A preliminary evaluation of bardoxolone methyl for the treatment of diabetic nephropathy

Thomas, Merlin C.

doi:10.1517/17425255.2012.697152

Cited by 9 publications

(5 citation statements)

References 34 publications

(40 reference statements)

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“…Another Nrf2inducing compound is bardoxolone methyl, which has mainly been described as a potential treatment of chronic kidney disease. Although bardoxolone methyl has not so far been described in relation to GLO1 activation, its potential to induce Nrf2 may result in GLO1 induction [290][291][292][293].…”

Section: Glo1-inducing Compoundsmentioning

confidence: 99%

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015

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The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

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Section: Glo1-inducing Compoundsmentioning

confidence: 99%

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015

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“…38 Less well known Nrf2 activators include MG132, the specific, potent, reversible, and cell-permeable proteasome inhibitor, 39 and ebselen, the synthetic mimetic of the antioxidant enzyme, glutathione peroxidase-1 (GPx). 40 Our group previously has shown that ebselen reduced oxidative stress in animal models of T1D and attenuated diabetes-associated atherosclerosis and diabetic nephropathy.…”

Section: Nrf2 Activatorsmentioning

confidence: 99%

Combating oxidative stress in diabetic complications with Nrf2 activators: How much is too much?

Tan

Haan

2014

Redox Report

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Diabetes is increasing at an alarming rate and, despite anti-hypertensive and insulin therapies, diabetic patients are still at risk of developing complications such as chronic kidney disease, cardiovascular disease, and retinopathy. There is therefore an urgent need for more effective therapies to prevent the development and progression of diabetic complications. Oxidative stress is a major player in the aetiology of diabetic complications. However, results from clinical trials thus far using general antioxidants have been disappointing. Mechanism-based antioxidants have gained considerable attention due to their more targeted approach at reducing oxidative stress and associated complications in diabetes. The transcription factor, NFE2-related factor 2 (Nrf2), is a master regulator of redox homeostasis and the cellular detoxification response. Instead of relying on a single antioxidant, activation of Nrf2 results in the concerted upregulation of several antioxidant enzymes and cytoprotective genes, making it an attractive therapeutic target for diabetic complications. Several Nrf2 activators have been discovered and have proven effective at activating Nrf2 signalling through different mechanisms in both in vitro and in vivo models of diabetes. This review will address some of the most promising and well-known Nrf2 activators and their roles in preventing the development and progression of diabetic complications. Challenges facing the advancement of this drug class into the clinic will be discussed, as will be the future of Nrf2 activation as a therapeutic strategy in preventing the development of diabetic complications.

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“…The C max was 25 ± 13 ng/mL and the C min was 8.8 ± 4.3 ng/mL. CDDO-Me also has low bioavailability, but this was improved by using an amorphous spray dried dispersion dosage form [124]. This highlights the potential pharmacokinetic advantages offered by novel delivery approaches.…”

Section: -Cyano-312-dioxo-oleana-19-dien-28-oic Acid-imidazolidementioning

confidence: 99%

Untitled

2021

Planta Med

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BackgroundThe retina is a light-sensitive layer at the rear of the eye that converts light into neuronal impulses to obtain vision. Retinal cells such as the RPE, photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, ganglion cells, and Müller cells have been identified and their major circuitry and connections in the tissue have been summarised in detail recently [1]. The retina is one of the most metabolically active tissues in the body and requires appropriate levels of nutrients and oxygen for normal function [2]. Blood flow disruption and excessive oxygen consumption are leading causes of impaired energy production in the retina and may also promote inflammation, neovascularisation, and even retinal cell death. Other factors like hypertension, high blood sugar level, and inheritance also contribute to disease progression [3,4]. Common retinal diseases include AMD, DR, retinal detachment, and retinitis pigmentosa [5][6][7]. Patients suffering from these diseases have blurred or distorted vision, and their lives can be seriously affected [7]. However, effective treatments are few and current interventions are limited to intravitreal injections of anti-VEGF antibody or corticosteroids, surgery, laser treatment, and/or nutrient supplementations [8,9].

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A preliminary evaluation of bardoxolone methyl for the treatment of diabetic nephropathy

Cited by 9 publications

References 34 publications

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

Combating oxidative stress in diabetic complications with Nrf2 activators: How much is too much?

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