scholarly journals P0916OLIVE LEAF EXTRACT IMPROVES RENAL ANTIOXIDANT DEFENSE WITHOUT ALTERING THE HEME OXYGENASE-1/BILIVERDIN REDUCTASE PATHWAY IN HYPERTENSIVE RATS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Danijela Karanovic ◽  
Nevena Mihailovic-Stanojevic ◽  
Zoran Miloradovic ◽  
Milan Ivanov ◽  
Jelica Grujic-Milanovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Western Blot ◽  
Heme Oxygenase ◽  
Leaf Extract ◽  
Model Group ◽  
Hypertensive Rats ◽  
Biliverdin Reductase ◽  
Protein Expressions

Abstract Background and Aims Oxidative stress is implicated in the pathophysiology of chronic kidney disease. Previously, we showed that adriamycin (anticancer agent, enhances reactive oxygen species production) induced focal segmental glomerular sclerosis (FSGS) with massive proteinuria in spontaneously hypertensive rats (SHR). The heme oxygenase (HO) system plays an important role in regulating oxidative stress and is protective in chronic kidney disease. HO-1 is a cytoprotective enzyme that catalyzes the conversion of highly reactive free heme molecules into biliverdin, carbon monoxide, and iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase and has potent antioxidant effect. Olive leaf extract (OLE, Olea europaea L.) is rich in phenolic compounds that are known to possess powerful antioxidant properties. Here, we aimed to investigate the effects of OLE, focusing on its modulatory role on oxidative stress and HO-1/BVR pathway in the kidney of SHR with adriamycin-induced FSGS. Method Adult females SHR were divided into three groups. Control rats received vehicle. Two other groups, FSGS and FSGS+OLE, received adriamycin (2 mg/kg body weight i.v.) twice in 3-week-interval. After the second injection, FSGS+OLE group received OLE (80 mg/kg/day) by gavage for 6 weeks. Mean blood pressure (MAP), urine albumin-to-creatinine (Ualb/cr), renal HO-1 and biliverdin reductase protein expressions (Western Blot), protein carbonyl content (PCOs), and antioxidant capacity (ABTS) were analyzed. Results In FSGS group albuminuria was significantly increased in comparison to the level in control. Chronic consumption of OLE markedly, but not significantly decreased Ualb/cr compared to that in control. Analysis of renal PCOs revealed that significant enhancement of protein oxidation in the kidney of model group was reduced after OLE treatment to the level as in control. The ABTS level in kidney homogenates significantly decreased in FSGS group in comparison to the level in control. OLE significantly increased renal antioxidant capacity in FSGS+OLE group compared to that in model group. Western blot analysis of HO-1, and biliverdin reductase in the kidney revealed that protein expressions of both enzymes were significantly decreased in FSGS group compared to that in control. Following OLE treatment in FSGS+OLE group protein expressions of HO-1, and biliverdin reductase remained at similar level as in model group. No change in MAP values were observed between control and model groups. OLE significantly decreased MAP in FSGS+OLE group in comparison to the value of model group, and nearly significant reduction of MAP compared to the value of control. Conclusion Collectively, our results showed that OLE expressed its antioxidant property and improved oxidative status in the kidney of SHR with ADR-induced FSGS, independently of the HO-1/BVR pathway.

scholarly journals Atractylenolide III Attenuates Muscle Wasting in Chronic Kidney Disease via the Oxidative Stress-Mediated PI3K/AKT/mTOR Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Mingqing Wang ◽  
Rong Hu ◽  
Yanjing Wang ◽  
Lingyu Liu ◽  
Haiyan You ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Skeletal Muscles ◽  
Muscle Wasting ◽  
Mtor Pathway ◽  
C2c12 Myoblast ◽  
Model Group ◽  
Atractylenolide Iii

Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.

scholarly journals Oxidative Stress in Non-Dialysis-Dependent Chronic Kidney Disease Patients

2021 ◽  
Vol 18 (15) ◽  
pp. 7806
Author(s):  
Patricia Tomás-Simó ◽  
Luis D’Marco ◽  
María Romero-Parra ◽  
Mari Carmen Tormos-Muñoz ◽  
Guillermo Sáez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reduced Glutathione ◽  
Genetic Material ◽  
Future Research ◽  
Control Group ◽  
Dialysis Patients ◽  
Early Stages ◽  
Molecular Lines

Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. Methods: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2’-deoxyguanosine (8-oxo-dG). Results: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. Conclusions: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

scholarly journals Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease

2021 ◽  
Vol 164 ◽  
pp. 139-148
Author(s):  
Ting Gui ◽  
Yunlun Li ◽  
Shijun Zhang ◽  
Irina Alecu ◽  
Qingfa Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease

scholarly journals In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 309
Author(s):  
Olukayode O. Aremu ◽  
Adebola O. Oyedeji ◽  
Opeoluwa O. Oyedeji ◽  
Benedicta N. Nkeh-Chungag ◽  
Constance R. Sewani Rusike
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Methyl Ester ◽  
Leaf Extract ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Hypertensive Rats ◽  
Total Antioxidant

Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.

scholarly journals Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 936
Author(s):  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Kuo-Cheng Lu ◽  
Min-Tser Liao ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Wasting ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubulointerstitial Injury

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

scholarly journals Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era

2021 ◽  
Author(s):  
Sandro Mazzaferro ◽  
◽  
Domenico Bagordo ◽  
Natalia De Martini ◽  
Marzia Pasquali ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease

scholarly journals Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 472
Author(s):  
Elisabetta Margiotta ◽  
Lara Caldiroli ◽  
Maria Luisa Callegari ◽  
Francesco Miragoli ◽  
Francesca Zanoni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Uremic Toxins ◽  
Interleukin 12 ◽  
European Working ◽  
And Oxidative Stress

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

scholarly journals Role of mitochondria-derived reactive oxygen species in microvascular dysfunction in chronic kidney disease

2018 ◽  
Vol 314 (3) ◽  
pp. F423-F429 ◽  
Author(s):  
Danielle L. Kirkman ◽  
Bryce J. Muth ◽  
Meghan G. Ramick ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Heating ◽  
Reactive Oxygen ◽  
Microvascular Dysfunction ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Cutaneous Vasodilation

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in stage 3–5 CKD. Cutaneous vasodilation in response to local heating was assessed in 20 CKD patients [60 ± 13 yr; estimated glomerular filtration rate (eGFR) 46 ± 13 ml·kg−1·1.73 m−2] and 11 matched healthy participants (58 ± 2 yr; eGFR >90 ml·kg−1·1.73 m−2). Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution, and 2) the mitochondria- specific superoxide scavenger MitoTempo. Skin blood flow was measured via laser Doppler flowmetry during standardized local heating (42°C). Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum conductance achieved with sodium nitroprusside infusion at 43°C. Urinary isofuran/F2-isoprostane ratios were assessed by gas-chromatography mass spectroscopy. Isofuran-to-F2-isoprostane ratios were increased in CKD patients (3.08 ± 0.32 vs. 1.69 ± 0.12 arbitrary units; P < 0.01) indicative of mitochondria-derived oxidative stress. Cutaneous vasodilation was impaired in CKD compared with healthy controls (87 ± 1 vs. 92 ± 1%CVCmax; P < 0.01). Infusion of MitoTempo significantly increased the plateau phase CVC in CKD patients (CKD Ringer vs. CKD MitoTempo: 87 ± 1 vs. 93 ± 1%CVCmax; P < 0.01) to similar levels observed in healthy controls ( P = 0.9). These data provide in vivo evidence that mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in CKD and suggest that mitochondrial dysfunction may be a potential therapeutic target to improve CKD-related vascular dysfunction.

scholarly journals New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
José Pedraza-Chaverri ◽  
Laura G. Sánchez-Lozada ◽  
Horacio Osorio-Alonso ◽  
Edilia Tapia ◽  
Alexandra Scholze
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Cardiovascular Complications ◽  
Vitamin D Metabolism ◽  
Therapy Options ◽  
Mitochondrial Alterations ◽  
Inflammatory Processes ◽  
The Impact

In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies.

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