scholarly journals Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Edilia Tapia ◽  
Virgilia Soto ◽  
Karla Mariana Ortiz-Vega ◽  
Guillermo Zarco-Márquez ◽  
Eduardo Molina-Jijón ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Protective Effect ◽  
Renal Injury ◽  
Nuclear Translocation ◽  
Interstitial Fibrosis ◽  
Oxidant Stress ◽  
Systemic Hypertension ◽  
Glomerular Sclerosis ◽  
Renal Ablation ◽  
Glomerular Hypertension

Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX+CUR,and (4) CUR (n=8–10). Curcumin was given by gavage to NX5/6+CURand CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

The Relevance of Periglomerular Fibrosis in the Evaluation of Routine Needle Core Renal Biopsies

2011 ◽  
Vol 135 (1) ◽  
pp. 117-122
Author(s):  
Joseph Jenkins ◽  
Sergey V. Brodsky ◽  
Anjali A. Satoskar ◽  
Gyongyi Nadasdy ◽  
Tibor Nadasdy
Keyword(s):  
Renal Function ◽  
Renal Biopsy ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Poor Renal Function ◽  
Renal Biopsies ◽  
Biopsy Report ◽  
Relationship Of

Abstract Context—Renal interstitial fibrosis and, to a lesser extent, sclerotic glomeruli correlate with poor renal function. However, not all nonfunctional glomeruli are sclerotic. Many or most glomeruli with periglomerular fibrosis, while retaining blood flow, probably do not filter; therefore, they may not contribute to renal function. Objective—To examine the relationship of periglomerular fibrosis and the sum of globally sclerotic glomeruli and glomeruli with periglomerular fibrosis (GSG+PF) with interstitial fibrosis and renal function. Design—Native kidney biopsies from 177 patients with chronic renal injury were assessed for interstitial fibrosis, glomerular sclerosis, and GSG+PF. Renal biopsies with active or acute lesions were not included. The percentage of globally sclerotic glomeruli and GSG+PF was correlated with the degree of interstitial fibrosis and serum creatinine levels. Results—The percentage of GSG+PF correlates better with the degree of interstitial fibrosis and renal function than does the percentage of globally sclerotic glomeruli alone. This appears particularly true in chronic renal diseases of patients without diabetes. The number of globally sclerotic glomeruli correlates better with interstitial fibrosis and renal function than does the sum of globally and segmentally sclerotic glomeruli. Conclusions—The percentage of GSG+PF in a renal biopsy specimen provides a better estimate of chronic renal injury than does the percentage of sclerotic glomeruli alone, probably because many or most glomeruli with periglomerular fibrosis are nonfunctional. Therefore, we recommend that the number of glomeruli with periglomerular fibrosis also be provided in the renal biopsy report.

scholarly journals Protective Effect of Astaxanthin on Blue Light Light-Emitting Diode-Induced Retinal Cell Damage via Free Radical Scavenging and Activation of PI3K/Akt/Nrf2 Pathway in 661W Cell Model

Marine Drugs ◽  
2020 ◽  
Vol 18 (8) ◽  
pp. 387 ◽  
Author(s):  
Chao-Wen Lin ◽  
Chung-May Yang ◽  
Chang-Hao Yang
Keyword(s):  
Antioxidant Enzymes ◽  
Free Radical ◽  
Protective Effect ◽  
Blue Light ◽  
Nuclear Translocation ◽  
Light Exposure ◽  
Cell Damage ◽  
Radical Scavenging ◽  
Photoreceptor Cells ◽  
Light Emitting

Light-emitting diodes (LEDs) are widely used and energy-efficient light sources in modern life that emit higher levels of short-wavelength blue light. Excessive blue light exposure may damage the photoreceptor cells in our eyes. Astaxanthin, a xanthophyll that is abundantly available in seafood, is a potent free radical scavenger and anti-inflammatory agent. We used a 661W photoreceptor cell line to investigate the protective effect of astaxanthin on blue light LED-induced retinal injury. The cells were treated with various concentrations of astaxanthin and then exposed to blue light LED. Our results showed that pretreatment with astaxanthin inhibited blue light LED-induced cell apoptosis and prevented cell death. Moreover, the protective effect was concentration dependent. Astaxanthin suppressed the production of reactive oxygen species and oxidative stress biomarkers and diminished mitochondrial damage induced by blue light exposure. Western blot analysis confirmed that astaxanthin activated the PI3K/Akt pathway, induced the nuclear translocation of Nrf2, and increased the expression of phase II antioxidant enzymes. The expression of antioxidant enzymes and the suppression of apoptosis-related proteins eventually protected the 661W cells against blue light LED-induced cell damage. Thus, our results demonstrated that astaxanthin exerted a dose-dependent protective effect on photoreceptor cells against damage mediated by blue light LED exposure.

scholarly journals Asymmetric dimethylarginine in angiotensin II-induced hypertension

2010 ◽  
Vol 298 (3) ◽  
pp. R740-R746 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Natasha C. Moningka ◽  
Mark W. Cunningham ◽  
Byron Croker ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Renal Injury ◽  
Asymmetric Dimethylarginine ◽  
Renal Cortex ◽  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Plasma Adma ◽  
Induced Hypertension

Recent studies have shown that asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, is increased in hypertension and chronic kidney disease. However, little is known about the effects of hypertension per se on ADMA metabolism. The purpose of this study was to test the hypothesis that ANG II-induced hypertension, in the absence of renal injury, is associated with increased oxidative stress and plasma and renal cortex ADMA levels in rats. Male Sprague-Dawley rats were treated with ANG II at 200 ng·kg−1·min−1 sc (by minipump) for 1 or 3 wk or at 400 ng·kg−1·min−1 for 6 wk. Mean arterial pressure was increased after 3 and 6 wk of ANG II; however, renal injury (proteinuria, glomerular sclerosis, and interstitial fibrosis) was only evident after 6 wk of treatment. Plasma thiobarbituric acid reactive substances concentration and renal cortex p22phox protein abundance were increased early (1 and 3 wk), but urinary excretion of isoprostane and H2O2 was only increased after 6 wk of ANG II. An increased in plasma ADMA after 6 wk of ANG II was associated with increased lung protein arginine methyltransferase-1 abundance and decreased renal cortex dimethylarginine dimethylaminohydrolase activity. No changes in renal cortex ADMA were observed. ANG II hypertension in the absence of renal injury is not associated with increased ADMA; however, when the severity and duration of the treatment were increased, plasma ADMA increased. These data suggest that elevated blood pressure alone, for up to 3 wk, in the absence of renal injury does not play an important role in the regulation of ADMA. However, the presence of renal injury and sustained hypertension for 6 wk increases ADMA levels and contributes to nitric oxide deficiency and cardiovascular disease.

Ovariectomy is protective against renal injury in the high-salt-fed older mRen2.Lewis rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2064-H2071 ◽  
Author(s):  
Liliya M. Yamaleyeva ◽  
Karl D. Pendergrass ◽  
Nancy T. Pirro ◽  
Patricia E. Gallagher ◽  
Leanne Groban ◽  
...  
Keyword(s):  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
High Salt ◽  
Glomerular Sclerosis ◽  
Tubular Damage ◽  
Lewis Rat ◽  
Lewis Rats ◽  
Ovx Rats ◽  
Igf I

Studies in experimental animals and younger women suggest a protective role for estrogen; however, clinical trials may not substantiate this effect in older females. Therefore, the present study assessed the outcome of ovariectomy in older mRen2.Lewis rats subjected to a high-salt diet for 4 wk. Intact or ovariectomized (OVX, 15 wk of age) mRen2.Lewis rats were aged to 60 wk and then placed on a high-salt (HS, 8% sodium chloride) diet for 4 wk. Systolic blood pressures were similar between groups [OVX 169 ± 6 vs. Intact 182 ± 7 mmHg; P = 0.22] after the 4-wk diet; however, proteinuria [OVX 0.8 ± 0.2 vs. Intact 11.5 ± 2.6 mg/mg creatinine; P < 0.002, n = 6], renal interstitial fibrosis, glomerular sclerosis, and tubular casts were lower in OVX vs. Intact rats. Kidney injury molecule-1 mRNA, a marker of tubular damage, was 53% lower in the OVX HS group. Independent from blood pressure, OVX HS rats exhibited significantly lower cardiac (24%) and renal (32%) hypertrophy as well as lower C-reactive protein (28%). Circulating insulin-like growth factor-I (IGF-I) levels were not different between the Intact and OVX groups; however, renal cortical IGF-I mRNA and protein were attenuated in OVX rats [ P < 0.05, n = 6]. We conclude that ovariectomy in the older female mRen2.Lewis rat conveys protection against salt-dependent increase in renal injury.

Abstract 514: Jak2 Tyrosine Kinase Mediates Angiotensin II Renal Pathogenesis via its Pressor Dependent Actions

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Peter P Sayeski ◽  
Sung O Park ◽  
Annet Kirabo ◽  
Rebekah Baskin ◽  
Dale M Seth ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Critical Role ◽  
Glomerular Sclerosis ◽  
Control Group ◽  
Mrna Levels ◽  
Ang Ii ◽  
Urine Albumin ◽  
Independent Events

We previously found that Jak2 kinase, expressed within vascular smooth muscle cells (VSMC), plays a critical role in angiotensin II (Ang II)-mediated hypertension. Given that Jak2 mediates both pressor-dependent and pressor-independent events, we sought to determine the role of blood pressure (BP), per se, on the deleterious effects of Jak2 within the kidney. To investigate this, three groups of mice were examined; i) wild type mice (Controls) that received Ang II infusion, ii) mice lacking Jak2 expression within the VSMC (VSMC Jak2 Null) that also received Ang II, and iii) Control mice that received Ang II plus an anti-hypertensive triple therapy (3Rx). After baseline BP recordings, Ang II was infused (1000 ng/kg/min, SC) to all groups and the 3Rx regimen (80 mg/L hydralazine, 5 mg/L reserpine, 30 mg/L hydrochlorothiazide in the drinking water) was initiated two days later to the 3Rx group, in order to maintain BP at similar levels to the VSMC Jak2 Null group. After 28 days of Ang II, mice were euthanized and the kidneys were assessed via histological, molecular, and functional approaches. Chronic Ang II infusion significantly increased the levels of intrarenal Ang II in all three groups; Control = 1,262±283 fmol/g, VSMC Jak2 Null = 1,655±666 fmol/g, and 3Rx = 2,174±588. While Ang II infusion significantly increased the mean BP in the Control group (152 ± 2 mm Hg), it was significantly, and similarly, lower in both the VSMC Jak2 Null and 3Rx groups (125 ± 5 mm Hg and 131 ± 5 mm Hg, respectively). Glomerular sclerosis was absent and interstitial fibrosis ranged from absent- mild- moderate, and was similar in all groups. The increases in i) perivascular infiltration of CD3+ lymphocytes, ii) CTGF gene expression, iii) tubule casts and iv) albuminuria that were observed in the Control mice, were significantly reduced in both the VSMC Jak2 Null and 3Rx groups. [CTGF mRNA Levels: Control = 100%±17, VSMC Jak2 Null = 70%±12*, 3Rx= 56%±17*. Urine Albumin (ng/day): Control = 414 ± 262, VSMC Jak2 Null = 138 ± 172*, 3Rx= 101 ± 89* (*, p<0.05 vs. Control)]. Thus, the early renal injury due to chronic Ang II infusion correlates with increased BP and not with the expression of VSMC-derived Jak2, suggesting that Jak2 contributes to early Ang II-mediated renal injury via its pressor-dependent actions.

Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy

2018 ◽  
Vol 35 (6) ◽  
pp. 1009-1016 ◽  
Author(s):  
Yu An ◽  
Changming Zhang ◽  
Feng Xu ◽  
Wei Li ◽  
Caihong Zeng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Tubular Atrophy ◽  
Cox Regression Analysis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Recent data suggest that miR-196a is predominantly expressed in the kidney and plays an inhibitory role in the progress of renal interstitial fibrosis (IF). However, the predictive value of miR-196a in diabetic nephropathy (DN) remains unknown. We validated the role of urinary miR-196a in the progression of renal injury in a cohort of patients with type 2 diabetes mellitus. Methods Our study included 209 patients with biopsy-proven DN. The mean follow-up time was 54.03 ± 32.94 months. Histological lesions were assessed using the pathological classification established by the Renal Pathology Society. Percentages of IF and tubular atrophy were assessed using the Aperio ScanScope system. We measured the correlation of urinary miR-196a with clinical and pathological parameters using the Spearman’s correlation test. The influence of urinary miR-196a on renal outcomes was assessed using Cox regression analysis. Results Urinary miR-196a levels correlated positively with proteinuria (ρ = 0.385, P &lt; 0.001), duration of diabetes mellitus (ρ = 0.255, P &lt; 0.001) and systolic blood pressure (ρ = 0.267, P &lt; 0.001). The baseline estimated glomerular filtration rate (eGFR) and hemoglobin level showed a negative correlation with urinary miR-196a (ρ = −0.247, P &lt; 0.001 and ρ = −0.236, P = 0.001, respectively). Pathologically, urinary miR-196a levels correlated with glomerular sclerosis and IF in patients with DN. Urinary miR-196a was significantly associated with progression to end-stage renal disease [hazard ratio (HR) 2.03, P &lt; 0.001] and a 40% reduction of baseline eGFR (HR 1.75, P = 0.001), independent of age, gender, body mass index, mean arterial pressure and hemoglobinA1c level. However, urinary miR-196a did not improve predictive power to proteinuria and eGFR in DN patients. Conclusions Increased urinary miR-196a was significantly associated with the progression of renal injury and might be a noninvasive prognostic marker of renal fibrosis in DN patients.

scholarly journals Is there a "point of no return" in progressive renal disease?

1991 ◽  
Vol 2 (4) ◽  
pp. 832-840
Author(s):  
G Maschio ◽  
L Oldrizzi ◽  
C Rugiu
Keyword(s):  
Renal Disease ◽  
Dietary Protein ◽  
Antihypertensive Drugs ◽  
Interstitial Fibrosis ◽  
Chronic Renal Disease ◽  
Disease Process ◽  
Systemic Hypertension ◽  
Glomerular Sclerosis ◽  
Renal Disease Progression ◽  
Point Of No Return

The pathogenesis of progressive renal damage is most probably multifactorial. Whatever the mechanisms involved in renal disease progression, the existence of a "point of no return" has been hypothesized, that is, a stage of structural and functional damage beyond which progression of renal disease occurs independently of dietary measures and/or pharmacological treatment. In experimental animals, dietary protein and phosphate restriction is not fully successful in ameliorating the progression of functional deterioration if administered when renal injury is severe and long standing. Similarly, late treatment with various pharmacological agents (mainly antihypertensive drugs) is less effective than early administration of the same substances. A serum creatinine of 176 mumol/L seems a critical point discriminating the results of either dietary protein and phosphate restriction or antihypertensive treatment in patients with chronic renal disease. The protective effects of both dietary and nondietary intervention seem to be most effective when at least 50% of the residual renal mass is still functioning. The extent to which glomerular sclerosis, vascular hyalinosis, and interstitial fibrosis have already developed can probably blunt or avert the expected results of treatment. Some clinical tests may identify those patients who would benefit from measures such as the reduction in glomerular hemodynamic stress, the long-term inhibition of the renin-angiotensin system, and the aggressive treatment of systemic hypertension. The continuous search for a rational preventive treatment before the disease process has reached the "point of no return" will undoubtedly constitute a formidable task for the modern nephrologist.

Chronic inhibition of nuclear factor-κB attenuates renal injury in the 5/6 renal ablation model

2007 ◽  
Vol 292 (1) ◽  
pp. F92-F99 ◽  
Author(s):  
Clarice K. Fujihara ◽  
Gláucia R. Antunes ◽  
Ana L. Mattar ◽  
Denise M. A. C. Malheiros ◽  
José M. Vieira ◽  
...  
Keyword(s):  
Renal Injury ◽  
Immunohistochemical Analysis ◽  
Nuclear Factor Κb ◽  
Pyrrolidine Dithiocarbamate ◽  
Sham Operation ◽  
Ang Ii ◽  
Renal Ablation ◽  
Glomerular Hypertension ◽  
New Strategy ◽  
Ablation Model

Recent studies indicated that the nuclear transcription factor, NF-κB, activates a number of proinflammatory genes in subjects with progressive nephropathies. We investigated whether NF-κB inhibition limits progressive renal injury in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats were subdivided in four groups: S ( n = 16), subjected to sham operation; S+PDTC ( n = 18), sham-operated rats receiving the NF-κB inhibitor pyrrolidine-dithiocarbamate (PDTC; 60 mg·kg−1·day−1) in drinking water; Nx ( n = 16), Nx rats receiving vehicle only; and Nx+PDTC ( n = 19), Nx rats given PDTC as above. Thirty days after renal ablation, Nx rats exhibited systemic and glomerular hypertension. Only the former was attenuated by PDTC treatment. Sixty days after renal ablation, Nx rats exhibited marked hypertension, albuminuria and creatinine retention, as well as glomerulosclerosis and cortical interstitial expansion/inflammation. Immunohistochemical analysis of Nx rats showed renal interstitial infiltration by macrophages and by cells staining positively for ANG II and its receptor, AT1. Glomerular and interstitial cells expressing the p65 subunit of the NF-κB system were also found. PDTC treatment attenuated renal injury and inflammation, as well as the density of cells staining positively for the p65 subunit. Activation of the NF-κB system plays an important role in the pathogenesis of renal injury in the Nx model. Inhibition of this system may represent a new strategy to prevent the progression of chronic kidney disease.

Gastrointestinal protective effect of dietary spices during ethanol-induced oxidant stress in experimental rats

2010 ◽  
Vol 35 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Usha N.S. Prakash ◽  
Krishnapura Srinivasan
Keyword(s):  
Antioxidant Enzymes ◽  
Protective Effect ◽  
Intestinal Mucosa ◽  
Oxidant Stress ◽  
Mucosal Injury ◽  
Black Pepper ◽  
Protective Role ◽  
Glutathione S Transferase ◽  
Dietary Spices ◽  
Positive Effect

Spices are traditionally known to have digestive stimulant action and to cure digestive disorders. In this study, the protective effect of dietary spices with respect to activities of antioxidant enzymes in gastric and intestinal mucosa was examined. Groups of Wistar rats were fed for 8 weeks with diets containing black pepper (0.5%), piperine (0.02%), red pepper (3.0%), capsaicin (0.01%), and ginger (0.05%). All these spices significantly enhanced the activities of antioxidant enzymes — superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase — in both gastric and intestinal mucosa, suggesting a gastrointestinal protective role for these spices. In a separate study, these dietary spices were found to alleviate the diminished activities of antioxidant enzymes in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the spices was also reflected in their positive effect on mucosal glycoproteins, thereby lowering mucosal injury. The amelioration of the ethanol-induced decrease in the activities of antioxidant enzymes in gastric and intestinal mucosa by dietary spices suggests their beneficial gastrointestinal protective role. This is the first report on the gastrointestinal protective potential of dietary spices.

Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition

1994 ◽  
Vol 266 (5) ◽  
pp. F697-F705 ◽  
Author(s):  
C. K. Fujihara ◽  
S. M. Michellazzo ◽  
G. de Nucci ◽  
R. Zatz
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Methyl Ester ◽  
Renal Injury ◽  
Systemic Hypertension ◽  
Glomerular Injury ◽  
No Inhibition ◽  
Glomerular Hypertension ◽  
Sodium Overload ◽  
Parenchymal Injury

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.

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