scholarly journals Cruciferous vegetables: rationale for exploring potential salutary effects of sulforaphane-rich foods in patients with chronic kidney disease

2020 ◽  
Author(s):  
Ludmila F M F Cardozo ◽  
Livia A Alvarenga ◽  
Marcia Ribeiro ◽  
Lu Dai ◽  
Paul G Shiels ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nutritional Intervention ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Antioxidant Responses ◽  
Nuclear Transcription Factor ◽  
Potential Benefits ◽  
Sulfur Containing ◽  
Inflammatory Burden

Abstract Sulforaphane (SFN) is a sulfur-containing isothiocyanate found in cruciferous vegetables (Brassicaceae) and a well-known activator of nuclear factor-erythroid 2-related factor 2 (Nrf2), considered a master regulator of cellular antioxidant responses. Patients with chronic diseases, such as diabetes, cardiovascular disease, cancer, and chronic kidney disease (CKD) present with high levels of oxidative stress and a massive inflammatory burden associated with diminished Nrf2 and elevated nuclear transcription factor-κB-κB expression. Because it is a common constituent of dietary vegetables, the salutogenic properties of sulforaphane, especially it’s antioxidative and anti-inflammatory properties, have been explored as a nutritional intervention in a range of diseases of ageing, though data on CKD remain scarce. In this brief review, the effects of SFN as a senotherapeutic agent are described and a rationale is provided for studies that aim to explore the potential benefits of SFN-rich foods in patients with CKD.

GSTM1 Gene, Diet, and Kidney Disease: Implication for Precision Medicine?: Recent Advances in Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Thu H. Le
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Precision Medicine ◽  
Disease Progression ◽  
Angiotensin Receptor Blockers ◽  
The United States ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Environment Interaction

In the United States, the prevalence of chronic kidney disease in adults is ≈14%. The mainstay of therapy for chronic kidney disease is angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but many patients with chronic kidney disease still progress to end-stage kidney disease. Increased oxidative stress is a major molecular underpinning of chronic kidney disease progression. In humans, a common deletion variant of the glutathione-S-transferase μ-1 ( GSTM1 ) gene, the GSTM1 null allele ( GSTM1(0 )), results in decreased GSTM1 enzymatic activity and is associated with higher levels of oxidative stress. GSTM1 belongs to the superfamily of GSTs that are phase II antioxidant enzymes and are regulated by Nrf2 (nuclear factor erythroid 2-related factor 2). Cruciferous vegetables in general, and broccoli in particular, are rich in glucoraphanin, a precursor of sulforaphane that has been shown to have protective effects against oxidative damage through the activation of Nrf2. This review will highlight recent human and animal studies implicating the role of GSTM1 deficiency in hypertension and kidney disease, and its impact on the effects of cruciferous vegetables on kidney injury and disease progression, illustrating the significance of gene and environment interaction and a potential for targeted precision medicine in the treatment of kidney disease.

scholarly journals Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage

2020 ◽  
Vol 35 (Supplement_2) ◽  
pp. ii31-ii37 ◽  
Author(s):  
Lu Dai ◽  
Leon J Schurgers ◽  
Paul G Shiels ◽  
Peter Stenvinkel
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Damage ◽  
Kidney Disease ◽  
Vitamin K ◽  
Strong Predictor ◽  
Related Factor ◽  
Clinical Model ◽  
Novel Treatments ◽  
Vascular Ageing ◽  
Cardiovascular Morbidity And Mortality

Abstract Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage–induced cellular senescence and ‘inflammaging’ may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2–related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.

scholarly journals Senescent Cells in Early Vascular Ageing and Bone Disease of Chronic Kidney Disease—A Novel Target for Treatment

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 82 ◽  
Author(s):  
Sam Hobson ◽  
Samsul Arefin ◽  
Karolina Kublickiene ◽  
Paul Shiels ◽  
Peter Stenvinkel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Treatment Options ◽  
Related Factor ◽  
Vascular Ageing ◽  
Novel Target ◽  
Stage Renal Disease ◽  
End Stage ◽  
Treatment Alternatives ◽  
Bone Ageing

Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other treatment alternatives have proven insufficient. Chronic kidney disease (CKD) has been proposed as a model of early vascular and bone ageing, with accumulating evidence supporting the contribution of cellular senescence and the senescence-associated secretory phenotype (SASP) to cardiovascular pathology in CKD. Correspondingly, novel therapies based around the use of senolytic compounds and nuclear factor-erythroid-2-related factor 2 (Nrf2) agonists, have been suggested as attractive novel treatment options. In this review, we detail the contribution of the uremic environment to these processes underpinning ageing and how these relate to vascular health.

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.

Effects of Low Protein Diet on Nuclear Factor Erythroid 2–Related Factor 2 Gene Expression in Nondialysis Chronic Kidney Disease Patients

2020 ◽  
Vol 30 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Juliana Saraiva dos Anjos ◽  
Ludmila Ferreira Medeiros de França Cardozo ◽  
Ana Paula Black ◽  
Greicielle Santos da Silva ◽  
Drielly Cristhiny Mendes de Vargas Reis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Related Factor ◽  
Nuclear Factor ◽  
Low Protein

scholarly journals Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2–KEAP1–CUL3 Interactions in Chronic Kidney Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 783
Author(s):  
Bowen Sun ◽  
Xifan Wang ◽  
Xiaoxue Liu ◽  
Longjiao Wang ◽  
Fazheng Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Hippuric Acid ◽  
Redox Homeostasis ◽  
Pathological Process ◽  
Related Factor ◽  
Kidney Fibrosis ◽  
Nrf2 Activator

Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFβ/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.

Systematic review of the nuclear factor erythroid 2-related factor 2 (NRF2) system in human chronic kidney disease: alterations, interventions, and relation to morbidity

2021 ◽  
Author(s):  
Christoffer Juul-Nielsen ◽  
Jianlin Shen ◽  
Peter Stenvinkel ◽  
Alexandra Scholze
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Inclusion Criteria ◽  
High Quality Research ◽  
System Components ◽  
Positive Correlations ◽  
Nrf2 Expression

Abstract Background NRF2 and its effectors NAD(P)H:quinoneoxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) are of interest in kidney disease. We therefore reviewed studies about their status in patients with chronic kidney disease (CKD). Methods We undertook systematic searches of PubMed and EMBASE databases. Alterations of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their relation to clinically relevant parameters were reported. Results We identified 1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were decreased in the majority of analyses of CKD patients. Half of the analyses showed a similar or increased NQO1 level vs. control, whereas NQO1 was decreased in half of the analyses. Most of the studies reported either an increased or similar HO-1 level in CKD patients compared to controls. For patients with CKD stages 1-4, studies reported positive correlations to markers of kidney disease severity. Also, positive associations of NQO1/HO-1 levels to inflammation and comorbidities were reported. One third of the studies showed discordant changes between gene expression and protein level of NRF2 system components. Two thirds of intervention studies (50% dietary, such as using resistant starch) reported an increase of NRF2, NQO1, or HO-1. Conclusions In patients with CKD, NRF2 expression was downregulated, while NQO1 and HO-1 showed varying alterations related to inflammation, comorbidities, and severity of kidney damage. Interventions that increased NRF2 system components were described, but their effectiveness and clinical relevance require further clinical studies of high quality. Research on gene expression together with protein analyses is indispensable to understand NRF2 system alterations in CKD.

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