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Nrf2 AND NQO1

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https://www.readbyqxmd.com/read/28214984/dl-3-n-butylphthalide-nbp-provides-neuroprotection-in-the-mice-models-after-traumatic-brain-injury-via-nrf2-are-signaling-pathway
#1
Zhengwei Liu, Handong Wang, Xiaofeng Shi, Liwen Li, Mengliang Zhou, Hui Ding, Youqing Yang, Xiang Li, Ke Ding
The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28212397/a-targeted-gene-expression-platform-allows-for-rapid-analysis-of-chemical-induced-antioxidant-mrna-expression-in-zebrafish-larvae
#2
Margaret G Mills, Evan P Gallagher
Chemical-induced oxidative stress and the biochemical pathways that protect against oxidative damage are of particular interest in the field of toxicology. To rapidly identify oxidative stress-responsive gene expression changes in zebrafish, we developed a targeted panel of antioxidant genes using the Affymetrix QuantiGene Plex (QGP) platform. The genes contained in our panel include eight putative Nrf2 (Nfe2l2a)-dependent antioxidant genes (hmox1a, gstp1, gclc, nqo1, prdx1, gpx1a, sod1, sod2), a stress response gene (hsp70), an inducible DNA damage repair gene (gadd45bb), and three reference genes (actb1, gapdh, hprt1)...
2017: PloS One
https://www.readbyqxmd.com/read/28211606/nrf2-a-novel-therapeutic-target-in-fragile-x-syndrome-is-modulated-by-nnz2566
#3
Robert M J Deacon, Michael J Hurley, Camila Martínez Rebolledo, Mike Snape, Francisco J Altimiras, Leandro Farías, Michael Pino, Rodolfo Biekofsky, Larry Glass, Patricia Cogram
Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autism. Progress in basic neuroscience has led to identification of molecular targets for treatment in FXS; however, there is a gap in translation to targeted therapies in humans. The present study introduces a novel therapeutic target for FXS: nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor known to induce expression of over 100 cytoprotective genes...
February 17, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28202547/post-translational-activation-of-glutamate-cysteine-ligase-with-dimercaprol-a-novel-mechanism-of-inhibiting-neuroinflammation-in-vitro
#4
Pallavi B McElroy, Ashwini Sri Hari, Brian J Day, Manisha Patel
Neuroinflammation and oxidative stress are hallmarks of various neurological diseases. However, whether and how the redox processes control neuroinflammation is incompletely understood. We hypothesized that increasing cellular glutathione (GSH) levels would inhibit neuroinflammation. A series of thiol compounds were identified to elevate cellular GSH levels by a novel approach i.e. post-translational activation of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH biosynthesis. These small thiolcontaining compounds were examined for their ability to increase intracellular GSH levels in a murine microglial cell line (BV2), of which dimercaprol [2,3-dimercapto-1-propanol (DMP)] was found to be the most effective compound...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#5
Hongming Lv, Qinmei Liu, Junfeng Zhou, Guangyun Tan, Xuming Deng, Xinxin Ci
Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28169530/intranasal-pretreatment-with-z-ligustilide-the-main-volatile-component-of-rhizoma-chuanxiong-confers-prophylaxis-against-cerebral-ischemia-via-nrf2-and-hsp70-signaling-pathways
#6
Juan Li, Jie Yu, Hui Ma, Na Yang, Li Li, Ding-Ding Zheng, Ming-Xia Wu, Zhi-Long Zhao, Hong-Yi Qi
Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0...
February 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28157180/toxic-metabolites-mapk-and-nrf2-keap1-signaling-pathways-involved-in-oxidative-toxicity-in-mice-liver-after-chronic-exposure-to-mequindox
#7
Qianying Liu, Zhixin Lei, Anxiong Huang, Qinghua Wu, Shuyu Xie, Ihsan Awais, Menghong Dai, Xu Wang, Zonghui Yuan
Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28156185/evidence-of-activation-of-the-nrf2-pathway-in-multiple-sclerosis-patients-treated-with-delayed-release-dimethyl-fumarate-in-the-phase-3-define-and-confirm-studies
#8
Sreeja Gopal, Alvydas Mikulskis, Ralf Gold, Robert J Fox, Katherine T Dawson, Lakshmi Amaravadi
BACKGROUND: Delayed-release dimethyl fumarate (DMF) is an approved oral treatment for relapsing forms of multiple sclerosis (MS). Preclinical studies demonstrated that DMF activated the nuclear factor E2-related factor 2 (Nrf2) pathway. DMF and its primary metabolite monomethyl fumarate (MMF) were also shown to promote cytoprotection of cultured central nervous system (CNS) cells via the Nrf2 pathway. OBJECTIVE: To investigate the activation of Nrf2 pathway following ex vivo stimulation of human peripheral blood mononuclear cells (PBMCs) with DMF or MMF, and in DMF-treated patients from two Phase 3 relapsing MS studies DEFINE and CONFIRM...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28145852/safranal-prevents-rotenone-induced-oxidative-stress-and-apoptosis-in-an-in-vitro-model-of-parkinson-s-disease-through-regulating-keap1-nrf2-signaling-pathway
#9
P-K Pan, L-Y Qiao, X-N Wen
Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenone-induced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28142143/nrf2-and-bach1-may-play-a-role-in-the-modulation-of-ultraviolet-a-induced-oxidative-stress-by-acetyl-11-keto-%C3%AE-boswellic-acid-in-skin-keratinocytes
#10
Shiying Yang, Bin Zhou, Wei Xu, Fangfang Xue, Muhammad Farrukh Nisar, Chunxiang Bian, Xiao Huang, Li Yang, Yiguo Zhang, Jörg W Bartsch, Julia Li Zhong
BACKGROUND: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. OBJECTIVE: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. METHODS: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined...
February 1, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28108387/inhibition-of-monoamine-oxidase-b-by-selegiline-reduces-cigarette-smoke-induced-oxidative-stress-and-inflammation-in-airway-epithelial-cells
#11
Yuting Cui, Kenneth W K Liu, Yingmin Liang, Mary S M Ip, Judith C W Mak
Chronic obstructive pulmonary disease (COPD) is caused by the build-up of oxidative stress-induced damages due to cigarette smoking, but how monoamine oxidase (MAO)-B signaling is involved remains unclear. This study aims to establish the involvement of MAO-B signaling pathways in cigarette smoke medium (CSM)-induced oxidative stress and inflammation in human airway epithelial cells (AECs). CSM treatment increased MAO-B activity, ROS levels and IL-8 release in AECs. Pretreatment with MAO-B selective inhibitor selegiline reversed the CSM-induced changes in MAO-B activity, ROS levels and IL-8 release in a dose-dependent manner...
February 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28107678/nobiletin-and-its-colonic-metabolites-suppress-colitis-associated-colon-carcinogenesis-by-down-regulating-inos-inducing-antioxidative-enzymes-and-arresting-cell-cycle-progression
#12
Xian Wu, Mingyue Song, Zili Gao, Yue Sun, Minqi Wang, Fang Li, Jinkai Zheng, Hang Xiao
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice...
January 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28068647/berberine-an-isoquinoline-alkaloid-suppresses-txnip-mediated-nlrp3-inflammasome-activation-in-msu-crystal-stimulated-raw-264-7-macrophages-through-the-upregulation-of-nrf2-transcription-factor-and-alleviates-msu-crystal-induced-inflammation-in-rats
#13
Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264...
January 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28025122/protective-effect-of-rutaecarpine-against-t-bhp-induced-hepatotoxicity-by-upregulating-antioxidant-enzymes-via-the-camkii-akt-and-nrf2-are-pathways
#14
Sun Woo Jin, Yong Pil Hwang, Chul Yung Choi, Hyung Gyun Kim, Se Jong Kim, Yongan Kim, Young Chul Chung, Kyung Jin Lee, Tae Cheon Jeong, Hye Gwang Jeong
Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, has been shown to have cytoprotective potential, but the molecular mechanism underlying this activity remains unclear. Our study was designed to investigate the cytoprotective effect of rutaecarpine against tert-butyl hydroperoxide (t-BHP) and to elucidate its action mechanism of action of rutaecarpine in a cultured HepG2 cell line and in mouse liver. Rutaecarpine decreased t-BHP-induced reactive oxygen species (ROS) production, cytotoxicity, and apoptosis in HepG2 cells...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28012970/isoliquiritigenin-inhibits-tnf-%C3%AE-induced-release-of-high-mobility-group-box-1-through-activation-of-hdac-in-human-intestinal-epithelial-ht-29-cells
#15
Jin-Hua Chi, Geom Seog Seo, Jae Hee Cheon, Sung Hee Lee
The suppression of pro-inflammatory cytokine-induced inflammation responses is an attractive pharmacological target for the development of therapeutic strategies for inflammatory bowel disease (IBD). In the present study, we evaluated the anti-inflammatory properties of flavonoid isoliquiritigenin (ISL) in intestinal epithelial cells and determined its mechanism of action. ISL suppressed the expression of inflammatory molecules, including IL-8, IL-1β and COX-2, in TNF-α-stimulated HT-29 cells. Moreover, ISL induced activation of Nrf2 and expression of its target genes, such as HO-1 and NQO1...
December 21, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28012535/peanut-sprout-extract-attenuates-cisplatin-induced-ototoxicity-by-induction-of-the-akt-nrf2-mediated-redox-pathway
#16
Cha Kyung Youn, Eu-Ri Jo, Ju-Hwan Sim, Sung Il Cho
OBJECTIVE: Cisplatin is commonly used to treat solid tumors. However, permanent hearing loss is a major side effect of cisplatin chemotherapy and often results in dose reduction of the cisplatin chemotherapy. Peanut sprouts show cytoprotective properties owing to their antioxidant activities. This study was designed to investigate the effect of peanut sprout extract (PSE) on cisplatin-induced ototoxicity in an auditory cell line, HEI-OC1 cells. METHODS: Cells were exposed to cisplatin for 24 h, with or without pre-treatment with PSE, cell viability was examined using the MTT assay...
January 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28000844/cytoprotective-effects-of-esculetin-against-oxidative-stress-are-associated-with-the-upregulation-of-nrf2-mediated-nqo1-expression-via-the-activation-of-the-erk-pathway
#17
Min Ho Han, Cheol Park, Dae-Sung Lee, Su-Hyun Hong, Il-Whan Choi, Gi-Young Kim, Sung Hyun Choi, Jung-Hyun Shim, Jung-Il Chae, Young Hyun Yoo, Yung Hyun Choi
Esculetin, a coumarin derivative isolated from a variety of medicinal herbs, has been reported to possess multiple therapeutic and pharmacological actions. Although several studies have demonstrated the antioxidant activity of esculetin, its mechanisms of action have not been clearly established. The aim of this study was to evaluate the effects of esculetin against hydrogen peroxide (H2O2)‑induced oxidative stress in C2C12 myoblasts and to investigate the mechanisms involved in this process. Our data indicated that esculetin preconditioning significantly attenuated H2O2‑induced growth inhibition and DNA damage and the apoptosis of C2C12 cells by suppressing intracellular reactive oxygen species (ROS) accumulation...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27977895/a-soluble-form-of-p-selectin-glycoprotein-ligand-1-requires-signaling-by-nuclear-factor-erythroid-2-related-factor-2-to-protect-liver-transplant-endothelial-cells-against-ischemia-reperfusion-injury
#18
C Zhang, Y Zhang, Y Liu, Y Liu, S Kageyama, X-D Shen, F Gao, S Zheng, R W Busuttil, G D Shaw, H Ji, J W Kupiec-Weglinski
Liver endothelial cell (LEC) damage is essential in the pathogenesis of ischemia-reperfusion injury (IRI) in transplant recipients. We analyzed the mechanism of LEC resistance against IRI by using a novel recombinant soluble form of P selectin glycoprotein ligand 1, tandem P selectin glycoprotein ligand immunoglobulin (TSGL-Ig), in a mouse model of hepatic cold preservation (4°C in University of Wisconsin solution for 20 h) and syngeneic orthotopic liver transplantation (OLT). Unlike controls, TSGL-Ig protected orthotopic liver transplants against ischemia-reperfusion (IR) stress, shown by depressed serum alanine aminotransferase levels, well-preserved hepatic architecture, and improved survival (42% vs...
December 15, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27973423/regressive-effect-of-myricetin-on-hepatic-steatosis-in-mice-fed-a-high-fat-diet
#19
Shu-Fang Xia, Guo-Wei Le, Peng Wang, Yu-Yu Qiu, Yu-Yu Jiang, Xue Tang
Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities...
December 11, 2016: Nutrients
https://www.readbyqxmd.com/read/27939991/protective-effect-of-3h-1-2-dithiole-3-thione-on-cellular-model-of-alzheimer-s-disease-involves-nrf2-are-signaling-pathway
#20
Lan Wang, Min Wang, Jing Hu, Wei Shen, Junjie Hu, Yi Yao, Xifeng Wang, Curimbacus M Afzal, Rong Ma, Gang Li
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms. Our assays demonstrated that D3T was able to attenuate reactive oxygen species generation, increase MMP level as well as decrease MDA content...
December 8, 2016: European Journal of Pharmacology
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