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Aim. To study the effect of the Leu-Ile-Lys (leucine-isoleucine-lysine) tripeptide on the course of experimental urate nephrolithiasis. Methods. The experiment was carried out on 23 male Wistar rats weighing 200220 grams that were divided into a control (n=8, modeling of urate nephrolithiasis) and an experimental (n=15, modeling of urate nephrolithiasis + administration of Leu-Ile-Lys tripeptide) groups. The tripeptide was administered intragastrically through a tube at a dose of 11.5 mg/kg. Daily urine was collected on a weekly basis, and the activity of lactate dehydrogenase and gamma-glutamyl transpeptidase was determined. After three weeks of the experiment, the animals were euthanized, and kidneys were removed to determine the parameters of free radical oxidation [concentration of thiobarbituric acid reactive substances (TARS), total pro-oxidant and total antioxidant activity, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX)] and conduct a morphological study in which the number and area of calculi and the condition of the renal tissues were determined. Statistical data processing was performed using the Statistica 12.0 software. We used the MannWhitney U test, the Wilcoxon signed rank test. The results are presented as median with the 25th and 75th percentiles. The differences were considered significant at p 0.05. Results. In the kidneys of the rats of the experimental group, the number of deposits decreased twofold, as compared with the control group (1.60.2 and 3.20.4, respectively, p=0.001). Lactate dehydrogenase activity in the urine of rats increased from 0.10 (0.06; 0.21) units/mg of creatinine per day initially to 0.75 (0.44; 1.07) units/mg creatinine per day on day 21 (p=0.012) in the control group, and from 0.10 (0.06; 0.12) units/mg creatinine per day to 0.45 (0.34; 0.71) units/mg creatinine per day on 21st day (p=0.003) in the experimental group. The concentration of thiobarbituric acid reactive substances in the experimental group was 1.2 times lower than that of the control group: 4.2 (3.9; 4.6) mol and 5.1 (4.7; 5.5) mol, respectively (p 0.001). In addition, in the kidneys of the rats of the experimental group, the total antioxidant activity was 1.3 times higher than in control: 70.4 (65.4; 74.1)% and 53.8 (33.3; 62.2)% respectively (p 0.001). Superoxide dismutase activity in the experimental group was 1.5 times higher than in the control group: 12.4 (11.0; 13.2)% against 8.1 (6.4; 13.1)% (p=0.016). Catalase activity in the experimental group was 1.2 times higher than in the control group: 31.1 (26.4; 36.1)% against 25.1 (20.3; 27.1)% (p=0.005). Conclusion. The Leu-Ile-Lys tripeptide has a litholytic effect, manifested in a statistically significant decrease in the activity of oxidative stress markers (p 0,001) and a twofold decrease in the average amount of uric acid kidney stones (p 0,001).

We studied the effect of tripeptide Leu-Ile-Lys on the course of chronic 16-week oxalate nephrolithiasis in rats modeled by administration of 1% ethylene glycol solution in drinking water for 16 weeks. The tripeptide Leu-Ile-Lys obtained by chemical synthesis (sample purity ≥98%) was administered intragastrically through a probe in a dose of 11.5 mg/kg in 1 ml saline. It was found that during tripeptide Leu-Ile-Lys significantly alleviated the course of experimental pathology, which was confirmed by characteristic biochemical and morphological indicators. We observed a decrease in the concentration of calcium ions by 4.4 times, weakening of oxidative stress in the renal tissue due to a decrease in the total prooxidant activity by 1.2 times, normalization of increased catalase activity, and reduction of superoxide dismutase activity by 2.4 times relative to disease control. Histological signs of nephrolithiasis were recorded in 9% cases (vs. 75% cases in disease control).

We studied the effect of Leu-Ile-Lys tripeptide on the course of experimental oxalate nephrolithiasis modeled in rats by administration of 1% ethylene glycol solution instead of drinking water for 6 weeks. The Leu-Ile-Lys tripeptide obtained by chemical synthesis (purity ≥98%) was administered through a gastric tube (11.5 mg/kg in 1 ml saline). Administration of Leu-Ile-Lys tripeptide against the background of experimental oxalate nephrolithiasis significantly alleviated the course of experimental pathology, which was confirmed by typical biochemical and morphological changes: decrease in urinary activity of γ-glutamyltransferase (by 2.1 times in comparison with the initial level) and intensity of oxidative stress (the content of TBA-reactive products decreased by 1.3 times in comparison with that in untreated animals) and increase in glutathione peroxidase activity by 1.8 times; no histological signs of nephrolithiasis were found in animals treated with the tripeptide.

to study the pathologic features of chronic oxalate stone disease.a model of the experimental oxalate stone disease was done in rats that drank the 1% ethylene glycol solution for 16 weeks. The pathologic analysis of the rats kidneys was done.After 16 weeks of oxalate stone disease modeling in all parts of kidneys the large crystals deposits were found, which plugged renal tubules. Moreover, purulent calculous pyelonephritis developed complicated by fibrosis.

Intermittent hypercapnic hypoxia was accompanied by increases in cerebral vascular resistance, decreases in the reactivity of cerebral vessels to hypercapnia, and increases in the collateral reserve and rate of autoregulation of brain blood flow. These changes were an important component of the mechanism increasing the tolerance of the brain to ischemia in response to training with hypercapnic hypoxia.

The effectiveness of hypercapnic hypoxic training in the prevention of acute disturbances in cerebral circulation was studied under experimental conditions. Hypercapnic hypoxic training was followed by a significant decrease in the severity of neurological deficit and locomotor and coordination disorders after cerebral ischemic injury.