Dietary (–)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.

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6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats

Tissue and Cell ◽

10.1016/j.tice.2016.03.006 ◽

2016 ◽

Vol 48 (3) ◽

pp. 208-216 ◽

Cited By ~ 13

Author(s):

Ahmed M.S. Hegazy ◽

Mohammed M. Mosaed ◽

Saad H. Elshafey ◽

Naglaa A. Bayomy

Keyword(s):

Oxidative Stress ◽

Adult Male ◽

Renal Cortex ◽

Albino Rats

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A maternal low-protein diet and neonatal overnutrition result in similar changes to glomerular morphology and renal cortical oxidative stress measures in male Wistar rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0288 ◽

2019 ◽

Vol 44 (2) ◽

pp. 164-171 ◽

Cited By ~ 3

Author(s):

Anderson Pedroza ◽

Diorginis Soares Ferreira ◽

David F. Santana ◽

Pedro Thiago da Silva ◽

Francisco Carlos Amanajás de Aguiar Júnior ◽

...

Keyword(s):

Oxidative Stress ◽

Wistar Rats ◽

Renal Cortex ◽

Protein Diet ◽

Antioxidant Defenses ◽

Low Protein Diet ◽

Low Protein ◽

Oxidative Balance ◽

Male Wistar Rats ◽

Glomerular Morphology

There is a strong correlation between inadequate gestational and postpartum nutrition and the occurrence of cardiovascular diseases. The present study investigated the effects of a maternal low-protein diet and neonatal overfeeding on the oxidative balance and morphology of the renal cortex of male Wistar rats. Two independent protocols were used. First, pregnant Wistar rats received diets containing either 17% (normal protein) or 8% (low protein) casein throughout pregnancy and lactation. Second, the litter size was reduced by one-third on the third postnatal day to induce overnourishment in offspring. At 30 days, the oxidative balance and morphology of the renal cortex were analyzed. There was a small but significant increase in renal corpuscle area in the low protein (LP, 5%) and overnutrition (ON, 8%) groups. Glomerular tuft area also increased in LP (6%) and ON (9%), as did glomerular cellularity (LP, +11%; ON, +12%). In the oxidative stress analyses, both nutritional insults significantly elevated lipid peroxidation (LP, +18%; ON, +135%) and protein oxidation (LP, +40%; ON, +65%) while significantly reducing nonenzymatic antioxidant defenses, measured as reduced glutathione (LP, –32%; ON, –45%) and total thiol content (LP, –28%; ON, –24%). We also observed a decrease in superoxide dismutase (LP, –78%; ON, –51%), catalase (LP, –18%; ON, –61%), and glutathione S-transferase (only in ON, –44%) activities. Our results demonstrate that nutritional insults, even those of a very different nature, during perinatal development can result in similar changes in oxidative parameters and glomerular morphology in the renal cortex.

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Aging increases Oxidative Stress and Renal Expression of Oxidant and Antioxidant Enzymes that Are Associated with an Increased Trend in Systolic Blood Pressure

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.2.3.8819 ◽

2009 ◽

Vol 2 (3) ◽

pp. 138-145 ◽

Cited By ~ 36

Author(s):

Pedro Gomes ◽

Sónia Simão ◽

Elisabete Silva ◽

Vanda Pinto ◽

João S. Amaral ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Lipid Peroxidation ◽

Renal Function ◽

Antioxidant Enzymes ◽

Systolic Blood Pressure ◽

Renal Cortex ◽

Antioxidant Defenses ◽

Wky Rats ◽

Old Rats

The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age-associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H2O2) levels, as well as renal H2O2production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H2O2production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22phoxin the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52-week period. It is concluded that overexpression of renal Nox4 and p22phoxand the increases in renal H2O2levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress-associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H2O2.

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Protective effects of the angiotensin II type I (ATI) receptor blockade in low-renin deoxycorticosterone acetate (DOCA)-treated spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs20030299 ◽

2004 ◽

Vol 106 (3) ◽

pp. 251-259 ◽

Cited By ~ 13

Author(s):

Virginia CHAMORRO ◽

Rosemary WANGENSTEEN ◽

Juan SAINZ ◽

Juan DUARTE ◽

Francisco O'VALLE ◽

...

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Urinary Excretion ◽

Renal Injury ◽

Spontaneously Hypertensive Rats ◽

Ventricular Hypertrophy ◽

Renal Cortex ◽

Ang Ii ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

The present study evaluates the participation of oxidative stress, tissue angiotensin II (Ang II) and endothelin (ET) in the effects of losartan on blood pressure (BP), ventricular hypertrophy and renal injury in spontaneously hypertensive rats (SHRs), and explores how these effects are modified when spontaneous hypertension is transformed in a low-renin model by the administration of deoxycorticosterone acetate (DOCA). The following groups were used: SHR-control, SHR+DOCA, SHR+losartan and SHR+DOCA+losartan. Tail systolic BP was measured once a week. After 9 weeks of treatment, direct BP and metabolic, morphological, biochemical and renal variables were measured. DOCA administration to SHRs produced an increase in BP, ventricular hypertrophy, renal weight, proteinuria, renal histopathological lesions, urinary excretion of isoprostane F2α and ET levels in the renal cortex. Losartan reduced BP, plasma malondialdehyde levels, urinary excretion of isoprostane F2α, renal Ang II and renal and urinary levels of ET in the SHR and DOCA-treated SHR groups. Losartan increased plasma nitrite/nitrate in SHRs, but not in low-renin DOCA-treated SHRs. Losartan reduced ventricular hypertrophy and ventricular Ang II in SHRs, but not in DOCA-treated SHRs. Losartan significantly decreased proteinuria and renal injury in DOCA-treated SHRs. We conclude that (i) the DOCA-induced aggravation of hypertension, ventricular hypertrophy and renal injury in SHRs is accompanied by augmented oxidative stress and increased levels of ET in the renal cortex, which could contribute to their development; and (ii) losartan reduced oxidative stress and renal Ang II and ET in SHRs and DOCA-treated SHRs, which might contribute to its antihypertensive and renoprotective effects, regardless of renin status.

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(−)-Epicatechin administration protects kidneys against modifications induced by short-term l-NAME treatment in rats

Food & Function ◽

10.1039/c9fo02234a ◽

2020 ◽

Vol 11 (1) ◽

pp. 318-327 ◽

Cited By ~ 2

Author(s):

Paula D. Prince ◽

Cesar G. Fraga ◽

Monica Galleano

Keyword(s):

Oxidative Stress ◽

Kidney Function ◽

Renal Cortex ◽

Short Term ◽

No Bioavailability

(−)-Epicatechin mitigates NO-mediated impairment of kidney function due to its capacity to modulate NOXs, NOSs, and consequently oxidative stress, and NO bioavailability in the renal cortex of l-NAME treated rats.

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Is oxidative stress differentially regulated in the renal cortex and medulla?

Nature Clinical Practice Nephrology ◽

10.1038/ncpneph0083 ◽

2006 ◽

Vol 2 (3) ◽

pp. 118-119 ◽

Cited By ~ 8

Author(s):

Thomas L Pallone

Keyword(s):

Oxidative Stress ◽

Renal Cortex

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Prediabetic Nephropathy as an Early Consequence of the High-Calorie/High-Fat Diet: Relation to Oxidative Stress

Endocrinology ◽

10.1210/en.2011-1997 ◽

2012 ◽

Vol 153 (3) ◽

pp. 1152-1161 ◽

Cited By ~ 26

Author(s):

Hanna Shevalye ◽

Sergey Lupachyk ◽

Pierre Watcho ◽

Roman Stavniichuk ◽

Khaled Khazim ◽

...

Keyword(s):

Oxidative Stress ◽

High Fat Diet ◽

Renal Cortex ◽

Fold Increase ◽

Sirtuin 1 ◽

Initiation Factor ◽

High Fat ◽

Alimentary Obesity ◽

Factor Α ◽

High Calorie

This study evaluated early renal functional, structural, and biochemical changes in high-calorie/high-fat diet fed mice, a model of prediabetes and alimentary obesity. Male C57BL6/J mice were fed normal (11 kcal% fat) or high-fat (58 kcal% fat) diets for 16 wk. Renal changes were evaluated by histochemistry and immunohistochemistry, Western blot analysis, ELISA, enzymatic assays, and chemiluminometry. High-fat diet consumption led to increased body and kidney weights, impaired glucose tolerance, hyperinsulinemia, polyuria, a 2.7-fold increase in 24-h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. It also resulted in a 5.3-fold increase in urinary 8-isoprostane excretion and a 38% increase in renal cortex 4-hydroxynonenal adduct accumulation. 4-hydroxynonenal adduct level and immunoreactivity or Sirtuin 1 expression in renal medulla were not affected. Studies of potential mechanisms of the high-fat diet induced renal cortex oxidative injury revealed that whereas nicotinamide adenine dinucleotide phosphate reduced form oxidase activity only tended to increase, 12/15-lipoxygenase was significantly up-regulated, with approximately 12% increase in the enzyme protein expression and approximately 2-fold accumulation of 12(S)-hydroxyeicosatetraenoic acid, a marker of 12/15-lipoxygenase activity. Accumulation of periodic acid-Schiff -positive material, concentrations of TGF-β, sorbitol pathway intermediates, and expression of nephrin, CAAT/enhancer-binding protein homologous protein, phosphoeukaryotic initiation factor-α, and total eukaryotic initiation factor-α in the renal cortex were indistinguishable between experimental groups. Vascular endothelial growth factor concentrations were reduced in high-fat diet fed mice. In conclusion, systemic and renal cortex oxidative stress associated with 12/15-lipoxygenase overexpression and activation is an early phenomenon caused by high-calorie/high-fat diet consumption and a likely contributor to kidney disease associated with prediabetes and alimentary obesity.

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Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor

AJP Renal Physiology ◽

10.1152/ajprenal.00322.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. F1191-F1200 ◽

Cited By ~ 26

Author(s):

Sebastiaan Wesseling ◽

David A. Ishola ◽

Jaap A. Joles ◽

Hans A. Bluyssen ◽

Hein A. Koomans ◽

...

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Renal Injury ◽

Renal Cortex ◽

Lipid Peroxide ◽

Receptor Expression ◽

Heme Oxygenase 1 ◽

Receptor Blockade ◽

Ang Ii ◽

Nitric Oxide Metabolites

Wild-type mice are resistant to ANG II-induced renal injury and hence form an attractive model to study renal defense against ANG II. The present study tested whether ANG II induces expression of antioxidative genes via the AT2 receptor in renal cortex and thereby counteracts prooxidative forces. ANG II was infused in female C57BL/6J mice for 28 days and a subgroup received AT2 receptor antagonist (PD-123,319) for the last 3 days. ANG II induced hypertension and aortic hypertrophy; proteinuria and renal injury were absent. Urinary nitric oxide metabolites (NOx) were decreased, and lipid peroxide (TBARS) excretion remained unchanged. Expression of NADPH oxidase components was decreased in renal cortex but induced in aorta. Heme oxygenase-1 (HO-1) was induced in both renal cortex and aorta. In contrast, ANG II suggestively increased AT2 receptor expression in kidney but not in aorta. AT2 receptor blockade enhanced hypertension in ANG II-infused mice, reversed ANG II effects on NOx excretion, but did not affect TBARS. Despite its prohypertensive effect, expression of prooxidative genes in the renal cortex decreased rather than increased after short-term AT2 receptor blockade and renal HO-1 induction after ANG II was normalized. Thus chronic ANG II infusion in mice induces hypertension but not oxidative stress. In contrast to the response in aorta, gene expression of components of NADPH-oxidase was not enhanced in renal cortex. Although ANG II administration induced renal cortical AT2 receptor expression, blockade of that receptor did not unveil the AT2 receptor as intrarenal dampening factor of prooxidative forces.

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