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

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Abstract

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).

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A Yu Zharikov

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

O N Mazko

Altai State Medical University; Altai State University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia; Barnaul, Russia

O G Makarova

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

I P Bobrov

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

A S Kalnitsky

Altai State Medical University

Author for correspondence.
Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

G V Zharikova

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

N N Yakushev

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

I E Gossen

Altai State Medical University

Email: artem_kalnitsky@mail.ru
Russian Federation, Barnaul, Russia

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Supplementary files

Supplementary Files
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1. Рис. 1. Сравнение показателей прооксидантного статуса в почках крыс контрольной группы и подопытной группы; ТБРП — тиобарбитурат-реактивные продукты; ОПА — общая прооксидантная активность. По горизонтальной оси — название показателя и единицы измерения. По вертикальной оси — значение показателя. Значения представлены в виде медианы и интерквартильного размаха. Звёздочкой обозначены статистически значимые различия в подопытной группе по сравнению с контрольной

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2. Рис. 2. Сравнение показателей общей антиоксидантной активности (ОАА) и активности антиоксидантных ферментов в почках крыс контрольной группы и подопытной группы. По горизонтальной оси — название показателя и единицы измерения. По вертикальной оси — значение показателя. Значения представлены в виде медианы и интерквартильного размаха. Звёздочкой обозначены статистически значимые различия в подопытной группе по сравнению с контрольной. СОД — супероксиддисмутаза; КАТ — каталаза; ГПО — глутатионпероксидаза

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3. Рис. 3. Гистологическая картина уратного нефролитиаза в почках экспериментальных крыс. Окраска по Коссу. Увеличение ×400: а — уратные депозиты в кистозно-изменённом канальце почки у животного контрольной группы; б — уратные депозиты в канальце почки на 21-й день эксперимента при применении трипептида Leu-­Ile-Lys

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© 2021 Zharikov A.Y., Mazko O.N., Makarova O.G., Bobrov I.P., Kalnitsky A.S., Zharikova G.V., Yakushev N.N., Gossen I.E.

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