Biochanin‐A has anti‐diabetic, anti‐hyperlipidemic, anti‐oxidant and protective effects on diabetic nephropathy via suppression of TGF‐β1 and PAR‐2 genes expression in kidney tissues of STZ‐induced diabetic rats

2021 ◽  
Author(s):  
Jamal Amri ◽  
Mona Alaee ◽  
Rasool Babaei ◽  
Zahra Salemi ◽  
Reza Meshkani ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Rats ◽  
Biochanin A ◽  
Protective Effects ◽  
Genes Expression ◽  
Anti Oxidant ◽  
Tgf Β1

scholarly journals Protective Effects of Luteolin on Diabetic Nephropathy in STZ-Induced Diabetic Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Guo Guang Wang ◽  
Xiao Hua Lu ◽  
Wei Li ◽  
Xue Zhao ◽  
Cui Zhang
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Sod Activity ◽  
Matrix Expression

Diabetic nephropathy is a long-term complication of diabetic mellitus. Many experimental evidences suggest that persistent hyperglycaemia generates intracellular reactive oxygen species (ROS) and upregulates transforming growth factor-b1 and extracellular matrix expression in mesangial and tubular epithelial cells, which is involved of free radicals in the pathogenesis of diabetes and more importantly in the development of diabetic complications. Antioxidants effectively inhibit high-glucose- and H2O2-induced transforming growth factor-b1 and fibronectin upregulation, thus providing evidence that ROS play an important role in high glucose-induced renal injury. The flavonoid luteolin has been shown to possess direct antioxidant activity, therefore we hypothesize that it may be useful in treatment of many chronic disease associated with oxidative stress, such as diabetic nephropathy via its antioxidant properties. Our results suggested that protection against development of diabetic nephropathy by luteolin treatment involved changes in superoxide dismutase (SOD) activity, the malondialdehyde (MDA) content and expression of Heme Oxygenase-1 (HO-1) protein.

scholarly journals Lovastatin Inhibits Transforming Growth Factor-β1 Expression in Diabetic Rat Glomeruli and Cultured Rat Mesangial Cells

2000 ◽  
Vol 11 (1) ◽  
pp. 80-87
Author(s):  
SUNG IL KIM ◽  
DONG CHEOL HAN ◽  
HI BAHL LEE
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Kidney Weight ◽  
Urine Albumin Excretion ◽  
Urine Albumin ◽  
Ecm Proteins ◽  
Tgf Β1

Abstract. Diabetic nephropathy is a leading cause of end-stage renal disease and is characterized by excessive deposition of extracellular matrix (ECM) proteins in the glomeruli. Transforming growth factor-β (TGF-β) is the major mediator of excessive accumulation of ECM proteins in diabetic nephropathy through upregulation of genes encoding ECM proteins as well as downregulation of genes for ECM-degrading enzymes. It has been shown that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, delays the onset and progression of different models of experimental nephropathy. To evaluate the effect of lovastatin on the development and progression of diabetic nephropathy, streptozotocin-induced diabetic rats were studied for 12 mo. In untreated diabetic rats, there were significant increases in blood glucose, urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression in the glomeruli compared with normal control rats treated with citrate buffer only. Treatment with lovastatin in diabetic rats significantly suppressed the increase in urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression despite high blood glucose levels. To elucidate the mechanisms of the renal effects of lovastatin, rat mesangial cells were cultured under control (5.5 mM) or high (30 mM) glucose with lovastatin alone, mevalonate alone, or with both. Under high glucose, TGF-β1 and fibronectin mRNA and proteins were upregulated. These high glucose-induced changes were suppressed by lovastatin (10 μM) and nearly completely restored by mevalonate (100 μM). These results suggest that lovastatin has a direct cellular effect independent of a cholesterol-lowering effect and delays the onset and progression of diabetic nephropathy, at least in part, through suppression of glomerular expression of TGF-β1.

scholarly journals Protective effects of alkali‐extracted rice protein on diabetic nephropathy in obese type 2 diabetic rats

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Masatoshi Kubota ◽  
Reiko Watanabe ◽  
Miki Yamaguchi ◽  
Michihiro Hosojima ◽  
Akihiko Saito ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Rice Protein ◽  
Type 2 Diabetic

scholarly journals Anti Hyperglycemic, Anti Oxidant, Anti Hyperlipidemic & Nephroprotective Effect of Stevioside in Diabetic Rats

2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Ambily Scaria ◽  
Jagadhish V Kamath ◽  
Manodeep Chakraborty
Keyword(s):  
Lipid Peroxidation ◽  
Diabetic Nephropathy ◽  
Protective Effect ◽  
Total Cholesterol ◽  
Serum Levels ◽  
Diabetic Rats ◽  
High Density Lipoproteins ◽  
Anti Oxidant ◽  
Nephroprotective Effect

Objective: The present study aimed to evaluate in vivo the antihyperglycemic, anti oxidant,antihyperlipidemic and nephroprotective effects of Stevioside against Alloxan induced diabetic nephropathy in rats. Materials and Methods: In this model diabetes was induced using Alloxan (125 mg/kg, i.p) and the prophylactic treatment was started 48 hours after Alloxan injection for 28 days. The protective effect of the treatment with standard (Glibenclamide 0.5mg/kg, p.o) and Stevioside (250 mg/kg. p.o) were analyzed by estimating the serum levels of glucose, urea, creatinine, albumin, total protein, total cholesterol (TCH), triglycerides (TG), high density lipoproteins (HDL) and antioxidants like SOD, catalase and lipid peroxidation. Key Findings: This study demonstrates that Stevioside improved hyperglycemia and maintained antioxidant status and reduced total cholesterol, TG, urea, creatinine and albumin and lipid peroxidation levels when compared to toxic control. The protective effect of Stevioside against Alloxan induced diabetic nephropathy in rats was also supported by histopathologic findings.The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies.

Triptolide Improves Renal Injury in Diabetic Nephropathy Rats through TGF-β1/Smads Signal Pathway

2020 ◽  
Vol 20 ◽  
Author(s):  
Ruoyu Pang ◽  
Donghai Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Inflammatory Factor ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Smad7 Expression ◽  
Tgf Β1

Objective: To investigate the therapeutic effect and mechanism of Triptolide on renal injury in diabetic nephropathy rats. Methods: A total of 15 male SD rats aged 8 weeks were randomly divided into five groups (3 rats in each group): control group, model group, Triptolide low-dose (Triptolide-L) group, Triptolide medium-dose (Triptolide-M) group, Triptolide high-dose (Triptolide-H) group. The rats models of diabetic nephropathy (DN) were established by a single intraperitoneal injection of STZ after being fed with high-fat and high-sugar diet for 4 weeks, and the fasting blood glucose (FBG) concentration of rats was detected. After 4 weeks, HE-staining was used to evaluate the renal pathological damage in rats; biochemical analysis was used to determine the blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG); ELISA was used to measure the serum inflammatory factor levels; Western blot (WB) was used to detect the expression of TGF-β1/Smads pathway proteins. Results: In the four FBG tests (once a week), the FBG concentration in the model group was significantly higher than that in the control group, while Triptolide-treated rats were significantly lower than that in the model group. Rats in Model group showed obvious renal injury, and Triptolide significantly improved the renal injury in DN rats. Compared with the control group, the expression of BUN, SCr, TC, TG, inflammatory factors TNF-α, IL-6 and IL-1β in the model group increased significantly. WB results showed that the expressions of TGF-β1, Smad3, α-SMA and vimentin in the kidney significantly increased, while the Smad7 expression significantly decreased. Triptolide significantly reduced the levels of BUN, SCr, TC, TG and TNF-α, IL-6, IL-1β in diabetic rats, decreased the expression of TGF-β1, Smad3, α-SMA, vimentin, and increased the Smad7 expression. In different doses of Triptolide treatment group, its effect showed a significant concentration dependence. Conclusion: Triptolide alleviates renal injury in diabetic rats by inhibiting the TGF-β1/Smads signaling pathway.

scholarly journals Aminoguanidine Ameliorates Overexpression of Prosclerotic Growth Factors and Collagen Deposition in Experimental Diabetic Nephropathy

2001 ◽  
Vol 12 (10) ◽  
pp. 2098-2107 ◽  
Author(s):  
DARREN J. KELLY ◽  
RICHARD E. GILBERT ◽  
ALISON J. COX ◽  
TINA SOULIS ◽  
GEORGE JERUMS ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factors ◽  
Growth Factor ◽  
Experimental Diabetes ◽  
Fold Increase ◽  
Diabetic Rats ◽  
Renal Tubules ◽  
Collagen Deposition ◽  
Matrix Deposition ◽  
Tgf Β1

Abstract. Profibrotic cytokines and the formation of advanced-glycation end products (AGE) have both been implicated in the pathogenesis of glomerulosclerosis in diabetic kidney disease. However, tubulointerstitial pathology is also an important determinant of progressive renal dysfunction in diabetic nephropathy. This study sought to investigate the expression of profibrotic growth factors and matrix deposition in the glomerulus and the tubulointerstitium and to examine the effect of blocking AGE formation in experimental diabetic nephropathy. Thirty-six male Sprague-Dawley rats were randomized into control and diabetic groups. Diabetes was induced in 24 rats by streptozotocin. Twelve diabetic rats were further randomized to receive the inhibitor of AGE formation, aminoguanidine (1 g/l drinking water). At 6 mo, experimental diabetes was associated with a three-fold increase in expression of transforming growth factor (TGF)-β1 (P< 0.01versuscontrol) and five-fold increase in platelet-derived growth factor (PDGF)-B gene expression (P< 0.01versuscontrol) in the tubulointerstitium.In situhybridization demonstrated a diffuse increase in both TGF-β1 and PDGF-B mRNA in renal tubules. Aminoguanidine attenuated not only the overexpression of TGF-β1 and PDGF-B but also reduced type IV collagen deposition in diabetic rats (P< 0.05). TGF-β1 and PDGF mRNA within glomeruli were also similarly increased with diabetes and attenuated with aminoguanidine. The observed beneficial effects of aminoguanidine on the tubulointerstitium in experimental diabetes suggest that AGE-mediated expression of profibrotic cytokines may contribute to tubulointerstitial injury and the pathogenesis of diabetic nephropathy.

scholarly journals Transcriptional Suppression of Diabetic Nephropathy with Novel Gene Silencer Pyrrole-Imidazole Polyamides Preventing USF1 Binding to the TGF-β1 Promoter

2021 ◽  
Vol 22 (9) ◽  
pp. 4741
Author(s):  
Makiyo Okamura ◽  
Noboru Fukuda ◽  
Shu Horikoshi ◽  
Hiroki Kobayashi ◽  
Akiko Tsunemi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Glomerular Injury ◽  
Upstream Stimulatory Factor ◽  
Injury Score ◽  
Upstream Stimulatory Factor 1 ◽  
Tgf Β1

Upstream stimulatory factor 1 (USF1) is a transcription factor that is increased in high-glucose conditions and activates the transforming growth factor (TGF)-β1 promoter. We examined the effects of synthetic pyrrole-imidazole (PI) polyamides in preventing USF1 binding on the TGF-β1 promoter in Wistar rats in which diabetic nephropathy was established by intravenous administration of streptozotocin (STZ). High glucose induced nuclear localization of USF1 in cultured mesangial cells (MCs). In MCs with high glucose, USF1 PI polyamide significantly inhibited increases in promoter activity of TGF-β1 and expression of TGF-β1 mRNA and protein, whereas it significantly decreased the expression of osteopontin and increased that of h-caldesmon mRNA. We also examined the effects of USF1 PI polyamide on diabetic nephropathy. Intraperitoneal injection of USF1 PI polyamide significantly suppressed urinary albumin excretion and decreased serum urea nitrogen in the STZ-diabetic rats. USF1 PI polyamide significantly decreased the glomerular injury score and tubular injury score in the STZ-diabetic rats. It also suppressed the immunostaining of TGF-β1 in the glomerulus and proximal tubules and significantly decreased the expression of TGF-β1 protein from kidney in these rats. These findings indicate that synthetic USF1 PI polyamide could potentially be a practical medicine for diabetic nephropathy.

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