Role of NRF2 in protection of the gastrointestinal tract against oxidative stress

Yanaka, Akinori

doi:10.3164/jcbn.17-139

Cited by 68 publications

(49 citation statements)

References 124 publications

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“…Of these, the Keap1-Nrf2 protein complex becomes activated under stress conditions to release the active transcription factor that stimulates a raft of antioxidant systems ( Tu et al., 2019 ). The master regulator Nrf2 is known to mitigate intestinal inflammation ( Yanaka, 2018 ) by downregulating NFκB, thereby inhibiting downstream proinflammatory cytokine release ( Puscheck et al., 2015 ). Consistent with others, we have shown an upregulation of Nrf2 immunofluorescence in the AZD3241-treated group compared to mice treated with DSS alone, which showed a diminution of immunofluorescence signal for Nrf2.…”

Section: Discussionmentioning

confidence: 99%

The Synthetic Myeloperoxidase Inhibitor AZD3241 Ameliorates Dextran Sodium Sulfate Stimulated Experimental Colitis

et al. 2020

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Chronic inflammatory bowel disease (IBD) is a condition with multifactorial pathophysiology. To date, there is no permanent cure and the disease is primarily managed by immunosuppressive drugs; long-term use promotes serious side effects including increased risk malignancies. The current study aimed to target neutrophilmyeloperoxidase, a key contributor to the pathogenesis of IBD, through the use of AZD3241that inhibits extracellular myeloperoxidase. Experimental colitis was induced in C57BL/6 male mice by 2% dextran sodium sulfate in drinking water ad libitum over 9 days. Mice received either normal drinking water and peanut butter (control), 2% DSS in drinking water and peanut butter or 2% DSS in drinking water and AZD3241 (30 mg/kg) dispersed in peanut butter daily for 9 days. Administered AZD3241 attenuated body weight loss (10% p<0.05) and improved clinical score (9 fold p<0.05; a score comprising the timedependent assessment of stool consistency and extent of rectal bleeding), loss of colonic crypts (p<0.001), preserved surface epithelium (p<0.001) and enhanced expression of the transcription factor Nrf-2 (regulator of antioxidants) and enhanced expression of the downstream antioxidant response element haeoxygenase-1 (HO-1) in the colon tissue. Also, the concentration of fecal hemoglobin and the myeloperoxidase specific oxidative damage biomarker 3-chlorotyrosine in the colon were significantly decreased in the presence of AZD3241. This latter result was consistent with AZD3241 inhibiting MPO activity in vitro. Overall, AZD3241 ameliorated the course and severity of experimental colitis through ameliorating MPO derived tissue damage and could be considered a potential therapeutic option, subject to further validation in chronic IBD models.

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Section: Discussionmentioning

confidence: 99%

The Synthetic Myeloperoxidase Inhibitor AZD3241 Ameliorates Dextran Sodium Sulfate Stimulated Experimental Colitis

et al. 2020

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“…This observation may describe the protective effect of SFN against inflammation. Previous studies described that Nrf2/HO-1 signaling pathway could be a promising strategy in preventing neuroinflammation [51] and gastrointestinal tract inflammation [52], and in exerting vital roles in the treatment of a variety of diseases [53].…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages

Ruhee

2019

Antioxidants

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Inflammation is an essential part for the general or innate immune defenses to defend against tissue damage and accelerate the curing process by providing protection against pathogens. Sulforaphane (SFN) is a natural isothiocyanate that has potential properties against inflammation, along with other protective functions. The purpose of this study was to examine the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophages. Here, we compared LPS-challenged macrophages with or without SFN pretreatment. Macrophages were pre-incubated for 6 h with a wide range of concentrations of SFN (0 to 50 µM), and then treated with LPS for 24 h. Nitric oxide (NO) concentration and gene expression of different inflammatory mediators, i.e., interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were measured. SFN neither directly reacted with cytokines, nor with NO. To understand the mechanisms, we performed analyses of the expression of regulatory enzyme inducible nitic oxide synthase (iNOS), the transcription factor NF-E2-related factor 2 (Nrf2), and its enzyme heme-oxygenase (HO)-1. Our results revealed that LPS increased significantly the expression of inflammatory cytokines and concentration of NO in non-treated cells. SFN was able to prevent the expression of NO and cytokines through regulating inflammatory enzyme iNOS and activation of Nrf2/HO-1 signal transduction pathway.

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“…That being so, whether OS preconditioning can also enhance anti‐OS ability of BMSCs, protect the survival of BMSCs under OS conditions? For the possible mechanism of antioxidant stress in cells, nuclear factor erythroid 2‐related factor 2 (Nrf2) is the most important and classical one among many signaling pathways . Nrf2 nuclear translocation, which promotes the expression of antioxidant enzymes genes, is essential for antioxidant stress …”

Section: Introductionmentioning

confidence: 99%

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning

Zhang

Peng

Zhang

et al. 2019

J of Cellular Biochemistry

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Clinically, bone marrow mesenchymal stem cells (BMSCs) have been used in treatment of many diseases, but the local oxidative stress (OS) of lesion severely limits the survival of BMSCs, which reduces the efficacy of BMSCs transplantation. Therefore, enhancing the anti-OS stress ability of BMSCs is a key breakthrough point. Preconditioning is a common protective mechanism for cells or body. Here, the aim of this study was to investigate the effects of OS preconditioning on the anti-OS ability of BMSCs and its mechanism.Fortunately, OS preconditioning can increase the expression of superoxide dismutase, catalase, NQO1, and heme oxygenase 1 through the nuclear factor erythroid 2-related factor 2 pathway, thereby decreased the intracellular reactive oxygen species (ROS) levels, relieved the damage of ROS to mitochondria, DNA and cell membrane, enhanced the anti-OS ability of BMSCs, and promoted the survival of BMSCs under OS.

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Role of NRF2 in protection of the gastrointestinal tract against oxidative stress

Cited by 68 publications

References 124 publications

The Synthetic Myeloperoxidase Inhibitor AZD3241 Ameliorates Dextran Sodium Sulfate Stimulated Experimental Colitis

The Synthetic Myeloperoxidase Inhibitor AZD3241 Ameliorates Dextran Sodium Sulfate Stimulated Experimental Colitis

Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning

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