Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice

Tsai, Pei-Yi; Ka, Shuk‐Man; Chao, Tai-Kuang; Chang, Jia‐Ming; Lin, Shih‐Hua; Li, Chenyun; Kuo, Mao-Tien; Chen, Peini; Chen, Ann

doi:10.1016/j.freeradbiomed.2011.02.029

Cited by 71 publications

(52 citation statements)

References 60 publications

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“…These findings support the hypothesis that defective Nrf2 function contributes to the pathogenesis of oxidative stress and inflammation and progression of kidney disease. This supposition is also supported by the occurrence of renal disease in Nrf2-deficient mice and the reported salutary action of natural compounds with Nrf2 activating properties on progression of kidney disease of various etiologies in experimental animals (Ghosh et al, 2009; Lee et al, 2012; Li et al, 2011; Palsamy & Subramanian, 2011; Peng et al, 2011; Ruiz et al, 2013; Soetikno et al, 2013; Tapia et al, 2012; Tsai et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

“…Given the central role of Nrf2 in the regulation of cellular antioxidant and anti-inflammatory machinery (Yoh et al, 2001, 2008), strategies aimed at restoring Nrf2 activity are effective in preventing or hindering CKD progression (Ruiz et al, 2013). In fact, a number of studies have shown salutary effects of natural compounds with weak Nrf2 activating properties such as curcumin, the green tea polyphenol (−)-epigallocatechin-3-gallate, resveratrol, antroquinonol and ankaflavin, as well as the synthetic antioxidant tertbutylhydroquinone, in experimental animals with CKD of diverse etiologies (Ghosh et al, 2009; Lee et al, 2012; Li et al, 2011; Palsamy & Subramanian, 2011; Peng et al, 2011; Soetikno et al, 2013; Tapia et al, 2012; Tsai et al, 2011). As the 5/6 nephrectomy model is the one that produces pressure overload, it is worthy to note that blood pressure was lowered in the above studies which included it as a measured parameter (Ghosh et al, 2009; Soetikno et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

et al. 2013

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Chronic oxidative stress and inflammation are major mediators of chronic kidney disease (CKD) and result in impaired activation of the cytoprotective transcription factor Nrf2. Given the role of oxidative stress and inflammation in CKD pathogenesis, strategies aimed at restoring Nrf2 activity may attenuate CKD progression.The present study investigated whether the synthetic triterpenoid RTA dh404 (2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-9,11-dihydro-trifluoroethyl amide or CDDO-dhTFEA) would afford renal protection in a 5/6 nephrectomized rat model of CKD. RTA dh404 (2 mg/kg/day) was orally administered once daily for 12 weeks after 5/6 nephrectomy surgery.The remnant kidneys from the vehicle-treated CKD rats showed activation of nuclear factor kappaB (NF-κB), upregulation of NAD(P)H oxidase, glomerulosclerosis, interstitial fibrosis and inflammation, as well as marked reductions in Nrf2 and its target gene products (i.e. catalase, heme oxygenase-1, thioredoxin 1, thioredoxin reductase 1 and peroxiredoxin 1). The functional and structural deficits in the kidney were associated with increased (∼30%) mean arterial pressure (MAP). Treatment with RTA dh404 restored MAP, increased Nrf2 and expression of its target genes, attenuated activation of NF-κB and transforming growth factor-β pathways, and reduced glomerulosclerosis, interstitial fibrosis and inflammation in the CKD rats.Thus, chronic treatment with RTA dh404 was effective in restoring Nrf2 activity and slowing CKD progression in rats following 5/6 nephrectomy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

et al. 2013

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“…32,33 Specifically, Nrf2-deficient mice demonstrate increased glomerular sclerosis in response to hyperglycemia, 34 whereas elevated Nrf2 levels by using a pharmacological agent inducer improve renal function in mice. 35 Thus, decreased binding affinity of Nrf2 to the regulatory region of yet to be identified gene(s) in Rf-1a+4_a animals could adversely influence the antioxidant response and thereby contribute to increased glomerular damage. Although we found no gene expression differences in kidneys of young (6-weekold) animals, the role of Nrf2, either alone or in association with other regulatory elements, could be influencing gene expression only after the induction of oxidative stress by unilateral nephrectomy and L-NAME treatments, because these Figure 3.…”

Section: Discussionmentioning

confidence: 99%

A 4.1-Mb Congenic Region of Rf-4 Contributes to Glomerular Permeability

O’Meara

Lutz²,

Sarkis

et al. 2012

Journal of the American Society of Nephrology

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The combined transfer of two renal function quantitative trait loci (QTLs), Rf-1 (rat chromosome 1) and Rf-4 (rat chromosome 14), from the Fawn-hooded hypertensive rat onto the August Copenhagen Irish genetic background significantly increases proteinuria and demonstrates an interaction between these QTLs. Because the original Rf-4 congenic region is 61.9 Mbp, it is necessary to reduce this interval to feasibly search for variants responsible for renal susceptibility in this region. Here, we generated a minimal congenic line (Rf-1a+4_a) to identify a 4.1-Mb region of the Rf-4 QTL that significantly contributes to the severity of proteinuria in the Fawn-hooded hypertensive rat. Rf-1a+4_a animals have an increased glomerular permeability to albumin without significant changes in BP, indicating that at least one genetic element in this refined region directly affects renal function. Sequence analysis revealed no variants predicted to damage protein function, implying that regulatory elements are responsible for the Rf-4 phenotype. Multiple human studies, including recent genome-wide association studies, link the homologous human region with susceptibility to renal disease, suggesting that this congenic line is an important model for studying pathways that contribute to the progression of kidney disease.

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“…MSC therapies were tested in lung, heart, and chronic diseases and were found to be effective on reducing the fibrosis [83]. TGF- β 1 is known to play an important role in the pathogenesis of glomerulosclerosis and tubulointerstitial fibrosis in progressive renal disease [84, 85]. Connective tissue growth factor (CTGF) expression has been found to be lower when there was no obvious interstitial disease, while it has been found to be increasing as the disease became worse.…”

Section: Potential Mechanisms Of Actions Of Stem Cells In Glomerulmentioning

confidence: 99%

Stem Cell-Based Cell Therapy for Glomerulonephritis

Jin

Chen

2014

BioMed Research International

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Glomerulonephritis (GN), characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells.

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Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice

Cited by 71 publications

References 60 publications

The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

A 4.1-Mb Congenic Region of Rf-4 Contributes to Glomerular Permeability

Stem Cell-Based Cell Therapy for Glomerulonephritis

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