Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats
DOI:
https://doi.org/10.12775/JEHS.2020.10.11.033Keywords
uric acid, creatinine, urea, bilirubin, immunity, relationships, rats.Abstract
Background. The study of the effect of end products of protein and nucleic acid metabolism on the immune system is of interest not only theoretical but also practical in line with the problems of urotoxins and hemodialysis. In previous studies, we found significant links between uricemia and uricosuria, on the one hand, and immune parameters, on the other hand. In this study, the spectrum of nitrogenous metabolites was expanded due to creatinine, urea and bilirubin. Material and methods. Experiment was performed on 60 healthy female Wistar rats. The plasma level and urinary excretion of the nitrogenous metabolites were determined. Immune status was assessed by thymocytogram, splenocytogram, blood leukocytogram and immunocytogram, as well as phagocytosis of blood neutrophils and monocytes. Results. Both negative and positive metabolic-immune correlations were revealed. Calculation of multiple correlation coefficients between individual metabolite parameters and constellations of immune parameters revealed the maximum immunotropic effect of uricosuria (R=0,637). This is followed by excretion of urea (R=0,617) and creatinine (R=0,606), bilirubinemia (R=0,589), creatinineemia (R=0,567), uricemia (R=0,566) and plasma urea level (R=0,500). The canonical correlation between the constellation of nitrogenous metabolites, on the one hand, and the parameters of immunity, on the other hand, was very strong: R=0,921; χ2(154)=282; p<10-6. Conclusion. Nitrogen metabolites exhibit significant immunotropic activity, both suppressor and enhancing.
References
Apasov S, Chen JF, Smith P, Sitkovsky M. A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in condicion of adenosine deaminase deficiency. Blood. 2000; 95(12): 3859-3867.
Avilla MN, Malecki KMC, Hahn ME, Wilson RH, Bradfield CA. The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model. Chem Res Toxicol. 2020; 33(4): 860-879.
Bazarnova MA. Cytology investigation of the punctates of the spleen. In: Guide to practical training in clinical laboratory diagnostics [in Russian]. Kyiv. Vyshcha shkola; 1988: 263-264.
Belousova OI, Fedotova MI. Comparative data on changes in spleen, thymus and bone marrow lymphocyte counts in the early post-irradiation period over a wide range of doses [in Russian]. Radiobiology-Radiotherapy. 1968; 9(3): 309-313.
Bianco C. Population of lymphocytes bearing a membrane receptor for antigen-antibody complex. J Exp Med. 1970; 134(4): 702-720.
Bilas VR, Popovych IL. Role of microflora and organic substances of water Naftussya in its modulating influence on neuroendocrine-immune complex and metabolism [in Ukrainian]. Medical Hydrology and Rehabilitation. 2009; 7(1): 68-102.
Carvalho LAC, Lopes JPPB, Kaihami GH, Silva RP, Bruni-Cordoso A, Baldini RL, Meotti FC. Uric acid disrupts hypochlorous acid production and bactericidal activity of HL-60 cells. Redox Biology. 2018; 16: 179-188.
Cinel I, Gür S. Direct inotropic effects of propofol and adenosine on rat atrial muscle: possible mechanisms. Pharmacol Res. 2000; 42(2): 123-128.
Climaco-Arvizu S, Domínguez-Acosta O, Cabañas-Cortés MA, et al. Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization. Life Sci. 2016; 155: 76-84.
Díaz-Díaz CJ, Ronnekleiv-Kelly SM, Nukaya M, et al. The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse. Ann Surg. 2016; 264(3): 429-436.
Douglas SD, Quie PG. Investigation of Phagocytes in Disease. Churchil; 1981: 110 p.
Esser C, Rannug A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev. 2015; 67(2): 259-279.
Gao L, Jiang Y, Wang Y, Qu X, Li L, Lou X, Wang Y, GuoW, Liu Y. Male asymptomatic hyperuricemia patients display a lower number of NKG2D+ NK cells before and after a low-purine diet. Medicine (Baltimore). 2018; 97(50): e13668.
Ghaemi-Oskouie F, Shi Yan. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep. 2011; 13(2): 160-166.
Goryachkovskiy АМ. Clinical Biochemistry [in Russian]. Odesa: Astroprint; 1998: 608 p.
Gozhenko AI. Functional-metabolic continuum [in Russian]. J of NAMS of Ukraine. 2016; 22 (1): 3-8.
Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Functional relationships between parameters of uric acid exchange and immunity in female rats. Actual problems of transport medicine. 2019; 4(58): 123–131.
Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Features of immune status in different states of uric acid metabolism in female rats. Journal of Education, Health and Sport. 2019; 9(12): 167-180.
Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Relationships between parameters of uric acid exchange and immunity as well as microbiota in patients with neuroendocrine-immune complex dysfunction. Journal of Education, Health and Sport. 2020; 10(1): 165-175.
Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Relationships between changes in uric acid parameters metabolism and parameters of immunity and microbiota in patients with neuroendocrine-immune complex dysfunction. Journal of Education, Health and Sport. 2020; 10(2): 212-222.
Gozhenko AI, Zukow W, Polovynko IS, Zajats LM, Yanchij RI, Portnichenko VI, Popovych IL. Individual Immune Responses to Chronic Stress and their Neuro-Endocrine Accompaniment. RSW. UMK. Radom. Torun; 2019: 200 p.
Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J. Inhibition of T cell and NK cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol. 2008; 32(3): 527-535.
Huang S, Apasov S, Koshiba M, SitkovskiM. Role of A2A extracellular adenosine receptor mediated signaling in adenosine mediated inhibition of of T-cell activation and expansion. Blood. 1997; 90(4): 1600-1610.
Jondal M, Holm G, Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972; 136(2): 207-215.
Khaitov RM. Physiology of immune system [in Russian]. Moskva: VINITI RAN; 2005: 428 p.
Limatibul S, Shore A, Dosch HM, Gelfand EW. Theophylline modulation of E-rosette formation: an indicator of T-cell maturation. Clin Exp Immunol. 1978; 33(3): 503-513.
Martínez-Reyes CP, Manjarrez-Reyna AN, Méndez-García LA, et al. Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1. Biomolecules. 2020; 10(4): 576.
Monahan TS, Sawmiller DR, Fenton RA, Dobson JG Jr. Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts. Am J Physiol Heart Circ Physiol. 2000; 279(4): H1472-H1481.
Morelli M, Carta AR, Kachroo A, Schwarzschild A. Pathophysiological roles for purines: adenosine, caffeine and urate. Prog Brain Res. 2010; 183: 183-208.
Navalta JW, Fedor EA, Schafer MA, Lyons TS, Tibana RA, Pereira GB, Prestes J. Caffeine affects CD8+ lymphocyte differently in naїve and familiar individuals following moderate intensity exercise. Int J Immunopathol Pharmacol. 2016; 29(2): 288-294.
Perederiy VG, Zemskov AM, Bychkova NG, Zemskov VM. Immune status, principles of its evaluation and correction of immune disorders [in Russian]. Kyiv. Zdorovya; 1995: 211 p.
Phelan D, Winter GM, Rogers WJ, Lam JC, Denison MS. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys. 1998; 357(1): 155-163.
Popadynets’ OO, Gozhenko AI, Zukow W, Popovych IL. Relationships between the entropies of EEG, HRV, immunocytogram and leukocytogram. Journal of Education, Health and Sport. 2019; 9(5): 651-666.
Popovych IL. Functional interactions between neuroendocrine-immune complex in males rats [in Ukrainian]. Achievements of Clinical and Experimental Medicine. 2008; 2(9): 80-87.
Pousti A, Deemyad T, Malihi G. Mechanism of inhibitory effect of citalopram on isolated guinea-pig atria in relation to adenosine receptor. Hum Psychopharmacol. 2004; 19(5): 347-350.
Quintana FJ, Sherr DH. Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev. 2013; 65(4): 1148-1161.
Smagliy VS, Gozhenko AI, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. Variants of uric acid metabolism and their immune and microbiota accompaniments in patients with neuroendocrine-immune complex dysfunction. Actual problems of transport medicine. 2020; 1(59): 114–125.
Sternberg EM. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol. 2006; 6(4): 318-328.
Thayer JF, Sternberg EM. Neural aspects of immunomodulation: Focus on the vagus nerve. Brain Behav Immun. 2010; 24(8): 1223-1228.
Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009; 9(6): 418-428.
Uchakin PN, Uchakina ON, Tobin BV, Ershov FI. Neuroendocrine immunomodulation [in Russian]. Vestnik Ross AMN. 2007; 9: 26-32.
Vigano S, Alatzoglou D, Irving M, Menetrier-Caux Ch, Caux Ch, Romero P, Coukos G. Targeting adenosine in cancer immunotherapy to enhance T-cell function. Front Immunol. 2019; 10: 925.
Yang X, Liu H, Ye T, et al. AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization. Theranostics. 2020; 10(26): 12011-12025.
Zajats LM, Polovynko IS, Zukow W. Features neuro-endocrine support diversity of immune responses to chronic stress in male rats. Journal of Education, Health and Sport. 2017; 7(3): 97-105.
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