Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction

2008 ◽  
Vol 294 (2) ◽  
pp. F336-F344 ◽  
Author(s):  
Yasmir Quiroz ◽  
Atilio Ferrebuz ◽  
Freddy Romero ◽  
Nosratola D. Vaziri ◽  
Bernardo Rodriguez-Iturbe
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Renal Mass ◽  
Mass Reduction ◽  
Melatonin Treatment ◽  
Melatonin Administration ◽  
Renal Ablation ◽  
Remnant Kidney

The progressive deterioration of renal function and structure resulting from renal mass reduction are mediated by a variety of mechanisms, including oxidative stress and inflammation. Melatonin, the major product of the pineal gland, has potent_antioxidant and anti-inflammatory properties, and its production is impaired in chronic renal failure. We therefore investigated if melatonin treatment would modify the course of chronic renal failure in the remnant kidney model. We studied rats followed 12 wk after renal ablation untreated (Nx group, n = 7) and treated with melatonin administered in the drinking water (10 mg/100 ml) (Nx + MEL group, n = 8). Sham-operated rats ( n = 10) were used as controls. Melatonin administration increased 13–15 times the endogenous hormone levels. Rats in the Nx + MEL group had reduced oxidative stress (malondialdehyde levels in plasma and in the remnant kidney as well as nitrotyrosine renal abundance) and renal inflammation (p65 nuclear factor-κB-positive renal interstitial cells and infiltration of lymphocytes and macrophages). Collagen, α-smooth muscle actin, and transforming growth factor-β renal abundance were all increased in the remnant kidney of the untreated rats and were reduced significantly by melatonin treatment. Deterioration of renal function (plasma creatinine and proteinuria) and structure (glomerulosclerosis and tubulointerstitial damage) resulting from renal ablation were ameliorated significantly with melatonin treatment. In conclusion, melatonin administration improves the course of chronic renal failure in rats with renal mass reduction. Further studies are necessary to define the potential usefulness of this treatment in other animal models and in patients with chronic renal disease.

Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure

2010 ◽  
Vol 298 (3) ◽  
pp. F662-F671 ◽  
Author(s):  
Hyun Ju Kim ◽  
Nosratola D. Vaziri
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Glutathione Depletion ◽  
Heme Oxygenase 1 ◽  
Sham Operation ◽  
Gene Products ◽  
Quinone Oxidoreductase ◽  
Nrf2 Activation ◽  
Remnant Kidney

Oxidative stress and inflammation are constant features and major mediators of progression of chronic kidney disease (CKD). Nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against tissue injury by orchestrating antioxidant and detoxification responses to oxidative and electrophilic stress. While sources of oxidative stress and inflammation in the remnant kidney have been extensively characterized, the effect of CKD on Nrf2 activation and expression of its downstream gene products is unknown and was investigated. Subgroups of male Sprague-Dawley rats were subjected to 5/6 nephrectomy or sham operation and observed for 6 or 12 wk. Kidneys were then harvested, and Nrf2 activity and its downstream target gene products (antioxidant and phase II enzymes) were assessed. In addition, key factors involved in promoting inflammation and oxidative stress were studied. In confirmation of earlier studies, rats with chronic renal failure exhibited increased lipid peroxidation, glutathione depletion, NF-κB activation, mononuclear cell infiltration, and upregulation of monocyte chemoattractant protein-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase in the remnant kidney pointing to oxidative stress and inflammation. Despite severe oxidative stress and inflammation, remnant kidney tissue Nrf2 activity (nuclear translocation) was mildly reduced at 6 wk and markedly reduced at 12 wk, whereas the Nrf2 repressor Keap1 was upregulated and the products of Nrf2 target genes [catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase] were reduced or unchanged at 6 wk and significantly diminished at 12 wk. Thus oxidative stress and inflammation in the remnant kidney are compounded by conspicuous impairment of Nrf2 activation and consequent downregulation of the antioxidant enzymes.

scholarly journals The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
António Nogueira ◽  
Francisco Peixoto ◽  
Maria Manuel Oliveira ◽  
Carlos André Pires ◽  
Bruno Colaço ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Renal Mass ◽  
Wistar Rats ◽  
Reduced Glutathione ◽  
Mass Reduction ◽  
Significant Difference ◽  
Male Wistar Rats ◽  
And Oxidative Stress

Purpose.This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction.Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment(n=14); RMR + CAA: RMR rats treated with CAA(n=13); SO: SO rats without treatment(n=13); and SO + CAA: SO rats treated with CAA(n=13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months.Results.RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity(p<0.05)and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity(p<0.05)and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function.Conclusions.These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.

Enhanced renal IGF-I expression following partial kidney infarction

1993 ◽  
Vol 264 (6) ◽  
pp. F963-F967 ◽  
Author(s):  
S. A. Rogers ◽  
S. B. Miller ◽  
M. R. Hammerman
Keyword(s):  
Renal Failure ◽  
Steady State ◽  
Renal Mass ◽  
Renal Tissue ◽  
Renal Infarction ◽  
Mass Reduction ◽  
Igf I ◽  
Steady State Levels ◽  
Per Se ◽  
Remnant Kidney

Renal insulin-like growth factor (IGF)-I expression is enhanced in tissue that remains following removal of kidney mass. To characterize the expression of renal IGF-I after reduction of kidney mass by partial unilateral infarction, we measured levels of IGF-I extracted from noninfarcted (remnant) renal tissue that remained after one-half unilateral kidney infarction that was performed without (1/2NX) or with (1 1/2NX) contralateral nephrectomy. Levels of IGF-I extracted from remnant renal tissue after 1/2NX increased significantly, peaking on day 3 after renal mass reduction, and then returned toward baseline. Steady-state levels of IGF-I mRNA were also elevated on day 3, suggesting that the increase in IGF-I results from enhanced synthesis. A similar pattern of increased extracted IGF-I and elevated IGF-I mRNA occurred after 1 1/2NX. Levels of IGF-I extracted from remnant renal tissue 3 days after 1 1/2NX were not higher than levels extracted from remnant tissue 3 days after 1/2NX, and both were higher than levels of IGF-I extracted from contralateral kidneys 3 days after unilateral nephrectomy. Therefore, levels of IGF-I did not correlate with the extent of reduction of renal mass per se. We conclude that partial renal infarction provides a stimulus to enhance IGF-I expression. Increased renal IGF-I must be considered in the interpretation of findings originating from use of remnant kidney models of chronic renal failure.

scholarly journals Interaction of angiotensin II and TGF-beta 1 in the rat remnant kidney.

1997 ◽  
Vol 8 (11) ◽  
pp. 1732-1738 ◽  
Author(s):  
A Junaid ◽  
M E Rosenberg ◽  
T H Hostetter
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Renal Tissue ◽  
Negative Influence ◽  
Ang Ii ◽  
Tgf Beta ◽  
Renal Ablation ◽  
Remnant Kidney

An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-beta 1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-beta 1 is a potent fibrosis-promoting cytokine. We sought to determine whether the beneficial effects of renin-angiotensin system blockade on remnant kidney function were associated with a reduction in renal TGF-beta 1 in this model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduction in systolic BP (96 +/- 8 versus 130 +/- 8 mmHg, P < 0.05, losartan versus control) and urinary protein excretion (4 +/- 5 versus 23 +/- 20 g/d, P < 0.05, losartan versus control), but also exhibited a reduction in renal TGF-beta 1 mRNA (194 +/- 64 versus 411 +/- 101 optical density units, P < 0.05, losartan versus control) and TGF-beta 1 protein levels (9.8 +/- 2.5 versus 18.6 +/- 5.8 ng/g of renal tissue, P < 0.05, losartan versus control). The elevation of TGF-beta 1 in the remnant kidney was most pronounced in the scar region (22.9 +/- 13.1 versus 5.8 +/- 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of reserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not associated with a reduction in proteinuria or TGF-beta 1. We conclude that in this model of progressive renal injury, Ang II antagonism may exert a beneficial effect in part by its negative influence on TGF-beta 1.

scholarly journals Siwu Granules and Erythropoietin Synergistically Ameliorated Anemia in Adenine-Induced Chronic Renal Failure Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Yansheng Wu ◽  
Qiang Wan ◽  
Liqiang Shi ◽  
Jiaoying Ou ◽  
YingQiao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Combined Treatment ◽  
Inflammatory Factors ◽  
Control Group ◽  
Hemoglobin Content ◽  
End Stage

Objective. Renal anemia in patients with end-stage chronic kidney disease is closely related to the deterioration of cardiac function, renal function, and quality of life. This study involved adenine-induced renal anemic rat models and evaluated the treatment effect of Siwu granules and/or erythropoietin (EPO). Methods. Fifty SD rats were randomly divided into 5 groups: control, model, Siwu, EPO, and Siwu plus EPO groups. The expression levels of NO, MDA, SOD, CAT, IL-6, TNF-α, EPO, EPOR, α-SMA, and TGF-β1 were detected in rats after 8 weeks of treatment with Siwu granules and/or EPO. Results. After modeling, 47 rats entered the stage of treatment. Siwu plus EPO treatment significantly increased the rat hemoglobin content (p<0.05) and reduced blood urea nitrogen (p<0.05) and serum creatinine (p<0.001). Compared with the control group, the expression of EPO and EPOR in the kidney of rats with renal failure was significantly decreased (p<0.05). Moreover, the Siwu plus EPO group improved the level of oxidative stress in rats with chronic renal failure and reduced the expression of inflammatory factors. The expression of α-SMA and TGF-β1 in rats with renal failure was higher, but there was no expression in the control group. Conclusion. Combined treatment of Siwu granules with EPO increased the expression of EPO and EPOR in the renal tissues and inhibited oxidative stress and inflammatory factors, improving the renal function and anemia.

scholarly journals Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure

2015 ◽  
Vol 47 (1) ◽  
pp. 80 ◽  
Author(s):  
HiteshM Soni ◽  
PrafulP Patel ◽  
Savan Patel ◽  
AkshyayaC Rath ◽  
Aviseka Acharya ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Remnant Kidney

Oral and Maxillofacial Manifestations of Mineral and Bone Disorders Associated with Chronic Renal Failure

2017 ◽  
Vol 68 (6) ◽  
pp. 1325-1328
Author(s):  
Andrada Raluca Doscas ◽  
Mihail Balan ◽  
Mihai Liviu Ciofu ◽  
Doriana Agop Forna ◽  
Marius Cristian Martu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Health Concern ◽  
Oral Manifestations ◽  
End Stage Renal Failure ◽  
Brown Tumors ◽  
The Mean ◽  
End Stage

Chronic kidney disease (CKD) is a multifactorial syndrome and a global health concern. As renal function declines, there is a progressive deterioration of mineral homeostasis. Starting from stage 3 of CKD oral manifestations of mineral disorders can occasionally appear and become more frequent and evident in stage 5. We retrospectively analysed 43 patients diagnosed with end stage renal failure undergoing dialysis, hospitalized in our clinic for different oral and maxillofacial pathologies. The mean dialysis period was 5.43 years. Radiographic alterations afecting the jaws were found in all patients. The most common feature was partial or total loss of lamina dura, followed by alterations of the bony trabeculae. 9 patients presented brown tumors which are considered the final stage of secondary hyperparathyroidism associated with renal failure.

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