Efficacy of Leu-Ile-Lys tripeptide in the correction of experimental urate nephrolithiasis

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 200–220 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 Mann–Whitney 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 (1.6±0.2 and 3.2±0.4, 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) μmol and 5.1 (4.7; 5.5) μmol, 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).