Effects of Huangkui Capsule on the Expression of SPARC in the Kidney Tissue of a Rat Model with Diabetic Nephropathy

2019 ◽  
Vol 19 (4) ◽  
pp. 211-215 ◽  
Author(s):  
Xiaoyao Yang ◽  
Meng Luo ◽  
Qinghua Jiang ◽  
Yiwei Wang

Objective: The objective of the research is to investigate the effects of Huangkui capsule on the expression of SPARC in the kidney tissues of diabetic nephropathy. Methods: SD rats were divided into three groups: normal control group, untreated DN group and HKC-treated DN group. The therapeutic effects and underlying molecular mechanism of HKC on DN rats induced by streptozotocin were evaluated by the levels of serum creatinine, blood urea nitrogen, 24-hour urinary protein and the expression of SPARC. Pathological changes in kidney tissues were observed through hematoxylin-eosin (HE) staining. Moreover, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the variation of SPARC. Results: This study was performed to investigate the effects of HKC on DN in SD rats model and its molecular mechanism. Our results showed that the rats treated with HKC had an improved general state and reduced creatinine, blood urea nitrogen and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with HKC. HE staining was utilized to observe that HKC can improve histopathological findings in the kidney tissues of DN rats, including kidney fibrosis. Results of western blot and qRT-PCR showed that HKC can inhibit the expressions of SPARC in the rat model of DN. Conclusion: The present findings demonstrated that HKC inhibited SPARC level and had significant therapeutic effects on DN.

2020 ◽  
Vol 10 ◽  
Author(s):  
Dhrubajyoti Sarkar ◽  
Sekhar Kumar Bose ◽  
Tania Chakraborty ◽  
Souvik Roy

Background: Diabetic nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Method: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, blood urea nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chang Wang ◽  
Fei Peng ◽  
Bohua Zhong ◽  
Ying Shi ◽  
Xiaomei Wang ◽  
...  

Background and Aims: Therapeutic drugs that are used to treat cholestatic liver disease are limited; however, the results of clinical trials on primary biliary cholangitis treatment targeting peroxisome proliferator-activated receptors (PPARs) are encouraging. In this study, we aimed to identify the effects of MBT1805, a novel balanced PPARα/γ/δ agonist, on cholestasis induced by α-naphthylisothiocyanate (ANIT) and elucidate the underlying mechanisms through untargeted and bile acid-targeted metabolomic analysis.Methods: Levels of serum biochemical indicators (transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin) and liver histopathology were analyzed to evaluate the therapeutic effects of MBT1805 on ANIT-induced cholestasis in C57BL/6 mice. Untargeted and bile acid-targeted metabolomic analysis of liver tissues was performed using ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MC/MC). qRT-PCR and Western blot analysis were carried out to measure the expression of key enzymes and transporters regulating bile acid synthesis, biotransformation, and transport.Results: MBT1805 significantly improved abnormal levels of liver biochemical indicators and gallbladder enlargement induced by ANIT. Histopathological analysis showed that MBT1805 effectively relieved ANIT-induced necrosis, vacuolation, and inflammatory infiltration. Untargeted metabolomic analysis identified 27 metabolites that were involved in the primary biliary acid biosynthesis pathway. In addition, bile acid-targeted metabolomics showed that MBT1805 could alleviate the abnormal bile acid content and composition induced by ANIT. Furthermore, qRT-PCR and Western blot results confirmed that MBT1805 could effectively regulate bile acid synthesis, biotransformation, and transport which helps relieve cholestasis.Conclusions: MBT1805 is a potential candidate drug for cholestasis, with a balanced PPARα/γ/δ activation effect.


2017 ◽  
Vol 43 (2) ◽  
pp. 685-696 ◽  
Author(s):  
Suxia Yang ◽  
Junwei Zhang ◽  
Shiying Wang ◽  
Jun Shi ◽  
Xinxin Zhao

Background/Aims: Angiopoietin-like protein 2 (ANGPTL2) was reported to be implicated in the pathogenesis of inflammatory disease. Its role in diabetic nephropathy (DN) remained illdefined. Methods: qRT-PCR and western blot analysis were performed to detect the expressions of ANGPTL2 or TLR4 in streptozotocin (STZ)-induced DN rats and HG-stimulated podocytes. The renal injury index including 24-h proteinuria, blood glucose level, serum creatinine and blood urea nitrogen were measured in DN rats using corresponding commercial kits. The effect of ANGPTL2 knockdown on the secretion or expression of inflammatory cytokines was detected by ELISA or qRT-PCR analysis. The effect of ANGPTL2 knockdown on extracellular matrix (ECM) accumulation was determined by testing TGF-β1, Collagen-IV, fibronectin (FN) and PTEN expression via western blot. Results: ANGPTL2 and TLR4 were both highly expressed in DN rats compared with control group. ANGPTL2 knockdown alleviated renal injury in STZ-induced DN rat model. ANGPTL2 knockdown also suppressed inflammatory cytokines (IL-6, TNF-α, MCP-1, IL-1β) expression and ECM accumulation (TGF-β1, Collagen-IV, FN, PTEN) in HG-induced podocytes. Moreover, ANGPTL2 knockdown led to a significant decrease of TLR4 expression in both DN rat and cell model. Furthermore, TAK-242 treatment exacerbated the inhibitory effect of ANGPTL2 knockdown on inflammatory cytokines expression and ECM accumulation in HG-induced podocytes. Conclusion: ANGPTL2 knockdown ameliorates DN by inhibiting TLR4 expression, an observation contributing to a better understanding of DN pathogenesis.


2018 ◽  
Vol 45 (5) ◽  
pp. 1747-1758 ◽  
Author(s):  
Yingli Jia ◽  
Jinzhao He ◽  
Liang Wang ◽  
Limin Su ◽  
Lei Lei ◽  
...  

Background/Aims: A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Methods: Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson’s trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Results: Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. Conclusion: These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.


Author(s):  
DEEPTI D. BANDAWANE ◽  
SHRUTI B. MOOLIYA ◽  
SHAILAJA B. JADHAV

Objective: Diabetes mellitus is a serious, complex metabolic disorder and growing health threat disease in the world. Berberine, one of the main constituent in Rhizoma coptidis is widely used in the treatment of diabetes. Potential of berberine in the management of diabetic complications, namely diabetic nephropathy and cardiomyopathy, is however, not yet explored. The present study was, therefore, undertaken to explore the potential of berberine for the management of diabetic nephropathy and diabetic cardiomyopathy in high-fat diet (HFD) and low dose streptozotocin (STZ) induced diabetes in rats. Methods: Rats were fed a high-fat diet for 4 w followed by a single intraperitoneal dose of streptozotocin (35 mg/kg). Animals were divided in five groups. Berberine was given orally in two different dose levels (75 mg/kg and 150 mg/kg) for 28 d. Metformin (100 mg/kg) was used as a standard antidiabetic drug. At the end of the study, parameters evaluated includes glycemic profile, lipid profile, left ventricular indices, urinary protein, serum creatinine, blood urea nitrogen and cardiac antioxidants. Histopathology of kidney and pancreas was carried out. Results: Berberine treated groups showed a significant decrease in fasting blood glucose, glycosylated Hb, creatinine, blood urea nitrogen and urinary total proteins, whereas there was a significant improvement in serum insulin, liver glycogen, skeletal muscle glycogen and cardiac antioxidant enzymes. Conclusion: Present study indicated that berberine shows a protective role in diabetes-associated renal and cardiovascular complications.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  

Diabetic nephropathy is a severe microvascular complication of diabetes. Qishen Yiqi dripping pill (QYDP) has been reported to be a renal protective drug. However, the mechanisms remain unclear. This study was performed to investigate the mechanisms. In this study, Sprague-Dawley rats were injected with streptozotocin to generate a diabetes model. Diabetic rats were administered 150 or 300 mg/kg/day QYDP. After 8 weeks of treatment, serum creatinine, serum blood urea nitrogen, and 24-h urinary albumin were measured. Kidney histological staining and immunostaining were analyzed. Then, the renal tissue was analyzed with a genome expression array. The results showed that QYDP treatment reduced serum creatinine, blood urea nitrogen, and 24-h urinary albumin and improved kidney histology and fibrosis. The gene array revealed that the expression of 189 genes was increased, and that of 127 genes was decreased in the high dosage QYDP group compared with the diabetic group. Pathway and gene ontology analyses showed that the differentially expressed genes were involved in the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2 signaling pathways. QYDP reduced the renal Wnt1, catenin β1, Tgfb1, and Smad2 gene expression and β-catenin, TGF-β, Smad2, collagen I, α-smooth muscle actin, and fibronectin protein expression in diabetic rats. Our results provide the first evidence that QYDP performs its renal-protective function by inhibiting the Wnt/β-catenin and TGF-β/Smad2 signaling pathways in diabetic rats.


Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 560
Author(s):  
Yu-Teng Chang ◽  
Mu-Chi Chung ◽  
Chang-Chi Hsieh ◽  
Jeng-Jer Shieh ◽  
Ming-Ju Wu

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg, p < 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm2, db/db: 6538.5 ± 1818.6 μm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm2p < 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial–mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.


2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Xiong Chen ◽  
Rui Liu ◽  
Xiaoming Liu ◽  
Canxia Xu ◽  
Xiaoyan Wang

Aim. To investigate the role of Coxsackie-adenovirus receptor (CAR) in inflammatory bowel disease (IBD). Background. CAR, a type I transmembrane protein with functions in virus attachment, has been shown to be associated with epithelial tight junctions (TJs) and mediates cell adhesion, implying its potential roles in the pathogenesis of IBD. Methods and Materials. To determine the effect of CAR in IBD using QPCR and Western blotting to determine the expression of CAD in TNF-α induced NCM460 and SW480 cells and IBD tissues compared to control groups. Furthermore, TJs dysregulation, FITC-Dextran permeability assay, qRT-PCR, Western blot, and IF assessed the permeability in CAR overexpressed cells treated with TNF-α. HE, qRT-PCR, Western blot, and IHC assay were used to assess the CAR overexpressed cells whether they have the effect to cure DSS induced ulcerative colitis rat model in vivo. Result. We found CAR levels in human colon cell lines are significantly downregulated under the treatment of tumor necrosis factor-alpha (TNF-α). Furthermore, overexpression of CAR markedly prevented TNF-α induced inflammatory response, TJs dysregulation, and permeability disruption (FITC-Dextran permeability assay) in cells. Consistent with these findings in vitro, we found that CAR overexpression could suppress gut inflammation, attenuate the downregulation of TJ protein ZO-1 and Occludin, and limit the induction of barrier permeability in a DSS induced ulcerative colitis rat model in vivo. Together, our findings strongly suggest that CAR could protect tight junctions and has an anti-inflammatory effect during the pathogenesis of IBD. Thus CAR may serve as a therapeutic target for the diagnosis and treatment of IBD.


2018 ◽  
Vol 29 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Archana M. Navale ◽  
Archana Paranjape

Abstract Background Diabetic nephropathy is the leading cause of end-stage renal disease. Hyperglycemia, oxidative stress, and inflammation are some of the mechanisms involved in renal damage. Anogeissus acuminata (AA) is used in India as an antidiabetic agent and has potent antioxidant activity. However, it has never been evaluated for its effect on diabetic nephropathy. Hence, in the present study we aimed to evaluate its effect on streptozotocin-induced diabetes mellitus and its renal complications. Methods Diabetes mellitus was induced by injecting streptozotocin, 50 mg/kg, i.p. in rats fasted for 6 h. Rats with hyperglycemia were treated with extracts of AA for 8 weeks at doses of 100 and 300 mg/kg, orally. Human NPH insulin (4 IU/kg, s.c.) was used as standard treatment. Plasma glucose levels (at weeks 1, 2, 4, and 8) and oxidative stress parameters (at weeks 2 and 4) were assessed. Effect on diabetic nephropathy was evaluated by recording the urinary volume, urinary protein excretion, kidney weights, serum creatinine, and blood urea nitrogen levels at week 8. Results Methanolic extract of AA leaves produced statistically significant (p<0.05) hypoglycemic and antioxidant effect. It also resulted in improved urinary function, reflected by better urinary volume and reduced protein excretion in urine. AA treatment could prevent the elevation of serum creatinine and blood urea nitrogen level in a dose-dependent manner. Kidney hypertrophy could be attenuated remarkably, as reflected by the significantly lower kidney weight (KW) per 100 g body weight (p<0.05). Conclusions AA leaf extract attenuated the development of diabetic nephropathy and also demonstrated antidiabetic and antioxidant action.


Author(s):  
Farhana Mukhtar

Introduction: Pre-eclampsia is one of the most common causes of maternal and fetal complications in developing countries. Owing to its multisystem involvement, hypertension and proteinuria in pre-eclamptic women may lead to acute or chronic renal failure. Early diagnosis is vital to avoid this organ failure. Aims & Objectives: To assess renal function by measuring and comparing four renal function parameters including Blood urea Nitrogen (BUN),serum creatinine, creatinine clearance and 24-hr urinary protein in pre-eclamptic and normotensive pregnant women at different stages of pregnancy. Place and duration of study: This prospective and observational study was conducted in 2009 at Shaikh Zayed Hospital. The patients were taken from Gynae and Obstetrics OPD, with 24 weeks of gestation. Material & Methods: In this study, 25 normotensive Controls and 25 pre-eclamptic pregnant women (cases) were included. Serum and urinary samples were taken at 24 weeks, 28 weeks, 32 weeks of gestation as well as at term (38 weeks). Blood urea nitrogen (BUN), serum creatinine, spot urinary protein and urinary creatinine were measured by clinical Chemistry Auto analyzer Dimension AR. Whereas, 24 hours urinary protein and creatinine clearance were calculated later. Results: BUN level of cases were significantly high as compared to controls at 32 weeks and at term (p<0.01) however creatinine clearance was found to be significantly low (p>0.05) in pre-elamptic women only at 38 weeks. Apart from other results, 24-hours urinary protein was found to be significantly high (p<0.05) in pre-eclamptic women as compared to normotensive women at all stages of pregnancy. Conclusion: Our study showed that BUN, Creatinine clearance and most importantly 24-hr urinary protein may be used to assess the renal function in relation with the severity of pre-eclampsia. Key words: Pre-eclampsia, Blood Urea Nitrogen (BUN), Proteinuria.


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