scholarly journals Metformin reduces urate nephropathy in experimental nephrolithiasis

2017 ◽  
Vol 8 (4) ◽  
pp. 644-648
Author(s):  
V. Y. Perfil’ev ◽  
Y. F. Zverev ◽  
D. Y. Perfil’eva ◽  
I. V. Lysenko ◽  
A. G. Miroshnichenko

The objective of the article is to evaluate the effectiveness of metformin in the prevention and treatment of experimental urate nephropathy. About 33% of the populations of developed countries suffers from metabolic syndrome. The relationship between metabolic syndrome, especially insulin resistance, with gout and urate nephrolithiasis, is now proven. The search for a common pathophysiological link in the development of these conditions allows us to identify insulin-dependent excessive urinary acidification due to impaired education and renal ammonium transport. We suggested the use of drugs that can increase the sensitivity of tissues to insulin, and induce a decrease in the manifestations of urate nephropathy. The study was performed on 30 male Wistar rats weighing 250–300 g. For the induction of urate nephropathy in rats, we used the classical model of inhibition of uricase by oxononium acid. Metformin was administered at a dose of 150 mg/kg in the treatment and prophylactic regimens. It was found that the use of metformin both in prophylactic and therapeutic regimen leads to a reliable decrease the level of uric acid in blood plasma and urine in rats with experimental urate nephrolithiasis. We found that the preventive use of metformin brought significant relief after experimental urate nephropathy, as evidenced by a shift in urine pH to the alkaline side, a decreased lactate dehydrogenase activity in urine, as well as a decrease in the processes of free radical oxidation in the blood and in the kidneys of the animals. 

2017 ◽  
Vol 21 (1) ◽  
pp. 52-56
Author(s):  
V. Y. Perfiliev ◽  
Y. F. Zverev ◽  
A. Y. Zharikov ◽  
D. Y. Lukiyanenko ◽  
I. V. Lysenko ◽  
...  

THE AIM. To assess the effectiveness of selective agonist of PPAR gamma receptors (Peroxisome Proliferator-Activated Receptor) pioglitazone, as a drug of prevention and treatment of experimental urate nephropathy. MATERIAL AND METHODS. The study was conducted on 37 male rats Wistar stock. For the formation of urate nephropathy in rats inhibited uricase by co-administration of uric acid and oxonium. For the prevention and treatment of experimental pathology animals received pioglitazone. On day 21 using biochemical and morphological techniques were evaluated received changes. RESULTS. In the experimental condition were observed significant decrease of urate stones in kidneys, significant decrease of uric acid in blood plasma and urine of rats, increase of the urine pH, increase of glomerular filtration rate and inhibition processes of free radical oxidation in the blood of animals. CONCLUSION. Long-term use of pioglitazone in the preventive and therapeutic modes, significantly improves the experimental urate nephrolithiasis. 


Author(s):  
L. G. Petryna ◽  
M. I. Moiseienko

Experimental studies were performed on male Wistar rats. Single exposure of animals at doses of 1.0, 5.0, and 9.0 Gy was performed from a source with dose rates of 0.001, 0.01 0.1, and 1.0 Gy/min. The content of diene conjugates was determined at 0.5, 1, 2, 4, 6, 8, 10, 15, 20, and 30 days after exposure. It was found that the content of diene conjugates of blood varied wavy. The relative change in early products per 1 Gy irradiated at doses of 5.0 and 9.0 Gy was 1.5-2.0 and 4-5 times lower, respectively, than in animals irradiated at dose 1.0 Gy. After 4, 6, 8, 10 days, a clear dependence of the indicator on the magnitude of the radiation dose rate was not observed. The dynamics of accumulation of early LPO R products in the blood of rats, irradiated over a wide range of doses and capacities, indicates the nature of the development or inhibition of free radical oxidation processes.


2017 ◽  
Vol 163 (1) ◽  
pp. 28-30
Author(s):  
V. Yu. Perfil’ev ◽  
Ya. F. Zverev ◽  
A. Yu. Zharikov ◽  
V. M. Bryukhanov

2019 ◽  
Vol 100 (3) ◽  
pp. 439-444
Author(s):  
S E Lorents ◽  
E N Mazko ◽  
O G Makarova ◽  
A Yu Zharikov ◽  
Yu V Korenovskiy ◽  
...  

Aim. To determine the effect of Leu-Ile-Lys tripeptide on indicators of oxidative stress and expression of cyclooxygenase-1 and -2 in the gastric mucosa on the background of experimental indomethacin-induced ulcer. Methods. Experiments were performed on 35 male Wistar rats with a body mass of 200-250 g aged 2-3 months that were divided into 3 groups: the control group (intact rats, 8 animals), control group (simulation of indomethacin-induced gastropathy, 12 animals) experimental group (simulation of indomethacin-induced gastropathy + administration of Leu-Ile-Lys tripeptide, 15 animals). The tripeptide Leu-Ile-Lys obtained by chemical synthesis (sample purity at least 98%) was administered intragastrically daily for 7 days before the simulation of indomethacin-induced damage of the gastric mucosa in a dose of 11.5 mg/kg. The model of indomethacin-induced damage to the rodent gastric mucosa was reproduced by a single intragastric administration of indomethacin in a dose of 60 mg/kg in 1 ml of saline. In the stomach homogenate the activity of free radical oxidation was determined by conventional methods. For quantitative determination of cyclooxygenase-1, -2 in gastric homogenate the method of enzyme immunoassay was used. The concentration was determined spectrometrically by the color intensity of the samples. Results. With a prophylactic administration of tripeptide Leu-Ile-Lys, concentration of tiobarbiturate-reactive products was normalized, total antioxidant activity increased and the activity of antioxidant enzymes decreased compared to the control group. The concentration of cyclooxygenase-2 in gastric homogenate from the experimental animals was 2.3 times lower than that of the control rats. Conclusion. Use of Leu-Ile-Lys tripeptide in experimental indomethacin-induced gastric ulcer showed a significant decrease of oxidative damage and inflammation in the gastric mucosa.


Author(s):  
L. G. Petryna ◽  
M. I. Moiseienko

Experimental studies were performed on male Wistar rats. Single exposure of animals at doses of 1.0, 5.0, and 9.0 Gy was performed from a source with dose rates of 0.001, 0.01 0.1, and 1.0 Gy/min. The content of diene conjugates was determined at 0.5, 1, 2, 4, 6, 8, 10, 15, 20, and 30 days after exposure. It was found that the content of diene conjugates of blood varied wavy. The relative change in early products per 1 Gy irradiated at doses of 5.0 and 9.0 Gy was 1.5-2.0 and 4-5 times lower, respectively, than in animals irradiated at dose 1.0 Gy. After 4, 6, 8, 10 days, a clear dependence of the indicator on the magnitude of the radiation dose rate was not observed. The dynamics of accumulation of early LPO R products in the blood of rats, irradiated over a wide range of doses and capacities, indicates the nature of the development or inhibition of free radical oxidation processes.


2021 ◽  
Vol 11 (3) ◽  
pp. 296-300
Author(s):  
A. Yu. Zharikov ◽  
S.O. Filinova ◽  
O. N. Mazko ◽  
O. G. Makarova ◽  
I. P. Bobrov

The aim of this study was to evaluate the effect of alpha-tocopherol acetate (ATA) on the activity of free-radical oxidation (FRO) in renal tissue and renal function in rats with experimental streptozotocin (STZ)-induced diabetes mellitus (DM). Methods and Results: Experiments were conducted on 22 male Wistar rats aged 60-100 days and weighing 250-300g. The animals were divided into two groups (Group 1 (control) and Group 2 (experimental. To induce DM, the animals were injected intraperitoneally 1ml of STZ solution in the citrate buffer at a dose of 65mg/kg. For more selective modeling of type 2 DM, the rats were previously injected with an intraperitoneal solution of cytoflavin based on a nicotinamide dose of 115mg/kg In Croup 2, ATA was administered in the period from the fifth to eighth weeks, inclusive, intragastrically through a tube at a daily dose of 300mg/kg. Experiments showed that after a 4-week course of ATA, the concentration of thiobarbiturate-reactive products in the kidney tissues of the rats in Group 2 was 5.3 times lower than in Group 1. The activity of all antioxidant enzymes did not differ between the two groups. In both groups, during all 8 weeks of the experiment, the levels of renal excretion of glucose, protein, and creatinine significantly exceeded the initial level, while the level of diuresis remained stable. Conclusion: The long-term administration of ATA in experimental streptozotocin (STZ)-induced DM is accompanied by a significant suppression of the activity of the FRO processes in the kidneys, but does not lead to an improvement in the course of DN.


2021 ◽  
Vol 23 (1) ◽  
pp. 203
Author(s):  
Mariusz Flisiński ◽  
Andrzej Brymora ◽  
Natalia Skoczylas-Makowska ◽  
Anna Stefańska ◽  
Jacek Manitius

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR < 3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.


2012 ◽  
Vol 19 (1) ◽  
pp. 64-69
Author(s):  
Aleksey Valer'evich Ivanov ◽  
Yu P Orlov ◽  
V N Lukach ◽  
T V Pritykina ◽  
A M Ivanova ◽  
...  

Study of ferrum metabolism was performed in 30 patients with traumatic disease, i.e. fractures of the femur, pelvic bones, ribs accompanied by massive muscular hematomas. It has been detected that in severe bone injury besides extravascular hemolysis the intravascular hemolysis, that affects the ferrum metabolism, takes place. Excess of free ferrum activates free radical oxidation processes and results in reduction of total antioxidant activity that is proved by lability of Fe2+ - induced hemiluminescence indices as well as causes the disturbance of blood rheology that influences the course of traumatic disease. Results of experimental study on 30 male Wistar rats in which the conditions of I stage of traumatic shock were created showed that administration of Desferal contributed to blood viscosity improvement.


Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.


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