scholarly journals Effects of agmatine and red wine concentrate, enriched with polyphenolic compounds, on L-arginine / nitrogen oxide system in the brain of rats with experimental diabetes mellitus

2021 ◽  
Vol 15 (2) ◽  
pp. 25-34
Author(s):  
K. R. Spryn ◽  
◽  
M. V. Sabadashka ◽  
N. O. Sybirna ◽  
◽  
...  

Background. Diabetes mellitus is a chronic endocrine metabolic disease with absolute or relative insufficiency of insulin, accompanied by impaired metabolism. Endogenous bioamine agmatine may become a basis of new antidiabetic drugs, as it is capable to induce the release of some peptide hormones, in particular insulin, and can regulate NO synthesis. Natural polyphenols are potential multifunctional agents that also can reduce the risk of diabetes and diabetic complications. The aim of the study was to evaluate the effect of agmatine and red wine concentrate, enriched with polyphenolic compounds, on NO-synthase activity and the content of NO stable metabolites under experimental diabetes mellitus. Materials and Methods. The experiments were conducted on white Wistar male rats. Diabetes was induced by intra-abdominal injection of streptozotocin. From the 14th day after the induction of diabetes, agmatine was injected intramuscularly or red wine concentrate, enriched with polyphenolic compounds was administrated orally to animals for 14 days. Rats were decapitated under ether anesthesia on the 28th day of the experiment. In the brain of rats, the activity of constitutive (Ca2+-dependent) and inducible (Ca2+-independent) isoforms of NO-synthase and the content of nitrite and nitrate anions were determined. Results and Discussion. The activities of constitutive and inducible isoforms of NO-synthase were increased in the brain of diabetic rats. The administration of both agmatine and red wine concentrate, enriched with polyphenolic compounds, caused the reduction of the activities of NO-synthase isoforms. In the case of diabetes, the administration of agmatine contributes to the increase of nitrite and nitrate content in brain cells compared to diabetes. The administration of red wine concentrate, enriched with polyphenolic compounds, also promotes nitrite levels but does not affect the nitrate level. Conclusion. We found that the red wine concentrate, enriched with polyphenolic compounds, has a stronger effect on the activity of Ca2+-dependent and Ca2+-independent isoforms of NO-synthase, as well as the content of nitrites and nitrates in brain of rats with experimental diabetes mellitus, compared to the effect of agmatine.

2021 ◽  
Vol 15 (1) ◽  
pp. 37-48
Author(s):  
D. Yu. Hertsyk ◽  
◽  
M. V. Sabadashka ◽  
L. V. Kaprelyants ◽  
N. O. Sybirna ◽  
...  

Background. Diabetes mellitus is accompanied by oxidative-nitrative stress, which is caused both by an increased generation of the Reactive Oxygen Species and the Reactive Nitrogen Species under the conditions of this pathology and by the disorders of the antioxidant defense system, especially its enzymatic part. This leads alterations in the morpho-functional state of cells, organs, and the whole organism. Free radicals are involved in the destruction of pancreatic cells in type 1 diabetes mellitus, which leads to even greater inhibition of insulin secretion, worsening of the course of the disease and occurrence of diabetic complications. The complications of diabetes mellitus include often diagnosed cardiovascular diseases. Therefore, the use of treatments characterized not only by hypoglycemic properties for normalization of blood sugar level in diabetes mellitus, but also by antioxidant properties for normalization of oxidative/antioxidant balance of the organism in the studied pathology can be promising. Scientists pay a great attention to the study of substances with such properties, especially natural phenolic compounds of grape, which are also characterized by immunomodulatory properties. Materials and Methods. The study was performed on cardiac tissues of control rats, control animals treated with wine polyphenolic complex concentrate, animals with streptozotocin-induced diabetes mellitus and animals with experimental diabetes mellitus treated with a concentrate of wine polyphenolic complex. The activity of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase were detected to examine the corrective effect of the concentrate of red wine natural polyphenolic comp­lex on the state of the enzymatic part of the antioxidant defense system. Results. The results have shown the normalization of activity of catalase, superoxide dismutase, and changes in the activity of enzymes of glutathione cycle after oral administration of polyphenolic complex concentrate for 14 days to rats with streptozo­tocin-induced diabetes mellitus. Conclusions. The results confirm a hypothesis about the antioxidant effect of the studied concentrate and the ability of natural polyphenolic complexes to serve as the basis for new drugs for treatment of diabetes-induced disorders.


2020 ◽  
Vol 26 (2) ◽  
pp. 39-44
Author(s):  
I.A. Tymoshenko ◽  
L.M. Sokurenko ◽  
A.Ya. Yanchyshyn ◽  
V.A. Pastukhova

Currently, severe thermal injury is becoming one of the most important problems of practical medicine. Diabetes is also recognized as another global medical and social challenge of our century. The emergency situation for the treatment and prevention of the consequences of these pathologies is a consequence of the lack of a reliable theoretical basis for solving specific clinical problems regarding the course of burns, diabetes and their complications. The aim of the study is to establish the patterns of structural changes in the mucous membrane of the duodenum after burn injury of the skin of rats under conditions of experimental diabetes mellitus. The study was performed on 63 laboratory white adult male rats weighing 180-210 g, which were divided into 3 groups: intact animals, rats with skin burns and rats with skin burns on the background of diabetes. The model of experimental diabetes mellitus was reproduced by administering Streptozotocin to rats intraperitoneally once at a dose of 50 mg/kg, pre-dissolved in 0.1 M citrate buffer solution (pH=4.5). The control of the development of hyperglycemia in the experimental groups was the level of glucose in the blood 24.24±0.79 mmol/l. In the control group this index was 8.03±0.4 mmol/l. Rats with skin burns revealed destructive manifestations, which are accompanied by an active inflammatory reaction and corresponding necrotic changes, while rats with skin burns on the background of diabetes mellitus pathological processes are not just “summed up”, but in some way adaptively modified with the involvement of stress mechanisms of the endoplasmic reticulum and associated autophagy.


2020 ◽  
Vol 27 (4) ◽  
pp. E2020413
Author(s):  
Ihor Bilinskyi

The objective of the research was to determine the morphological features of the duodenal wall of animals within 14-56 days of developing streptozotocin-induced diabetes mellitus using light optical microscopy. Materials and Methods. The research was carried out on 40 white nonlinear adult male rats. Diabetes mellitus was simulated by a single intraperitoneal injection of streptozotocin (Sigma, USA) at a dose of 60 mg/kg body weight. The material was taken from the duodenum on the 14th, 28th and the 56th days after the onset of experimental diabetes mellitus. For histological study, the preparations were made using the conventional method, which included the staining of sections with hematoxylin and eosin. Results. Streptozotocin-induced diabetes mellitus was experimentally found to lead to dystrophic changes in the epithelial components of the duodenal mucosa from the 14th day of developing. There were observed a shortening of the villi of the mucous membrane and a lack of distinctness of striated border contours on the apical surface of epitheliocytes. Between the connective-tissue fibers of the lamina propria of the mucosa and thin-walled vessels, the cellular elements, including mainly macrophages, lymphocytes, were found. There was a shortening of the villi, edema and histiolymphocytic infiltration of the villous stroma 28 days after developing experimental diabetes mellitus. The epithelium covering was discontinuous; numerous areas of desquamation were found at the apex of the villi. Fifty-six days after developing experimental diabetes mellitus, the destruction and desquamation of the epithelium of the villi and crypts were observed. The surface of the duodenal mucosa smoothed down due to the shortening and flattening of the villi (indicating their atrophy), while the crypts elongated and their depth increased. Conclusions. Histological study of the duodenal wall of diabetic animals showed pronounced desquamation at the apex of the villi, destructive and dystrophic changes in the surface epithelium, edema and increased cellular infiltration of the lamina propria of the mucosa. Thus, in diabetes mellitus, structural changes in the duodenal wall of rats are characterized by the dystrophic processes, which can be considered as the morphological reflection of enteropathy.


Author(s):  
S.O. Filinova ◽  
A.Yu. Zharikov ◽  
O.N. Mazko ◽  
O.G. Makarova ◽  
B.A. Balandovich

Цель исследования - изучение активности процесса свободнорадикального окисления в почках крыс в условиях экспериментального сахарного диабета. Методика. Исследование выполнено на 25 самцах крыс Вистар. Животные были разделены на 2 группы: группа интактных крыс (контроль) и группа животных с сахарным диабетом (опыт) по 12 и 13 особей соответственно. Моделирование сахарного диабета осуществляли внутрибрюшинным введением стрептозотоцина (65 мг/кг). Для селективного моделирования сахарного диабета II типа крысам группы «опыт» предварительно вводили внутрибрюшинно 1 мл раствора цитофлавина (из расчета дозы никотинамида 115 мг/кг). Группе интактных крыс аналогичным способом вводили 1 мл физиологического раствора. На 28-е сут эксперимента животных декапитировали под эфирным наркозом с целью изучения активности процесса свободнорадикального окисления в почках. В тканях почек определяли концентрацию тиобарбитуратреактивных продуктов окисления жирных кислот, оценивали общую прооксидантную активность по интенсивности окраски флуоресцентного комплекса, образующегося при взаимодействии продуктов перекисного окисления ТВИН-80 с тиобарбитуровой кислотой. Определяли активность антиоксидантных ферментов: каталазы, супероксиддисмутазы и глутатионпероксидазы. Активность каталазы определяли по подавлению ферментом окисления молибдата натрия перекисью водорода. Активность супероксиддисмутазы оценивали по содержанию в пробе нитроформазана - окрашенного продукта восстановления нитротетразолия синего супероксидными радикалами. Определяли содержание неокисленного глутатиона (маркера активности глутатионпероксидазы) по цветной реакции с реактивом Эллмана. Результаты. В ходе исследования было установлено увеличение концентрации тиобарбитуратреактивных продуктов окисления жирных кислот, основным представителем которых является малоновый диальдегид, увеличение общей прооксидантной активности, а также активности глутатионпероксидазы и супероксиддисмутазы. Заключение. В условиях экспериментального сахарного диабета наблюдаются признаки выраженного оксидативного стресса в почечной ткани, о чем свидетельствует увеличение концентрации тиобарбитуратреактивных продуктов окисления жирных кислот и общей прооксидантной активности, а также повышение активности антиоксидантных ферментов.The aim of the study was to assess indexes of pro- and antioxidant status of the kidneys in experimental diabetes mellitus. Methods. The study was performed on 25 Wistar male rats in compliance with requirements of the Rules for Carrying Out Work using Experimental Animals. The animals were divided into two groups, a group of intact rats (control) and a diabetic group (experiment) containing 12 and 13 rats, respectively. Diabetes mellitus was modeled with an injection of streptozotocin (65 mg/kg, i.p.). For more specific modeling of type 2 diabetes, the rats of the experimental group received a solution of cytoflavin at a dose equivalent to nicotinamide 115 mg/kg, i.p. At 28 days of the experiment, rats were decapitated under ether anesthesia, and activity of free radical oxidation (FRO) was studied in the kidneys. The following indexes were determined in the kidney tissue: concentration of thiobarbiturate- reactive fatty acid oxidation products (TPBP); total pro-oxidant activity by color intensity of the fluorescent complex formed by the interaction of TWEEN-80 peroxidation products with thiobarbituric acid; activities of antioxidant enzymes, catalase (CAT), superoxide dismutase), and glutathione peroxidase (GPO). CAT activity was measured by the CAT inhibition of sodium molybdate oxidation with hydrogen peroxide. SOD activity was measured by the content of nitroformazan, a colored product of nitrotetrazolium reduction with superoxide radicals. The marker of GPO activity, unoxidized glutathione, was measured by the color reaction with Ellman’s reagent. Results. The study findings included increased TBP represented primarily by malonic dialdehyde, as well as increased TPOA (total pro-oxidant activity), and GPO and SOD activities in diabetic kidneys. Conclusion. Experimental diabetes mellitus was associated with pronounced oxidative stress in the kidney tissue, as evidenced by increased TPBP and TPOA, as well as by increased activities of antioxidant enzymes.


2019 ◽  
Vol 100 (1) ◽  
pp. 147-152 ◽  
Author(s):  
S O Filinova ◽  
A Yu Zharikov ◽  
I P Bobrov ◽  
O N Mazko ◽  
O G Makarova

Aim. To conduct a morphological study of the renal glomerulus in experimental diabetes mellitus and to study the pathomorphological features of the development of diabetic nephropathy. Methods. The study was carried out on 25 male Wistar rats. Modeling of diabetes mellitus was carried out by intraperitoneal injection of streptozotocin at a dose of 65 mg/kg. For more selective modeling of type 2 diabetes, the rats of the control group were intraperitoneally administered a solution of cytoflavin, calculated by the dosage of nicotinamide 115 mg/kg. In the comparison group 1 ml of physiological solution was administered in a similar manner. On day 28 of the experiment, the animals were euthanized under ether anesthesia, the kidneys were extracted, purified and washed with physiological saline. The material was fixed in a 10% neutral formalin solution. Using the morphometric method, the area of the renal glomeruli and the area of the capillary lumens were measured, and after special computer processing of digital photographs, the total area of the vascular bed in the glomerulus and the area of mesangium in the renal glomerulus were estimated. Results. After four weeks of experiment on rats with diabetes mellitus, some characteristic changes in the morphofunctional state of renal tissues developed: an increase of the area of renal glomeruli, thickening of the basement membrane of glomerular capillaries, an increase in the size of podocytes with a decrease of their number, and foci of nephrosclerosis. Conclusion. Based on the results of the study, characteristic pathomorphological phenomena in the kidneys of rats with experimental diabetes mellitus were recorded, which indicate the development of diabetic nephropathy.


2021 ◽  
Vol 15 (3) ◽  
pp. 3-16
Author(s):  
O. I. Karmash ◽  
◽  
M. Ya. Liuta ◽  
N. V. Yefimenko ◽  
N. O. Sybirna ◽  
...  

Background. Diabetes mellitus is a chronic endocrine-metabolic disease caused by an absolute or relative insulin deficiency. During diabetes, there are perfect conditions for the development of oxidative stress: the content of substrates for oxidation increases, the content of natural antioxidants decreases and the activity of antioxidant systems is suppressed. It is known that photobiomodulation therapy produce antioxidant and antihyperglycemic effects. Here we investigated its influence on blood system functioning. Materials and Methods. The study was performed on male Wistar rats. Experimental diabetes mellitus was induced by the intraperitoneal injection of streptozotocin. Leukocyte formula was calculated using blood smears stained by Romanowsky–Giemsa. Catalase activity was determined spectrophotometrically. Affinity of hemoglobin to oxygen was evaluated by spectrophotometric method in Ivanov’s modification by drawing oxygenation curves. The protoporphyrin content in whole blood was measured by analyzing its fluorescence spectra. The content of NO2-, total and inducible NO synthase activity was determined spectrophotometrically. Results. Under the action of photobiomodulation therapy on healthy animals, there was a shift of oxygenation curves to the left and a decrease of P50, whereas under irradiation of rats with diabetes, there was a shift of oxygenation curves to the right and increase in P50 compared to indices in nonirradiated animals. During diabetes, there was a decrease in protoporphyrin content compared to control, but there was a tendency to increase under photobiomodulation. Photobiomodulation therapy of rats with diabetes increased catalase activity in erythrocyte hemolysates. We revealed significant changes in leukocyte formula under photobiomodulation. The total NO synthase activity in leukocytes of rats with diabetes was higher compared to healthy animals, but decreased under the action of photobiomodulation. We found an increase in inducible NO synthase activity in leukocytes of rats with diabetes and in leukocytes of irradiated healthy animals. An increase in NO2- content in leukocytes of rats with diabetes was detected. Under photobiomodulation, NO2- content was significantly lower in rats with diabetes. Conclusion. Photobiomodulation therapy produces a corrective action on blood system during diabetes, in particular, it improves oxygen release from hemoglobin and prevents hypoxia. Simultaneously with the increase in tissue oxygen saturation, a decrease in NO synthase activity and nitrite content along with an increase in catalase activity prevents the development of oxidative stress.


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