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 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.

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.

scholarly journals Eat Your Broccoli: Oxidative Stress, NRF2, and Sulforaphane in Chronic Kidney Disease

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 266
Author(s):  
Scott E. Liebman ◽  
Thu H. Le
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Enzyme Inhibitors ◽  
Therapeutic Potential ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Receptor Blockers ◽  
End Stage

The mainstay of therapy for chronic kidney disease is control of blood pressure and proteinuria through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) that were introduced more than 20 years ago. Yet, many chronic kidney disease (CKD) patients still progress to end-stage kidney disease—the ultimate in failed prevention. While increased oxidative stress is a major molecular underpinning of CKD progression, no treatment modality specifically targeting oxidative stress has been established clinically. Here, we review the influence of oxidative stress in CKD, and discuss regarding the role of the Nrf2 pathway in kidney disease from studies using genetic and pharmacologic approaches in animal models and clinical trials. We will then focus on the promising therapeutic potential of sulforaphane, an isothiocyanate derived from cruciferous vegetables that has garnered significant attention over the past decade for its potent Nrf2-activating effect, and implications for precision medicine.

scholarly journals Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 258
Author(s):  
Md Jamal Uddin ◽  
Ee Hyun Kim ◽  
Md. Abdul Hannan ◽  
Hunjoo Ha
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Natural Products ◽  
Kidney Disease ◽  
Small Molecule ◽  
Kidney Diseases ◽  
Critical Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Major Health Problem

The global burden of chronic kidney disease (CKD) intertwined with cardiovascular disease has become a major health problem. Oxidative stress (OS) plays an important role in the pathophysiology of CKD. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) antioxidant system plays a critical role in kidney protection by regulating antioxidants during OS. Heme oxygenase-1 (HO-1), one of the targets of Nrf2-ARE, plays an important role in regulating OS and is protective in a variety of human and animal models of kidney disease. Thus, activation of Nrf2-HO-1 signaling may offer a potential approach to the design of novel therapeutic agents for kidney diseases. In this review, we have discussed the association between OS and the pathogenesis of CKD. We propose Nrf2-HO-1 signaling-mediated cell survival systems be explored as pharmacological targets for the treatment of CKD and have reviewed the literature on the beneficial effects of small molecule natural products that may provide protection against CKD.

scholarly journals Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana F. Saldanha ◽  
Viviane de O. Leal ◽  
Peter Stenvinkel ◽  
José Carlos Carraro-Eduardo ◽  
Denise Mafra
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Related Factor ◽  
Nuclear Factor ◽  
Family Protein ◽  
Nrf2 Activation ◽  
And Oxidative Stress

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promotetranscription factor nuclear factor-erythroid 2-related factor 2(Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

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