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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/28412310/increased-seizure-susceptibility-and-other-toxicity-symptoms-following-acute-sulforaphane-treatment-in-mice
#1
Katarzyna Socała, Dorota Nieoczym, Edyta Kowalczuk-Vasilev, Elżbieta Wyska, Piotr Wlaź
Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28408365/immunomodulators-targeting-marco-expression-improve-resistance-to-post-influenza-bacterial-pneumonia
#2
Muzo Wu, John G Gibbons, Glen M Deloid, Alice S Bedugnis, Rajesh K Thimmulappa, Shyam Biswal, Lester Kobzik
Down-regulation of the alveolar macrophage (AM) macrophage receptor with collagenous structure (MARCO) leads to susceptibility to post-influenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase of MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery...
April 13, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28389405/delayed-nrf2-regulated-antioxidant-gene-induction-in-response-to-silica-nanoparticles
#3
Hongqiao Zhang, Lulu Zhou, Jenay Yuen, Nancy Birkner, Valerie Leppert, Peggy A O'Day, Henry Jay Forman
Silica nanoparticles with iron on their surface cause the production of oxidants and stimulate an inflammatory response in macrophages. Nuclear factor erythroid-derived 2 - like factor 2 (Nrf2) signaling and its regulated antioxidant genes play critical roles in maintaining redox homeostasis. In this study we investigated the regulation of four representative Nrf2-regulated antioxidant genes; i.e., glutamate cysteine ligase (GCL) catalytic subunit (GCLC), GCL modifier subunit (GCLM), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1), by iron-coated silica nanoparticles (SiO2-Fe) in human THP-1 macrophages...
April 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28386307/sulforaphane-protects-against-high-cholesterol-induced-mitochondrial-bioenergetics-impairments-inflammation-and-oxidative-stress-and-preserves-pancreatic-%C3%AE-cells-function
#4
Catalina Carrasco-Pozo, Kah Ni Tan, Martin Gotteland, Karin Borges
Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28350841/correction-lack-of-effect-of-oral-sulforaphane-administration-on-nrf2-expression-in-copd-a-randomized-double-blind-placebo-controlled-trial
#5
Robert A Wise, Janet T Holbrook, Gerard Criner, Sanjay Sethi, Sobharani Rayapudi, Kuladeep R Sudini, Elizabeth A Sugar, Alyce Burke, Rajesh Thimmulappa, Anju Singh, Paul Talalay, Jed W Fahey, Charles S Berenson, Michael R Jacobs, Shyam Biswal
[This corrects the article DOI: 10.1371/journal.pone.0163716.].
2017: PloS One
https://www.readbyqxmd.com/read/28298215/nrf2-signaling-increases-expression-of-atp-binding-cassette-subfamily-c-mrna-transcripts-at-the-blood-brain-barrier-following-hypoxia-reoxygenation-stress
#6
Kathryn Ibbotson, Joshua Yell, Patrick T Ronaldson
BACKGROUND: Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model...
March 16, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28295950/sulforaphane-attenuates-di-n-butylphthalate-induced-reproductive-damage-in-pubertal-mice-involvement-of-the-nrf2-antioxidant-system
#7
Xu-Ping Jiang, Jing-Yuan Tang, Zhen Xu, Peng Han, Zhi-Qiang Qin, Cheng-di Yang, Shang-Qian Wang, Min Tang, Wei Wang, Chao Qin, Yang Xu, Bai-Xin Shen, Wei-Min Zhou, Wei Zhang
di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis...
March 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28278681/in-vitro-assessment-of-the-indirect-antioxidant-activity-of-sulforaphane-in-redox-imbalance-vanadium-induced
#8
Giuseppa Visalli, Alessio Facciolà, Maria Paola Bertuccio, Isa Picerno, Angela Di Pietro
Owing to sulforaphane presence, a dietary consumption of Brassicaceae prevents chronic diseases. This hormetic compound induces adaptive stress response at subtoxic doses, while doses that exceed the cellular defence are toxic. In HepG2, Caco-2 and Vero cells, we investigated the sulforaphane (SFN) (5 μM) role in counteracting redox imbalance induced by VOSO4 [V(IV)]. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test showed a dose-dependent viability reduction (r < -0.95; p < 0...
February 8, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#9
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28209760/glucoraphanin-ameliorates-obesity-and-insulin-resistance-through-adipose-tissue-browning-and-reduction-of-metabolic-endotoxemia-in-mice
#10
Naoto Nagata, Liang Xu, Susumu Kohno, Yusuke Ushida, Yudai Aoki, Ryohei Umeda, Nobuo Fuke, Fen Zhuge, Yinhua Ni, Mayumi Nagashimada, Chiaki Takahashi, Hiroyuki Suganuma, Shuichi Kaneko, Tsuguhito Ota
Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice...
February 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28191275/sulforaphane-prevents-angiotensin-ii-induced-testicular-cell-death-via-activation-of-nrf2
#11
Yonggang Wang, Hao Wu, Ying Xin, Yang Bai, Lili Kong, Yi Tan, Feng Liu, Lu Cai
Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28151586/nuclear-erythroid-2-related-factor-2-activation-inhibits-house-dust-mite-induced-sinonasal-epithelial-cell-barrier-dysfunction
#12
Nyall R London, Anuj Tharakan, Andrew P Lane, Shyam Biswal, Murugappan Ramanathan
BACKGROUND: Dysregulated sinonasal epithelial cell (SNEC) barrier function has been proposed to contribute to the pathogenesis of sinonasal inflammatory conditions such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Allergens such as house dust mite (HDM) have been reported to disrupt SNEC barrier integrity. We have recently identified nuclear erythroid 2-related factor 2 (Nrf2) activation via sulforaphane (SFN) stimulation to stabilize SNEC barrier function. The purpose of this study was to explore whether Nrf2 activation could ameliorate HDM-induced SNEC barrier dysfunction...
February 2, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28115273/ablation-of-akt2-prevents-paraquat-induced-myocardial-mitochondrial-injury-and-contractile-dysfunction-role-of-nrf2
#13
Shuyi Wang, Xiaoling Zhu, Lize Xiong, Jun Ren
Paraquat is a quaternary nitrogen herbicide triggering oxidative stress, mitochondrial damage and multi-organ injuries including hearts. To date, effective measure to combat paraquat toxicity is still lacking. Recent evidence has revealed a role for Akt in cardiac homeostasis. To this end, this study was designed to examine the role of Akt2 in acute paraquat exposure-induced cardiac contractile and mitochondrial injury using a unique murine model of Akt2 knockout. Cardiac contractile and intracellular Ca(2+) properties were evaluated...
March 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28062182/exposure-of-airway-epithelial-cells-to-pseudomonas-aeruginosa-biofilm-derived-quorum-sensing-molecules-decrease-the-activity-of-the-anti-oxidant-response-element-bound-by-nrf2
#14
Lucie Roussel, Simon Rousseau
Chronic bacterial infections in cystic fibrosis lung disease are often characterized by Pseudomonas aeruginosa biofilms that are regulated by bacterial intercellular signals termed quorum sensing (QS), such as N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL). This study reports that biofilm-derived exoproducts decrease the transcriptional activity of the anti-oxidant response element in bronchial epithelial cells. In a live co-culture assay of BEAS-2B cells and P. aeruginosa biofilm, the QS molecule 3OC12-HSL was an important but not sole contributor to the inhibition of basal NRF2 luciferase reporter activity...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28011874/activation-of-nrf2-reduces-uva-mediated-mmp-1-upregulation-via-mapk-ap-1-signaling-cascades-the-photoprotective-effects-of-sulforaphane-and-hispidulin
#15
Anyamanee Chaiprasongsuk, Jinaphat Lohakul, Kitipong Soontrapa, Somponnat Sampattavanich, Pravit Akarasereenont, Uraiwan Panich
UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT)...
March 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28001083/nrf2-targeting-by-sulforaphane-a-potential-therapy-for-cancer-treatment
#16
Maria Russo, Carmela Spagnuolo, Gian Luigi Russo, Krystyna Skalicka-Woźniak, Maria Daglia, Eduardo Sobarzo-Sánchez, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
In the past decades, extensive studies have reported the potential chemopreventive activity of sulforaphane, an isothiocyanate derived from glucoraphanin, occurring in large amounts in Brassica genus plants. Sulforaphane was found to be active against several forms of cancer. A growing body of data shows that sulforaphane acts against cancer at different levels, from development to progression, through pleiotropic effects. In this review, we discuss the available experimental and clinical data on the potential therapeutic role of sulforaphane against cancer...
December 21, 2016: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/27993529/sulforaphane-induces-differential-modulation-of-mitochondrial-biogenesis-and-dynamics-in-normal-cells-and-tumor-cells
#17
Mario Negrette-Guzmán, Sara Huerta-Yepez, Mario I Vega, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Omar Noel Medina-Campos, Esteban Rodríguez, Edilia Tapia, José Pedraza-Chaverri
Antioxidant-based chemotherapy has been intensely debated. Herein, we show that sulforaphane (SFN) induced mitochondrial biogenesis followed by mitochondrial fusion in a kidney cell line commonly used in nephroprotective models. At the same concentration and exposure time, SFN induced cell death in prostate cancer cells accompanied by mitochondrial biogenesis and fragmentation. Stabilization of the nuclear factor E2-related factor-2 (Nrf2) could be associated with these effects in the tumor cell line. An increase in the peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) level and a decrease in the hypoxia-inducible factor-1α (HIF1α) level would suggest a possible metabolic shift...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27982105/nrf2-inhibits-epithelial-mesenchymal-transition-by-suppressing-snail-expression-during-pulmonary-fibrosis
#18
Wencheng Zhou, Xiaoting Mo, Wenhui Cui, Zhihui Zhang, Delin Li, Liucheng Li, Liang Xu, Hongwei Yao, Jian Gao
Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2(-/-)) and wild-type mice to compare the development of PF...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911093/dna-microarray-profiling-highlights-nrf2-mediated-chemoprevention-targeted-by-wasabi-derived-isothiocyanates-in-hepg2-cells
#19
Phoebe Zapanta Trio, Atsuyoshi Kawahara, Shunsuke Tanigawa, Kozue Sakao, De-Xing Hou
6-MSITC and 6-MTITC are sulforaphane (SFN) analogs found in Japanese Wasabi. As we reported previously, Wasabi isothiocyanates (ITCs) are activators of Nrf2-antioxidant response element pathway, and also inhibitors of pro-inflammatory cyclooxygenase-2. This study is the first to assess the global changes in transcript levels by Wasabi ITCs, comparing with SFN, in HepG2 cells. We performed comparative gene expression profiling by treating HepG2 cells with ITCs, followed by DNA microarray analyses using HG-U133 plus 2...
January 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/27903744/metallothionein-is-downstream-of-nrf2-and-partially-mediates-sulforaphane-prevention-of-diabetic-cardiomyopathy
#20
Junlian Gu, Yanli Cheng, Hao Wu, Lili Kong, Shudong Wang, Zheng Xu, Zhiguo Zhang, Yi Tan, Bradley B Keller, Honglan Zhou, Yuehui Wang, Zhonggao Xu, Lu Cai
We have reported that sulforaphane (SFN) prevented diabetic cardiomyopathy in both type 1 and type 2 diabetes (T2DM) animal models via the upregulation of nuclear transcription factor erythroid 2-related factor 2 (Nrf2) and metallothionein (MT). In this study, we tested whether SFN protects the heart from T2DM directly through Nrf2, MT, or both. Using Nrf2-knockout (KO), MT-KO, and wild-type (WT) mice, T2DM was induced by feeding a high-fat diet for 3 months followed by a small dose of streptozotocin. Age-matched controls were given a normal diet...
February 2017: Diabetes
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