Nephroprotective Effect of Leu-Ile-Lys Tripeptide in Experimental Diabetes Mellitus

Bull Exp Biol Med. 2022 Jun;173(2):210-214. doi: 10.1007/s10517-022-05520-4. Epub 2022 Jun 23.

Abstract

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.

Keywords: diabetes mellitus; kidney function; tripeptide Leu-Ile-Lys.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Catalase / metabolism
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Glucose / metabolism
  • Glutathione Peroxidase / metabolism
  • Kidney / metabolism
  • Oxidative Stress
  • Rats
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glucose