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Eksperimental'naya i klinicheskaya urologiya

Therapy with xenogenic proteomic complex from embryonic brain cells inhibits the progression of experimentally induced chronic renal failure

Number №3, 2023 - page 26-37
DOI: 10.29188/2222-8543-2023-16-3-26-37
For citation: <p>&nbsp;Kirpatovskiy V.I., Sivkov A.V., Sokolov M.A., Golovanov S.A., Drozhzheva V.V., Sinyukhin V.N., Frolova E.V., Apolikhin O.I., Kaprin A.D. Therapy with xenogenic proteomic complex from embryonic brain cells inhibits the progression of experimentally induced chronic renal failure. Experimental and Clinical Urology 2023;16(3):26-37; https://doi.org/10.29188/2222‑8543‑2023‑16‑3‑26‑37</p>
Kirpatovskiy V.I. Sivkov A.V. Sokolov M.A. Golovanov S.A. Drozhzheva V.V. Sinyuhin V.N. Frolova E.V. Apolihin O.I. Kaprin A.D.
Information about authors:
  • Kirpatovskiy V.I. – Dr. Sci., professor, сhief scientific Researcher of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 604441; https://orcid.org/0000-0002-4356-9200
  • Sivkov A.V. – PhD, Deputy Director of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 622663, https://orcid.org/0000-0001-8852-6485
  • Sokolov M.A. – developer of the «Cellex», Deputy Director for new drugs of JSC «PharmSynthesis»; Moscow, Russia
  • Golovanov S.A. – Dr. Sci., head of clinical laboratory diagnostic group of scientific laboratory department of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 636685; https://orcid.org/0000-0002-6516-4730
  • Drozhzheva V.V. – researcher of scientific Laboratory Department of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 696724
  • Sinyukhin V.N. – Dr. Sci., professor, of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 698113
  • Frolova E.V. – Chief researcher, Department of «Biology» of All-Russian Institute of Scientific and Technical Information of RAS; Moscow, Russia
  • Apolikhin O.I. – Dr. Sci., professor, сor.-member of RAS, director of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation; Moscow, Russia; RSCI Author ID 683661; https://orcid.org/0000-0003-0206-043X
  • Kaprin A.D. – Dr. Sci., professor, academician of RAS, general director of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation, director of P.A. Herzen Institution, Head of Department of Oncology and Radiology named after V.P. Kharchenko of RUDN University; Moscow, Russia; RSCI Author ID 96775; https://orcid.org/0000-0001-8784-8415
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Introduction. In previously published experimental studies, we have shown that in rats with pre-modeled acute post-ischemic renal failure, therapy with a proteomic complex isolated from brain cells of pig embryos has a pronounced therapeutic effect, reducing the severity of functional and histological disorders and preventing the transition of the pathological process into chronic kidney insuffiency. The aim of this study is to evaluate the effectiveness of this therapy for the course of artificially induced chronic renal failure (CRF) in rats.

Material and methods. Experiments were carried out on 45 white mongrel male rats weighing 200-240 g. CRF was modeled by unilateral nephrectomy and resection of both poles of the remaining kidney, which reduced the mass of the functioning parenchyma by 80%. In the 1-st series of experiments no therapy was performed. In the 2-nd - 4-th series the animals were intraperitoneally injected with a fractionated xenogenic proteomic complex (secretom) from pig brain stem and progenitor cells (SSPC) at a daily dose of 0.1 ml in different modes: two 10-days courses with a 10-days break between them (2nd series); prolongation of the 1st course up to 20 days and a repeated 10-days course after 10 days (3rd series); continuous SSPC therapy for 30 days (4-th series). 5th series – intact animals. The effectiveness of therapy was evaluated based on the severity of the development of compensatory renal hypertrophy, the dynamics of biochemical parameters of kidney function, the activity of enzymes (ALT, AST, LDH, alkaline phosphatase) in blood and urine and the level of uremic neurotoxins 3-indoxyl sulfate and ptolyl sulfate in the blood.

Results. SSPC therapy in all variants contributed to a more pronounced compensatory hypertrophy of the remaining kidney, as well as a decrease in the severity of the main functional indicators after 30 and 60 days: the severity of polyuria decreased, the concentration of urea in the blood decreased to a greater extent, and the glomerular filtration rate and tubular reabsorption of sodium and calcium approached normal values, which was not observed in the control series. The severity of the therapeutic effect was more pronounced with continuous 30-day therapy. There was also a less pronounced increase in the activity of enzymes in the blood and their excretion in the urine, which indicated the cytoprotective effect of SSPC therapy. If in the control series of experiments, the deterioration of the studied indicators were noted with an increase in the observation period from 30 to 60 days, whereas in all experimental series they remained at a subnormal level. SSPC therapy also contributed to a lower accumulation of uremic toxins (3-indoxyl sulfate and p-tolyl sulfate) in the blood.

Conclusion. Prolonged therapy of SSPC prevents the progression of CRF by stimulating compensatory hypertrophy of the kidney and cytoprotective effect and promotes more effective elimination of uremic toxins, preventing their accumulation in the blood.

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Keywords: chronic renal failure; proteomic complex; stem cells; progenitor cells; secretom; uremic toxins