Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress

Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) is a common strategy used in the management of patients with chronic kidney disease (CKD). However, there is no universal therapy that can stop progression of CKD. Pentoxifylline (PTE) is a non-specific phosphodiesterase inhibitor with anti-inflammatory properties. It has been reported to have promising effects in CKD treatment. In a placebo-controlled, randomized, cross-over study we evaluated the influence of PTE (1200 mg/day) added to RAAS blockade on proteinuria, surrogate markers of tubular injury and oxidative stress-dependent products in 22 non-diabetic patients with proteinuria (0.4-4.3 g per 24 h) with normal or declined kidney function [eGFR 37-178 mL/min]. In an eight-week run-in period, therapy using ACEI and/or ARB was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: PTE/washout/placebo or placebo/washout/PTE. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. The PTE therapy reduced proteinuria (by 26%) as compared to placebo. There were no differences in alpha(1)-microglobulin, urine excretion of N-acetyl-beta-d-glucosaminidase (NAG), hsCRP, the urinary excretion of 15-F(2)t-isoprostane, blood pressure (BP), eGFR and serum creatinine between the PTE and placebo groups. Pentoxifylline may decrease proteinuria in non-diabetic patients with CKD.

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P0622FIGHTING AGAINST PROXIMAL AND DISTAL TUBULAR DAMAGE BY REDUCING INFLAMMATORY BURDEN AFTER CARDIAC SURGERY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0622 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Nooshin Dalili

Keyword(s):

Oxidative Stress ◽

Cardiac Surgery ◽

Inflammatory Markers ◽

Intervention Group ◽

Tubular Damage ◽

Tubular Injury ◽

History Of ◽

Anti Inflammatory ◽

And Oxidative Stress ◽

Damage Marker

Abstract Background and Aims Going on cardiopulmonary bypass (CPB) during cardiac surgery causes systemic inflammatory response syndrome. In different studies Pentoxifylline and Calcitriol have shown inhibitory effects on pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) accompanying with production of free oxygen radicals in the ischemic reperfusion injury. On the other hand, they have positive effects on reducing oxidative stress. To investigate the effects of these drugs on reducing tubular injury after CABG surgery, by their anti-inflammatory properties we compared pre- and postoperative levels of urinary NGAL (as a proximal tubular damage marker), KIM-1 level (as a distal tubular damage marker), serum level of Malondialdehyde (MDA) (as an oxidative stress marker) and serum inflammatory markers such as IL-6, IL-8, and TNF levels in two groups of patients undergoing CABG, those who received Pentoxifylline and Calcitriol before surgery and those who didn't Method After signing an informed consent, 150 consecutive adult patients undergoing elective on-pump CABG were enrolled in a randomized control trial. Patients with collagen-vascular disease or having a history of treatment with immunosuppressive agents, corticosteroids (> 3 days), Methylxantines, Diltiazem or sodium Nitroprusside and patients with a history of angiography in the past 7 days or hemorrhagic diathesis and coagulopathy, uncontrolled diabetes mellitus, sepsis, renal failure (sCr > 2 mg/dl), hepatic failure (AST or ALT > 40 U/L) or urinary tract infection were excluded. All patients received the same anesthetic regimen and routine CPB management. The patients were randomly assigned to one of two groups: PTX was administered as an oral 400 mg tab every 12hours plus IV Calcitriol (0.01 mcg/kg) daily starting from 3 days before surgery. In the control group placebo tab and IV injection of normal saline were prescribed in the same direction. Results Results demonstrated that after three days prophylactic use of oral pentoxifylline plus IV Calcitriol there is improvement in selected checked inflammatory markers in the intervention group. Moreover Pentoxifylline+ Calcitriol showed beneficial effects by controlling the oxidative stress burden and reducing the mean serum MDA level in the patients undergoing CABG who are at risk of developing AKI as a post surgery complication. Probably by reducing inflammation and oxidative stress combination of these two drugs before CABG could decrease proximal and distal tubular damage which presented with significantly lower levels of uNGAL and KIM-1, as markers of tubular injury, in the intervention group. Conclusion Combination of Pentoxifylline and Calcitriol showed a promising prophylactic role in patients undergoing CABG with anti-inflammatory, anti-oxidant properties. This study provided scope of add-on drug therapy for better prognosis in post CABG population, involving risk of endothelial dysfunction and renal tubular damage due to inflammatory milieu and renders support to future prospective clinical studies to demonstrate net control of inflammation and oxidative stress after cardiac surgery.

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Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0998-7985 ◽

2020 ◽

Cited By ~ 1

Author(s):

Miaoyuan Zhang ◽

Liyu He ◽

Jingsong Liu ◽

Lin Zhou

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Inflammatory Response ◽

Animal Experiments ◽

Pathological Feature ◽

Tubular Injury ◽

Oral Gavage ◽

Stat3 Pathway ◽

Kidney Protection ◽

And Oxidative Stress

Abstract Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN has many pathological changes, but tubular injury is considered to be a crucial pathological feature and plays a key role in the progression of DN. Accumulating studies have confirmed that Luteolin (3,4,5,7-tetrahydroxyflavone, Lut) possesses anti-inflammatory and antioxidant activities, which may play a role in kidney protection in DN. Objectives This paper described the effects of Lut on appropriated tubular injury in the kidneys of db/db mice and searched the possible mechanisms underlying the kidney protection effect in DN. Methods Twelve-week-old male C57BL/6 J db/db and C57BL/6 J db/m mice were used for the animal experiments. They were organized into the following five groups for the animal experiments: a db/m group (control, n=6); a db/db group(n=8) ; a db/db group receiving Lut (10 mg/kg/day, n=8)treatment by oral gavage; a db/db group receiving stattic (a selective STAT3 inhibitor,50 mg/Kg/day, n=8) treatment by oral gavage and a db/db group receiving both stattic and Lut treatment by oral gavage. Results In this study, we found that Lut might ameliorate glomerular sclerosis and interstitial fibrosis in DN mouse models through inhibiting the inflammatory response and oxidative stress. And it might play its biological function mainly through repressing the STAT3 activation. Conclusions Lut attenuates DN mainly via suppression of inflammatory response and oxidative response. STAT3 pathway is the potential target, which ultimately reduces renal fibrosis and delays the progress of DN.

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Oral Hydrogen-Rich Water Alleviates Oxalate-Induced Kidney Injury by Suppressing Oxidative Stress, Inflammation, and Fibrosis

Frontiers in Medicine ◽

10.3389/fmed.2021.713536 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yachen Si ◽

Lulu Liu ◽

Jin Cheng ◽

Tingting Zhao ◽

Qi Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Injury ◽

Kidney Injury ◽

Ros Production ◽

Rna Seq ◽

Tubular Injury ◽

Crystal Deposition ◽

Commercial Kits ◽

And Oxidative Stress ◽

Differential Genes

Objective: To explore the theraputic effects and potential mechanisms of hydrogen-rich water (HRW) against oxalate-induced kidney injury.Methods: The mouse model of Calcium oxalate (CaOx) crystallization was established by feeding a soluble oxalate diet. Crystal deposition, tubular injury, fibrosis and reactive oxygen species (ROS) production in kidneys were examined by histology. Serum indexes of renal injury, inflammation and oxidative stress were detected by commercial kits. RNA sequencing (RNA-seq) was performed to screen potential pathways and the expressions of key molecules in these pathways were determined by western blotting and immunohistochemistry.Results: Crystal deposition, tubular injury, fibrosis and increased ROS production in kidneys of mice induced by oxalate diet were improved with HRW administration. The indexes of renal injury, inflammation and oxidative stress in serum of mice were upregulated by oxalate diet, which were reduced by HRW. A total of 3,566 differential genes were screened by RNA-seq and these genes were analyzed by pathway enrichment and PI3K/AKT, NF-κB, and TGF-β pathways were selected for further verification. The expressions of molecules related to PI3K-AKT pathway (PI3K, AKT, and p-AKT), NF-κB pathway (NF-κB p65, p- NF-κB p65, NLRP3, and IL-1β) and TGF-β pathway (TGF-β, TGF-βRI, TGF-βRII, p-Smad2, and p-Smad3) in renal tissues were increased by oxalate diet, which were reduced by HRW administration.Conclusion: HRW may alleviate oxalate-induced kidney injury with its anti-oxidative, anti-inflammatory and anti-fibrotic effects via inhibiting PI3K/AKT, NF-κB, and TGF-β pathways.

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1638: Erectile Dysfunction and Oxidative Stress-Media Ted Cavernosal Cell Death in Spontaneously Hypertensive Rats

The Journal of Urology ◽

10.1016/s0022-5347(18)38846-3 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 433-433

Author(s):

Steven Kuntz ◽

Steven White ◽

Michael Alba ◽

Mahadevan Rajasekaran

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Erectile Dysfunction ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

And Oxidative Stress

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Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000641 ◽

2020 ◽

pp. 1-8

Author(s):

Hasan Haci Yeter ◽

Berfu Korucu ◽

Elif Burcu Bali ◽

Ulver Derici

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Antioxidant Status ◽

Total Antioxidant Status ◽

Stress Index ◽

Total Oxidant Status ◽

Vitamin D Analog ◽

Total Antioxidant ◽

Oxidant Status ◽

And Oxidative Stress

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

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