scholarly journals The Blocking on the Cathepsin B and Fibronectin Accumulation in Kidney Glomeruli of Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-11
Author(s):  
Aleksandra Wyczalkowska-Tomasik ◽  
Irena Bartlomiejczyk ◽  
Agnieszka Wirkowska ◽  
Lukasz Koperski ◽  
Barbara Gornicka ◽  
...  

Hyperglycemia results in the activation of tissue angiotensin II. Angiotensin II stimulates the synthesis of ECM proteins and causes a decrease activity of proteolytic enzymes. The aim of this study was to assess the impact of multilevel blocking of the RAAS, cathepsin B activity, and fibronectin accumulation in the glomerular in the rats diabetes model. Sixty male Wistar rats were initially included. Diabetes was induced by intravenous administration of streptozotocin. The animals were randomized to six groups of ten rats in group. Rats in the four groups were treated with inhibitors of the RAAS: enalapril (EN), losartan (LOS), enalapril plus losartan (EN+LOS), and spironolactone (SPIR); another group received dihydralazine (DIH) and the diabetic rats (DM) did not receive any drug. After six weeks, we evaluated blood pressure, 24 h urine collection, and blood for biochemical parameters and kidneys. In this study, fluorometric, ELISA, and immunohistochemical methods were used. Administration of EN+LOS increased activity of cathepsin B in homogenates of glomeruli compared to DM. Losartan treatment resulted in reduction of the ratio kidney weight/body weight compared to untreated diabetic rats. SPIR resulted in the increase activity of cathepsin B in the homogenate of glomeruli. The values of cathepsin B in the plasma of rats in all studied groups were similar and showed no tendency.

2021 ◽  
Author(s):  
Soraya Sajadimajd ◽  
Bahareh Mohammadi ◽  
Gholamreza Bahrami ◽  
Seyed Hamid Madani ◽  
Razieh Hatami ◽  
...  

Abstract Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of isolated polysaccharide from Memordica charantia in diabetic rats. The polysaccharide was isolated from Memordica charantia (MCP) and characterized using FTIR and LC-MS/MS. Diabetic model was established by intrapritoneal administration of STZ in male Wistar rats. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31 and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the carbohydrate structure of fraction. Blood glucose was halted by treatment with fraction. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1 and Hes1 while scaled down the levels of Notch1, Dll4 and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining of hes1, cyclin d1 and VEGF proteins was increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets regeneration and suggest that modulation of notch and angiogenesis pathways may play the pivotal role in the restoration of islets to relieve diabetes.


Biologia ◽  
2017 ◽  
Vol 72 (8) ◽  
Author(s):  
Syed Muhammad Nurulain ◽  
Shreesh Ojha ◽  
Mohamed Shafiullah ◽  
Javed Yasin ◽  
Tayyaba Yasmin ◽  
...  

AbstractThe consequences of chronic exposure of organophosphorus compounds (OPCs) on diabetic subjects have been seldom reported. The aim of the present study was to assess the impact of non-lethal dose of terbufos sulfone (TS), an organophosphate, on the kidney of non-diabetic and streptozotocin (STZ)- induced diabetic rats. The diabetogenic effect of TS was also examined. Male Wistar rats were treated for two weeks with 130 µg/kg body weight/day of TS. This dose was 1/20 of LD


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Zsolt Razga ◽  
Gabor Kovacs ◽  
Nikolett Bódi ◽  
Petra Talapka ◽  
Mária Bagyánszki

Objective. The nephron (pro)renin receptor may play a pathophysiological role in renal disorders in hypertension or diabetes. The aim of this study was to determine the relationship of (pro)renin receptors and transdifferentiation between the renin-negative and renin-positive SMCs in the afferent arteriole by estimating the distribution of (pro)renin receptors in renin-positive and renin-negative SMCs of the afferent arteriole of kidneys in normal and streptozotocin- (STZ-) induced diabetic rats. Therefore in diabetes the renin granulation of afferent arterioles is different as in normal, the diabetes model for finding the differences to normal in distribution of (pro)renin receptors of afferent arterioles was used. Method. To estimate the number of (pro)renin receptors in arteriolar SMCs a special protocol of immunohistochemistry to stereology was followed. Results. Our results showed that on the surface of renin-positive SMCs the number of (pro)renin receptors was upregulated, while in the cytoplasm of SMCs there was downregulation in comparison to renin-negative SMCs. There is a significant difference between the number of (pro)renin receptors on the surface and in the cytoplasm of renin-positive SMCs in normal rats. These differences in the number of (pro)renin receptors were not present in rats with STZ-induced diabetes. Any other differences in the number of (pro)renin receptors between the STZ-induced diabetic and normal rats were not detected. The tissue level of angiotensin II did not change in the kidneys of STZ-induced diabetic rats. Conclusion. The distribution of (pro)renin receptors in afferent arteriolar SMCs is related to renin granulation of SMCs, but independent of angiotensin II plasma or tissue levels in the kidney.


Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 203-210 ◽  
Author(s):  
E. M. Repetto ◽  
R. Sanchez ◽  
J. Cipelli ◽  
F. Astort ◽  
C. Martinez Calejman ◽  
...  

Abstract An increased activity of the hypothalamo-pituitary-adrenal axis resulting in exaggerated glucocorticoid secretion has been repeatedly described in patients with diabetes mellitus and in animal models of this disease. However, it has been pointed out that experimental diabetes is accompanied by a decreased glucocorticoid response to ACTH stimulation. Because previous studies from our laboratory demonstrate the involvement of nitric oxide (NO) in the modulation of corticosterone production, present investigations were designed to evaluate 1) the impact of streptozotocin (STZ)-induced diabetes on the adrenocortical nitrergic system and 2) the role of NO in the modulation of adrenal steroidogenesis in STZ-diabetic rats. Four weeks after STZ injection, increased activity and expression levels of proteins involved in l-arginine transport and in NO synthesis were detected, and increased levels of thiobarbituric acid reactive species, carbonyl adducts, and nitrotyrosine-modified proteins were measured in the adrenocortical tissue of hyperglycemic rats. An impaired corticosterone response to ACTH was evident both in vivo and in adrenocortical cells isolated from STZ-treated animals. Inhibition of NO synthase activity resulted in higher corticosterone generation in adrenal tissue from STZ-treated rats. Moreover, a stronger inhibition of steroid output from adrenal cells by a NO donor was observed in adrenocortical Y1 cells previously subjected to high glucose (30 mm) treatment. In summary, results presented herein indicate an inhibitory effect of endogenously generated NO on steroid production, probably potentiated by hyperglycemia-induced oxidative stress, in the adrenal cortex of STZ-treated rats.


Author(s):  
Aryaneh Sardarbandeh ◽  
Mohammad Reza Delnavazi ◽  
Mohammad Sharifzadeh ◽  
Mohammad Sharifzadeh ◽  
Masoumeh Ghajarieh Sepanlou ◽  
...  

Eryngium caeruleum (Apiacea) is native to the northern forests of Iran. The anti-diabetic effect of other species of the genus Eryngium has already been reported in previous studies. In this study, the anti-diabetic effect of this extract on animal blood lipid factors was investigated. Hydroalcoholic extract was obtained from different parts of the plant, including roots, leaves, and aerial branches with fruits were prepared by maceration with 70% ethanol. Oral acute toxicity of the extracts was assayed in different doses of 2000, 4000, and 8000 mg/kg in rats. To induce diabetes in the studied animals, 60-70 mg/kg of streptozotocin (STZ) was injected intraperitoneally (IP). For the purpose of this study, 72 male Wistar rats were randomly divided into different groups of normal, diabetic, and positive controls (metformin 500 mg/kg) as well as 9 diabetic groups that orally received 200, 400, and 800 mg/kg of extracts. The effects of the treatment with extracts for a 14-day period were investigated on weight, blood glucose, and lipid profile. By comparing the control groups with the groups of hydroalcoholic extracts of E. caeruleum showed that the most effective sample on weight gain and also on reducing blood glucose was the group receiving 800 mg/kg of the aerial branches extract (P < 0.01 and P < 0.001, respectively) after 14 days. As well, the most effective sample on lowering the blood lipid factors was the hydroalcoholic extract of the root of E. coareleum with a dose of 200 mg/kg, which showed a significant effect on lowering total cholesterol in diabetic rats compared to the diabetic controls (P < 0.05). Hydroalcoholic extract of leaves with 200 mg/kg also showed a better effect on lowering the LDL and VLDL levels compared to the diabetic control group (P < 0.001). The results of pancreatic histology in the samples showed that the extracts of the aerial branch and root (800 mg/kg) had significant effects on the regeneration of the islets of Langerhans compared to the diabetic control group. In conclusion, E. caeruleum could significantly improve glycemic and lipid profiles in diabetic rats.


2020 ◽  
Vol 319 (5) ◽  
pp. F833-F838
Author(s):  
Nima Nalin ◽  
Ali Al Dhanhani ◽  
Alia AlBawardi ◽  
Charu Sharma ◽  
Sanjana Chandran ◽  
...  

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg−1·min−1 for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ∼20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10–90 Å (Ficoll70–90 Å), were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (θ for Ficoll70–90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll70–90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.


2007 ◽  
Vol 177 (4S) ◽  
pp. 264-265
Author(s):  
Ling De Young ◽  
KokBin Lim ◽  
Jeffery Carson ◽  
Trustin Domes ◽  
Mussa Al-Numi ◽  
...  

2015 ◽  
Vol 2 (1) ◽  
pp. 30-34
Author(s):  
K. Korobkova ◽  
V. Patyka

Contemporary state of the distribution of mycoplasma diseases of cultivated crops in Ukraine was analyzed. The changes of the physiological state of plant cells under the impact of mollicutes were investigated. It was demonstrated that there is temporary increase in the activity of peroxidase, catalase, polyphenoloxidase, phenylalanine-ammonia-lyase at the early stages of interaction. The adhesive properties are changed in the mollicutes under the impact of plant lectin; there is synthesis of new polypeptides. It was determined that the phytopathogenic acholeplasma is capable of producing a complex of proteolytic enzymes into the culture me- dium. It was concluded that when plant cells are infected with acholeplasma, a number of signaling interactions and metabolic transformations condition the recognition of pathogenesis and ensure the aggregate response of a plant to stress in the form of defense reactions. It was assumed that some specifi cities of the biology of phy- topathogenic acholeplasma determine their avoiding the immune mechanisms of plants and promote long-term persistence of mollicutes.


2010 ◽  
Vol 6 (3) ◽  
pp. 33
Author(s):  
Robert J Petrella ◽  

It is widely recognised that hypertension is a major risk factor for the development of future cardiovascular (CV) events, which in turn are a major cause of morbidity and mortality. Blood pressure (BP) control with antihypertensive drugs has been shown to reduce the risk of CV events. Angiotensin-II receptor blockers (ARBs) are one such class of antihypertensive drugs and randomised controlled trials (RCTs) have shown ARB-based therapies to have effective BP-lowering properties. However, data obtained under these tightly controlled settings do not necessarily reflect actual experience in clinical practice. Real-life databases may offer alternative information that reflects an uncontrolled real-world setting and complements and expands on the findings of clinical trials. Recent analyses of practice-based real-life databases have shown ARB-based therapies to be associated with better persistence and adherence rates and with superior BP control than non-ARB-based therapies. Analyses of real-life databases also suggest that ARB-based therapies may be associated with a lower risk of CV events than other antihypertensive-drug-based therapies.


2021 ◽  
Vol 22 (9) ◽  
pp. 4961
Author(s):  
Maria Kovalska ◽  
Eva Baranovicova ◽  
Dagmar Kalenska ◽  
Anna Tomascova ◽  
Marian Adamkov ◽  
...  

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.


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