Antioxidants and their Role in the Prevention and Treatment of Chronic Kidney Disease-II

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 16909

Special Issue Editors

Nephrology and Dialysis Institute, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy
Interests: chronic kidney disease; dialysis; proteomics; red blood cells; end-stage renal disease; uremic toxins; selenium; nutritional molecules
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Special Issue Information

Dear Colleagues,

You are cordially invited to submit original research articles and reviews for a new Special Issue entitled "Antioxidants and Their Role in the Prevention and Treatment of Chronic Kidney Disease".

Oxidative imbalance is widely recognized as a key component of the pathogenesis of chronic kidney disease (CKD) and diabetic kidney disease (DKD; also known as diabetic nephropathy). Indeed, it is recognized as a potential cause and consequence of reduced kidney function. Although increased oxidative stress (OS) is unlikely to be the main event of CKD, it is known as a non-traditional risk factor which, along with other modifiable risk factors (e.g., drug toxicity, urinary tract infections, autoimmune diseases, hyperuricemia, hypertension, dyslipidemia, diabetes, obesity, and inflammation), contributes to the progression of kidney damage.

For these reasons, trying to counteract the increase in reactive oxygen (ROS) and nitrogen (RNS) species using specific antioxidants represents a contemporary challenge.

In this regard, several recent in vitro (cells), ex vivo (tissues and specimens), in vivo (animals), and clinical studies have shown that the use of dietary antioxidants (Mediterranean diet, polyphenols, curcumin, sulforaphane, quercetin, probiotics, etc.), antioxidant supplements (vitamins C and E, N-acetylcysteine, L-arginine, etc.), or their combination has potential protective effects for CKD and its main complications such as hypertension, atherosclerosis, inflammation, and anemia.

This Special Issue aims to provide a collection of the latest in vitro, in vivo, and clinical studies on antioxidants and their biological activities, with a view to a possible therapeutic application for CKD and DKD and their complications. Furthermore, as biomarkers of oxidative stress are critical for the development of novel treatments for CKD and DKD, studies on the discovery of novel oxidative stress biomarkers and other innovative biomarkers are also welcome.

Dr. Natalia Di Pietro
Prof. Dr. Mario Bonomini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antioxidants
  • dietary antioxidants
  • mediterranean diet
  • chronic kidney disease
  • dialysis
  • diabetic kidney disease
  • cardiovascular diseases
  • hypertension
  • inflammation
  • oxidative stress
  • biomarkers

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Published Papers (6 papers)

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Research

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18 pages, 3780 KiB  
Article
Dieckol, Derived from the Edible Brown Algae Ecklonia cava, Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction
by Chi-Heung Cho, Guijae Yoo, Mingyeong Kim, Ulfah Dwi Kurniawati, In-Wook Choi and Sang-Hoon Lee
Antioxidants 2023, 12(3), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12030593 - 27 Feb 2023
Cited by 2 | Viewed by 1374
Abstract
The formation of advanced glycation end products (AGE) is linked to the pathogenesis of diabetic nephropathy. The aim of this work was to assess the therapeutic potential and underlying mechanism of action of dieckol (DK), isolated from Ecklonia cava, on renal damage [...] Read more.
The formation of advanced glycation end products (AGE) is linked to the pathogenesis of diabetic nephropathy. The aim of this work was to assess the therapeutic potential and underlying mechanism of action of dieckol (DK), isolated from Ecklonia cava, on renal damage induced by methylglyoxal (MGO) in mouse glomerular mesangial cells. The antiglycation properties of DK were evaluated using ELISA. We conducted molecular docking, immunofluorescence analysis, and Western blotting to confirm the mechanism by which DK prevents AGE-related diabetic nephropathy. DK treatment exhibited antiglycation properties through the inhibition of AGE production, inhibition of cross-linking between AGE and collagen, and breaking of its cross-linking. DK pretreatment exhibited protective effects on renal cells by suppressing MGO-induced intracellular reactive oxygen species (ROS) formation, intracellular MGO and AGE accumulation, activation of the apoptosis cascade and apoptosis-related protein expression, activation of receptor for AGE (RAGE) protein expression, and suppression of the glyoxalase system. Furthermore, DK exhibited a stronger binding affinity for RAGE than AGE, which was confirmed as exerting a competitive inhibitory effect on the AGE–RAGE interaction. These results demonstrated that DK is a potential natural AGE inhibitor that can be utilized to prevent and treat AGE-induced diabetic nephropathy. Full article
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21 pages, 47018 KiB  
Article
Nephroprotective Effect of Fennel (Foeniculum vulgare) Seeds and Their Sprouts on CCl4-Induced Nephrotoxicity and Oxidative Stress in Rats
by Hassan Barakat, Ibrahim Ali Alkabeer, Sami A. Althwab, Hani A. Alfheeaid, Raghad M. Alhomaid, Mona S. Almujaydil, Raya S. A. Almuziree, Taqwa Bushnaq and Ahmed Mohamed
Antioxidants 2023, 12(2), 325; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12020325 - 30 Jan 2023
Cited by 1 | Viewed by 4744
Abstract
Functional and nutritional characteristics of seed sprouts and their association with oxidative stress-related disorders have recently become a focus of scientific investigations. The biological activities of fennel seeds (FS) and fennel seed sprouts (FSS) were investigated in vitro and in vivo. The total [...] Read more.
Functional and nutritional characteristics of seed sprouts and their association with oxidative stress-related disorders have recently become a focus of scientific investigations. The biological activities of fennel seeds (FS) and fennel seed sprouts (FSS) were investigated in vitro and in vivo. The total phenolic content (TPC), total flavonoids (TF), total flavonols (TFF), and antioxidant activity (AOA) of FS and FSS were examined. HPLC and GC–MS analyses for FS and FSS were carried out. Consequently, the nephroprotective and antioxidative stress potential of FS and FSS extracts at 300 and 600 mg kg−1 on CCl4-induced nephrotoxicity and oxidative stress in rats was investigated. In this context, kidney relative weight, blood glucose level (BGL), lipid profile, kidney function (T. protein, albumin, globulin, creatinine, urea, and blood urea nitrogen (BUN)), and oxidative stress biomarkers (GSH, CAT, MDA, and SOD) in the rat’s blood as well as the histopathological alteration in kidney tissues were examined. Results indicated that the sprouting process of FS significantly improved TPC, TF, TFL, and AOA in vitro. HPLC identified nineteen compounds of phenolic acids and their derivatives in FS. Thirteen phenolic compounds in FS and FSS were identified, the highest of which was vanillic acid. Six flavonoids were also identified with a predominance of kaempferol. GC–MS indicated that the trans-anethole (1-methoxy-4-[(E)-prop-1-enyl]benzene) component was predominant in FS and FSS, significantly increasing after sprouting. In in vivo examination, administering FS and FSS extracts ameliorated the BGL, triglycerides (TG), total cholesterol (CHO), and their derivative levels compared to CCl4-intoxicated rats. A notable improvement in FS and FSS with 600 mg kg−1 compared to 300 mg kg−1 was observed. A dose of 600 mg FSS kg−1 reduced the TG, CHO, and LDL-C and increased HDL-C levels by 32.04, 24.62, 63.00, and 67.17% compared to G2, respectively. The atherogenic index (AI) was significantly improved with 600 mg kg−1 of FSS extracts. FS and FSS improved kidney function, reduced malondialdehyde (MDA), and restored the activity of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Both FS and FSS extracts attenuated the histopathological alteration in CCl4-treated rats. Interestingly, FSS extract presented better efficiency as a nephroprotection agent than FS extract. In conclusion, FSS can potentially restore oxidative stability and improve kidney function after acute CCl4 kidney injury better than FS. Therefore, FS and FSS extracts might be used for their promising nephroprotective potential and to help prevent diseases related to oxidative stress. Further research on their application in humans is highly recommended. Full article
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17 pages, 3025 KiB  
Article
Sesamol Attenuates Renal Inflammation and Arrests Reactive-Oxygen-Species-Mediated IL-1β Secretion via the HO-1-Induced Inhibition of the IKKα/NFκB Pathway In Vivo and In Vitro
by Kuo-Feng Tseng, Ping-Hsuan Tsai, Jie-Sian Wang, Fang-Yu Chen and Ming-Yi Shen
Antioxidants 2022, 11(12), 2461; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11122461 - 14 Dec 2022
Cited by 6 | Viewed by 1585
Abstract
Chronic nephritis leads to irreversible renal fibrosis, ultimately leading to chronic kidney disease (CKD) and death. Macrophage infiltration and interleukin 1β (IL-1β) upregulation are involved in inflammation-mediated renal fibrosis and CKD. Sesamol (SM), which is extracted from sesame seeds, has antioxidant and anti-inflammatory [...] Read more.
Chronic nephritis leads to irreversible renal fibrosis, ultimately leading to chronic kidney disease (CKD) and death. Macrophage infiltration and interleukin 1β (IL-1β) upregulation are involved in inflammation-mediated renal fibrosis and CKD. Sesamol (SM), which is extracted from sesame seeds, has antioxidant and anti-inflammatory properties. We aimed to explore whether SM mitigates macrophage-mediated renal inflammation and its underlying mechanisms. ApoE–/– mice were subjected to 5/6 nephrectomy (5/6 Nx) with or without the oral gavage of SM for eight weeks. Blood and urine samples and all the kidney remnants were collected for analysis. Additionally, THP-1 cells were used to explore the mechanism through which SM attenuates renal inflammation. Compared with the sham group, the 5/6 Nx ApoE–/– mice exhibited a significant increase in the macrophage infiltration of the kidneys (nephritis), upregulation of IL-1β, generation of reactive oxygen species, reduced creatinine clearance, and renal fibrosis. However, the administration of SM significantly alleviated these effects. SM suppressed the H2O2-induced secretion of IL-1β from the THP-1 cells via the heme oxygenase-1-induced inhibition of the IKKα-NF-κB pathway. SM attenuated renal inflammation and arrested macrophage accumulation by inhibiting IKKα, revealing a novel mechanism of the therapeutic effects of SM on renal injury and offering a potential approach to CKD treatment. Full article
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24 pages, 6553 KiB  
Article
Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction
by Jae-Hyung Park, Jaechan Leem and Sun-Jae Lee
Antioxidants 2022, 11(12), 2341; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11122341 - 26 Nov 2022
Cited by 6 | Viewed by 1562
Abstract
Renal fibrosis is a common feature of chronic kidney disease and is a promising therapeutic target. However, there is still limited treatment for renal fibrosis, so the development of new anti-fibrotic agents is urgently needed. Accumulating evidence suggest that oxidative stress and endoplasmic [...] Read more.
Renal fibrosis is a common feature of chronic kidney disease and is a promising therapeutic target. However, there is still limited treatment for renal fibrosis, so the development of new anti-fibrotic agents is urgently needed. Accumulating evidence suggest that oxidative stress and endoplasmic reticulum (ER) stress play a critical role in renal fibrosis. Carnosol (CS) is a bioactive diterpene compound present in rosemary plants and has potent antioxidant and anti-inflammatory properties. In this study, we investigated the potential effects of CS on renal injury and fibrosis in a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice underwent sham or UUO surgery and received intraperitoneal injections of CS (50 mg/kg) daily for 8 consecutive days. CS improved renal function and ameliorated renal tubular injury and interstitial fibrosis in UUO mice. It suppressed oxidative injury by inhibiting pro-oxidant enzymes and activating antioxidant enzymes. Activation of ER stress was also attenuated by CS. In addition, CS inhibited apoptotic and necroptotic cell death in kidneys of UUO mice. Furthermore, cytokine production and immune cell infiltration were alleviated by CS. Taken together, these findings indicate that CS can attenuate renal injury and fibrosis in the UUO model. Full article
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19 pages, 4325 KiB  
Article
Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death
by Jixiao Zhu, Manqin Fu, Jian Gao, Guoyu Dai, Qiunong Guan and Caigan Du
Antioxidants 2022, 11(7), 1399; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071399 - 19 Jul 2022
Cited by 4 | Viewed by 1490
Abstract
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced [...] Read more.
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced cell death in renal tubular epithelial cells. Human kidney proximal tubular cells (HKC-8) were exposed to hypoxia (1% O2) in the presence of flavan-3-ols (catechin, epicatechin, procyanidin B1, and procyanidin B2). Cell death was examined using flow cytometric analysis. Gene expression was determined using a PCR array and Western blotting, and its network and functions were investigated using STRING databases. Here, we show that the cytoprotective activity of catechin was the highest among these flavan-3-ols against hypoxia-induced cell death in cultured HKC-8 cells. Exposure of HKC-8 cells to hypoxia induced oxidative stress leading to up-regulation of DUOX2, NOX4, CYBB and PTGS2 and down-regulation of TXNRD1 and HSP90AA1. Treatment with catechin or other flavan-3-ols prevented the down-regulation of TXNRD1 expression in hypoxic HKC-8 cells. Overexpression of TXNRD1 prevented hypoxia-induced cell death, and inactivation of TXNRD1 with TRi-1, a specific TXNRD1 inhibitor, reduced the catechin cytoprotection against hypoxia-induced HKC-8 cell death. In conclusion, flavan-3-ols prevent hypoxia-induced cell death in human proximal tubular epithelial cells, which might be mediated by their maintenance of TXNRD1 expression, suggesting that enhancing TXNRD1 expression or activity may become a novel therapeutic strategy to prevent hypoxia-induced kidney damage. Full article
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Review

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17 pages, 1383 KiB  
Review
Oxidative Stress and Ischemia/Reperfusion Injury in Kidney Transplantation: Focus on Ferroptosis, Mitophagy and New Antioxidants
by Simona Granata, Valentina Votrico, Federica Spadaccino, Valeria Catalano, Giuseppe Stefano Netti, Elena Ranieri, Giovanni Stallone and Gianluigi Zaza
Antioxidants 2022, 11(4), 769; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11040769 - 12 Apr 2022
Cited by 40 | Viewed by 5465
Abstract
Although there has been technical and pharmacological progress in kidney transplant medicine, some patients may experience acute post-transplant complications. Among the mechanisms involved in these conditions, ischemia/reperfusion (I/R) injury may have a primary pathophysiological role since it is one of the leading causes [...] Read more.
Although there has been technical and pharmacological progress in kidney transplant medicine, some patients may experience acute post-transplant complications. Among the mechanisms involved in these conditions, ischemia/reperfusion (I/R) injury may have a primary pathophysiological role since it is one of the leading causes of delayed graft function (DGF), a slow recovery of the renal function with the need for dialysis (generally during the first week after transplantation). DGF has a significant social and economic impact as it is associated with prolonged hospitalization and the development of severe complications (including acute rejection). During I/R injury, oxidative stress plays a major role activating several pathways including ferroptosis, an iron-driven cell death characterized by iron accumulation and excessive lipid peroxidation, and mitophagy, a selective degradation of damaged mitochondria by autophagy. Ferroptosis may contribute to the renal damage, while mitophagy can have a protective role by reducing the release of reactive oxygen species from dysfunctional mitochondria. Deep comprehension of both pathways may offer the possibility of identifying new early diagnostic noninvasive biomarkers of DGF and introducing new clinically employable pharmacological strategies. In this review we summarize all relevant knowledge in this field and discuss current antioxidant pharmacological strategies that could represent, in the next future, potential treatments for I/R injury. Full article
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