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https://www.readbyqxmd.com/read/27914365/developing-piperlongumine-directed-glutathione-s-transferase-inhibitors-by-an-electrophilicity-based-strategy
#1
Hai-Bo Wang, Xiao-Ling Jin, Jia-Fang Zheng, Fu Wang, Fang Dai, Bo Zhou
We report a case of successful design of glutathione S-transferase (GST) inhibitors via a natural product-inspired and electrophilicity-based strategy. Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.
November 15, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27913949/epigenetic-cpg-methylation-of-the-promoter-and-reactivation-of-the-expression-of-gstp1-by-astaxanthin-in-human-prostate-lncap-cells
#2
Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27913937/hypotensive-effect-and-accumulation-of-dinitrosyl-iron-complexes-in-blood-and-tissues-after-intravenous-and-subcutaneous-injection
#3
A A Timoshin, V L Lakomkin, A A Abramov, E K Ruuge, A F Vanin
Subcutaneous injection of Oxacom with glutathione-bound dinitrosyl iron complex as the active principle produced a slower drop of mean BP and longer accumulation of protein-bound dinitrosyl iron complexes in whole blood and tissues than intravenous injection of this drug, while durations of hypotensive effect in both cases were practically identical. In contrast to intravenous injection of the drug, its subcutaneous administration was not characterized by a high concentration of protein-bound dinitrosyl iron complexes in the blood at the onset of experiment; in addition, accumulation of these NO forms in the lungs was more pronounced after subcutaneous injection than after intravenous one...
December 2, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27913897/rainbow-trout-oncorhynchus-mykiss-pro-oxidant-and-genotoxic-responses-following-acute-and-chronic-exposure-to-the-antibiotic-oxytetracycline
#4
Sara Rodrigues, Sara C Antunes, Alberto T Correia, Bruno Nunes
Oxytetracycline (OTC), an antibacterial agent, is extensively used in aquaculture practices all over the world, but also in human and veterinary medicines. Because of its intensive use, low rates of absorption by treated animals, inadequate disposal, and low efficiency of removal in wastewater treatment plants, the potential harmful effects on aquatic organisms are of great concern. This work aimed to assess the effects of this antibiotic in rainbow trout, following both acute and chronic exposures. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers, in gills and liver...
December 2, 2016: Ecotoxicology
https://www.readbyqxmd.com/read/27913877/oxidative-stress-in-drug-na%C3%A3-ve-first-episode-patients-with-schizophrenia-and-major-depression-effects-of-disease-acuity-and-potential-confounders
#5
Wolfgang Jordan, Henrik Dobrowolny, Sabine Bahn, Hans-Gert Bernstein, Tanja Brigadski, Thomas Frodl, Berend Isermann, Volkmar Lessmann, Jürgen Pilz, Andrea Rodenbeck, Kolja Schiltz, Edzard Schwedhelm, Hayrettin Tumani, Jens Wiltfang, Paul C Guest, Johann Steiner
Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43)...
December 2, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27913845/mitogen-activated-protein-kinases-are-involved-in-hepatocanalicular-dysfunction-and-cholestasis-induced-by-oxidative-stress
#6
Flavia D Toledo, Cecilia L Basiglio, Ismael R Barosso, Andrea C Boaglio, Andrés E Zucchetti, Enrique J Sánchez Pozzi, Marcelo G Roma
In previous studies, we showed that the pro-oxidant model agent tert-butyl hydroperoxide (tBuOOH) induces alterations in hepatocanalicular secretory function by activating Ca(2+)-dependent protein kinase C isoforms (cPKC), via F-actin disorganization followed by endocytic internalization of canalicular transporters relevant to bile formation (Mrp2, Bsep). Since mitogen-activated protein kinases (MAPKs) may be downstream effectors of cPKC, we investigated here the involvement of the MAPKs of the ERK1/2, JNK1/2, and p38(MAPK) types in these deleterious effects...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913623/chac2-an-enzyme-for-slow-turnover-of-cytosolic-glutathione
#7
Amandeep Kaur, Ruchi Gautam, Ritika Srivastava, Avinash Chandel, Akhilesh Kumar, Subramanian Karthikeyan, Anand Kumar Bachhawat
Glutathione degradation plays an important role in glutathione and redox homeostasis and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows about 50% sequence identity. Human and mouse ChaC2 proteins, purified in vitro, show 10-20 fold lower catalytic efficiency than ChaC1, although they showed comparable Km values (Km of 3...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913287/ganoderma-atrum-polysaccharide-ameliorates-ros-generation-and-apoptosis-in-spleen-and-thymus-of-immunosuppressed-mice
#8
Wen-Juan Li, Lu Li, Weng-Ya Zhen, Le-Feng Wang, Meng Pan, Jia-Qian Lv, Fan Wang, Yu-Fei Yao, Shao-Ping Nie, Ming-Yong Xie
Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2...
November 29, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27913278/molecular-basis-for-the-dual-subcellular-distribution-of-microsomal-glutathione-transferase-1
#9
Miyuki Shimoji, Ricardo A Figueroa, Etienne Neve, Danuta Maksel, Gabriela Imreh, Ralf Morgenstern, Einar Hallberg
Microsomal glutathione transferase 1 (MGST1) is a membrane bound enzyme involved in the detoxification of reactive electrophiles and protection of membranes from oxidative stress. The enzyme displays an unusual and broad subcellular distribution with especially high levels in the endoplasmic reticulum (ER) and outer mitochondrial membrane (OMM). Here we examined the molecular basis for this dual distribution. We hypothesized that the amphipathic properties of the first transmembrane segment (TMS), that contains a positively charged lysine (K25), is a central feature guiding dual targeting...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913135/mycophenolate-mofetil-attenuates-uterine-ischaemia-reperfusion-injury-in-a-rat-model
#10
Gulcin Sahin Ersoy, Meryem Kurek Eken, Ozge Cevik, Ozlem T Cilingir, Reshef Tal
This study evaluated the effect of mycophenolate mofetil (MMF) on uterine tissue preservation following ischaemia/reperfusion (I/R) injury. Uterine I/R injury was induced in rats by clamping the lower abdominal aorta and ovarian arteries for 30 min. Group I/R + V (n = 7) received vehicle alone while Group I/R + M (n = 7) received 20 mg/kg/day MMF. Control groups underwent sham surgery and received vehicle (Group C) or 20 mg/kg/day MMF (Group M) (n = 7 for both). Four hours after detorsion, uterine tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione, malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and serum ischaemia modified albumin (IMA) concentrations were measured...
November 21, 2016: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27912887/nephroprotective-effects-of-%C3%AE-bisabolol-against-ischemic-reperfusion-acute-kidney-injury
#11
Tiago Lima Sampaio, Ramon Róseo Paula Pessoa Bezerra de Menezes, Marcus Felipe Bezerra da Costa, Gdayllon Cavalcante Meneses, Mauren Cristina Villalta Arrieta, Adriano José Maia Chaves Filho, Glayciane Bezerra de Morais, Alexandre Braga Libório, Renata Sousa Alves, Janaína Serra Azul Monteiro Evangelista, Alice Maria Costa Martins
BACKGROUND: Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity. STUDY DESIGN: This study intends to evaluate the nephroprotective activity of (-)-α-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R. METHODS: Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60min...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912883/miltirone-protects-human-ea-hy926-endothelial-cells-from-oxidized-low-density-lipoprotein-derived-oxidative-stress-via-a-heme-oxygenase-1-and-mapk-nrf2-dependent-pathway
#12
Liu Zhang, Hui Zhang, Xueyan Li, Bingjie Jia, Yuyu Yang, Ping Zhou, Ping Li, Jun Chen
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is an underlying cause of endothelial dysfunction, which is an early event in the pathogenesis of atherosclerosis. In our previous study, we established an ARE-driven luciferase reporter system and screened out several potential Nrf2 activators from Salvia miltiorrhiza Bunge. PURPOSE: Since miltirone showed the most potent ARE-driven luciferase activity, the aim of this study was to test the protective role of miltirone against oxidative stress in endothelial cell and to investigate the underlying mechanistic signaling pathways...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912877/riceberry-bran-extract-prevents-renal-dysfunction-and-impaired-renal-organic-anion-transporter-3-oat3-function-by-modulating-the-pkc-nrf2-pathway-in-gentamicin-induced-nephrotoxicity-in-rats
#13
Phatchawan Arjinajarn, Anchalee Pongchaidecha, Nuttawud Chueakula, Krit Jaikumkao, Varanuj Chatsudthipong, Sugunya Mahatheeranont, Orranuch Norkaew, Nipon Chattipakorn, Anusorn Lungkaphin
PURPOSE: This study investigated the protective effects of Riceberry bran extract (RBBE) on renal function, and the function and expression of renal organic anion transporter 3 (Oat3) in gentamicin-induced nephrotoxicity in rats and explored the mechanisms for its protective effects. MATERIAL AND METHODS: Male Sprague Dawley rats (n= 42) were divided into six groups to receive normal saline, gentamicin (100mg/kg), co-treatment of gentamicin and RBBE (at dose of 250, 500 and 1000mg/kg), and RBBE (at dose of 1000mg/kg) only, for consecutive fifteen days...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27911903/transfected-babesia-bovis-expressing-a-tick-gst-as-a-live-vector-vaccine
#14
Daiane P Oldiges, Jacob M Laughery, Nelson Junior Tagliari, Ronaldo Viana Leite Filho, William C Davis, Itabajara da Silva Vaz, Carlos Termignoni, Donald P Knowles, Carlos E Suarez
The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST)...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27911874/effects-of-dietary-vitamin-e-deficiency-on-systematic-pathological-changes-and-oxidative-stress-in-fish
#15
Kaiyu Wang, Erlong Wang, Zhenyang Qin, Zhen Zhou, Yi Geng, Defang Chen
The aim of this study was to investigate the effects of dietary vitamin E deficiency on systematic pathological changes and oxidative stress in fish. A total of 320 healthy common carp (Cyprinus carpio) were randomized into four groups; the control group was fed a basal diet supplemented with 100 IUkg-1 of vitamin E, while the three experimental groups were fed the same basal diet with reduced vitamin E content (0, 25, or 50 IUkg-1). Findings showed that fish in the experimental groups mainly presented with sekoke disease, exophthalmia, leprnorthsis, and ascites...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911855/glutamine-and-glutaminolysis-are-required-for-efficient-replication-of-infectious-spleen-and-kidney-necrosis-virus-in-chinese-perch-brain-cells
#16
Xiaozhe Fu, Xianqin Hu, Ningqiu Li, Feifei Zheng, Xingxing Dong, Jing Duan, Qiang Lin, Jiagang Tu, Lijuan Zhao, Zhibin Huang, Jianguo Su, Li Lin
Viruses rely on host cellular metabolism for energy and macromolecule synthesis during their replication. Infectious spleen and kidney necrosis virus (ISKNV) causes significant economic losses in the Chinese perch (Siniperca chuatsi) industry worldwide. However, little is known about the relationship between ISKNV replication and cellular metabolism. Using transcriptomic analysis, we observed that glutamine metabolism in Chinese perch brain (CPB) cells is altered during ISKNV infection. Moreover, ISKNV replication was decreased in CPB cells cultured in the glutamine-depleted medium...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910779/amelioration-of-doxorubicin-induced-cardiac-and-renal-toxicity-by-oxycarotenoid-lutein-and-its-mechanism-of-action
#17
Edakkadath Raghavan Sindhu, Thattaruparambil Raveendran Nithya, Ponnamparambil Purushothaman Binitha, Ramadasan Kuttan
We set out to determine the effect of oxycarotenoid lutein on reducing cardiac and renal toxicity induced by doxorubicin (DXR). We started with oral administration in rats of lutein for 15 d before administering DXR (30 mg/kg body weight, intraperitoneally, in a single dose). Animals in all groups were sacrificed 24 h after DXR administration. Serum markers of cardiac injury lactate dehydrogenase, creatine phosphokinase, serum glutamate oxaloacetate transaminase, and serum glutamate pyruvate transaminase increased drastically after DXR but decreased after lutein treatment (p < 0...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910769/anti-inflammatory-activity-of-biomass-extracts-of-the-bay-mushroom-imleria-badia-agaricomycetes-in-raw-264-7-cells
#18
Agata Grzywacz, Joanna Gdula Argasinska, Katarzyna Kala, Wlodzimierz Opoka, Bozena Muszynska
The popular edible bay mushroom, Imleria badia, is rich in phenolic and indole compounds, unsaturated fatty acids, and elements that have anti-inflammatory activity, including zinc. The aim of this study was to evaluate the pro- or anti-inflammatory impact of I. badia biomass extracts on RAW 264.7 cells. We analyzed the influence of I. badia extracts and/or lipopolysaccharide (LPS) cotreatment on the fatty acid profile of cell membranes. We also analyzed cyclooxygenase-2, prostaglandin E synthase, glutathione S transferase Mul, and nuclear factor (NF)-κB p50 and p65 protein expression, as well as the activity of peroxisome proliferator-activated receptor γ and NF-κB transcription factors...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/27910754/assessment-of-the-safety-of-the-shiitake-culinary-medicinal-mushroom-lentinus-edodes-agaricomycetes-in-rats-biochemical-hematological-and-antioxidative-parameters
#19
Denise Grotto, Daiane Cristovam Rosa Bueno, Gabriela Karine de Almeida Ramos, Susi Rosa da Costa, Sara Rosicler Vieira Spim, Marli Gerenutti
Lentinus edodes is an edible mushroom studied for use, or as an adjunct, in the prevention of illnesses such as hypertension, hypercholesterolemia, diabetes, and cancer. Despite the functional properties of L. edodes, the doses commonly reported in experimental studies are much higher than those actually consumed. Thus, we aimed to establish the optimum intake levels of L. edodes in vivo. Four groups of male Wistar rats received dry and powdered L. edodes reconstituted in water for 30 days: control (water only), L...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/27909746/brain-glutamate-in-anorexia-nervosa-a-magnetic-resonance-spectroscopy-case-control-study-at-7-tesla
#20
Beata R Godlewska, Alexandra Pike, Ann L Sharpley, Agnes Ayton, Rebecca J Park, Philip J Cowen, Uzay E Emir
RATIONALE: Anorexia nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. There are no established pharmacological treatments and the neurobiology of the condition is poorly understood. Previous studies using magnetic resonance spectroscopy (MRS) have shown that AN may be associated with reductions in indices of brain glutamate; however, at conventional field strengths (≤3 T), it is difficult to separate glutamate from its precursor and metabolite, glutamine...
December 1, 2016: Psychopharmacology
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