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Glucose toxicity

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https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#1
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#2
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using (1)H NMR based serum metabolomics...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#3
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#4
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28208765/synthesis-of-mono-and-di-glucosides-of-zearalenone-and-%C3%AE-%C3%AE-zearalenol-by-recombinant-barley-glucosyltransferase-hvugt14077
#5
Herbert Michlmayr, Elisabeth Varga, Francesca Lupi, Alexandra Malachová, Christian Hametner, Franz Berthiller, Gerhard Adam
Zearalenone (ZEN) is an estrogenic mycotoxin occurring in Fusarium-infected cereals. Glucosylation is an important plant defense mechanism and generally reduces the acute toxicity of mycotoxins to humans and animals. Toxicological information about ZEN-glucosides is limited due to the unavailability of larger amounts required for animal studies. HvUGT14077, a recently-validated ZEN-conjugating barley UDP-glucosyltransferase was expressed in Escherichia coli, affinity purified, and characterized. HvUGT14077 possesses high affinity (Km = 3 µM) and catalytic efficiency (kcat/Km = 190 s(-1)·mM(-1)) with ZEN...
February 9, 2017: Toxins
https://www.readbyqxmd.com/read/28208654/a-protein-isolate-from-moringa-oleifera-leaves-has-hypoglycemic-and-antioxidant-effects-in-alloxan-induced-diabetic-mice
#6
Paulo C Paula, Daniele O B Sousa, Jose T A Oliveira, Ana F U Carvalho, Bella G T Alves, Mirella L Pereira, Davi F Farias, Martonio P Viana, Flavia A Santos, Talita C Morais, Ilka M Vasconcelos
Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic and antioxidant effects on alloxan-induced diabetic mice were assessed. Mo-LPI was obtained by aqueous extraction, ammonium sulphate precipitation and dialysis. The electrophoresis profile and proteolytic hydrolysis confirmed its protein nature...
February 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28207788/self-complementary-adeno-associated-virus-serotype-6-mediated-knockdown-of-adamts4-induces-long-term-and-effective-enhancement-of-aggrecan-in-degenerative-human-nucleus-pulposus-cells-a-new-therapeutic-approach-for-intervertebral-disc-disorders
#7
Demissew Shenegelegn Mern, Anja Tschugg, Sebastian Hartmann, Claudius Thomé
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs...
2017: PloS One
https://www.readbyqxmd.com/read/28192173/evaluation-of-the-sub-chronic-toxicity-of-a-standardized-flavonoid-extract-of-safflower-in-rats
#8
Zhilin Zhang, Runzhe Liu, Xiaoping Pu, Yi Sun, Xin Zhao
Carthamus tinctorius L., or safflower, is an annual herbaceous crop belonging to the family Asteraceae, which is cultivated throughout China and used as a traditional Chinese medicine. Our previous study revealed anti-Parkinson's disease effects of an isolated standardized safflower flavonoid extract (SAFE). The purpose of this study is to evaluate the potential sub-chronic toxicity of SAFE. Male and female Sprague Dawley rats received three doses of SAFE (100, 300, and 500 mg/kg) q.d. by gavage for four weeks...
February 10, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28191664/direct-arterial-injection-of-hyperpolarized-13-c-labeled-substrates-into-rat-tumors-for-rapid-mr-detection-of-metabolism-with-minimal-substrate-dilution
#9
Steven Reynolds, Stephen Metcalf, Edward J Cochrane, Rebecca C Collins, Simon Jones, Martyn N J Paley, Gillian M Tozer
PURPOSE: A rat model was developed to enable direct administration of hyperpolarized (13) C-labeled molecules into a tumor-supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism. METHODS: Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized (13) C-molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein...
February 12, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28191023/major-phytochemical-as-%C3%AE-sitosterol-disclosing-and-toxicity-testing-in-lagerstroemia-species
#10
Prapaparn Sirikhansaeng, Tawatchai Tanee, Runglawan Sudmoon, Arunrat Chaveerach
Medicinal plants in genus Lagerstroemia were investigated for phytochemical contents by GC-MS and HPLC with ethanol and hexane extracts and their toxicity MTT and comet assay on human peripheral blood mononuclear cells (PBMCs). γ-Sitosterol is the major component found in all species at 14.70-34.44%. All of the extracts, except for L. speciosa ethanol extract, showed high percentages of cell viability. The IC50 value, 0.24 mg/mL, of ethanol L. speciosa extract predicted an LD50 of 811.78 mg/kg, which belongs to WHO Class III of toxic chemicals...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28185390/oxidative-stress-as-a-damage-mechanism-in-porcine-cumulus-oocyte-complexes-exposed-to-malathion-during-in-vitro-maturation
#11
Diana Flores, Verónica Souza, Miguel Betancourt, Mario Teteltitla, Humberto González-Márquez, Eduardo Casas, Edmundo Bonilla, Patricia Ramírez-Noguera, María Concepción Gutiérrez-Ruíz, Yvonne Ducolomb
Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage...
February 10, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28183059/copper-induced-metabolic-variation-of-oysters-overwhelmed-by-salinity-effects
#12
Chen Cao, Wen-Xiong Wang
In estuarine environments, Cu (copper) contamination is simultaneously coupled with salinity variation. In this study, (1)H NMR was applied to investigate the metabolic disturbance of estuarine oysters Crassostrea hongkongensis under both Cu and salinity stresses. Oysters were exposed to dissolved Cu (50 μg L(-1)) at different salinities (10, 15 and 25 psu) for six weeks, and the Cu accumulation in the oyster tissues was higher at lowered salinity. Based on the NMR-metabolomics results, disturbances induced by Cu and salinity was mainly related to osmotic regulation, energy metabolism and glycerophospholipid metabolism, as indicated by the alteration of important metabolic biomarkers such as alanine, citrate, glucose, glycogen, betaine, taurine, hypotaurine and homarine in the gills...
February 1, 2017: Chemosphere
https://www.readbyqxmd.com/read/28181678/safety-and-immunological-efficacy-of-a-dna-vaccine-encoding-the-androgen-receptor-ligand-binding-domain-ar-lbd
#13
Brian M Olson, Eric S Bradley, Thomas Sawicki, Weixiong Zhong, Erik A Ranheim, Jordan E Bloom, Viswa T Colluru, Laura E Johnson, Brian T Rekoske, Jens C Eickhoff, Douglas G McNeel
BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28179472/endothelin-confers-protection-against-high-glucose-induced-neurotoxicity-via-alleviation-of-oxidative-stress
#14
Mohamed Fouda, Abdel A Abdel-Rahman
Recent findings linked the inhibition in the neuromodulator peptide endothelin-1 (ET-1) level to the high glucose-evoked neurotoxicity. However, definitive neuroprotective role for ET-1, and the major neuronal ET (ET-3), against high glucose-evoked toxicity, and the implicated neurochemical responses triggered by their ET-A and ET-B receptors remain unknown. Here, we tested the hypothesis that ET-B activation alleviates high glucose-evoked oxidative stress and cell death. High glucose (100 mM for 48 hrs.)-evoked cell death was associated with elevation in reactive oxygen species, inhibition of catalase activity, and a paradoxical upregulation of hemeoxygenase-1 expression along with ET-A and ET-B receptors were down-regulated and up-regulated, respectively...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28179377/hepcidin-links-gluco-toxicity-to-pancreatic-beta-cell-dysfunction-through-inhibiting-pdx-1-expression
#15
Xuhua Mao, Hucheng Chen, Junmin Tang, Liangliang Wang, Tingting Shu
OBJECTIVE: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. DESIGN: We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6...
February 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28178390/metabolic-and-hemodynamic-effects-of-sodium-dependent-glucose-co-transporter-2-inhibitors-on-cardio-renal-protection-in-the-treatment-of-patients-with-type-2-diabetes-mellitus
#16
REVIEW
Atsunori Kashiwagi, Hiroshi Maegawa
The specific Na+/glucose co-transporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease due to urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors...
February 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28177776/characterization-of-a-salmonella-sugar-kinase-essential-for-utilization-of-fructose-asparagine
#17
Pradip K Biswas, Edward J Behrman, Venkat Gopalan
Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation due to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery...
August 10, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28165773/greenhouse-gas-emissions-from-a-cu-contaminated-soil-remediated-by-in-situ-stabilization-and-phytomanaged-by-a-mixed-stand-of-poplar-willows-and-false-indigo-bush
#18
M Šimek, D Elhottová, M Mench, L Giagnoni, P Nannipieri, G Renella
Phytomanagement of trace element-contaminated soils can reduce the soil toxicity and restore the soil ecological functions, including the soil gas exchange with the atmosphere. We studied the emission rate of the greenhouse gases (GHG) CO2, CH4 and N2O, and the potential CH4 oxidation, denitrification activity (DEA) and glucose mineralization of a Cu-contaminated soil amended with dolomitic limestone and compost, alone or in combination, after a 2 year-phytomanagement with a mixed stand of Populus nigra, Salix viminalis, S...
February 6, 2017: International Journal of Phytoremediation
https://www.readbyqxmd.com/read/28163246/triphenyl-phosphate-enhances-adipogenic-differentiation-glucose-uptake-and-lipolysis-via-endocrine-and-noradrenergic-mechanisms
#19
German Cano-Sancho, Anna Smith, Michele A La Merrill
The use of triphenyl phosphate (TPhP) as a flame retardant or plasticizer has increased during the last decade, resulting in widespread human exposure without commensurate toxicity assessment. The main objectives of this study were to assess the in vitro effect of TPhP and its metabolite diphenyl phosphate (DPhP) on the adipogenic differentiation of 3T3-L1 cells, as well as glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. TPhP increased pre-adipocyte proliferation and subsequent adipogenic differentiation of 3T3-L1 cells, coinciding with increased transcription in the CEBP and PPARG pathway...
February 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28163055/toxicology-of-the-aqueous-extract-from-the-flowers-of-butea-monosperma-lam-and-it-s-metabolomics-in-yeast-cells
#20
Washim Khan, Shreesh Gupta, Sayeed Ahmad
Due to lack of scientific evidence for the safety of Butea monosperma (Fabaceae), our study aimed to carry out its toxicological profile and to identify its metabolic pattern in yeast cell. The effect of aqueous extract of B. monosperma flower on glucose uptake in yeast cell was evaluated through optimizing pH, temperature, incubation time, substrate concentration and kinetic parameters. Further, the metabolic pattern of extract as such and in yeast cell were analyzed by gas chromatography-mass spectrometry...
February 2, 2017: Food and Chemical Toxicology
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