scholarly journals Beneficiary Effects of Colchicine on Inflammation and Fibrosis in A Mouse Model of Chronic Kidney Disease

2021 ◽  
Author(s):  
Daniel Landau ◽  
Nehoray Shukri ◽  
Eden Arazi ◽  
Ana Tobar ◽  
Yael Segev
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mouse Model ◽  
Macrophage Infiltration ◽  
Low Grade ◽  
Tubulin Polymerization ◽  
Mrna Levels ◽  
Caspase 1 ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Abstract Introduction: Low grade inflammation is seen in many chronic illnesses, including chronic kidney disease (CKD). We have recently reported on beneficiary effects of anti-inflammatory treatment in the interleukin (IL-)1 pathway on anemia as well as CKD extent in a mouse model. Colchicine has been shown to have beneficiary effects in several inflammatory conditions through various mechanisms, including inhibition of tubulin polymerization as well as caspase 1 mediated IL1 activation.Methods: CKD was induced by administering an adenine diet to 8-week-old C57BL/6J mice. Mice were treated with colchicine (Col) (30µg/kg) or saline injections for 3 weeks, generating 4 groups: C, C-Col, CKD and CKD-Col.Results: Uremic animals had an increase in inflammation indices in blood (neutrophils), liver and kidneys (p-STAT3, IL-6, SOCS-3). Increased kidney tubulin polymerization and caspase 1 in CKD, as well as kidney Mid88 and IRAK4 (downstream of IL1) were inhibited in CKD-Col. Kidney macrophage infiltration (F4/80 and MAC-2), the percentage of fibrotic area and TGFb mRNA levels were lower in CKD-Col Vs CKD.Conclusions: colchicine improves kidney macrophage infiltration and fibrosis in CKD through inhibition of tubulin polymerization and Caspase 1 activation. Given its reported safety profile for long term anti-inflammatory therapy without increasing infection tendency, it may serve as novel therapeutic approach in CKD.

scholarly journals Mechanisms Mediating Dose-Dependent Effects of Eicosapentaenoic Acid in White Adipose Tissue From High Fat Diet-Induced Obese Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1209-1209
Author(s):  
Hanna Davis ◽  
Mandana Pahlavani ◽  
Yujiao Zu ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
White Adipose Tissue ◽  
Macrophage Infiltration ◽  
Low Grade ◽  
Mrna Levels ◽  
Obese Mice ◽  
Adipocyte Size ◽  
M1 Macrophage ◽  
Anti Inflammatory

Abstract Objectives Obesity is a global epidemic and complex disease associated with an expansion of white adipose tissue (WAT). Obesity is accompanied by chronic low-grade inflammation, characterized by elevated levels of secreted pro-inflammatory cytokines and M1 macrophage infiltration into WAT. Eicosapentaenoic acid (EPA), a long-chain omega-3 polyunsaturated fatty acid, has been reported to have anti-obesity and anti-inflammatory properties. Moreover, we previously showed that EPA dose-dependently improved glucose intolerance, and inflammation in diet-induced obese mice. The objective of this study is to further determine mechanisms underlying these metabolic protective effects of EPA in epididymal WAT (e-WAT). Methods Male B6 mice were fed a HF diet (45% kcal fat) or a HF diet supplemented with 9, 18, or 36 g/kg of EPA-enriched fish oil (EPA 9, 18 or 36) for 14 weeks. We performed histological assessments in eWAT to determine adipocyte size; and measure macrophage infiltration by immunohistochemistry using galectin-3. RNA was isolated from eWAT for RNA sequencing and gene expression analyses. Data were analyzed using GraphPad Prism software. Results EPA36-fed mice had significantly lower body weight and fat percentage, compared to HF (P < 0.05). In addition, EPA18 and 36 significantly decreased weight of e-WAT (P < 0.05) and increased glucose clearance compared to HF (P < 0.05). Moreover, all EPA doses had smaller adipocytes (P < 0.05). Compared to HF, EPA18 and 36 significantly reduced macrophage infiltration in e-7.43 fold, respectively. Consistent with these changes, EPA18 and 36 reduced the mRNA levels of HF-induced inflammatory markers, including arachidonate 5-lipoxygenase (Alox5) and leukotriene B4 receptor (Ltb4r) compared to HF (P < 0.05). RNA Seq analyses revealed that EPA18 attenuated HF-induced inflammation in part by up-regulating cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathways and down-regulating triggering receptor expressed on myeloid cells 1 (TREM1) signaling. Conclusions EPA dose-dependently ameliorated HF-induced obesity and inflammation by reducing adipocyte size and macrophage infiltration and modulating pro- and anti-inflammatory pathways in e-WAT. These effects were achieved at human equivalent doses, that are currently prescribed for reducing triglycerides. Funding Sources USDA NIFA NIH.

scholarly journals Anti-Inflammatory Activity of Isomaltodextrin in a C57BL/6NCrl Mouse Model with Lipopolysaccharide-Induced Low-Grade Chronic Inflammation

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2791 ◽  
Author(s):  
Hann ◽  
Zeng ◽  
Zong ◽  
Sakurai ◽  
Taniguchi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protein Expression ◽  
Tight Junction ◽  
Chronic Inflammation ◽  
Inflammatory Mediators ◽  
Macrophage Infiltration ◽  
Inflammatory Activity ◽  
Low Grade ◽  
Junction Protein ◽  
Anti Inflammatory

：The purpose of this study was to identify the anti-inflammatory activity and mechanism of isomaltodextrin (IMD) in a C57BL/6NCrl mouse model with lipopolysaccharide (LPS)-induced systemic low-grade chronic inflammation and the effect on inflammation-induced potential risk of metabolic disorders. Pre-treatment of IMD decreased the production of pro-inflammatory mediators, TNF-α and MCP-1, and stimulated the production of the anti-inflammatory mediator, adiponectin by increasing the protein expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in the white adipose tissues. IMD administration reduced plasma concentrations of endotoxin, decreased macrophage infiltration into adipocytes, and increased expression of mucin 2, mucin 4, and the tight junction protein claudin 4. These results suggest that IMD administration exerted an anti-inflammatory effect on mice with LPS-induced inflammation, potentially by decreasing circulating endotoxin, suppressing pro-inflammatory mediators and macrophage infiltration, or by improving mucus or tight junction integrity. IMD exerted protein expression of insulin receptor subset-1 (IRS-1). IMD alleviated the disturbance of gut microflora in LPS-treated mice, as the number of B. bifidum, L. casei, and B. fragilis increased, and E. coli and C. difficile decreased, when compared to LPS-treated mice. The analysis of short chain fatty acids (SCFAs) further supported that the concentrations of acetic and butyric acids were positively correlated with IMD, as well as the number of beneficial bacteria. This study provides evidence that IMD possesses anti-inflammatory properties and exerts beneficial functions to prevent systemic low-grade chronic inflammation and reduces the risk of developing insulin resistance and associated metabolic diseases.

scholarly journals Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0122899 ◽  
Author(s):  
Ylenia Ingrasciotta ◽  
Janet Sultana ◽  
Francesco Giorgianni ◽  
Andrea Fontana ◽  
Antonio Santangelo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Case Control Study ◽  
Population Based ◽  
Case Control ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Control Study

scholarly journals Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease

Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 50
Author(s):  
Satoshi Kumakura ◽  
Emiko Sato ◽  
Akiyo Sekimoto ◽  
Yamato Hashizume ◽  
Shu Yamakage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Kidney Disease ◽  
Mouse Model ◽  
Metabolic Pathways ◽  
Krebs Cycle ◽  
Inflammatory Reactions ◽  
Progression Of Kidney Disease ◽  
Progression Of Renal Failure

Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.

Nephroprotective effect of novel oral sugar-reducing medicines: glyflosins

2021 ◽  
Vol 25 (4) ◽  
pp. 11-22
Author(s):  
Ya. F. Zverev ◽  
A. Ya. Rykunova
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Initial Period ◽  
Sglt2 Inhibitors ◽  
Tubuloglomerular Feedback ◽  
Renal Tubules ◽  
Anti Inflammatory ◽  
Energy Deprivation ◽  
Nephroprotective Effect

The review is devoted to the consideration of the nephroprotective effect and its mechanisms in new hypoglycemic drugs gliflozins, identified in largescale randomized placebo-controlled trials and experimental studies. It was found that inhibition of sodium-glucose co-transporter 2 (SGLT2) in the proximal tubules of the kidneys when using these drugs not only leads to a decrease in blood glucose levels, a decrease in blood pressure, body weight, and uric acid content in blood plasma but also delays the progression of chronic kidney disease, inhibiting the development of diabetic nephropathy. This beneficial effect is multifactorial. It is caused by the diuretic and natriuretic effects, a decrease in albuminuria, a decrease in glucotoxicity in the cells of the renal tubules, a hemodynamic effect on kidney function, and a direct anti-inflammatory effect. It is discussed why the use of SGLT2 inhibitors restores tubuloglomerular feedback, which is disrupted in the initial period of diabetic nephropathy and leads to hyperfiltration in the remaining nephrons. Information is provided on the restoration of impaired mitochon drial function due to the positive effect of drugs on the ionic composition of renal tubule cells. This greatly contributes to the enhancement of autophagy, the lysosome-mediated pathway of degradation and removal of damaged organelles, and normalizes intracellular homeostasis. The probable mechanism of autophagy enhancement through increased activity of energy deprivation sensors of AMPK and SIRT1 cells is considered. Possible mechanisms of development of anti-inflammatory and antioxidant action of SGLT2 inhibitors through inhibition of inflammasome activity are discussed. The question of the possible use of gliflozins in chronic kidney disease, the pathogenesis of which is not associated with diabetes mellitus, is considered.

scholarly journals Delivery of a nutritional prescription by enteral tube feeding in children with chronic kidney disease stages 2–5 and on dialysis—clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

2020 ◽  
Vol 36 (1) ◽  
pp. 187-204
Author(s):  
Lesley Rees ◽  
◽  
Vanessa Shaw ◽  
Leila Qizalbash ◽  
Caroline Anderson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Growth Parameters ◽  
Tube Feeding ◽  
Low Grade ◽  
Enteral Tube Feeding ◽  
Practice Recommendations ◽  
The Individual ◽  
Disease Stages

AbstractThe nutritional prescription (whether in the form of food or liquid formulas) may be taken orally when a child has the capacity for spontaneous intake by mouth, but may need to be administered partially or completely by nasogastric tube or gastrostomy device (“enteral tube feeding”). The relative use of each of these methods varies both within and between countries. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPRs) based on evidence where available, or on the expert opinion of the Taskforce members, using a Delphi process to seek consensus from the wider community of experts in the field. We present CPRs for delivery of the nutritional prescription via enteral tube feeding to children with chronic kidney disease stages 2–5 and on dialysis. We address the types of enteral feeding tubes, when they should be used, placement techniques, recommendations and contraindications for their use, and evidence for their effects on growth parameters. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgement. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

scholarly journals Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease

2018 ◽  
Vol 51 (3) ◽  
pp. 1287-1300 ◽  
Author(s):  
Manel Vera ◽  
Sergi Torramade-Moix ◽  
Susana Martin-Rodriguez ◽  
Aleix Cases ◽  
Josep M. Cruzado ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Glutathione Peroxidase ◽  
Antioxidant Properties ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Anti Inflammatory

Background/Aims: Accelerated atherosclerosis in chronic kidney disease (CKD) is preceded by endothelial dysfunction (ED), which exhibits a proinflammatory and prothrombotic phenotype and enhanced oxidative stress. In this study, the effect of several compounds with anti-inflammatory and/or antioxidant properties on uremia-induced endothelial dysfunction has been evaluated in an in vitro model. Methods: Endothelial cells (ECs) were exposed to sera from uremic patients in the absence and presence of the flavonoids apigenin, genistein and quercetin, the antioxidant enzyme mimetics (AEM) ebselen (glutathione peroxidase mimetic), EUK-134 and EUK-118 (both superoxide dismutase mimetics), and the pharmacological drug N-acetylcysteine (NAC). We explored changes in the expression of adhesion receptors on the cell surface, by immunofluorescence, the production of radical oxygen species (ROS), by fluorescence detection, and the activation of signaling proteins related to inflammation, by both a phosphospecific antibody cell-based ELISA and immunoblotting techniques. Results: Uremic media induced a significantly increased expression of ICAM-1, overproduction of radical oxygen species (ROS) and activation of p38 mitogen activated protein kinase (p38MAPK) and Nuclear Factor kB (NFkB) in ECs. Quercetin, the AEM and NAC showed a significant inhibitory effect on both ICAM-1 expression and ROS generation (p<0.05). All the compounds reduced p38MAPK activation, but only the AEM, especially ebselen, and NAC, both potentiating the glutathione peroxidase pathway, also inhibited NFkB activation. These two compounds were capable of increasing endothelial glutathione levels, especially in response to uremia. Conclusion: Our results indicate that the potentiation of the antioxidant pathways can be an effective strategy to improve endothelial dysfunction in uremia and a potential target to reduce the cardiovascular risk in this population.

scholarly journals Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patricia Rivera ◽  
Catalina Miranda ◽  
Nicole Roldán ◽  
Aaron Guerrero ◽  
Javier Olave ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Young Adults ◽  
Body Weight ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Simple Method ◽  
Renin Angiotensin

AbstractObesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

scholarly journals Two in one: Neuregulin 1 improves cardiac diastolic and kindney funtcion in chronic kidney disease in rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kiss ◽  
E Acar ◽  
S Watzinger ◽  
Z.S Kovacs ◽  
F Marvanykovi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Diastolic Dysfunction ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Low Grade ◽  
Funding Source ◽  
Neuregulin 1 ◽  
Expression Levels

Abstract Introduction The prevalence of chronic renal disease (CKD) is continuously increasing in developed countries. Uremic cardiomyopathy characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) is a common cardiovascular complication of CKD. Cardiac microvascular low-grade inflammation and altered expression of endothelium derived Neuregulin-1 (NRG-1) are contributed to left ventricular DD. Our aim was to charachterize the effects of CKD on the expression of NRG-1 and 2) NRG-1 treatment on myocardial hypertrophy, diastolic dysfunction and renal function in the rat model of CKD. Methods Male Wistar rats were used and randomized into 3 groups: 1) Sham-operated,2) CKD induced by 5/6 nephrectomy (CKD) and 3) NRG-1-treated CKD group (CKD+NRG-1). In this group, 2 weeks after the CKD induction, the rats were treated with recombinant human NRG-1 (rhNRG-1) at the dose of 10 μg/kg/d for consecutive 10 days with tail vein injection of NRG-1. Serum and urea creatinine levels were measured to verify the development of CKD and transthoracic echocardiography was performed to monitor cardiac morphology and function. Furthermore, total RNA was isolated and RT-qPCR was performed to evaluate the expression levels of inflammatory chemokine and cytokines (TNF-α, TGF-β). In addition, NRG-1 protein levels were assessed in both kidney and heart tissue by ELISA. To clarify the underling anti-fibrotic mechanism, human ventricular cardiac fibroblasts (HCF) were cultured and treated with the TGF-β (20 ng/ml), and TGF-β + hrNRG-1 for 24 h, respectively. Confocal microscopy was used to detect α-smooth muscle actin (α-SMA) expression, marker for fibroblast to myofibroblast transtion. Results 10 weeks after the 5/6 nephrectomy, serum carbamide and creatinine levels were significantly increased and creatinine clearence was significantly decreased as compared to sham-operated animals proving the development of chronic kidney disease (CKD). This was accompanied by a significant decrease in NRG-1 protein expression levels in both cardiac and kidney tissue. Of note, NRG-1 treatment markedly reduced these changes, suggesting its renoprotective effects in CKD. In addition, In CKD animals, the significantly increased anterior, posterior and septal wall thicknesses with decreased end-diastolic and end-systolic diameters proved the development of concentric left ventricular hypertrophy. In CKD, the septal e' was significantly decreased and E/e' increased indicating the developemnt of diastolic dysfunction. These parameters were significantly improved by NRG-1 treatment. Mechanistically, NRG-1 treatment reduced the expression of inflammatory cytokines in compared to untreat group. Furthermore, TGF-β induced α-SMA and Col I upregulation was markedly reduced by hrNRG-1 treatment. Conclusions NRG-1 treatment improved both renal and cardiac funtion in CKD, via a mechansim including the anti-inflammatory and anti-fibrotic properties of NRG-1. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Österreichischer Austauschdienst

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