Experimental study of the nephroprotective properties of cryoextracts of the placenta and spleen, and the conditioned medium of mesenchymal stem cells on the background of autoimmune membranous nephropathy
DOI:
https://doi.org/10.32782/2077-6594/2024.3/17Keywords:
Heymann autoimmune nephritis, membranous nephropathy, proteinuria, creatinine, cell-free cryopreserved biological agentsAbstract
Purpose: the aim is to evaluate the effect of cryoextracts of the placenta (CEP) and seryozina (CES), as well as the conditioned medium of mesenchymal stem cells (MSC-CM) on the functional state of the kidneys of rats with Heiman’s autoimmune nephritis. Materials and methods. Studies of the effectiveness of cell-free cryopreserved biological agents were conducted on 42 male shurens. Heymann’s autoimmune nephritis (AIN) was reproduced according to the method of Heymann W.R. and sang on the 70th day of the experiment, the functional state of the kidneys was assessed under the conditions of spontaneous diuresis, after which the animals were removed from the experiment and blood samples were taken. The protein content was determined spectrophotometrically using the biuret reaction. Creatinine content was determined spectrophotometrically by the Jaffe reaction. Results. A decrease in the excretion of protein by the kidneys was noted on the bodies of the application of the investigated cellfree cryopreserved biological agents. Thus, studies have shown that the greatest decrease in proteinuria was observed against the background of administration of MSC-CM to rats with AIN – the rate of proteinuria decreased by 65,8% (р ˂ 0,001) and amounted to 9,7 ± 0,9 mg/day, which is 29,9% exceeded the efficiency (p = 0,04) according to the similar type of activity of the reference drug canefron. The introduction of CEP and CES was accompanied by the ability to reduce creatinine clearance in rats comparable to canefron, and AIN – the specified indicator was 0,31 ± 0,03 ml/min and 0,32 ± 0,01 ml/min, respectively. Conclusions. Cell-free cryopreserved biological agents show pronounced nephroprotective activity against the background of Heimann’s autoimmune nephritis in rats. According to the ability to eliminate proteinuria in rats with AIN (% relative to untreated rats with AIN), the studied agents can be arranged in the following sequence: MSC-CM (65,8%; p ˂ 0,001) ˃ CEP (58,3%; p ˂ 0,001) ˃ CES (49,7%; p ˂ 0,001). According to the ability to restore creatinine clearance in rats with AIN (% relative to untreated rats with AIN), the studied cell-free cryopreserved biological agents can be arranged in the following sequence: MSC-CM (123,4%; p ˂ 0,001) ˃ CES (99,3%; p ˂ 0,001) ˃ CEP (92,4%; p ˂ 0,001).
References
Cybulsky AV, Quigg RJ, Salant DJ. Experimental membranous nephropathy redux. American Journal of Physiology-Renal Physiology. 2005; 289 (4): 660–671. DOI: 10.1152/ajprenal.00437.2004.
Ma H, Sandor DG, Beck LH Jr. The role of complement in membranous nephropathy. Seminars in Nephrology. 2013; 33 (6): 531–542. DOI: 10.1016/j.semnephrol.2013.08.004.
Mellors RC, Ortega LG. Analytical pathology. III. New observations on the pathogenesis of glomerulonephritis, lipid nephrosis, periarteritis nodosa, and secondary amyloidosis in man. The American Journal of Pathology. 1956; 32 (3): 455–499.
Liu W, Gao C, Liu Z, Dai H, Feng Z, Dong Z, Zheng Y, Gao Y, Tian X, Liu B. Idiopathic membranous nephropathy: glomerular pathological pattern caused by extrarenal immunity activity. Frontiers in Immunology. 2020; 11: 1846. DOI: 10.3389/fimmu.2020.01846.
East L, Isacke CM. The mannose receptor family. Biochimica et Biophysica Acta. 2002; 1572 (2–3): 364–386. DOI: 10.1016/s0304-4165(02)00319-7.
Dantas M, Silva LBB, Pontes BTM, Dos Reis MA, de Lima PSN, Moysés Neto M. Membranous nephropathy. Brazilian Journal of Nephrology. 2023; 45 (2): 229–243. DOI: 10.1590/2175-8239-JBN-2023-0046en.
McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrology Dialysis Transplantation. 2011; 26 (2): 414–430. DOI: 10.1093/ndt/gfq665.
Bobart SA, Tehranian S, Sethi S, Alexander MP, Nasr SH, Moura Marta C, Vrana JA, Said S, Giesen CD, Lieske JC, Fervenza FC, de Vriese AS. A Target antigen-based approach to the classification of membranous nephropathy. Mayo Clinic Proceedings. 2021; 96 (3): 577–591. DOI: 10.1016/j.mayocp.2020.11.028.
Akiyama S, Imai E, Maruyama S. Immunology of membranous nephropathy. F1000Res. 2019; 8: 734. DOI: 10.12688/f1000research.17589.1.
Heymann W, Kmetec EP, Wilson SG, Hunter JL, Hackel DB, Okuda R, Cuppage F. Experimental autoimmune renal disease in rats. Annals of the New York Academy of Sciences. 1965; 124 (1): 310–322. DOI: 10.1111/j.1749-6632.1965.tb18966.x.
Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA, Aslam N, Jefferson JA, Gipson PE, Rizk DV, Sedor JR, Simon JF, McCarthy ET, Brenchley P, Sethi S, Avila-Casado C, Beanlands H, Lieske JC, Philibert D, Li T, Thomas LF, Green DF, Juncos LA, Beara-Lasic L, Blumenthal SS, Sussman AN, Erickson SB, Hladunewich M, Canetta PA, Hebert LA, Leung N, Radhakrishnan J, Reich HN, Parikh SV, Gipson DS, Lee DK, da Costa BR, Jüni P, Cattran DC. MENTOR Investigators. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. The New England Journal of Medicine. 2019; 381 (1): 36–46. DOI: 10.1056/NEJMoa1814427.
Hladkykh FV. Evaluation of tentative and research activity in rats with experimental allergic encephalomyelitis against the administration of cell-free cryopreserved biological agents. Psychiatry, Neurology and Medical Psychology. 2024; 11 (2 (24)): 124–137. DOI: 10.26565/2312-5675-2024-24-02.
Hladkykh FV. Nonsteroidal anti-inflammatory drugs: therapeutic and undesirable effects, ways of their optimization. Vinnytsia, 2022. 216 p. DOI: 10.46879/2022.1.
Koshurba IV, Hladkнkh FV, Chyzh MO. Assessment of antiulcerogenic effect of cryopreserved placenta extract on the model of alcohol-prednisolone damage of the stomach. Medical science of Ukraine. 2022; 18 (2): 3–9. DOI: 10.32345/2664-4738.2.2022.01.
Hladkykh FV. Prospects for the use of immunomodulators in the treatment of patients with autoimmune diseases: focus on extracts of biological tissues (cryoextract of the placenta and cryoextract of the spleen). Immunology and allergology: science and practice. 2023; 4: 29–46. DOI: 10.37321/immunology.2023.4-04.
Shebeko SK. Experimental substantiation of the combined use of amino sugar derivatives and flavonoids in the therapy of chronic kidney disease. Dissertation. Kharkiv, 2017. 516 p. URL: https://nrat.ukrintei.ua/searchdoc/0521U100125/.
Deepthi R, Suhasin G. A review on animal models of chronic kidney disease – an update. Biomedical and Pharmacology Journal. 2023; 16 (3): 1319–1327. DOI: 10.13005/bpj/2711.
Zahraa Mohammed-Ali, Rachel E. Carlisle, Samera Nademi, Jeffrey G. Dickhout, Chapter 16 – Animal Models of Kidney Disease. 2017: 379–417. DOI: 10.1016/B978-0-12-809468-6.00016-4.
Jefferson JA, Pippin JW, Shankland SJ. Experimental models of membranous nephropathy. Drug Discovery Today: Disease Models. 2010; 7 (1–2): 27–33. DOI: 10.1016/j.ddmod.2010.11.001.
Becker GJ, Hewitson TD. Animal models of chronic kidney disease: useful but not perfect. Nephrology Dialysis Transplantation. 2013; 28 (10): 2432–2438. DOI: 10.1093/ndt/gft071.
Wang YM, Lee VWS, Wu H, Harris DCH, Alexander SI. Heymann nephritis in Lewis rats. Current Protocols in Immunology. 2015; 109: 1–6. DOI: 10.1002/0471142735.im1529s109.
Shtryhol SYu, Lisovyi VM, Zupanets IA, Shebeko SK, Maslova NF, Hozhenko AI, Kharchenko DS. Methods of experimental modeling of kidney damage for pharmacological research: methodical recommendations. Kharkiv, 2009. 48 p.
Podpletnia OA, Khomyak NV, Sokolova KV, Kaidash SP, Khomyak OV. Phytotherapeutic drugs with nephroprotective activity (review). Medical perspectives. 2017; 22 (17): 10–7. DOI: 10.26641/2307-0404.2017.1.100866.
Shebeko SK, Chernykh VV, Zupanets KO. Nephroprotective effect of the herbal composition BNO 2103 in rats with renal failure. Health of Man. 2021; 4: 48–56. DOI: 10.30841/2307-5090.4.2021.252396.
Monatko KV. Experimental study of the nephroprotective effect of freeze-dried watermelon powder. Dissertation. Kharkiv, 2014. 217 p. URL: https://nrat.ukrintei.ua/searchdoc/0414U004729/.
Borisov SO, Kolosov OM, Kostev FI, Borisov OV. Study of the functional state of the kidneys of rats with acute pyelonephritis on the background of diabetes under the conditions of drug exposure in the experiment. Health of Man. 2020; 72 (1): 80–83. DOI: 10.30841/2307-5090.1.2020.205494.
Rybolovlev YuR, Rybolovlev RS. Dosage of substances for mammals according to biological activity constants. Proceedings of the Academy of Sciences of the USSR. 1979; 247 (6): 1513–1516.
Freund J. Some aspects of active immunization. Annual Review of Microbiology. 1947; 1: 291–308. DOI: 10.1146/annurev.mi.01.100147.001451.
Shepitko VI. Structural and functional indicators of the cryopreserved liver and the effect of its transplantation on the morphofunctional state of a number of internal organs: dissertation. Dissertation. Kharkiv, 2004. 326 p. URL: https://nrat.ukrintei.ua/searchdoc/0504U000610/.
Prokopyuk OS. Placenta cryopreservation and determination of the mechanisms of its influence on the body of recipients of late ontogenesis (experimental study). Dissertation. Kharkiv, 2011. 351 p. URL: https://nrat.ukrintei.ua/searchdoc/0514U000218/.
Bespalova IG. Peptide composition and biological action of extracts of cryopreserved pig spleen fragments and piglet skin. Dissertation. Kharkiv, 2016. 162 p. URL: https://nrat.ukrintei.ua/searchdoc/0416U004539/.
Golubinskaya PA., Sarycheva MV., Dolzhikov AA, Bondarev VP, Stefanova MS, Soldatov VO, Nadezhdin SV, Korokin MV, et al. Application of multipotent mesenchymal stem cell secretome in the treatment of adjuvant arthritis and contact-allergic dermatitis in animal models. Pharmacy & Pharmacology. 2020; 8 (6): 416–425. DOI: 10.19163/2307-9266-2020-8-6-416-425.
Globa VYu. Use of cryopreserved cell cultures and neurotrophic factors in experimental infravesical obstruction. Dissertation. Kharkiv, 2021. 156 p. URL: https://nrat.ukrintei.ua/searchdoc/0821U100913/.
Stefanov OV, ed. Preclinical studies of medicinal products: methodical recommendations. Kyiv: Avicenna, 2001. 527 p.
Kamyshnikov VS. Handbook of clinical and biochemical research and laboratory diagnostics. MEDpress-inform; 2009. 896 p.
Lowry OH, Rosenbrougn NI, Farr AL, Randall RI. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry. 1951; 193. 265–75.
Jaffe M. Concerning both the precipitation caused in normal urine by picric acid and a new reaction with creatinine. Zeitschrift Fuer Physiologische Chemie. 1886; 10: 391–400.
Zar JH. Biostatistical analysis (5 ed.). Prentice-Hall, Englewood. 2014; 960 р.
