter of the germinal center, the thickness of the periarterial lymphoid sheath and the Kernoghan index were increased, and the lymphoid coefficient was reduced. At the ultramicroscopic level, an increase in the number of plasma cells was detected in group N3, as well as the number of swollen mitochondria in lymphocytes. In group 4, an increase in the area and the diameter of lymphoid nodules, the germinal center, as well as the lymphoid coefficient was determined, and the Kernoghan index was unchanged. When studying ultrathin sections in group 4 lymphocytes of various transitional forms were revealed. Conclusions. It was found that against the background of selenium intake into the body of male rats, a morphological rearrangement of the white pulp of the spleen occurred, probably associated with the reaction of T-lymphocytes. Ethyl carbamate injection resulted in a predominant effect on the B-cell link of the immune response of the spleen. In combined intake of selenium and ethyl carbamate, hyperplasia of the white pulp was revealed, consisting in an increase in its structures.
References
- Volkov V.P. Novyi algoritm morfometricheskoi otsenki funktsional’noi immunomorfologii selezenki [A new algorithm for morphometric evaluation of functional immunomorphology of the spleen]. Universum: meditsina i farmakologiya, 2015, vol. 19, no. 2, p. 6.
- Zaitsev V.B., Fedorovskaya N.S., Zheleznov L.M. Morfometricheskie osobennosti struktury selezenki [Morphometric features of the spleen structure]. Vestnik novykh meditsinskikh tekhnologii, 2018, vol. 25, no. 3, pp. 153–159.
- Arlashkina O.M., Struchko G.Yu, Merkulova L.M., Mikhaylova M.N. Izmeneniya beloi pulpy selezenki u potomstva splenektomirovannykh krys razlichnykh vozrastnykh periodov posle vvedeniya 1, 2-dimetilgidrazina [Changes in the white pulp of the spleen in the offspring of splenectomized rats of various age periods after administration of 1, 2-dimethylhydrazine]. Nauchno-prakticheskii retsenziruemyi zhurnal Klinicheskaya i eksperimentalnaya morfologiya, 2019, vol. 8, no. 4, pp. 49–58.
- Abramtsova A.V., Sagradyan G.V., Pigunova L.A. et al. Mekhanizmy deistviya modifitsirovannoi nanochastitsami selena mineral’noi vody «Krasnoarmeiskii novyi» [Mechanisms of action of mineral water modified with selenium nanoparticles “Krasnoarmeysky novy”]. Kurortnaya meditsina, 2016, no. 1, pp. 26–34.
- Tsvetkov I.S., Dobrynina M.T., Mkhitarov V.A. et al. Morfologicheskie izmeneniya organov immunnoi sistemy u samtsov myshei S57BL/6 pri vozdeistvii vysokoi dozy testosterona [Morphological changes in the immune system organs of male C57BL/6 mice under the influence of a high dose of testosterone]. Klinicheskaya i eksperimental’naya morfologiya, 2018, no. 2(26), pp. 19–24. DOI: 10.31088/2226-5988-2018-26-2-19-24.
- Nikitenko O.V., Putalova I.N. Strukturno-kletochnye perestroiki limfoidnykh organov posle vnutribryushinnogo vvedeniya selenita natriya v toksicheskoi doze [Structural and cellular rearrangements of lymphoid organs after intraperitoneal administration of sodium selenite in a toxic dose]. Vestnik novykh meditsinskikh tekhnologii, 2010, vol. 17, no. 2, pp. 32–35.
- Sindireva A.V., Maidanyuk G.A., Golubkina N.A. Vliyanie selena na soderzhanie mikroelementov v pecheni krys linii wistar [The effect of selenium on the content of trace elements in the liver of wistar rats]. Vestnik Nizhnevartovskogo gosudarstvennogo universiteta, 2018, no. 3, pp. 103–109.
- Fedorovskaya N.S., Zheleznov L.M., Petrov S.V., Zaitsev V.B. Kharakteristika immunomorfologicheskikh protsessov v selezenke patsientov s immunnoi trombotsitopeniei [Characteristics of immunomorphological processes in the spleen of patients with immune thrombocytopenia]. Zhurnal anatomii igistopatologii, 2020, vol. 9, no. 3, pp. 54–63.
- Sharafutdinova L.A., Valiullin V.V. Morfologicheskaya kharakteristika selezenki krys pri vozdeistvii na organizm nanochastits dioksida titana [Morphological characteristics of rats spleen when exposed to the nanoparticles of titanium dioxide]. Vestnik Ural’skoi meditsinskoi aka-demicheskoi nauki, 2018, vol. 15, no. 6, рр. 830–839.
- Bae M., Kim H. The role of vitamin C, vitamin D, and selenium in immune system against COVID-19. Molecules, 2020, vol. 25, no. 22, pp. 5346.
- Crane G.M., Liu Y.C., Chadburn A. Spleen: development, anatomy and reactive lymphoid proliferations. Seminars in Diagnostic Pathology. – WB Saunders, 2021, vol. 38, no. 2, pp. 112–124.
- Elmore S.A. Enhanced histopathology of the spleen. Toxicologic pathology, 2006, vol. 34, no. 5, pp. 648–655.
- Ermolina E.V., Stadnikov A.A., Smoliagin A.I. Morphological features of the organs of the immune system in conditions of exposure to chromium and benzene. Gigiena i Sanitariia, 2012, vol. 3, pp. 69–71.
- Fazliddinovna M.G., Uygunovich N.A. Comparison of the results of morphological changes observed in the spleen under the influence of carcinogens in the experiment. IQRO, 2023, vol. 2, no. 1, pp. 273–278.
- Guo C.H., Wang S.Y., Chung C.H. et al. Selenium modulates AR/IGF-1R/EGFR and TROP2 signaling pathways and improves anticancer efficacy in murine mammary carcinoma 4T1. The Journal of Nutritional Biochemistry, 2023, vol. 120, pp. 109417.
- Jiao Z., Dong Y., Chen Q. Ethyl carbamate in fermented beverages: presence, analytical chemistry, formation mechanism, and mitigation proposals. Comprehensive Reviews in Food Science and Food Safety, 2014, vol. 13, no. 4, pp. 611–626.
- Ju W., Li X., Li Z. et al. The effect of selenium supplementation on coronary heart disease: A systematic review and meta-analysis of randomized controlled trials. Journal of Trace Elements in Medicine and Biology, 2017, vol. 44, pp. 8–16.
- Li G. et al. A survey of ethyl carbamate in beer from Chinese market. Food Control, 2017, 79, pp. 254–257.
- Li G.G., Guo Z.Z., Ma X.F. et al. The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis. Developmental & Comparative Immunology, 2016, vol. 59, pp. 89–
- Mebius R.E., Kraal G. Structure and function of the spleen. Nature reviews immunology, 2005, vol. 5, no. 8, pp. 606–616.
- Munn L. L. Cancer and inflammation. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2017, vol. 9, no. 2, p. 1370.
- Qin S. et al. Effects of selenium-chitosan on blood selenium concentration, antioxidation status, and cellular and humoral immunity in mice. Biological Trace Element Research, 2015, vol. 165, pp. 145–152.
- Rataan A.O., Geary S.M., Zakharia Y. et al. Potential role of selenium in the treatment of cancer and viral infections. International journal of molecular sciences, 2022, vol. 23, no. 4, p. 2215.
- Razaghi A., Geary S.M., Zakharia Y. et al. Selenium stimulates the antitumour immunity: Insights to future research. European Journal of Cancer, 2021, vol. 155, pp. 256–267.
- Roman M., Jitaru P., Barbante C. Selenium biochemistry and its role for human health. Metallomics, 2014, vol. 6, no. 1, pp. 25–54.
- Rosin F.C.P. et al. Identification of myeloid-derived suppressor cells and T regulatory cells in lung microenvironment after Urethane-induced lung tumor. International immunopharmacology, 2011, vol. 11, no. 7, pp. 873–878.
- Ruseva B., Atanasova M., Georgieva M. et al. Effects of selenium on the vessel walls and anti-elastin antibodies in spontaneously hypertensive rats. Experimental Biology and Medicine, 2012, vol. 237, no. 2, pp. 160–166.
- Sozio F., Schioppa T., Sozzani S. et al. Urethane-induced lung carcinogenesis //Methods in cell biology. Academic Press, 2021, vol. 163, pp. 45–57.
- Stathopoulos G. T. et al. Epithelial NF-κB activation promotes urethane-induced lung carcinogenesis. Proceedings of the National Academy of Sciences, 2007, vol. 104, no. 47, pp. 18514–18519.
- Steiniger B.S. Human spleen microanatomy: why mice do not suffice. Immunology, 2015, vol. 145, no. 3, pp. 334–346.
- Stupin A., Cosic A., Novak S. et al. Reduced dietary selenium impairs vascular function by increasing oxidative stress in Sprague-Dawley rat aortas. International Journal of Environmental Research and Public Health, 2017, vol. 14, no. 6, p. 591.
- Tai Y. et al. Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Frontiers in pharmacology, 2018, vol. 9, pp. 642.
- Wen Y. et al. Chronic inflammation, cancer development and immunotherapy. Frontiers in pharmacology, 2022, vol. 13, pp. 1040163.
- Xu C. et al. Inflammation has a role in urethane‑induced lung cancer in C57BL/6J mice. Molecular medicine reports, 2016, vol. 14, no. 4, pp. 3323–3328.
- Zhang X. et al. Effects of dietary selenium on immune function of spleen in mice. Journal of Functional Foods, 2022, vol. 89, p. 104914.
- Zhu Y.,Pu Q., Zhang Q. et al. Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer. Cancer medicine, 2022, 12, no. 16, pp. 17149–17170.
About authors
- Samakina Ekaterina S.
- Senior Lecturer, Department of Faculty Therapy, Chuvash State University, Russia, Cheboksary (ekaterina1996.96@mail.ru; ORCID: https://orcid.org/0000-0002-9515-0639)
- Struchko Gleb Yu.
- Doctor of Medical Sciences, Professor, Head of Normal and Topographic Anatomy Department, Chuvash State University, Russia, Cheboksary (glebstr@mail.ru; ORCID: https://orcid.org/0000-0002-0549-5116)
- Merkulova Larisa M.
- Doctor of Medical Sciences, Professor of Normal and Topographic Anatomy Department, Chuvash State University, Russia, Cheboksary (merkulova192@mail.ru; ORCID: https://orcid.org/0000-0001-7460-6791)
- Kostrova Olga Yu.
- Candidate of Medical Sciences, Assistant Professor, Department of Faculty Therapy, Chuvash State University, Russia, Cheboksary (evkbiz@yandex.ru; ORCID: https://orcid.org/0000-0002-7057-9834)
- Nyuganen Anna O.
- Junior Researcher, Pathologist, N.N. Petrov National Medical Research Center of Oncology, Russia, St. Petersburg (carridwenmcfall@gmail.com; ORCID: https://orcid.org/0000-0003-2685-5093)
Article link
Samakina E.S., Struchko G.Yu., Merkulova L.M., Kostrova O.Yu., Nyuganen A.O. Assessment of Rat Spleen Structure under an Isolated and Combined Action of Selenium and Ethyl Carbamat [Electronic resource] // Acta medica Eurasica. – 2024. – №4. P. 64-75. – URL: https://acta-medica-eurasica.ru/en/single/2024/4/7/. DOI: 10.47026/2413-4864-2024-4-64-75.