scholarly journals Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

2019 ◽  
Vol 10 (1) ◽  
pp. 216-226 ◽  
Author(s):  
Ghada Alomari ◽  
Bahaa Al-Trad ◽  
Salehhuddin Hamdan ◽  
Alaa Aljabali ◽  
Mazhar Al-Zoubi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gold Nanoparticles ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Protein Expression ◽  
Male Rats ◽  
Extracellular Matrix Protein ◽  
Membrane Thickness ◽  
Podocyte Injury ◽  
Basement Membrane Thickness

Abstract Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.

scholarly journals 1α,25-Dihydroxyvitamin D3 prevents renal oxidative damage via the PARP1/SIRT1/NOX4 pathway in Zucker diabetic fatty rats

2020 ◽  
Vol 318 (3) ◽  
pp. E343-E356
Author(s):  
Dongxia Wang ◽  
Yanyan Li ◽  
Ning Wang ◽  
Gang Luo ◽  
Jun Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Oxidative Damage ◽  
Sirtuin 1 ◽  
Diabetic Rat ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
Rat Kidneys

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.

scholarly journals CORRELATION BETWEEN OXIDATIVE STRESS AND ANTIOXIDANT IN DIABETIC NEPHROPATHY

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Bhagwan Singh Meena ◽  
B.K. Agarwal ◽  
Arun Mishra ◽  
Mahesh Kumar
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Early Recognition ◽  
Antioxidant Defense System ◽  
Extracellular Proteins ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Healthy Control ◽  
End Stage

Background: Diabetic Nephropathy is consider as one of the major micro-vascular problems of diabetes mellitus and has become the most general single factor of end stage of kidney disease. It is defined traditionally by kidney morphological and modification like: glomerular hyper filtration, glomerular and kidney hypertrophy, increased urinary albumin excretion (> 300 mg/24 hours), increased GBM (Glomerular Basement Membrane) thickness and mesangial expansion and also accumulation of extracellular proteins comprising laminin, collagens and fibronectin worldwide. Oxidative stress (OS) has been characterized as the imbalance between reactive oxygen species (ROS) yielding and the possessive antioxidant defense system. Objective of the study: Correlation between oxidative stress and antioxidant in diabetic nephropathy. Materials and methods: The investigation was conducted on 100 DN subjects of both sex and aged 20 or more and 100 age and sex matched healthy control subjects. MDA, SOD and Catalase of each subject was measured. Results: the present investigation shows that the MDA was elevated significantly and SOD and Catalase level was found to be significantly low in DN individuals as compared to controls. Conclusion: This study concluded that the MDA could be better marker for early recognition of DN. Keywords: Diabetic nephropathy (DN), MDA, SOD, Catalase, Kidney disease

scholarly journals Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy

2020 ◽  
Vol 21 (12) ◽  
pp. 4225
Author(s):  
Lucas Opazo-Ríos ◽  
Anita Plaza ◽  
Yenniffer Sánchez Matus ◽  
Susana Bernal ◽  
Laura Lopez-Sanz ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Binding Domain ◽  
Inflammatory Factors ◽  
Preclinical Model ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Nemo Binding Domain ◽  
Nbd Peptide

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.

Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats

2020 ◽  
Vol 11 (4) ◽  
pp. 3706-3718 ◽  
Author(s):  
Min-you Qi ◽  
Xu-tao Wang ◽  
Hui-lin Xu ◽  
Zhang-liang Yang ◽  
Yin Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Protective Effect ◽  
Ferulic Acid ◽  
Podocyte Injury

Ferulic acid protects against diabetic nephropathy in STZ-induced rats by attenuating oxidative stress, inflammation, fibrosis and podocyte injury.

scholarly journals Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis

2010 ◽  
Vol 299 (1) ◽  
pp. F99-F111 ◽  
Author(s):  
Youli Wang ◽  
Kathleen Heilig ◽  
Thomas Saunders ◽  
Andrew Minto ◽  
Dilip K. Deb ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Glomerular Disease ◽  
Membrane Thickness ◽  
Renal Tubules ◽  
Glomerular Mesangial Cells ◽  
Diabetic Glomerulosclerosis ◽  
Basement Membrane Thickness ◽  
Intracellular Glucose

Previous work identified an important role for hyperglycemia in diabetic nephropathy (The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977–986, 1993; UK Prospective Diabetes Study Group. Lancet 352: 837–853, 1998), and increased glomerular GLUT1 has been implicated. However, the roles of GLUT1 and intracellular glucose have not been determined. Here, we developed transgenic GLUT1-overexpressing mice (GT1S) to characterize the roles of GLUT1 and intracellular glucose in the development of glomerular disease without diabetes. GLUT1 was overexpressed in glomerular mesangial cells (MC) of C57BL6 mice, a line relatively resistant to diabetic nephropathy. Blood pressure, blood glucose, glomerular morphometry, matrix proteins, cell signaling, transcription factors, and selected growth factors were examined. Kidneys of GT1S mice overexpressed GLUT1 in glomerular MCs and small vessels, rather than renal tubules. GT1S mice were neither diabetic nor hypertensive. Glomerular GLUT1, glucose uptake, mean capillary diameter, and mean glomerular volume were all increased in the GT1S mice. Moderately severe glomerulosclerosis (GS) was established by 26 wk of age in GT1S mice, with increased glomerular type IV collagen and fibronectin. Modest increases in glomerular basement membrane thickness and albuminuria were detected with podocyte foot processes largely preserved, in the absence of podocyte GLUT1 overexpression. Activation of glomerular PKC, along with increased transforming growth factor-β1, VEGFR1, VEGFR2, and VEGF were all detected in glomeruli of GT1S mice, likely contributing to GS. The transcription factor NF-κB was also activated. Overexpression of glomerular GLUT1, mimicking the diabetic GLUT1 response, produced numerous features typical of diabetic glomerular disease, without diabetes or hypertension. This suggested GLUT1 may play an important role in the development of diabetic GS.

scholarly journals Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

2016 ◽  
Vol 17 (12) ◽  
pp. 2066 ◽  
Author(s):  
Lucía Calatrava-Ferreras ◽  
Rafael Gonzalo-Gobernado ◽  
Diana Reimers ◽  
Antonio Herranz ◽  
María Casarejos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Protein Expression ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Liver Growth

scholarly journals Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Chao Wang ◽  
Xiao-xia Hou ◽  
Hong-liang Rui ◽  
Li-jing Li ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Expression ◽  
Nlrp3 Inflammasome ◽  
Kidney Tissue ◽  
Therapeutic Effects ◽  
Low Grade ◽  
Podocyte Injury ◽  
Ophiocordyceps Sinensis ◽  
Caspase 1 ◽  
Mrna And Protein Expression

Background/Aims. It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). Methods. A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed. The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined. The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1β and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively. Results. The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages. ACOS significantly antagonized the above changes. The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1β, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively. ACOS also significantly antagonized all the above changes. Conclusion. Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.

Sign in / Sign up

Export Citation Format

Share Document