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

Liebman, Scott E.; Le, Thu H.

doi:10.3390/nu13010266

Cited by 33 publications

(24 citation statements)

References 140 publications

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“…Therefore, the activation of Nrf2 has been related to the decrease in ROS overproduction, conferring protection against renal damage [ 19 , 28 ]. The Nrf2-activation-induced renal protection is promoted by using agents or molecules that enhance Nrf2 activity [ 25 , 29 ]. For instance, sulforaphane (SFN), an isothiocyanate derived from cruciferous green vegetables, has been shown to activate Nrf2 by reversibly modifying Keap1 cysteine residues [ 30 ].…”

Section: Preclinical Data Of Salutary Ambiguous or Disadvantageous Ef...mentioning

confidence: 99%

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

et al. 2022

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The nuclear factor erythroid 2-related factor 2 (Nrf2) protects the cell against oxidative damage. The Nrf2 system comprises a complex network that functions to ensure adequate responses to redox perturbations, but also metabolic demands and cellular stresses. It must be kept within a physiologic activity range. Oxidative stress and alterations in Nrf2-system activity are central for chronic-kidney-disease (CKD) progression and CKD-related morbidity. Activation of the Nrf2 system in CKD is in multiple ways related to inflammation, kidney fibrosis, and mitochondrial and metabolic effects. In human CKD, both endogenous Nrf2 activation and repression exist. The state of the Nrf2 system varies with the cause of kidney disease, comorbidities, stage of CKD, and severity of uremic toxin accumulation and inflammation. An earlier CKD stage, rapid progression of kidney disease, and inflammatory processes are associated with more robust Nrf2-system activation. Advanced CKD is associated with stronger Nrf2-system repression. Nrf2 activation is related to oxidative stress and moderate uremic toxin and nuclear factor kappa B (NF-κB) elevations. Nrf2 repression relates to high uremic toxin and NF-κB concentrations, and may be related to Kelch-like ECH-associated protein 1 (Keap1)-independent Nrf2 degradation. Furthermore, we review the effects of pharmacological Nrf2 activation by bardoxolone methyl, curcumin, and resveratrol in human CKD and outline strategies for how to adapt future Nrf2-targeted therapies to the requirements of patients with CKD.

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Section: Preclinical Data Of Salutary Ambiguous or Disadvantageous Ef...mentioning

confidence: 99%

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

et al. 2022

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“…SFN is well established as one of the most important bioactive components of broccoli (Brassica oleracea var. Italica) and other cruciferous vegetables [38][39][40][41]. SFN is an isothiocyanate generated by the hydrolysis of glucosinolate glucoraphanin by myrosinase (this enzyme is present in plants and gastrointestinal microflora) [42][43][44][45].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

et al. 2022

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Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.

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“…However, the conformational alterations of KEAP1, due to the oxidation of some of its cysteine residues, prevent the degradation of NRF2, leading to its nuclear translocation and action upon gene expression [31,34]. Studies in human and animal models of different diseases such as cancer, cardiac pathologies, kidney disorders, diabetes or obesity have revealed a protective effect of the positive regulation of NRF2 in reducing the severity of the disease [35,36]. Interestingly, it has been demonstrated that consuming a diet rich in cruciferous vegetables can affect the KEAP1-NRF2 pathway [37].…”

Section: Health and Health Benefits Are Human Inventionsmentioning

confidence: 99%

Antioxidant Supplements versus Health Benefits of Brief/Intermittent Exposure to Potentially Toxic Physical or Chemical Agents

Franco

Casanovas

Camps

et al. 2021

CIMB

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Although antioxidants can act locally to react with an oxidant, oral administration of “antioxidants” is quite useless in treating oxidative stress in tissues. Furthermore, it does not make sense to consider a vitamin as an antioxidant, but vitamin B3 leads to the in vivo formation of compounds that are essential for reducing this stress. A rigorous treatment of the subject indicates that to deal with oxidative stress, the most direct approach is to enhance the innate antioxidant mechanisms. The question is whether this is possible through daily activities. Diets can contain the necessary components for these mechanisms or may induce the expression of the genes involved in them. Another possibility is that pro-oxidant molecules in food increase the sensitivity and power of the detoxification pathways. This option is based on well-known DNA repair mechanisms after exposure to radiation (even from the Sun), or strong evidence of induction of antioxidant capacity after exposure to powerful pro-oxidants such as H2O2. More experimental work is required to test whether some molecules in food can increase the expression of antioxidant enzymes and/or improve antioxidant mechanisms. Identifying effective molecules to achieve such antioxidant power is critical to the food and nutraceutical industries. The potential of diet-based interventions to combat oxidative stress must be viewed from a new perspective.

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

Cited by 33 publications

References 140 publications

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Antioxidant Supplements versus Health Benefits of Brief/Intermittent Exposure to Potentially Toxic Physical or Chemical Agents

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