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Glucose toxicity

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https://www.readbyqxmd.com/read/28098449/targeting-type-2-diabetes-with-c-glucosyl-dihydrochalcones-as-selective-sodium-glucose-co-transporter-2-sglt2-inhibitors-synthesis-and-biological-evaluation
#1
Ana R Jesus, Diogo Vila-Viçosa, Miguel Machuqueiro, Ana P Marques, Timothy M Dore, Amélia P Rauter
Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC50 = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC50 = 10-19 μM)...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28095173/performance-of-a-trigger-tool-for-identifying-adverse-events-in-oncology
#2
Allison Lipitz-Snyderman, David Classen, David Pfister, Aileen Killen, Coral L Atoria, Elizabeth Fortier, Andrew S Epstein, Christopher Anderson, Saul N Weingart
PURPOSE: Although patient safety is a priority in oncology, few tools measure adverse events (AEs) beyond treatment-related toxicities. The study objective was to assemble a set of clinical triggers in the medical record and assess the extent to which triggered events identified AEs. METHODS: We performed a retrospective cohort study to assess the performance of an oncology medical record screening tool at a comprehensive cancer center. The study cohort included 400 patients age 18 years or older diagnosed with breast (n = 128), colorectal (n = 136), or lung cancer (n = 136), observed as in- and outpatients for up to 1 year...
January 17, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28092483/photodynamic-inactivation-of-cariogenic-pathogens-using-curcumin-as-photosensitizer
#3
Natália Costa Araújo, Rebeca Ferraz de Menezes, Vanda Sanderana Macêdo Carneiro, Alexandrino Pereira Dos Santos-Neto, Carla Raquel Fontana, Vanderlei Salvador Bagnato, Catherine Malinda Harvey, Marleny Elizabeth Martinez Gerbi
OBJECTIVE: This investigation assessed the susceptibility of Streptococcus mutans and Lactobacillus acidophilus to Photodynamic Therapy (PDT) when grown simultaneously in dentine carious lesions. BACKGROUND DATA: PDT is a technique that utilizes light to activate photosensitizers in the presence of oxygen to produce reactive radicals. MATERIALS AND METHODS: A culture medium of 1% glucose, 2% sucrose, 1% young primary culture of L. acidophilus 10(8) CFU/mL, and S...
January 12, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28090457/glucose-6-phosphate-dehydrogenase-deficiency-does-not-increase-the-susceptibility-of-sperm-to-oxidative-stress-induced-by-h2o2
#4
Shiva Roshankhah, Zahra Rostami-Far, Farhad Shaveisi-Zadeh, Abolfazl Movafagh, Mitra Bakhtiari, Jila Shaveisi-Zadeh
OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H2O2. We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H2O2, which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility...
December 2016: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#5
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28087233/anti-diabetic-effects-of-inonotus-obliquus-polysaccharides-chromium-iii-complex-in-type-2-diabetic-mice-and-its-sub-acute-toxicity-evaluation-in-normal-mice
#6
Cong Wang, Zhongqin Chen, Yuxiang Pan, Xudong Gao, Haixia Chen
Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 (4) Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond...
January 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28075412/the-antagonistic-effect-of-mycotoxins-deoxynivalenol-and-zearalenone-on-metabolic-profiling-in-serum-and-liver-of-mice
#7
Jian Ji, Pei Zhu, Fangchao Cui, Fuwei Pi, Yinzhi Zhang, Yun Li, Jiasheng Wang, Xiulan Sun
Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0...
January 10, 2017: Toxins
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#8
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28070753/dodecyl-amino-glucoside-enhances-transdermal-and-topical-drug-delivery-via-reversible-interaction-with-skin-barrier-lipids
#9
Monika Kopečná, Miloslav Macháček, Eva Prchalová, Petr Štěpánek, Pavel Drašar, Martin Kotora, Kateřina Vávrová
PURPOSE: Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. METHODS: To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. RESULTS: Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer...
January 9, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28069988/exposure-to-concentrated-ambient-pm2-5-shortens-lifespan-and-induces-inflammation-associated-signaling-and-oxidative-stress-in-drosophila
#10
Xiaoke Wang, Minjie Chen, Mianhua Zhong, Ziying Hu, Lianglin Qiu, Sanjay Rajagopalan, Nancy G Fossett, Lung-Chi Chen, Zhekang Ying
BACKGROUND: Exposure to ambient PM2.5 is associated with human premature mortality. However, it has not yet been toxicologically replicated, likely due to the lack of suitable animal models. Drosophila is frequently used in longevity research due to many incomparable merits. OBJECTIVE: The present study aims to validate Drosophila models for PM2.5 toxicity study through characterizing their biological responses to exposure to concentrated ambient PM2.5 (CAP). RESULTS: The survivorship curve demonstrated that exposure to CAP markedly reduced lifespan of Drosophila...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28069436/streptozotocin-causes-neurotoxic-effect-in-cultured-cerebellar-granule-neurons
#11
Elisaveta E Genrikhs, Elena V Stelmashook, Sergey A Golyshev, Olga P Aleksandrova, Nickolay K Isaev
Streptozotocin (STZ) is a glucosamine-nitrosourea compound used for experimental simulation of sporadic Alzheimer's disease at intracerebroventricular administration in vivo. The studies of STZ influence on neurons of central nervous system performed on the primary cultures are practically absent. We have shown the application of STZ (1-5mM) in primary culture for 48h induced strong dose-dependent death in cultured cerebellar granule neurons. This toxic effect was decreased by pyruvate, insulin partially. Using the indicator Fluo-4 AM for measurements of intracellular calcium ions and tetramethylrhodamine ethyl ester (TMRE) for detection of changes of mitochondrial membrane potential in live cells we have shown that 5 h-exposure to STZ induced intensive increase of Fluo-4 and decrease TMRE fluorescence in neurons...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28062998/high-glucose-enhances-isoflurane-induced-neurotoxicity-by-regulating-trpc-dependent-calcium-influx
#12
ZhongJie Liu, ChangQing Ma, Wei Zhao, QingGuo Zhang, Rui Xu, HongFei Zhang, HongYi Lei, ShiYuan Xu
Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca(2+)). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca(2+) influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca(2+) influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure...
January 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28049397/insulin-resistance-in-alzheimer-disease-p53-and-micrornas-as-important-players
#13
Kazimierz Gąsiorowski, Barbara Brokos, Jerzy Leszek, Ghulam Md Ashraf, Gjumrakch Aliev
Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e...
January 3, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28042834/phlorotannins-towards-new-pharmacological-interventions-for-diabetes-mellitus-type-2
#14
REVIEW
Graciliana Lopes, Paula B Andrade, Patrícia Valentão
Diabetes mellitus is a group of metabolic disorders characterized by hyperglycaemia, and predicted by the World Health Organization as the expected 7th leading cause of death in 2030. Diabetes mellitus type 2 (DMT2) comprises the majority of diabetic individuals around the world (90%-95%). Pathophysiologically, this disorder results from a deregulation of glucose homeostasis, worsened by overweight and by a sedentary lifestyle, culminating in life-threatening cardiovascular events. The currently available anti-diabetic drugs are not devoid of undesirable side effects, sometimes responsible for poor therapeutic compliance...
December 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28033103/the-sublethal-effects-of-2-4-dichlorophenoxy-acetic-acid-2-4-d-on-narrow-clawed-crayfish-astacus-leptodactylus-eschscholtz-1823
#15
A Çağlan Karasu Benli, Duygu Şahin, Rabia Sarıkaya, Burcu Koçak Memmi, Aylin Sepici Dinçel
2,4-D is a widely used phenoxy herbicide, potentially toxic to humans and biota. The objective of the present study was to reveal short term sublethal effects of 2,4-D on narrow-clawed freshwater crayfish (Astacus leptodactylus Eschscholtz, 1823), based on histology, total haemocyte counts, selected haemolymph parameters, and oxidative stress parameters. In the laboratory conditions crayfish specimens were exposed to 9 mg L-1 of 2,4-D for one week. Experiments were conducted under semi-static conditions in 20 L-capacity aquaria where 10 freshwater crayfish were stocked per aquarium...
December 1, 2016: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/28030790/nutrient-deprivation-in-neuroblastoma-cells-alters-4-hydroxynonenal-induced-stress-response
#16
Lars Zimmermann, Rudolf Moldzio, Katarina Vazdar, Christopher Krewenka, Elena E Pohl
4-hydroxy-2-nonenal (HNE), a toxic lipid peroxidation product, is associated with oxidative damage in cells and involved in various diseases including the initiation and progression of cancer. Cancer cells have a high, adaptable metabolism with a shift from oxidative phosphorylation to glycolysis and rely on high levels of glucose and glutamine as essential nutrients for cell growth. Here we investigated whether the toxic effects of HNE on the mitochondrial membrane potential (MMP) of cancer cells depends on their metabolic state by deprivation of glucose and/or glutamine...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030590/redox-balance-in-lactobacillus-reuteri-dsm20016-roles-of-iron-dependent-alcohol-dehydrogenases-in-glucose-glycerol-metabolism
#17
Lu Chen, Paul David Bromberger, Gavin Nieuwenhuiys, Rajni Hatti-Kaul
Lactobacillus reuteri, a heterofermentative bacterium, metabolizes glycerol via a Pdu (propanediol-utilization) pathway involving dehydration to 3-hydroxypropionaldehyde (3-HPA) followed by reduction to 1,3-propandiol (1,3-PDO) with concomitant generation of an oxidized cofactor, NAD+ that is utilized to maintain cofactor balance required for glucose metabolism and even for oxidation of 3-HPA by a Pdu oxidative branch to 3-hydroxypropionic acid (3-HP). The Pdu pathway is operative inside Pdu microcompartment that encapsulates different enzymes and cofactors involved in metabolizing glycerol or 1,2-propanediol, and protects the cells from the toxic effect of the aldehyde intermediate...
2016: PloS One
https://www.readbyqxmd.com/read/28026809/-trophic-factors-deprivation-induces-long-term-protection-of-neurons-against-excitotoxic-damage
#18
A A Yakovlev, A A Lyzhin, O P Aleksandrova, L G Khaspekov, N V Gulyaeva
One of the strategies to induce tolerance of neurons to toxic injury is preconditioning. Preconditioning is caused by a weak damage of cells, which become more resistant to subsequent, more severe damage. We found that preconditioning by deprivation of trophic factors, or deprivation of trophic factor and glucose effectively protects neurons against subsequent toxic effects of glutamate. Deprivation of trophic factors plays a decisive role in the development of resistance, regardless of whether it has been combined with glucose deprivation or not...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28025494/effect-of-elderberry-sambucus-nigra-l-extract-supplementation-in-stz-induced-diabetic-rats-fed-with-a-high-fat-diet
#19
Ângelo C Salvador, Ewelina Król, Virgínia C Lemos, Sónia A O Santos, Fernanda P M S Bento, Carina P Costa, Adelaide Almeida, Dawid Szczepankiewicz, Bartosz Kulczyński, Zbigniew Krejpcio, Armando J D Silvestre, Sílvia M Rocha
Elderberry (Sambucus nigra L.) lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an Aliivibrio fischeri bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between A...
December 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28024293/modulation-of-the-lipid-profile-and-insulin-levels-of-streptozotocin-induced-diabetic-rats-by-ethanol-extract-of-cnidoscolus-aconitifolius-leaves-and-some-fractions-effect-on-the-oral-glucose-tolerance-of-normoglycemic-rats
#20
N K Achi, O C Ohaeri, I I Ijeh, C Eleazu
BACKGROUND: No study to date has investigated the effect of different polar solvent extracts from Cnidoscolus aconitifolius leaves on glycemic control as used in folk medicine. Hence this study which investigated the effect of ethanol extract and fractions of C. aconitifolius leaves on body weights, relative organ weights, serum levels of glucose, lipid profiles and insulin in streptozotocin induced diabetic rats and on oral glucose tolerance of normoglycemic rats. METHODS: The ethanol extract was partitioned using methanol, hexane and chloroform to obtain different fractions...
December 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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