Role of oxidative stress in pathophysiology of rheumatoid arthritis: insights into NRF2-KEAP1 signalling

Kaur, Gurjasmine; Sharma, Aman; Bhatnagar, Archana

doi:10.1080/08916934.2021.1963959

Cited by 43 publications

(26 citation statements)

References 91 publications

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“…It was found that adding dried tomato pomace to the diet could improve the activities of superoxide dismutase and catalase in the plasma of the Lohman Layer ( 14 ), the laying rate increased, and malondialdehyde content in serum and eggs decreased ( 15 ), indicating that the lycopene has an antioxidant function, but few studies about the antioxidant mechanisms of lycopene are found. The Kelch-like ech-associated protein-1/Nuclear Factor E2-related factor 2 ( Keap1-Nrf2 ) signaling pathway regulates the transcription of antioxidant genes, which is considered to be the most critical pathway in the cellular antioxidant mechanism ( 16 , 17 ). Wang et al ( 18 ) found that the lycopene degraded intracellular Keap1 and activated Nrf2 could prevent cutaneous tumors.…”

Section: Introductionmentioning

confidence: 99%

Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers

Wang

Zhu

et al. 2022

Front. Vet. Sci.

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The objective of this study was to determine the effect of dietary lycopene supplementation on the growth performance, antioxidant enzyme activity of serum and liver, and gene expressions associated with Kelch-like ech-associated protein-1 (Keap1)/Nuclear Factor E2-related factor 2 (Nrf2) pathway in liver of Arbor Acres broilers. A total of 288 1-day-old male broilers were randomly divided into 4 treatments with 6 replicates and 12 chickens for each replicate. The control group was fed with the basal diet, while the treated groups were fed with the basal diet with 10, 20, and 30 mg/kg lycopene in powder. Feed and water were provided ad libitum for 42 days. Compared with the control group, (a) the average daily gain increased (p = 0.002 vs. p = 0.001) and the feed conversion ratio decreased (p = 0.017 vs. p = 0.023) in groups treated with lycopene in the grower and whole phases, and the average daily feed intake was quadratically affected (p = 0.043) by lycopene in the grower phase; (b) the serum superoxide dismutase content was linearly affected (p = 0.035) by lycopene at 21 days; (c) the serum glutathione peroxidase content, superoxide dismutase content, and total antioxidant capability were higher (p = 0.014, p = 0.003, and p = 0.016, respectively) in the 30 mg/kg lycopene group at 42 days; (d) the liver glutathione peroxidase and superoxide dismutase contents in groups treated with lycopene were higher (p ≤ 0.001 vs. p ≤ 0.001) at 21 days; (e) the liver glutathione peroxidase content was higher (p ≤ 0.001) in the 20 and 30 mg/kg lycopene groups, at 42 days; (f) the mRNA expression levels of Nrf2, superoxide dismutase 2, NAD(P)H quinone dehydrogenase 1, and heme oxygenase 1 genes were higher (21 days: p = 0.042, p = 0.021, p = 0.035, and p = 0.043, respectively; 42 days: p = 0.038, p = 0.025, p = 0.034, and p = 0.043, respectively) in the 20 and 30 mg/kg lycopene groups at 21 and 42 days. The 30 mg/kg lycopene concentration improved the growth performance, antioxidant enzyme activity in serum and liver, and gene expression in the Keap1-Nrf2 signaling pathway of Arbor Acres broilers.

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Section: Introductionmentioning

confidence: 99%

Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers

Wang

Zhu

et al. 2022

Front. Vet. Sci.

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“… 33 Nrf2 is a major transcription factor regulating HO‐1, NQO1, and other antioxidant enzymes. 34 , 35 In this study, the data of IF and Western blot showed that transfection of pcDNA‐LINC00638 increased Nrf2 and HO‐1 expression in RA‐FLS, while transfection of si‐LINC00638 substantially decreased the levels of these proteins. This observation suggested that LINC00638 could regulate inflammation and oxidative stress in RA‐FLS by activating the Nrf2/HO‐1 pathway.…”

Section: Discussionmentioning

confidence: 53%

Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast‐like synoviocytes by regulating the Nrf2/HO‐1 pathway

Sun

Liu

Wen

et al. 2022

Immunity Inflam & Disease

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Background Abnormal expression of long noncoding RNAs (lncRNAs) is involved in several autoimmune diseases including rheumatoid arthritis (RA). In this study, we intended to explore the expression of lncRNA LINC00638 in RA and its potential mechanism of action related to inflammation and oxidative stress. Methods The level of LINC00638 in the peripheral blood mononuclear cells (PBMCs) obtained from 45 RA patients and 30 normal controls was analyzed and its correlation with clinical indicators was investigated. In vitro, we used tumor necrosis factor‐α to stimulate fibroblast‐like synoviocytes (FLS) of RA patients for cell based experiments. Subsequently, the overexpressed plasmid and small interfering RNA of LINC00638 were designed. Furthermore, we further analyzed the potential effects of LINC00638 on the proliferation and migration of RA‐FLS and the nuclear factor erythrocyte derived 2 related factor 2 (Nrf2)/heme oxygenase 1 (HO‐1) pathway. Results LINC00638 expression was found to be significantly decreased in PBMCs of RA patients, and it was negatively correlated with erythrocyte sedimentation rate, interleukin (IL)‐17, reactive oxygen species (ROS), and disease activity scores for 28 joints (DAS28). Overexpression of LINC00638 activated the Nrf2/HO‐1 pathway, markedly decreased the expressions of IL‐6, IL‐17, IL‐23, ROS, as well as malondialdehyde, increased the total antioxidant capacity, and attenuated the proliferation and migration of RA‐FLS, while silencing of LINC00638 reversed these manifestations. Conclusions LINC00638 was found to be expressed at low levels in RA patients and was associated with immune inflammation, oxidative stress, and disease activity. Overexpression of LINC00638 can reduce the proliferation as well as migration of RA‐FLS, and activate the Nrf2/HO‐1 pathway to inhibit the inflammation and oxidative stress.

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“…Oxidative stress plays a detrimental role in the pathophysiology of RA [ 176 ]. Indeed, emerging evidence from various disease models shows that activation of Nrf2 improves RA.…”

Section: Role Of Nrf2 Agonism In Chronic Inflammatory Diseasesmentioning

confidence: 99%

Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases

Kim

Jeon

2022

IJMS

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Oxidative stress is a major component of cell damage and cell fat, and as such, it occupies a central position in the pathogenesis of metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), a key transcription factor that coordinates expression of genes encoding antioxidant and detoxifying enzymes, is regulated primarily by Kelch-like ECH-associated protein 1 (Keap1). However, involvement of the Keap1–Nrf2 pathway in tissue and organism homeostasis goes far beyond protection from cellular stress. In this review, we focus on evidence for Nrf2 pathway dysfunction during development of several metabolic/inflammatory disorders, including diabetes and diabetic complications, obesity, inflammatory bowel disease, and autoimmune diseases. We also review the beneficial role of current molecular Nrf2 agonists and summarize their use in ongoing clinical trials. We conclude that Nrf2 is a promising target for regulation of numerous diseases associated with oxidative stress and inflammation. However, more studies are needed to explore the role of Nrf2 in the pathogenesis of metabolic/inflammatory diseases and to review safety implications before therapeutic use in clinical practice.

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Role of oxidative stress in pathophysiology of rheumatoid arthritis: insights into NRF2-KEAP1 signalling

Cited by 43 publications

References 91 publications

Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers

Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers

Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast‐like synoviocytes by regulating the Nrf2/HO‐1 pathway

Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases

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