ABSTRACT
The effect of carnosine on MMP-2 activity and oxidative stress in the kidneys in experimental urate nephrolithiasis was studied. Urate nephrolithiasis was modeled in Wistar rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of MMP-2 in the urine decreased by 3.7 times, and the excretion of MMP-2 with urine decreased by 4.3 times. In the homogenate of the kidneys from rats treated with carnosine, the concentration of TBA-reactive substances decreased by 5 times and the concentration of MMP-2 decreased by 12.7%. After treatment with carnosine, the number of histologically confirmed cases of urate nephrolithiasis decreased by 2 times, while the mean size of urate deposits decreased by 2.7 times. Thus, carnosine inhibits MMP-2 and reduces the intensity of oxidative stress in the kidneys, which prevents the development of urate nephrolithiasis.
Subject(s)
Carnosine , Nephrolithiasis , Animals , Rats , Carnosine/pharmacology , Kidney , Matrix Metalloproteinase 2 , Nephrolithiasis/chemically induced , Nephrolithiasis/drug therapy , Nephrolithiasis/urine , Oxidative Stress , Rats, Wistar , Uric AcidABSTRACT
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.
Subject(s)
Diabetes Mellitus, Experimental , 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/metabolismABSTRACT
The prospect of using the antioxidant dipeptide carnosine for the treatment of urate nephrolithiasis was evaluated. Urate nephrolithiasis was modeled in rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of TBA-reactive products decreased by 1.4 times, the total antioxidant activity increased by 1.4 times, and catalase activity increased by 1.3 times. By the end of the experiment, the lactate dehydrogenate level in experimental rats was 2-fold lower than in the control, and the number of urate deposits decreased by 1.6 times with a concomitant alleviation of the inflammatory processes. Thus, the use of direct peptide antioxidant carnosine attenuated the manifestations of urate nephrolithiasis.
