THE FUNCTIONAL STATE OF THE KIDNEYS IN EXPERIMENTAL AUTOIMMUNE HEYMAN NEPHRITIS AGAINST THE BACKGROUND OF THE INTRODUCTION OF CRYOEXTRACTS OF THE PLACENTA AND SPLEEN, AS WELL AS THE CONDITIONED MEDIUM OF MESENCHYMAL STEM CELLS
DOI:
https://doi.org/10.32689/2663-0672-2024-2-2Keywords:
Heymann autoimmune nephritis, placenta cryoextract, mesenchymal stem cells, glomerular filtration rate, creatinineAbstract
Introduction. Among all autoimmune glomerulonephritis (GN), idiopathic membranous nephropathy (MN) is the leading cause of chronic kidney disease. Idiopathic MN is a primary membranous GN characterized by damage to podocytes mediated by antibodies against podocyte antigens deposited under glomerular visceral epithelial cells to activate complement. Cell-free cryopreserved biological agents – cryopreserved extracts of biological tissues, in particular the spleen (as an immunocompetent organ) and the placenta (as a key regulator of intrauterine fetal development) have attracted our attention as innovative biotechnological drugs for the treatment of MN. Products of cell cultivation – the so-called conditioned media, in particular, conditioned media obtained from mesenchymal stromal cells (MSC-СM) – deserve no less attention. Previous studies have shown convincing evidence of distinct immunomodulating activity in other autoimmune diseases (in particular, in autoimmune arthritis and allergic encephalomyelitis, etc.) in cryoextract of the placenta (CEP), cryoextract of the spleen (CES) and MSC-CM. The aim of the study is to characterize the influence of CEP, CES and MSС-CM on the functional state of kidneys in experimental autoimmune Heimann nephritis. Materials and methods. Studies on the effectiveness of cell-free cryopreserved biological agents in Heimann's autoimmune nephritis (AIN) were conducted on 42 male rats. AIN was reproduced according to the method of Heymann W.R. and sang (1965) in the modification of Wichert A.M. (1973). 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 content of urea in the blood was determined spectrophotometrically by the reaction of ammonia with 2-oxoglutarate with the participation of glutamate dehydrogenase. The content of creatinine in the blood was determined spectrophotometrically by the reaction of picrates with creatinine. Glomerular filtration rate (GFR) was calculated according to the method of Besseling P.J. and all. Research results and their discussion. It was established that on the 70th day of the experiment, a statistically significant (p˂0.001) decrease in the volume of daily diuresis by 47.2% compared to the parameters of intact rats was noted, which was 3.7±0.2 ml/day. Biochemical blood tests showed that against the background of a decrease in daily diuresis in rats with AIN, a statistically significant (p˂0.001) increase in creatinine concentration by 111.3% and urea by 233.3% compared to the parameters of intact rats was noted. Against the background of the use of CEP, the lowest decrease in the concentration of creatinine in the blood (p=0.01) was noted – 16.8%. The use of CES in rats with AIN had nephroprotective properties comparable in expression to canefron, which was indicated by a statistically significant (p=0.002) increase in GFR by 64.3% (551±43 μl/min) compared to the indicators of rats in the control group. The most pronounced restoration of the functional state of the kidneys of rats was established against the background of the use of MSC-CM. Conclusions. The study showed that the studied cell-free cryopreserved biological agents have nephroprotective activity against the background of Hayman's nephritis in rats, which was indicated by the restoration of the functional activity of the kidneys, which was confirmed by the increase in the gastrointestinal tract and the decrease in the concentration of creatinine and urea in the blood of rats with AIN. According to the expressiveness of the nephroprotective effect (according to GFR indicators), the studied cell-free cryopreserved biological agents can be placed in the following sequence: MSC-CM (GFR: 856±59 ml/min) ˃ CES (GFR: 551±43 mh/min) ˃ CEP (GFR: 504±19 ml/min).
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