Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy.

ABSTRACT: Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin-angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg^-1) compared to that of enalapril at a dose of 10 mg·kg^-1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.

SUBMITTER: El-Kady MM

PROVIDER: S-EPMC8308627 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice.

Project description:Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.

| S-EPMC5838225 | biostudies-literature

Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy.

Project description:IntroductionSeveral studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins.Materials and methodsPatients with diabetic nephropathy, selected as those with a serum creatinine level of 0.9-1.5 mg/dL and simultaneously having either microalbuminuria or positive proteinuria, were randomly assigned to one of three groups: a conventional diet therapy group, a group given 10 mg of pravastatin and a group given 10 mg of atorvastatin. Renal function was evaluated before and after a 12-month period of therapy.ResultsThe atorvastatin group had a significant decrease in low-density lipoprotein cholesterol at 3 months and thereafter compared with the other groups. The urinary albumin-to-creatinine ratio significantly decreased in the atorvastatin group; the degree of this decrease was significantly greater than that in the diet therapy group. The kidney function estimated with cystatin C (CysC) and the estimated glomerular filtration rate calculated from CysC were significantly preserved in the atorvastatin group compared with the pravastatin group. In a multivariate regression analysis, the use of atorvastatin was the only explanatory variable for the changes in CysC; this was independent of changes in low-density lipoprotein cholesterol.ConclusionsAtorvastatin is more effective than pravastatin for the prevention of increase in CysC, and this renoprotective effect was considered to a result of the pleiotropic effect of atorvastatin independent of its lipid-lowering effect. This study was registered with UMIN (no. UMIN 000001774).

| S-EPMC4420568 | biostudies-literature

Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats.

Project description:Gushen Jiedu capsule (GSJD) is a formula that has been widely used in traditional Chinese medicine for the prevention and treatment of diabetic nephropathy (DN). However, the mechanism underlying the protective effects of GSJD on DN is still unclear. This study was performed to clarify the therapeutic effects of GSJD on DN and its underlying mechanisms. High-fat diet- and streptozotocin-induced DN rats were treated with or without GSJD suspension by gavage for 8 weeks, and biochemical changes in blood and urine were analysed. Kidneys were isolated for histological, TUNEL and Western blot analysis. Compared to the DN group, the GSJD-treated groups exhibited decreased urinary albumin, ameliorated renal dysfunction, including serum creatinine and blood urea nitrogen, and attenuated total cholesterol, triglyceride and total protein levels. However, there were no significant effects of GSJD on body weight, fasting blood glucose or albuminuria. Histology showed that GSJD could retard the progression of DN and decrease the apoptosis rate from 52% to less than 20%. Western blot analysis showed that GSJD could regulate the mitochondrial apoptotic pathway by downregulating the expression of Bax and upregulating the expression of BCL-2 in the kidneys of DN rats. Moreover, the Akt pathway, an upstream signalling pathway of the BCL-2 family, was also ameliorated by GSJD. Further, the podocyte foot process markers podocin and nephrin were upregulated by GSJD in DN rats. This study demonstrated that GSJD might play a renoprotective role by inhibiting apoptosis and regulating the mitochondrial apoptotic and Akt pathways during pathological changes in DN.

| S-EPMC7005167 | biostudies-literature

Renoprotective effect of <i>Stat1</i> deletion in murine aristolochic acid nephropathy.

Project description:Injured tubule epithelium stimulates a profibrotic milieu that accelerates loss of function in chronic kidney disease (CKD). This study tested the role of signal transducer and activator of transcription 1 (STAT1) in the progressive loss of kidney function in aristolochic acid (AA) nephropathy, a model of CKD. Mean serum creatinine concentration increased in wild-type (WT) littermates treated with AA, whereas Stat1-/- mice were protected. Focal increases in the apical expression of kidney injury molecule (KIM)-1 were observed in the proximal tubules of WT mice with AA treatment but were absent in Stat1-/- mice in the treatment group as well as in both control groups. A composite injury score, an indicator of proximal tubule injury, was reduced in Stat1-/- mice treated with AA. Increased expression of integrin-β6 and phosphorylated Smad2/3 in proximal tubules as well as interstitial collagen and fibronectin were observed in WT mice following AA treatment but were all decreased in AA-treated Stat1-/- mice. The data indicated that STAT1 activation facilitated the development of progressive kidney injury and interstitial fibrosis in AA nephropathy.

| S-EPMC7847048 | biostudies-literature

Interaction between diabetes and hypertension in a rat model of diabetic nephropathy

Project description:Fisher male Cyp1a1mRen2 rats were allocated into four groups of four biological replicates each: control; streptozotocin-induced diabetes alone; indole-3-carbinol induced hypertension alone; combined induced diabetes and hypertension. <br>Kidneys were harvested for microarray analysis.analysis.

2011-12-31 | E-MEXP-3165 | biostudies-arrayexpress

Diabetes and hypertension then reversal in a rat model of diabetic nephropathy

Project description:Fisher male Cyp1a1mRen2 rats were allocated into three groups of four or eight biological replicates each: control; combined induced diabetes and hypertension; removal of combined treatments. Kidneys were harvested for gene expression microarray analysis on Affymetrix GeneChip Rat Genome 230 2.0 GeneChips

2013-04-10 | E-MEXP-3739 | biostudies-arrayexpress

Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes.

Project description:The present study aimed to explore the renoprotective effect of metformin on diabetic nephropathy in type 2 diabetic rats. A rat model of type 2 diabetic nephropathy (T2DN) was successfully induced via a high-fat diet combined with a single low-dose of streptozotocin. Metformin was administered intragastrically for 13 weeks, and fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), HDL-c, LDL-c, urinary and serum creatinine levels were subsequently examined at the end of administration. Renal function was determined after the treatment protocol. Expression levels of transforming growth factor (TGF)-?1 and connective tissue growth factor (CTGF) were assessed via immunohistochemical analysis. Superoxide dismutase activity, malondialdehyde content and glutathione peroxidase levels were assessed in kidney tissues using commercially available kits. The results of the present study demonstrated that metformin administration significantly decreased the levels of serum blood urea nitrogen, serum creatinine, creatinine clearance, urinary albumin excretion and fasting blood glucose in rats with T2DN. Furthermore, TG, TC and LDL-c levels were significantly decreased following metformin treatment, whereas HDL-c was increased. Metformin treatment significantly increased SOD activity and significantly decreased malondialdehyde levels, as compared with the model group. It was also demonstrated that metformin administration significantly decreased the expression levels of TGF-?1 and attenuated the morphological changes associated with T2DN in rats. These data clearly demonstrated the renoprotective effects of metformin against the development and progression of T2DN in rats. The underlying mechanism of this protective effect may be associated with glycemic control, lipid metabolism, and anti-oxidative and anti-inflammatory functions.

| S-EPMC5488633 | biostudies-literature

The Combinational Effect of Inulin and Resveratrol on the Oxidative Stress and Inflammation Level in a Rat Model of Diabetic Nephropathy.

Project description:BackgroundUsing inulin can enhance resveratrol's effects by improving the intestinal microbiome and the stability of resveratrol.ObjectivesWe aimed to investigate the effect of therapeutic intervention with combined inulin and resveratrol on kidney function in diabetic rats.MethodsDiabetic model was induced by intraperitoneal injection of streptozotocin. Afterward, rats were divided into 6 groups: control, diabetic without treatment, diabetic treated with insulin, diabetic treated with resveratrol, diabetic treated with inulin, and diabetic treated with a combination of inulin and resveratrol. After 10 wk, the creatinine, urea, insulin, urinary proteins, and inflammatory and oxidative stress markers were evaluated. Pathologic changes were examined in kidney tissues.ResultsRenal dysfunction, accompanied by increased inflammation and oxidative stress, was observed. Our results showed that treatment with resveratrol and inulin had antidiabetic effects and was associated with reduced renal dysfunction, oxidative stress, and kidney inflammation. In addition, it was observed that combined treatment with inulin and resveratrol outperformed monotherapies in improving kidney function and reducing oxidative stress and inflammation.ConclusionsTreatment with resveratrol and inulin can have renoprotective effects by improving oxidative stress and inflammation in kidney tissues. Therefore, employing these 2 compounds is suggested as an inexpensive and available method for diabetic nephropathy.

| S-EPMC10826146 | biostudies-literature

Data on nephroprotective effect of all-trans retinoic acid in early diabetic nephropathy.

Project description:Data showed in this report are related to the research article entitled "All-trans retinoic acid ameliorates inflammatory response mediated by TLR4/NF-кB during the initiation of diabetic nephropathy" by Sierra-Mondragon et al. (2018) [1]. Diabetic nephropathy (DN) has become the main cause of renal failure. Inflammatory molecules such as cytokines, chemokines and growth factors play a key role in DN-induced renal injury Pichler et al. (2016) [2]. Results illustrate the effect of all-trans retinoic acid (ATRA), an active metabolite of vitamin A, on the renal alterations related to diabetes, among them glomerular and tubular dysfunction, and its effect on renal inflammation in different nephron segments: glomeruli, proximal and distal tubules in an initial stage of DN. Data were obtained by physical-biochemical measurements and Western blot assays performed on isolated glomeruli, proximal and distal tubules from rat kidneys.

| S-EPMC6129741 | biostudies-literature

Pan-ampk activation improves renal function in a rat model of progressive diabetic nephropathy

Project description:Chronic kidney disease (CKD) remains a tremendous and growing burden on the healthcare system and new therapies are needed to prevent or slow disease progression. Metabolic dysregulation and mitochondrial dysfunction are important features of acute and chronic tissue injury across species, and human genetics and preclinical data suggest that the master metabolic regulator 5'-adenosine monophosphate activated protein kinase (AMPK) may be an effective therapeutic target for CKD. Merck has recently disclosed a pan-AMPK activator MK-8722 which was shown to have beneficial effects on metabolic parameters in preclinical models. In this study we investigate the effects of MK-8722 in a progressive model of diabetic nephropathy to determine whether activation of AMPK would be of therapeutic benefit. We find that MK-8722 administration in a therapeutic paradigm is profoundly reno-protective. We provide evidence that the therapeutic effects may be mediated by modulation of renal mitochondrial quality control as well as by attenuating fibrotic and lipotoxic mechanisms in kidney cells. These data further validate the concept that targeting metabolic dysregulation in CKD could be a potential therapeutic approach.

2019-07-25 | GSE134804 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data