We studied the effect of tripeptide Leu-Ile-Lys on kidney function in rats with experimental diabetes mellitus modeled by single intraperitoneal administration of streptozotocin (65 mg/kg). The tripeptide was intragastrically administrated in a dose of 11.5 mg/kg from week 5 to week 8 of the pathological process. The concentrations of glucose, protein, and creatinine in the urine were measured before and then weekly throughout the experiment. In 8 weeks, the markers of activity of the free radical oxidation process (concentration of TBA-reactive substances, total prooxidant activity, and total antioxidant activity, as well as activities of catalase, superoxide dismutase, and glutathione peroxidase) were assayed and a morphological study was conducted. After administration of the tripeptide Leu-Ile-Lys for 4 weeks, glucose concentration in the urine decreases by 3-44 times (p<0.001) and protein concentration by 2.3-3.7 times (p=0.007). The concentration of TBA-reactive substances decreased by 1.3 times (p<0.001), and the total antioxidant activity increased by 2.3 times (p<0.001). Administration of the tripeptide Leu-Ile-Lys to animals with experimental diabetes mellitus led to significant improvement of the renal function against the background of significant alleviation of oxidative damage and an increase in the antioxidant protection of the renal tissues. Improvement of the morphofunctional state of tissues and cells of the renal glomerulus was confirmed histologically, in particular, an increase in the number of podocytes by 1.5 times was observed.
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Bryukhanov VM, Zverev YaF, Lampatov VV, Zharikov AYu, Talalaeva OS. Methods of Preclinical (Experimental) Study of the Effect of Drugs on the Kidney Function. Novosibirsk, 2013. Russian.
Zharikov AYu, Yakushev NN, Zharikova GV, Mazko ON, Makarova OG, Lepilov AV. Effect of tripeptide Leu-Ile-Lys on the course of experimental nephrolithiasis. Kazan. Med. Zh. 2021;102(4):494-500. doi: https://doi.org/10.17816/KMJ2021-494. Russian.
Spasov AA, Voronkova MP, Snigur GL, Cheplyaeva NI, Chepurnova MV. Experimental model of a type 2 diabetes. Biomeditsina. 2011;(3):12-18. Russian.
Filinova SO, Zharikov AY, Bobrov IP, Mazko ON, Makarova OG. Pathomorphological picture of diabetic nephropathy in experimental diabetes mellitus. Kazan. Med. Zh. 2019;100(1):147-152. doi: https://doi.org/10.17816/KMJ2019-147. Russian.
Filinova SO, Zharikov AYu, Mazko ON, Makarova OG, Balandovich BA. Indexes of proand antioxidant status in kidneys of rats with experimental diabetes mellitus. Patol. Fiziol. Eksp. Ter. 2020;64(1):124-127. doi: https://doi.org/10.25557/0031-2991.2020.01.124-127. Russian.
Khafaziyanova RKh, Burykin IM, Aleeva GN. Mathematical Statistics in Experimental and Clinical Pharmacology. Kazan, 2006. Russian.
Bhatti AB, Usman M. Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy. Cureus. 2015;7(12):e393. doi: https://doi.org/10.7759/cureus.393
Gerardo Yanowsky-Escatell F, Andrade-Sierra J, Pazarín-Villaseñor L, Santana-Arciniega C, De Jesús Torres-Vázquez E, Samuel Chávez-Iñiguez J, Ángel Zambrano-Velarde M, Martín Preciado-Figueroa F. The Role of Dietary Antioxidants on Oxidative Stress in Diabetic Nephropathy. Iran. J. Kidney Dis. 2020;14(2):81-94.
Podgórski P, Konieczny A, Lis Ł, Witkiewicz W, Hruby Z. Glomerular podocytes in diabetic renal disease. Adv. Clin. Exp. Med. 2019;28(12):1711-1715. doi: https://doi.org/10.17219/acem/104534
Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal. Biochem. 2017;524:13-30. doi: https://doi.org/10.1016/j.ab.2016.10.021
Zhang J, Liu J, Qin X. Advances in early biomarkers of diabetic nephropathy. Rev. Assoc. Med. Bras. (1992). 2018;64(1):85-92. doi: https://doi.org/10.1590/1806-9282.64.01.85
Zharikov AY, Yakushev NN, Mazko ON, Makarova OG, Lepilov AV, Bobrov IP, Zharikova GV, Kiselev VI. Experience of Using Tripeptide Leu-Ile-Lys for Experimental Therapy of Chronic 16-Week Oxalate Nephrolithiasis in Rats. Bull. Exp. Biol. Med. 2020;169(2):237-241. doi: https://doi.org/10.1007/s10517-020-04858-x
Zharikov AY, Yakushev NN, Zharikova GV, Mazko ON, Makarova OG, Lepilov AV, Bobrov IP. Effect of Tripeptide Leu-Ile-Lys on the Course of Experimental Nephrolithiasis. Bull. Exp. Biol. Med. 2019;167(6):747-750. doi: https://doi.org/10.1007/s10517-019-04614-w
Zharikov AYu, Lorentz SE, Bobrov IP, Mazko O.N., Makarova O.G. Pharmacologically active tripeptide Leu-Ile-Lys in indomethacin-induced gastric ulcer. Int. J. Biomed. 2018;8(4):351-354. doi: https://doi.org/10.21103/Article8(4)_OA17
Zimmet P, Alberti KG, Magliano DJ, Bennett PH. Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat. Rev. Endocrinol. 2016;12(10):616-22. doi: https://doi.org/10.1038/nrendo.2016.105
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 173, No. 2, pp. 182-187, February, 2022
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Zharikova, G.V., Zharikov, A.Y., Mazko, O.N. et al. Nephroprotective Effect of Leu-Ile-Lys Tripeptide in Experimental Diabetes Mellitus. Bull Exp Biol Med 173, 210–214 (2022). https://doi.org/10.1007/s10517-022-05520-4
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DOI: https://doi.org/10.1007/s10517-022-05520-4