scholarly journals Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1342 ◽  
Author(s):  
Maria V. Irazabal ◽  
Vicente E. Torres
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reactive Oxygen ◽  
Public Health Problem ◽  
Redox Signaling ◽  
Cellular Damage ◽  
Antioxidant Systems ◽  
Related Factor ◽  
Oxygen Species

Chronic kidney disease (CKD) remains a worldwide public health problem associated with serious complications and increased mortality rates. Accumulating evidence indicates that elevated intracellular levels of reactive oxygen species (ROS) play a major role in the pathogenesis of CKD. Increased intracellular levels of ROS can lead to oxidation of lipids, DNA, and proteins, contributing to cellular damage. On the other hand, ROS are also important secondary messengers in cellular signaling. Consequently, normal kidney cell function relies on the “right” amount of ROS. Mitochondria and NADPH oxidases represent major sources of ROS in the kidney, but renal antioxidant systems, such as superoxide dismutase, catalase, or glutathione peroxidase counterbalance ROS-mediated injury. This review discusses the main sources of ROS and antioxidant systems in the kidney, and redox signaling pathways leading to inflammation and fibrosis, which result in abnormal kidney function and CKD progression. We further discuss the important role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating antioxidant responses, and other mechanisms of redox signaling.

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 Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches

2010 ◽  
Vol 3 (2) ◽  
pp. 109-121 ◽  
Author(s):  
Kurt M. Sowers ◽  
Melvin R. Hayden
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Smooth Muscle ◽  
Reactive Oxygen ◽  
Morbidity And Mortality ◽  
Oxygen Species ◽  
Calcific Uremic Arteriolopathy

Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.

scholarly journals The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1082 ◽  
Author(s):  
Christina Thanas ◽  
Panos G. Ziros ◽  
Dionysios V. Chartoumpekis ◽  
Cédric O. Renaud ◽  
Gerasimos P. Sykiotis
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Antioxidant Systems ◽  
Related Factor ◽  
Oxygen Species ◽  
Nrf2 Signaling Pathway ◽  
The Face ◽  
Antioxidant Defense Systems ◽  
The One ◽  
Endogenous Antioxidant

The thyroid gland has a special relationship with oxidative stress. On the one hand, like all other tissues, it must defend itself against reactive oxygen species (ROS). On the other hand, unlike most other tissues, it must also produce reactive oxygen species in order to synthesize its hormones that contribute to the homeostasis of other tissues. The thyroid must therefore also rely on antioxidant defense systems to maintain its own homeostasis in the face of continuous self-exposure to ROS. One of the main endogenous antioxidant systems is the pathway centered on the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1). Over the last few years, multiple links have emerged between the Keap1/Nrf2 pathway and thyroid physiology, as well as various thyroid pathologies, including autoimmunity, goiter, hypothyroidism, hyperthyroidism, and cancer. In the present mini-review, we summarize recent studies shedding new light into the roles of Keap1/Nrf2 signaling in the thyroid.

scholarly journals NADPH oxidase-derived reactive oxygen species contribute to impaired cutaneous microvascular function in chronic kidney disease

2014 ◽  
Vol 306 (12) ◽  
pp. F1499-F1506 ◽  
Author(s):  
Jennifer J. DuPont ◽  
Meghan G. Ramick ◽  
William B. Farquhar ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Oxidase Inhibition

Oxidative stress promotes vascular dysfunction in chronic kidney disease (CKD). We utilized the cutaneous circulation to test the hypothesis that reactive oxygen species derived from NADPH oxidase and xanthine oxidase impair nitric oxide (NO)-dependent cutaneous vasodilation in CKD. Twenty subjects, 10 stage 3 and 4 patients with CKD (61 ± 4 yr; 5 men/5 women; eGFR: 39 ± 4 ml·min−1·1.73 m−2) and 10 healthy controls (55 ± 2 yr; 4 men/6 women; eGFR: >60 ml·min−1·1.73 m−2) were instrumented with 4 intradermal microdialysis fibers for the delivery of 1) Ringer solution (Control), 2) 10 μM tempol (scavenge superoxide), 3) 100 μM apocynin (NAD(P)H oxidase inhibition), and 4) 10 μM allopurinol (xanthine oxidase inhibition). Skin blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Ng-nitro-l-arginine methyl ester (l-NAME; 10 mM) was infused to quantify the NO-dependent portion of the response. Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum CVC achieved during sodium nitroprusside infusion at 43°C. Cutaneous vasodilation was attenuated in patients with CKD (77 ± 3 vs. 88 ± 3%, P = 0.01), but augmented with tempol and apocynin (tempol: 88 ± 2 ( P = 0.03), apocynin: 91 ± 2% ( P = 0.001). The NO-dependent portion of the response was reduced in patients with CKD (41 ± 4 vs. 58 ± 2%, P = 0.04), but improved with tempol and apocynin (tempol: 58 ± 3 ( P = 0.03), apocynin: 58 ± 4% ( P = 0.03). Inhibition of xanthine oxidase did not alter cutaneous vasodilation in either group ( P > 0.05). These data suggest that NAD(P)H oxidase is a source of reactive oxygen species and contributes to microvascular dysfunction in patients with CKD.

scholarly journals REACTIVE OXYGEN SPECIES AND CHRONIC KIDNEY DISEASE: REVIEW

2014 ◽  
Vol 6 (2) ◽  
pp. 69-80 ◽  
Author(s):  
André Luiz Baptista Galvão ◽  
Elzylene Léga Palazzo ◽  
Mildre Loraine Pinto ◽  
Manuela Cristina Vieira
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Pioglitazone Improves the Function of Human Mesenchymal Stem Cells in Chronic Kidney Disease Patients

2019 ◽  
Vol 20 (9) ◽  
pp. 2314 ◽  
Author(s):  
Yeo Min Yoon ◽  
Jun Hee Lee ◽  
Chul Won Yun ◽  
Sang Hun Lee
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Er Stress ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Cellular Prion Protein ◽  
Oxygen Species

Mesenchymal stem cells (MSCs) are optimal sources of autologous stem cells for cell-based therapy in chronic kidney disease (CKD). However, CKD-associated pathophysiological conditions, such as endoplasmic reticulum (ER) stress and oxidative stress, decrease MSC function. In this work, we study the protective effect of pioglitazone on MSCs isolated from CKD patients (CKD-MSCs) against CKD-induced ER stress. In CKD-MSCs, ER stress is found to induce mitochondrial reactive oxygen species generation and mitochondrial dysfunction. Treatment with pioglitazone reduces the expression of ER stress markers and mitochondrial fusion proteins. Pioglitazone increases the expression of cellular prion protein (PrPC) in CKD-MSCs, which is dependent on the expression levels of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Treatment with pioglitazone is found to protect CKD-MSCs against reactive oxygen species generation, aberrant mitochondrial oxidative phosphorylation of complexes I and IV, and aberrant proliferation capacity through the PGC-1α-PrPC axis. These results indicate that pioglitazone protects the mitochondria of MSCs from CKD-induced ER stress. Pioglitazone treatment of CKD-MSCs may be a potential therapeutic strategy for CKD patients.

Uremic Toxicity-Induced Eryptosis and Monocyte Modulation: The Erythrophagocytosis as a Novel Pathway to Renal Anemia

2016 ◽  
Vol 41 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Natalia Borges Bonan ◽  
Thiago M. Steiner ◽  
Viktoriya Kuntsevich ◽  
Grazia Maria Virzì ◽  
Marina Azevedo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Reactive Oxygen ◽  
Renal Anemia ◽  
Healthy Controls ◽  
Oxygen Species

Background: We tested the effect of uremia on red blood cell (RBC) eryptosis, CD14++/CD16+ monocytes and erythrophagocytosis. Design: RBC and monocytes from chronic kidney disease (CKD) stages 3/4 (P-CKD3/4) or hemodialysis (HD) patients and healthy controls (HCs) cells incubated with sera pools from patients with CKD stages 2/3 (S-CKD2/3) or 4/5 (S-CKD4/5) were evaluated to assess eryptosis, monocyte phenotypes and reactive oxygen species (ROS) by cytometer. Erythrophagocytosis was evaluated by subsequent co-incubation of preincubated HC-monocytes and autologous-RBC. Results: HC-eryptosis (1.3 ± 0.9%) was lower than in HD (4.3 ± 0.5%) and HC-RBC incubated with S-CKD4/5 (5.6 ± 1%). CD14++/CD16+ were augmented in P-CKD3/4 (34.6 ± 8%) and HC-monocytes incubated with S-CKD4/5 (26.4 ± 7%) than in HC (5.4 ± 1%). In these cells, ROS was increased (44.5 ± 9%; control 9.6 ± 2%) and inhibited by N-acetylcysteine (25 ± 13%). Erythrophagocytosis was increased in CD14++/CD16+ (60.8 ± 10%) than in CD14++/CD16- (15.5 ± 2%). Conclusions: Sera pools from CKD patients increase eryptosis and promote a proinflammatory monocyte phenotype. Both processes increased erythrophagocytosis, thereby suggesting a novel pathway for renal anemia.

scholarly journals Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Hasna Tirichen ◽  
Hasnaa Yaigoub ◽  
Weiwei Xu ◽  
Changxin Wu ◽  
Rongshan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Cellular Reactive Oxygen Species ◽  
Kidney Disease Progression ◽  
Cellular Components

Mitochondria are known to generate approximately 90% of cellular reactive oxygen species (ROS). The imbalance between mitochondrial reactive oxygen species (mtROS) production and removal due to overproduction of ROS and/or decreased antioxidants defense activity results in oxidative stress (OS), which leads to oxidative damage that affects several cellular components such as lipids, DNA, and proteins. Since the kidney is a highly energetic organ, it is more vulnerable to damage caused by OS and thus its contribution to the development and progression of chronic kidney disease (CKD). This article aims to review the contribution of mtROS and OS to CKD progression and kidney function deterioration.

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