scholarly journals Effects of Low-Dose and Early versus Late Perindopril Treatment on the Progression of Severe Diabetic Nephropathy in (mREN-2)27 Rats

2002 ◽  
Vol 13 (3) ◽  
pp. 684-692
Author(s):  
Sally A. Mifsud ◽  
Sandford L. Skinner ◽  
Mark E. Cooper ◽  
Darren J. Kelly ◽  
Jennifer L. Wilkinson-Berka
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Early Treatment ◽  
Enzyme Inhibitor ◽  
Late Onset ◽  
Diabetic Rats ◽  
Moderate Increase ◽  
Citrate Buffer ◽  
Late Intervention ◽  
Kidney Hypertrophy

ABSTRACT. It was previously reported that transgenic (mRen-2)27 rats with streptozotocin-induced diabetes mellitus progressively develop advanced nephropathy in 12 wk. These lesions are largely prevented when the angiotensin-converting enzyme inhibitor perindopril is administered from the time of induction of diabetes mellitus. This study aimed to determine the lowest dose of early perindopril treatment required for substantial improvement of renal function and structure and to investigate whether late intervention prevents or reverses the progression of established renal lesions. At 6 wk of age, female heterozygous Ren-2 rats were randomized to receive either streptozotocin (diabetic) or citrate buffer (control). Rats were gavaged, beginning early after the induction of diabetes mellitus or the administration of control vehicle, with 0, 0.02, 0.2, or 2 mg/kg per d perindopril for 12 wk. A separate group of diabetic Ren-2 rats received late treatment with 2 mg/kg per d perindopril throughout week 8 to week 12, when rats were hypertensive and albuminuric and exhibited increased kidney weight and glomerulosclerotic index (GSI). Among diabetic rats, early 0.02 mg/kg per d perindopril treatment reduced systolic BP, GSI, and renal collagen staining but had no effect on albuminuria or kidney hypertrophy. Early 0.2 or 2 mg/kg per d perindopril treatment further reduced systolic BP, GSI, and renal collagen staining and decreased albuminuria and kidney hypertrophy. Late intervention was as antihypertensive and antialbuminuric as early 0.2 or 2 mg/kg per d perindopril treatment but did not prevent a moderate increase in GSI. In conclusion, early treatment with 0.2 mg/kg per d perindopril was the lowest dosage to largely prevent severe diabetic nephropathy in transgenic Ren-2 rats. Late-onset perindopril treatment of diabetic rats with established nephropathy was as efficacious as early treatment with respect to various renal parameters, such as albuminuria, but was associated with moderate progression of glomerulosclerosis.

scholarly journals The role of nicotinamide in the correction of renal function in diabetic nephropathy

2019 ◽  
Vol 23 (2) ◽  
pp. 218-221
Author(s):  
L. V. Yanitskaya ◽  
L. F. Osinskaya ◽  
A. V. Redko
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Diabetic Nephropathy ◽  
Statistical Analysis ◽  
Rat Kidney ◽  
Clinical Manifestations ◽  
Diabetic Rats ◽  
Cortical Layer ◽  
The Difference

Hyperglycemia of diabetes mellitus leads to the activation of the polyol way of oxidation of glucose with the activation of the enzymes of aldose reductase and sorbitol dehydrogenase and of their coenzymes NADPH and NAD, which triggers the mechanism of formation of sorbitol. The consequences of these changes lead to microangiopathy of the tissues of the kidneys, which may be one of the pathogenetic mechanisms of diabetic nephropathy. In an accessible literature, the role of coenzymes of sorbitol pathway in the development of diabetic nephropathy is not sufficiently defined. The purpose of the study was to study the content of NAD and NADPH coenzymes, their correlation, and their role in the mechanism of kidney damage in diabetes mellitus and to predict the possible correction of these changes with the NAD-nicotinamide derivative. The study was conducted on a model of streptotrozectinic diabetes mellitus (single administration of streptozotocin in a dose of 60 mg per 1 kg of body weight). Four weeks after induction of diabetes, nicotinamide (100 mg per 1 kg body weight) was injected. The level of glucose was determined by the Accu-chek (Roshe Diagnostics, Switzerland) glucose meter. The content of NAD and NADH was determined in the non-protein extracts. The statistical analysis was carried out using the Microsoft Excel statistical analysis program. The difference between the indicators was considered statistically significant (p<0.05). The NAD level was reduced by 31%, the NAD/NADN ratio was 32%. The dependence of the ratio of NADP/NADPN in conditions of hyperglycemia of diabetes mellitus with clinical manifestations of diabetic nephropathy is determined. A decrease in the ratio of NADP/NADPN to 38% in the rat kidney in the cortical layer was detected. The introduction of nicotinamide normalized the reduced content of NAD diabetic rats. These results provide perspectives for further research in which nicotinamide can be used as a renal protector.

scholarly journals Arginase inhibition: a new treatment for preventing progression of established diabetic nephropathy

2015 ◽  
Vol 309 (5) ◽  
pp. F447-F455 ◽  
Author(s):  
Hanning You ◽  
Ting Gao ◽  
Timothy K. Cooper ◽  
Sidney M. Morris ◽  
Alaa S. Awad
Keyword(s):  
Diabetic Nephropathy ◽  
Early Treatment ◽  
Enzyme Inhibitor ◽  
Thiobarbituric Acid ◽  
Standard Of Care ◽  
Macrophage Infiltration ◽  
Current Standard ◽  
Histological Changes ◽  
Late Treatment ◽  
New Treatment

Our previous publication showed that inhibition of arginase prevents the development of diabetic nephropathy (DN). However, identification of targets that retard the progression of established DN–which is more clinically relevant–is lacking. Therefore, we tested the hypothesis that arginase inhibition would prevent the progression of established DN. Effects of arginase inhibition were compared with treatment with the angiotensin-converting enzyme inhibitor captopril, a current standard of care in DN. Experiments were conducted in Ins2 Akita mice treated with the arginase inhibitor S-(2-boronoethyl)-l-cysteine (BEC) or captopril starting at 6 wk of age for 12 wk (early treatment) or starting at 12 wk of age for 6 wk (late treatment). Early and late treatment with BEC resulted in protection from DN as indicated by reduced albuminuria, histological changes, kidney macrophage infiltration, urinary thiobarbituric acid-reactive substances, and restored nephrin expression, kidney nitrate/nitrite, kidney endothelial nitric oxide synthase phosphorylation, and renal medullary blood flow compared with vehicle-treated Ins2 Akita mice at 18 wk of age. Interestingly, early treatment with captopril reduced albuminuria, histological changes, and kidney macrophage infiltration without affecting the other parameters, but late treatment with captopril was ineffective. These findings highlight the importance of arginase inhibition as a new potential therapeutic intervention in both early and late stages of diabetic renal injury.

scholarly journals Diabetic Rats Present High Mean Platelet Count in the Presence of Oral Infections

2017 ◽  
Vol 28 (5) ◽  
pp. 548-551 ◽  
Author(s):  
Luciana Louzada Ferreira ◽  
João Eduardo Gomes Filho ◽  
Dóris Hissako Sumida ◽  
Suely Regina Mogami Bonfim ◽  
Gustavo Sivieri-Araújo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Count ◽  
Periodontal Disease ◽  
Rat Model ◽  
Inflammatory Diseases ◽  
Diabetic Rats ◽  
Apical Periodontitis ◽  
Buffer Solution ◽  
Citrate Buffer ◽  
Oral Infections

Abstract Platelet count is associated with inflammatory diseases like diabetes mellitus (DM), which in turn, is related in a bidirectional manner with apical periodontitis and periodontal disease. The aim of this study was to evaluate the effects of apical periodontitis and/or periodontal disease on mean platelet count in a rat model of diabetes mellitus. Eighty Wistar rats were randomly divided into 8 groups (n=10): control (C), apical periodontitis (AP), periodontal disease (PD), apical periodontitis with periodontal disease (AP-PD), diabetes mellitus (DM), diabetes mellitus with apical periodontitis (DM-AP), diabetes mellitus with periodontal disease (DM-PD) and diabetes mellitus with apical periodontitis and periodontal disease (DM-AP-PD). Rats were anesthetized and DM was induced with a single dose of streptozotocin diluted in citrate buffer solution. After 6 days, the DM was confirmed. The animals were sedated and apical periodontitis was induced by dental exposure and periodontal disease was induced by periodontal ligature. After 30 days, animals were anesthetized and the blood was collected by cardiac puncture. Samples were processed and the mean platelet count was obtained. Data were tabulated and subjected to statistical analysis (p<0.05). Diabetic rats had higher mean glycemic levels compared with nondiabetic rats at 6 and 36 days after DM induction (p<0.05). The DM-PD and DM-PD-AP groups showed increased mean platelet count compared to control and AP groups (p<0.05). The periodontal disease alone or associated with apical periodontitis influence mean platelet count in a rat model of diabetes mellitus.

scholarly journals Beneficial effects of valencene on altered glycoprotein components in streptozotocin-nicotinamide induced diabetic rats

2019 ◽  
Vol 9 (4-A) ◽  
pp. 191-196
Author(s):  
Ellappan Pari ◽  
Pari Leelavinothan ◽  
Thangasamy Gunaseelan ◽  
Duraisamy Kannan
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Experimental Diabetes ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Glycemic Status ◽  
Experimental Diabetes Mellitus ◽  
Citrate Buffer ◽  
Beneficial Effects

ABSTRACT Objective: To investigate the effect of valencene on dearrangement in glycoprotein levels in the streptozotocin(STZ)-nicotinamide(NA)induced diabetic rats. Materials and Methods: Diabetes was induced in experimental rats by a single intraperitoneal (i.p) injection of STZ (45 mg/kg b.w) dissolved in 0.1 M citrate buffer (pH 4.5) 15 minutes after the i.p injection of NA (110 mg/kg b.w). The levels of glycoproteins were altered in experimental diabetes mellitus. Valencene were administered to diabetic rats intragastrically at 100 & 200mg/kg bw for 30days. The effects of valencene on plasma glucose, insulin, plasma and tissue glycoproteins were studied. Results: Oral administration of valencene (200mg/kg b.w)for 30d, dose dependently improved the glycemic status in STZ-NA induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin level. The altered levels of plasma and tissue glycoprotein components were restored to near normal. Conclusions: The results of the present study show the potent beneficial effects of valencene in modifying the levels of glycoprotein components in plasma and tissues of diabetic rats.

scholarly journals Anti-diabetic effects of Campomanesia xanthocarpa (Berg) leaf decoction

2010 ◽  
Vol 46 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Anapaula Sommer Vinagre ◽  
Ângela Della'Santa Rubio Origuella Rönnau ◽  
Sabrina Francisco Pereira ◽  
Lídia Uliano da Silveira ◽  
Elenir de Fátima Wiilland ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Citrate Buffer ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Toxicological Studies ◽  
Liver And Kidney ◽  
Diabetes Mellitus Management

The objective of this research was to identify the effects of 3-week treatment of normal and streptozotocin-induced diabetic rats using a leaf decoction of Campomanesia xanthocarpa Berg. (20 g/L) on physiological, biochemical and histological parameters. Streptozotocin (STZ, 70 mg/kg in citrate buffer, pH 4.5) was administered IP to induce experimental diabetes one week prior to the treatment. STZ caused typical diabetic symptoms: polydypsia, polyuria, polyphagia, hyperglycemia, hypertriglyceridemia and histopathological modifications in the pancreas, liver and kidney. The treatment of diabetic rats using the decoction decreased blood glucose levels, inhibited hepatic glycogen loss, and prevented potential histopathological alterations in the pancreas and kidneys. No differences were found between the control rats treated with the decoction and the control rats maintained on water only. In conclusion, these results suggest that C. xanthocarpa leaf decoction (20g/L) might be useful for diabetes mellitus management, but further pharmacological and toxicological studies are needed.

scholarly journals Silver/chitosan/ascorbic acid nanocomposites ameliorate diabetic nephropathy in the model of type 1 diabetes

2021 ◽  
Vol 16 (3) ◽  
pp. 091-102
Author(s):  
Esraa Abu El Qassem Mahmoud ◽  
Ayman S Mohamed ◽  
Sohair R Fahmy ◽  
Amel Mahmoud Soliman ◽  
Khadiga Gaafar
Keyword(s):  
Ascorbic Acid ◽  
Diabetic Nephropathy ◽  
Single Dose ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Citrate Buffer ◽  
Type 1Diabetes ◽  
Wistar Albino Rats ◽  
Ag Ncs

Aims: The present study aimed to evaluate anti-diabetic properties of AgNPs/chitosan/ascorbic acid nanocomposites (Ag-NCs) in streptozotocin-induced diabetic rats. Main methods: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic and Ag-NCs groups. Control group: after a single dose of citrate buffer (0.1 mol/l, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1diabetes. Diabetic groups were treated orally with and Ag-NCs (0.25mg/Kg body weight) daily for four weeks. Key findings: AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, creatinine, urea and uric acid. At the same time, it appeared a general increase in insulin, CAT, and SOD activities and GSH concentration. The histopathological investigation illustrated a clear improvement in renal architecture. Significance: The suggested mechanism of action for Ag-NCs in decreasing diabetic nephropathy includes two pathways; the hypoglycemic activity and the antioxidant role of Ag-NCs

scholarly journals Renoprotective Effect of Yiqi Yangyin Huayu Tongluo Formula against Diabetic Nephropathy in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Feng-li Wang ◽  
Yue-hua Wang ◽  
Lin Han ◽  
Hai-yan An ◽  
Jiang-hua Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Transplantation ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Protective Effect ◽  
Diabetic Rats ◽  
Jnk Signaling ◽  
Patients With Diabetes ◽  
Jnk Signaling Pathway

Diabetic nephropathy is developed in 20-40% of patients with diabetes mellitus, and patients with diabetic nephropathy require dialysis and renal transplantation. Traditional Chinese medicine has been widely used in treating patients with diabetic nephropathy in China. However, the detailed mechanisms of traditional Chinese medicine remain unclear. Yiqi Yangyin Huayu Tongluo formula (ZY formula) is a traditional Chinese medicinal formula. Here, we demonstrated kidney protective effect of ZY formula on the rats with diabetic nephropathy. The therapeutic effect of ZY formula on the diabetic nephropathy was almost the same as that of Irbesartan, which proved to have excellent curative effects on diabetic nephropathy. We also demonstrated the mechanism of ZY formula effect on the diabetic nephropathy. First, we validated that the activation of ROS-JNK signaling pathway in diabetic rats could be reduced by ZY. Furthermore, collagen I expression could be downregulated by ZY formula treatment. Meanwhile, cell apoptosis in the kidney of diabetic rats could be alleviated by ZY formula.

Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat

1996 ◽  
Vol 271 (3) ◽  
pp. F595-F602 ◽  
Author(s):  
T. M. Kennefick ◽  
T. T. Oyama ◽  
M. M. Thompson ◽  
J. P. Vora ◽  
S. Anderson
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Left Renal Artery ◽  
Ang Ii ◽  
Hemodynamic Effects ◽  
Angiotensin System

The renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. In diabetes, renal RAS components are dysregulated, potentially increasing renal RAS effects. To explore the renal RAS, studies were conducted in control and diabetic rats. In both groups, intravenous angiotensin (ANG) I and ANG II produced similar increases in mean arterial pressure (MAP). In contrast, glomerular filtration rate defined only in diabetic rats. Renal plasma flow fell in both groups but decreased more in diabetic rats. Additional groups were given the same dose of ANG I directly into the left renal artery, and hemodynamics were studied in the treated and untreated kidneys. In contrast to the intravenous studies, intra-arterial ANG I had no effect on MAP in either group. The renal hemodynamic effects were similar to those in intravenous studies. Additionally, diabetic rats exhibited enhanced hemodynamic sensitivity in the untreated kidney, suggesting that renal effects could occur at nonpressor concentrations of circulating ANG II. Thus renal (but not systemic) responsiveness to angiotensins is enhanced in diabetic rats.

Antihyperglycemic activity of Ficus carica leaves extracts on Streptozotocin induced diabetic rats

2021 ◽  
pp. 4151-4156
Author(s):  
Tathagata Roy ◽  
Susanta Paul ◽  
Victor Roy Chowdhury ◽  
Arijit Das ◽  
Srikanta Chandra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Wistar Rats ◽  
Diabetic Rats ◽  
Ficus Carica ◽  
Citrate Buffer ◽  
Antihyperglycemic Activity ◽  
Treatment Of Diabetes

Antihyperglycemic activity of leave extracts of Ficus carica was evaluated on STZ induced diabetic rats. Diabetes was induced in albino Wistar rats of either sex by intraperitoneal (60mg/kg b.w.) of STZ, freshly dissolved in citrate buffer (0.01 M, pH 4.5). Ficus carica leave extract in different solution (viz. petroleum ether, ethyloacetate, methanol and aqueous) were administered to diabetic rats for 9 days. The effect of extracts on blood glucose and body weight was studies on day 1st and 9th. The study showed that the ethyl acetate, methanolic and aqueous extract of Ficus sarmentosa leaves reduced blood glucose level and body weight significantly. This may justify the use of ficus species as ethanomedical medicine for treatment of diabetes mellitus.

scholarly journals Therapeutic activity of sarpogrelate, and dopamine D2 receptor agonists on cardiovascular and renal systems in alloxan-induced diabetic rats

2020 ◽  
Author(s):  
Mohamed Fouad ◽  
Hekma A. Abd El Latif ◽  
May Galal ◽  
Mohammed El Yamani ◽  
Sherifa Hassaneen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Myocardial Injury ◽  
Troponin I ◽  
Staining Method ◽  
Diabetic Rats ◽  
Tetrazolium Chloride ◽  
Blood Concentrations ◽  
Dopamine D2 ◽  
Long Term Treatment ◽  
Kidney Hypertrophy

Abstract Background: The investigation aims to represent the activity of sarpogrelate, a particular 5-HT (2A) receptor blocker, in reducing myocardial injury prompted by extended haul utilization of D2 agonist drugs in diabetic rats. Dopamine D2 agonists are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation showed between the enlistment of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial initiation of 5-HT 2a receptors. Methods: Both bromocriptine and cabergoline were managed independently and combined with sarpogelate for about a month to diabetic nephropathy rats. Both tail-cuff blood pressure and BGL were recorded weekly. For all animals, kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of LDH-1, cardiac troponin I, and TNFα. Triphenyl tetrazolium chloride staining method used to determine experimental myocardial infarction (MI) size. Results: Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine, cabergoline, alone, or in combination with sarbogrelate fundamentally diminished blood concentrations of ALP, AST, urea, and creatinine. Bromocriptine and cabergoline alone showed noteworthy ascending of LDH-1, Troponin I, and TNFα1 levels in the serum (p<0.05). Paradoxically, utilizing bromocriptine and cabergoline with sarpogrelate treatment altogether diminished the degree of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed utilizing the TTC staining method. Conclusions: The examination exhibited that both bromocriptine and cabergoline could be utilized safely in blend with sarpogrelate for a long duration of treatment for diseases like hypertension and diabetes.

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