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Sample records for nonischemic oxidative metabolic

  1. Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

    Science.gov (United States)

    Sawamura, Akinori; Okumura, Takahiro; Hiraiwa, Hiroaki; Aoki, Soichiro; Kondo, Toru; Ichii, Takeo; Furusawa, Kenji; Watanabe, Naoki; Kano, Naoaki; Fukaya, Kenji; Morimoto, Ryota; Bando, Yasuko K; Murohara, Toyoaki

    2017-06-01

    Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6μg/mL, lathosterol 1.4μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  2. Oxidative metabolism in muscle.

    OpenAIRE

    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  3. Role of cardiac MRI in nonischemic cardiomyopathies.

    Science.gov (United States)

    Anand, Senthil; Janardhanan, Rajesh

    2016-01-01

    Cardiac magnetic resonance (CMR) with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies. Published by Elsevier B.V.

  4. Role of cardiac MRI in nonischemic cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Senthil Anand

    2016-05-01

    Full Text Available Cardiac magnetic resonance (CMR with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies.

  5. Bystander signaling via oxidative metabolism.

    Science.gov (United States)

    Sawal, Humaira Aziz; Asghar, Kashif; Bureik, Matthias; Jalal, Nasir

    2017-01-01

    The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.

  6. Bystander signaling via oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Sawal HA

    2017-08-01

    Full Text Available Humaira Aziz Sawal,1 Kashif Asghar,2 Matthias Bureik,3 Nasir Jalal4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 2Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; 3Health Science Platform, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; 4Health Science Platform, Department of Molecular and Cellular Pharmacology, Tianjin University, Tianjin, China Abstract: The radiation-induced bystander effect (RIBE is the initiation of biological end points in cells (bystander cells that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to

  7. Nitric oxide and mitochondria in metabolic syndrome

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    Litvinova, Larisa; Atochin, Dmitriy N.; Fattakhov, Nikolai; Vasilenko, Mariia; Zatolokin, Pavel; Kirienkova, Elena

    2015-01-01

    Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS. PMID:25741283

  8. Lactate: link between glycolytic and oxidative metabolism.

    Science.gov (United States)

    Brooks, George A

    2007-01-01

    Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

  9. Influence of nutrition on liver oxidative metabolism.

    Science.gov (United States)

    Jorquera, F; Culebras, J M; González-Gallego, J

    1996-06-01

    The liver plays a major role in the disposition of the majority of drugs. This is due to the presence of several drug-metabolizing enzyme systems, including a group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine metabolism. Different drugs and other factors may induce or inhibit the cytochrome P450-dependent system. This effect is important in terms of the efficacy or toxicity of drugs that are substrates for the system. Microsomal oxidation in animals fed with protein-deficient diets is depressed. The mixed-function oxidase activity recovers after a hyperproteic diet or the addition of lipids. Similar findings have been reported in patients with protein-calorie malnutrition, although results in the elderly are conflicting. Different studies have revealed that microsomal oxidation is impaired by total parenteral nutrition and that this effect is absent when changing the caloric source from carbohydrates to a conventional amino acid solution or after lipid addition, especially when administered as medium-chain/long-chain triglyceride mixtures. Peripheral parenteral nutrition appears to increase antipyrine clearance.

  10. Intraventricular vortex properties in nonischemic dilated cardiomyopathy

    Science.gov (United States)

    Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Martínez-Legazpi, Pablo; del Villar, Candelas Pérez; Pérez-David, Esther; González-Mansilla, Ana; Santa-Marta, Cristina; Barrio, Alicia; Fernández-Avilés, Francisco; del Álamo, Juan C.

    2014-01-01

    Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1–74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m2/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound. PMID:24414062

  11. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

    Science.gov (United States)

    Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  12. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    OpenAIRE

    Moustafa Elsheshtawy; Priatharsini Sriganesh; Vasudev Virparia; Falgun Patel; Ashok Khanna

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  13. Mitochondria Play a Central Role in Nonischemic Cardiomyocyte Necrosis: Common to Acute and Chronic Stressor States

    Science.gov (United States)

    Khan, M. Usman; Cheema, Yaser; Shahbaz, Atta U.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2012-01-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiologic and pathophysiologic demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis which are initiated from ischemic or nonischemic origins. Herein we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone- mediated intracellular Ca2+ overloading which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  14. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

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    Moustafa Elsheshtawy

    2016-01-01

    Full Text Available Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  15. Skeletal muscle capillarization and oxidative metabolism in healthy smokers

    NARCIS (Netherlands)

    Wüst, Rob C. I.; Jaspers, Richard T.; van der Laarse, Willem J.; Degens, Hans

    2008-01-01

    We investigated whether the lower fatigue resistance in smokers than in nonsmokers is caused by a compromised muscle oxidative metabolism. Using calibrated histochemistry, we found no differences in succinate dehydrogenase (SDH) activity, myoglobin concentration, or capillarization in sections of

  16. Electrochemical Oxidation by Square-Wave Potential Pulses in the Imitation of Oxidative Drug Metabolism

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Permentier, Hjalmar P.; Bischoff, Rainer; Bruins, Andries P.

    2011-01-01

    Electrochemistry combined with mass spectrometry (EC-MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wave potential pulses for the oxidation of

  17. Oxidative status and lipid profile in metabolic syndrome: gender differences.

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    Kaya, Aysem; Uzunhasan, Isil; Baskurt, Murat; Ozkan, Alev; Ataoglu, Esra; Okcun, Baris; Yigit, Zerrin

    2010-02-01

    Metabolic syndrome is associated with cardiovascular disease and oxidative stress. The aim of this study was to investigate the differences of novel oxidative stress parameters and lipid profiles in men and women with metabolic syndrome. The study population included 88 patients with metabolic syndrome, consisting of 48 postmenauposal women (group I) and 40 men (group II). Premenauposal women were excluded. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using the Erel automated measurement method, and oxidative stress index (OSI) was calculated. To perform the calculation, the resulting unit of TAS, mmol Trolox equivalent/L, was converted to micromol equivalent/L and the OSI value was calculated as: OSI = [(TOS, micromol/L)/(TAS, mmol Trolox equivalent/L) x 100]. The Student t-test, Mann-Whitney-U test, and chi-squared test were used for statistical analysis; the Pearson correlation coefficient and Spearman rank test were used for correlation analysis. P women and men had similar properties regarding demographic characteristics and biochemical work up. Group II had significantly lower levels of antioxidant levels of TAS and lower levels of TOS and OSI compared with group I (P = 0.0001, P = 0.0035, and P = 0,0001). Apolipoprotein A (ApoA) levels were significantly higher in group I compared with group II. Our findings indicate that women with metabolic syndrome have a better antioxidant status and higher ApoA levels compared with men. Our findings suggest the existence of a higher oxidative stress index in men with metabolic syndrome. Considering the higher risk of atherosclerosis associated with men, these novel oxidative stress parameters may be valuable in the evaluation of patients with metabolic sydrome.

  18. Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

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    Faer Morrison

    2012-01-01

    Full Text Available Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L, ambient (11 mmol/L, and high (28 mmol/L glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS production was evident in INS-1 cells after 48 hours (P<0.05. TLDA analysis revealed a significant (P<0.05 upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

  19. The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

    Science.gov (United States)

    Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

    2018-04-03

    Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Sugar alcohols-induced oxidative metabolism in cotton callus culture

    African Journals Online (AJOL)

    Sugar alcohols (mannitol and sorbitol) may cause oxidative damage in plants if used in higher concentration. Our present experiment was undertaken to study physiological and metabolic responses in cotton (Gossypium hirsutum L.) callus against mannitol and sorbitol higher doses. Both markedly declined mean values of ...

  1. Oxidative Stress and the Homeodynamics of Iron Metabolism

    Science.gov (United States)

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

  2. Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy

    DEFF Research Database (Denmark)

    Iversen, Peter; Mouridsen, Kim; Hansen, Mikkel B

    2014-01-01

    In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [(11)C]acetate PET...... of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes...

  3. Stratification of the Risk of Sudden Death in Nonischemic Heart Failure

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    Maurício Pimentel

    2014-10-01

    Full Text Available Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure.

  4. Energy Metabolism during Anaerobic Methane Oxidation in ANME Archaea

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    McGlynn, Shawn E.

    2017-01-01

    Anaerobic methane oxidation in archaea is often presented to operate via a pathway of “reverse methanogenesis”. However, if the cumulative reactions of a methanogen are run in reverse there is no apparent way to conserve energy. Recent findings suggest that chemiosmotic coupling enzymes known from their use in methylotrophic and acetoclastic methanogens—in addition to unique terminal reductases—biochemically facilitate energy conservation during complete CH4 oxidation to CO2. The apparent enzyme modularity of these organisms highlights how microbes can arrange their energy metabolisms to accommodate diverse chemical potentials in various ecological niches, even in the extreme case of utilizing “reverse” thermodynamic potentials. PMID:28321009

  5. Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

    DEFF Research Database (Denmark)

    Rosenkilde, M; Nordby, P; Nielsen, L B

    2010-01-01

    OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive...... the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma...... triglycerides (Pexercise was positively correlated with plasma free fatty acid concentration at rest (Pexercise and a healthy metabolic...

  6. Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Summermatter, Serge [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Troxler, Heinz [Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University Children' s Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich (Switzerland); Santos, Gesa [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland)

    2011-04-29

    Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

  7. Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

    International Nuclear Information System (INIS)

    Summermatter, Serge; Troxler, Heinz; Santos, Gesa; Handschin, Christoph

    2011-01-01

    Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.

  8. Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications

    Science.gov (United States)

    Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

    2016-01-01

    Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID:27200002

  9. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  10. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Science.gov (United States)

    Price, Alex; Pearson, Victoria K.; Schwenzer, Susanne P.; Miot, Jennyfer; Olsson-Francis, Karen

    2018-01-01

    This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

  11. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Directory of Open Access Journals (Sweden)

    Alex Price

    2018-03-01

    Full Text Available This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with

  12. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism.

    Science.gov (United States)

    Price, Alex; Pearson, Victoria K; Schwenzer, Susanne P; Miot, Jennyfer; Olsson-Francis, Karen

    2018-01-01

    This work considers the hypothetical viability of microbial nitrate-dependent Fe 2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe 2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe 2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1-3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe 2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

  13. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Spitz, Douglas R.

    2014-01-01

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  14. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  15. State of dog's metabolism in the remote period after the oxide tritium influence

    International Nuclear Information System (INIS)

    Kalistratova, V.S.; Tishchenko, G.S.; Bortnik, L.A.; Nisimov, P.G.; Romanova, I.B.

    2000-01-01

    Influence of tritium oxide on the metabolism by some indices of lipid metabolism (common lipids, β-lipoproteins, cholesterin), protein metabolism (cholinesterase) and carbohydrate metabolism (blood sugar) was studied. It was established that the introduction into organism of tritium oxide in the quantities, which could form lethal and sublethal doses of internal radiation, provoked the main changes of values of mentioned indices of metabolism. The character of metabolism changes in the remote period allows to judge about the development of sclerosis processes which can be the result of radiation-stipulated acceleration of organism aging [ru

  16. Nonischemic Priapism in Childhood: A Case Series and Review of Literature.

    Science.gov (United States)

    Hacker, Hans-Walter; Schwoebel, Marcus G; Szavay, Philipp O

    2018-06-01

    Nonischemic priapism (NIP) in childhood is a very rare affection. In the literature, patients with NIP are described mainly incidental after perineal trauma. Many of them underwent embolization of either internal pudendal artery or bulbocavernosal arteries.  We report on six boys between 4 and 13 years of age with NIP, treated at our institution between 2008 and 2014. Color Doppler ultrasound (CDU) was performed in all patients as emergency diagnostic evaluation. Patients were treated conservatively, including bed rest, local cooling, and perineal compression. History, etiological factors, clinical findings, diagnostics, and follow-up are presented.  Out of the six patients, only one boy had a history of perineal injury with subsequent arteriocavernosal fistula, revealed in CDU. Five patients were circumcised, and one of them suffered from thalassemia minor, but no other underlying disease or etiological factors could be found. In all patients, normal to high blood flow velocities were detected in the cavernosal arteries. Detumescence started with nonoperative treatment within 24 hours in five boys and in one patient with recurrent priapism after 1 week. All six patients remained painless without evidence for an ischemic priapism. None of them suffered from relapse and further erections were observed during follow-up from 3 to 87 months.  In contrast to the literature, five out of six boys developed NIP without a previous perineal trauma. The etiology of idiopathic NIP in childhood remains unclear; however, circumcision may play a role as a conditional factor. One etiological thesis could be the release of the neurotransmitter nitric oxide after stimulation of the corpora cavernosa. Conservative treatment proved to be successful in all six patients. During a median follow-up of 55 months (3-87 months), none of the patients showed signs of erectile dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

  17. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Shu-Ju Chen

    Full Text Available Metabolic syndrome (MS represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72. The control group (n = 105 comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP and interleukin-6 (IL-6, adiponectin, an oxidative stress marker (malondialdehyde, and antioxidant enzymes activities [catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L, or IL-6 (≥1.50 pg/mL or a lower level of adiponectin (<7.90 µg/mL were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.

  18. Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vemuri, Goutham; Eiteman, M.A; McEwen, J.E

    2007-01-01

    effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in S. cerevisiae was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation...... Crabtree effect.’’ The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely...... respiratory to mixed respiratory and fermentative. It is well known that glucose repression of respiratory pathways occurs at high glycolytic fluxes, resulting in a decrease in respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree...

  19. Assessment of oxidative metabolism in Brown Fat using PET imaging

    Directory of Open Access Journals (Sweden)

    Otto eMuzik

    2012-02-01

    Full Text Available Objective: Although it has been believed that brown adipose tissue (BAT depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog FDG has shown unequivocally the existence of functional BAT in humans. The objective of this study was to determine, using dynamic oxygen-15 (15O PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake.Methods: Fourteen adult normal subjects (9F/5M, 30+7 years underwent triple oxygen scans (H215O, C15O, 15O2 as well as indirect calorimetric measurements at rest and following exposure to mild cold (60F. Subjects were divided into two groups (BAT+ and BAT- based on the presence or absence of FDG tracer uptake (SUV > 2 in supraclavicular BAT. Blood flow (BF and oxygen extraction fraction (OEF was calculated from dynamic PET scans at the location of BAT, muscle and white adipose tissue (WAT. The metabolic rate of oxygen (MRO2 in BAT was determined and used to calculate the contribution of activated BAT to daily energy expenditure (DEE.Results: The median mass of activated BAT in the BAT+ group (5F, 31+8yrs was 52.4 g (14-68g and was 1.7 g (0-6.3g in the BAT- group (5M/4F, 29+6yrs. SUV values were significantly higher in the BAT+ as compared to the BAT- group (7.4+3.7 vs 1.9+0.9; p=0.03. BF values in BAT were significantly higher in the BAT+ as compared to the BAT- group (13.1+4.4 vs 5.7+1.1 ml/100g/min, p=0.03, but were similar in WAT (4.1+1.6 vs 4.2+1.8 ml/100g/min and muscle (3.7+0.8 vs 3.3+1.2 ml/100g/min. Calculated MRO2 values in BAT increased from 0.95+0.74 to 1.62+0.82 ml/100g/min in the BAT+ group and were significantly higher than those determined in the BAT- group (0.43+0.27 vs 0.56+0.24; p=0.67. The DEE associated with BAT oxidative metabolism was highly variable in the BAT+ group, with an average of 5.5+6.4 kcal/day (range 0.57–15.3 kcal/day.

  20. Effects of Graphene Oxide and Oxidized Carbon Nanotubes on the Cellular Division, Microstructure, Uptake, Oxidative Stress, and Metabolic Profiles.

    Science.gov (United States)

    Hu, Xiangang; Ouyang, Shaohu; Mu, Li; An, Jing; Zhou, Qixing

    2015-09-15

    Nanomaterial oxides are common formations of nanomaterials in the natural environment. Herein, the nanotoxicology of typical graphene oxide (GO) and carboxyl single-walled carbon nanotubes (C-SWCNT) was compared. The results showed that cell division of Chlorella vulgaris was promoted at 24 h and then inhibited at 96 h after nanomaterial exposure. At 96 h, GO and C-SWCNT inhibited the rates of cell division by 0.08-15% and 0.8-28.3%, respectively. Both GO and C-SWCNT covered the cell surface, but the uptake percentage of C-SWCNT was 2-fold higher than that of GO. C-SWCNT induced stronger plasmolysis and mitochondrial membrane potential loss and decreased the cell viability to a greater extent than GO. Moreover, C-SWCNT-exposed cells exhibited more starch grains and lysosome formation and higher reactive oxygen species (ROS) levels than GO-exposed cells. Metabolomics analysis revealed significant differences in the metabolic profiles among the control, C-SWCNT and GO groups. The metabolisms of alkanes, lysine, octadecadienoic acid and valine was associated with ROS and could be considered as new biomarkers of ROS. The nanotoxicological mechanisms involved the inhibition of fatty acid, amino acid and small molecule acid metabolisms. These findings provide new insights into the effects of GO and C-SWCNT on cellular responses.

  1. Role of nitric oxide in cellular iron metabolism.

    Science.gov (United States)

    Kim, Sangwon; Ponka, Prem

    2003-03-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  2. Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress.

    Science.gov (United States)

    Gao, Mingjing; Zhao, Zhen; Lv, Pengyu; Li, YuFang; Gao, Juntao; Zhang, Michael; Zhao, Baolu

    2015-12-01

    Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic

  3. Microbiological Diversity Demonstrates the Potential which Collaboratively Metabolize Nitrogen Oxides ( NOx) under Smog Environmental Stress

    Science.gov (United States)

    Chen, X. Z.; Zhao, X. H.; Chen, X. P.

    2018-03-01

    Recently, smoggy weather has become a daily in large part of China because of rapidly economic growth and accelerative urbanization. Stressed on the smoggy situation and economic growth, the green and environment-friendly technology is necessary to reduce or eliminate the smog and promote the sustainable development of economy. Previous studies had confirmed that nitrogen oxides ( NOx ) is one of crucial factors which forms smog. Microorganisms have the advantages of quickly growth and reproduction and metabolic diversity which can collaboratively Metabolize various NOx. This study will design a kind of bacteria & algae cultivation system which can metabolize collaboratively nitrogen oxides in air and intervene in the local nitrogen cycle. Furthermore, the nitrogen oxides can be transformed into nitrogen gas or assembled in protein in microorganism cell by regulating the microorganism types and quantities and metabolic pathways in the system. Finally, the smog will be alleviated or eliminated because of reduction of nitrogen oxides emission. This study will produce the green developmental methodology.

  4. Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis.

    Science.gov (United States)

    Altindag, Ozlem; Erel, Ozcan; Aksoy, Nurten; Selek, Sahabettin; Celik, Hakim; Karaoglanoglu, Mustafa

    2007-02-01

    The purpose of this study was to determine serum oxidative/antioxidative status in patients with knee osteoarthritis and its relation with prolidase activity, which plays an important role in collagen metabolism. Serum antioxidative status was evaluated by measuring total antioxidant capacity (TAC), thiol level and catalase enzyme activity in patients with osteoarthritis and in healthy controls. Serum oxidative status was evaluated by measuring total peroxide (TP) and lipid hydroperoxide. Oxidative stress index (OSI) was calculated. Prolidase enzyme activity was measured to investigate the collagen metabolism. Serum TAC, thiol level, catalase activity and prolidase activity were significantly lower in patients than in controls (P antioxidant parameters decreased in patients with osteoarthritis; therefore, these patients may be exposed to a potent oxidative stress. Decreased collagen metabolism may be related with oxidative stress, which has a role in the ethiopathogenesis and/or in the progression of the disease.

  5. Metabolic and oxidative stress markers in Wistar rats after 2?months on a high-fat diet

    OpenAIRE

    Auberval, Nathalie; Dal, St?phanie; Bietiger, William; Pinget, Michel; Jeandidier, Nathalie; Maillard-Pedracini, Elisa; Schini-Kerth, Val?rie; Sigrist, S?verine

    2014-01-01

    Background Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress. Materials and methods Metabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared ...

  6. The Association between Oxidative Stress and Metabolic Syndrome in Adults

    OpenAIRE

    Chung, So-Won; Kang, Sung-Goo; Rho, Jun-Seung; Kim, Ha-Na; Song, In-Sun; Lee, Yun-Ah; Heo, Soo-Jeong; Song, Sang-Wook

    2013-01-01

    Background In this Study, we investigated the effects of lifestyle and metabolic syndrome on free oxygen radical levels in men and women in Korea. Methods A total of 254 adults were included in this study from February 2011 to June 2012 at a health promotion center. Information of the lifestyles and presence of metabolic syndrome factors was obtained. Biochemical markers were measured and free oxygen radicals test (FORT) was performed on the blood. Results Of the 254 subjects, 86 (33.9%) had ...

  7. Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

    DEFF Research Database (Denmark)

    Munk, Michael; Rom Poulsen, Frantz; Larsen, Lykke

    2018-01-01

    BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible...... with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral...... dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed...

  8. Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Bruins, Andries P.; Bischoff, Rainer; Permentier, Hjalmar P.

    2012-01-01

    Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by

  9. Arsenic triggers the nitric oxide (NO) and S-nitrosoglutathione (GSNO) metabolism in Arabidopsis

    International Nuclear Information System (INIS)

    Leterrier, Marina; Airaki, Morad; Palma, José M.; Chaki, Mounira; Barroso, Juan B.; Corpas, Francisco J.

    2012-01-01

    Environmental contamination by arsenic constitutes a problem in many countries, and its accumulation in food crops may pose health complications for humans. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved at various levels in the mechanism of responding to environmental stress in higher plants. Using Arabidopsis seedlings exposed to different arsenate concentrations, physiological and biochemical parameters were analyzed to determine the status of ROS and RNS metabolisms. Arsenate provoked a significant reduction in growth parameters and an increase in lipid oxidation. These changes were accompanied by an alteration in antioxidative enzymes and the nitric oxide (NO) metabolism, with a significant increase in NO content, S-nitrosoglutathione reductase (GSNOR) activity and protein tyrosine nitration as well as a concomitant reduction in glutathione and S-nitrosoglutathione (GSNO) content. Our results indicate that 500 μM arsenate (AsV) causes nitro-oxidative stress in Arabidopsis, being the glutathione reductase and the GSNOR activities clearly affected. - Highlights: ► In Arabidopsis, arsenate provokes damages in the membrane integrity of root cells. ► As induces an oxidative stress according to an increase in lipid oxidation. ► NO content and protein tyrosine nitration increases under arsenate stress. ► Arsenate provokes a reduction of GSH, GSSG and GSNO content. ► Arsenate induces a nitro-oxidative stress in Arabidopsis. - Arsenic stress affects nitric oxide (NO) and glutathione (GSH) metabolism which provokes a nitro-oxidative stress.

  10. Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Yu, Long; Zhou, Zhaoye; Killingsworth, Cheryl R; He, Bin

    2015-01-15

    Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs. Copyright © 2015 the American Physiological Society.

  11. Electrochemistry in the mimicry of oxidative drug metabolism by cytochrome P450s.

    Science.gov (United States)

    Nouri-Nigjeh, Eslam; Bischoff, Rainer; Bruins, Andries P; Permentier, Hjalmar P

    2011-05-01

    Prediction of oxidative drug metabolism at the early stages of drug discovery and development requires fast and accurate analytical techniques to mimic the in vivo oxidation reactions by cytochrome P450s (CYP). Direct electrochemical oxidation combined with mass spectrometry, although limited to the oxidation reactions initiated by charge transfer, has shown promise in the mimicry of certain CYP-mediated metabolic reactions. The electrochemical approach may further be utilized in an automated manner in microfluidics devices facilitating fast screening of oxidative drug metabolism. A wide range of in vivo oxidation reactions, particularly those initiated by hydrogen atom transfer, can be imitated through the electrochemically-assisted Fenton reaction. This reaction is based on O-O bond activation in hydrogen peroxide and oxidation by hydroxyl radicals, wherein electrochemistry is used for the reduction of molecular oxygen to hydrogen peroxide, as well as the reduction of Fe(3+) to Fe(2+). Metalloporphyrins, as surrogates for the prosthetic group in CYP, utilizing metallo-oxo reactive species, can also be used in combination with electrochemistry. Electrochemical reduction of metalloporphyrins in solution or immobilized on the electrode surface activates molecular oxygen in a manner analogous to the catalytical cycle of CYP and different metalloporphyrins can mimic selective oxidation reactions. Chemoselective, stereoselective, and regioselective oxidation reactions may be mimicked using electrodes that have been modified with immobilized enzymes, especially CYP itself. This review summarizes the recent attempts in utilizing electrochemistry as a versatile analytical and preparative technique in the mimicry of oxidative drug metabolism by CYP. © 2011 Bentham Science Publishers Ltd.

  12. Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine.

    Science.gov (United States)

    Nouri-Nigjeh, Eslam; Bruins, Andries P; Bischoff, Rainer; Permentier, Hjalmar P

    2012-10-21

    Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by direct electron transfer. In the case of substituted-aromatic compounds, oxidation proceeds through a Wheland-type intermediate where resonance stabilization of the positive charge determines the regioselectivity of the anodic substitution reaction, and hence limits the extent of generating drug metabolites in comparison with in vivo oxygen insertion reactions. In this study, we show that the electrocatalytic oxidation of hydrogen peroxide on a platinum electrode generates reactive oxygen species, presumably surface-bound platinum-oxo species, which are capable of oxygen insertion reactions in analogy to oxo-ferryl radical cations in the active site of Cytochrome P450. Electrochemical oxidation of lidocaine at constant potential in the presence of hydrogen peroxide produces both 3- and 4-hydroxylidocaine, suggesting reaction via an arene oxide rather than a Wheland-type intermediate. No benzylic hydroxylation was observed, thus freely diffusing radicals do not appear to be present. The results of the present study extend the possibilities of electrochemical imitation of oxidative drug metabolism to oxygen insertion reactions.

  13. A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction.

    Science.gov (United States)

    Muñoz Calvo, Benjamín; Villa Martínez, Ana; López Orgil, Susana; López Andrés, Natalia; Román García, Feliciano; Víctor Palomares, Virginia; de la Calle de la Villa, Esther; Nadador Patiño, Verónica; Arribas-Gómez, Ignacio

    2018-05-25

    Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. We detected raised cpLOX values and found that they correlated with calculated E/E' ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed. Copyright © 2018. Published by Elsevier España, S.L.U.

  14. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  15. Nitrogen metabolism and kinetics of ammonia-oxidizing archaea.

    Science.gov (United States)

    Martens-Habbena, Willm; Stahl, David A

    2011-01-01

    The discovery of ammonia-oxidizing mesophilic and thermophilic Group I archaea changed the century-old paradigm that aerobic ammonia oxidation is solely mediated by two small clades of Beta- and Gammaproteobacteria. Group I archaea are extremely diverse and ubiquitous in marine and terrestrial environments, accounting for 20-30% of the microbial plankton in the global oceans. Recent studies indicated that many of these organisms carry putative ammonia monooxygenase genes and are more abundant than ammonia-oxidizing bacteria in most natural environments suggesting a potentially significant role in the nitrogen cycle. The isolation of Nitrosopumilus maritimus strain SCM1 provided the first direct evidence that Group I archaea indeed gain energy from ammonia oxidation. To characterize the physiology of this archaeal nitrifier, we developed a respirometry setup particularly suited for activity measurements in dilute microbial cultures with extremely low oxygen uptake rates. Here, we describe the setup and review the kinetic experiments conducted with N. maritimus and other nitrifying microorganisms. These experiments demonstrated that N. maritimus is adapted to grow on ammonia concentrations found in oligotrophic open ocean environments, far below the survival threshold of ammonia-oxidizing bacteria. The described setup and experimental procedures should facilitate physiological studies on other nitrifying archaea and oligotrophic microorganisms in general. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Abcc9 is required for the transition to oxidative metabolism in the newborn heart.

    Science.gov (United States)

    Fahrenbach, John P; Stoller, Douglas; Kim, Gene; Aggarwal, Nitin; Yerokun, Babatunde; Earley, Judy U; Hadhazy, Michele; Shi, Nian-Qing; Makielski, Jonathan C; McNally, Elizabeth M

    2014-07-01

    The newborn heart adapts to postnatal life by shifting from a fetal glycolytic metabolism to a mitochondrial oxidative metabolism. Abcc9, an ATP-binding cassette family member, increases expression concomitant with this metabolic shift. Abcc9 encodes a membrane-associated receptor that partners with a potassium channel to become the major potassium-sensitive ATP channel in the heart. Abcc9 also encodes a smaller protein enriched in the mitochondria. We now deleted exon 5 of Abcc9 to ablate expression of both plasma membrane and mitochondria-associated Abcc9-encoded proteins, and found that the myocardium failed to acquire normal mature metabolism, resulting in neonatal cardiomyopathy. Unlike wild-type neonatal cardiomyocytes, mitochondria from Ex5 cardiomyocytes were unresponsive to the KATP agonist diazoxide, consistent with loss of KATP activity. When exposed to hydrogen peroxide to induce cell stress, Ex5 neonatal cardiomyocytes displayed a rapid collapse of mitochondria membrane potential, distinct from wild-type cardiomyocytes. Ex5 cardiomyocytes had reduced fatty acid oxidation, reduced oxygen consumption and reserve. Morphologically, Ex5 cardiac mitochondria exhibited an immature pattern with reduced cross-sectional area and intermitochondrial contacts. In the absence of Abcc9, the newborn heart fails to transition normally from fetal to mature myocardial metabolism.-Fahrenbach, J. P., Stoller, D., Kim, G., Aggarwal, N., Yerokun, B., Earley, J. U., Hadhazy, M., Shi, N.-Q., Makielski, J. C., McNally, E. M. Abcc9 is required for the transition to oxidative metabolism in the newborn heart. © FASEB.

  17. MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

    Science.gov (United States)

    Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

    2017-02-01

    Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

  18. Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo.

    Science.gov (United States)

    Jiang, Lihong; Herzog, Raimund I; Mason, Graeme F; de Graaf, Robin A; Rothman, Douglas L; Sherwin, Robert S; Behar, Kevin L

    2009-06-01

    The objective of this study was to characterize the changes in brain metabolism caused by antecedent recurrent hypoglycemia under euglycemic and hypoglycemic conditions in a rat model and to test the hypothesis that recurrent hypoglycemia changes the brain's capacity to utilize different energy substrates. Rats exposed to recurrent insulin-induced hypoglycemia for 3 days (3dRH rats) and untreated controls were subject to the following protocols: [2-(13)C]acetate infusion under euglycemic conditions (n = 8), [1-(13)C]glucose and unlabeled acetate coinfusion under euglycemic conditions (n = 8), and [2-(13)C]acetate infusion during a hyperinsulinemic-hypoglycemic clamp (n = 8). In vivo nuclear magnetic resonance spectroscopy was used to monitor the rise of(13)C-labeling in brain metabolites for the calculation of brain metabolic fluxes using a neuron-astrocyte model. At euglycemia, antecedent recurrent hypoglycemia increased whole-brain glucose metabolism by 43 +/- 4% (P glucose utilization in neurons. Although acetate metabolism remained the same, control and 3dRH animals showed a distinctly different response to acute hypoglycemia: controls decreased pyruvate dehydrogenase (PDH) flux in astrocytes by 64 +/- 20% (P = 0.01), whereas it increased by 37 +/- 3% in neurons (P = 0.01). The 3dRH animals decreased PDH flux in both compartments (-75 +/- 20% in astrocytes, P neurons, P = 0.005). Thus, acute hypoglycemia reduced total brain tricarboxylic acid cycle activity in 3dRH animals (-37 +/- 4%, P = 0.001), but not in controls. Our findings suggest that after antecedent hypoglycemia, glucose utilization is increased at euglycemia and decreased after acute hypoglycemia, which was not the case in controls. These findings may help to identify better methods of preserving brain function and reducing injury during acute hypoglycemia.

  19. Oxidative stress among subjects with metabolic syndrome in Sokoto ...

    African Journals Online (AJOL)

    2015-08-20

    Aug 20, 2015 ... Background: Oxidative stress is known to play a role in the ... others to remix, tweak, and build upon the work non-commercially, as long as the ..... Report of the National Heart, Lung, and Blood Institute/American Heart.

  20. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  1. A RAPID THIN-LAYER CHROMATOGRAPHIC PROCEDURE TO IDENTIFY POOR AND EXTENSIVE OXIDATIVE DRUG METABOLIZERS IN MAN USING DEXTROMETHORPHAN

    NARCIS (Netherlands)

    DEZEEUW, RA; EIKEMA, D; FRANKE, JP; JONKMAN, JHG

    A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its

  2. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency......, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all...

  3. Changes in oxidative properties of Kalanchoe blossfeldiana leaf mitochondria during development of Crassulacean acid metabolism.

    Science.gov (United States)

    Rustin, P; Queiroz-Claret, C

    1985-06-01

    Kalanchoe blossfeldiana plants grown under long days (16 h light) exhibit a C3-type photosynthetic metabolism. Switching to short days (9 h light) leads to a gradual development of Crassulacean acid metabolism (CAM). Under the latter conditions, dark CO2 fixation produces large amounts of malate. During the first hours of the day, malate is rapidly decarboxylated into pyruvate through the action of a cytosolic NADP(+)-or a mitochondrial NAD(+)-dependent malic enzyme. Mitochondria were isolated from leaves of plants grown under long days or after treatment by an increasing number of short days. Tricarboxylic acid cycle intermediates as well as exogenous NADH and NADPH were readily oxidized by mitochondria isolated from the two types of plants. Glycine, known to be oxidized by C3-plant mitochondria, was still oxidized after CAM establishment. The experiments showed a marked parallelism in the increase of CAM level and the increase in substrate-oxidation capacity of the isolated mitochondria, particularly the capacity to oxidize malate in the presence of cyanide. These simultaneous variations in CAM level and in mitochondrial properties indicate that the mitochondrial NAD(+)-malic enzyme could account at least for a part of the oxidation of malate. The studies of whole-leaf respiration establish that mitochondria are implicated in malate degradation in vivo. Moreover, an increase in cyanide resistance of the leaf respiration has been observed during the first daylight hours, when malate was oxidized to pyruvate by cytosolic and mitochondrial malic enzymes.

  4. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Science.gov (United States)

    Hutcheson, Rebecca; Rocic, Petra

    2012-01-01

    The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome. PMID:22829804

  5. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Directory of Open Access Journals (Sweden)

    Rebecca Hutcheson

    2012-01-01

    Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

  6. Urinary F2-Isoprostanes and Metabolic Markers of Fat Oxidation

    Directory of Open Access Journals (Sweden)

    Dora Il’yasova

    2015-01-01

    Full Text Available Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682. Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P < 0.05. For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs of incident diabetes are calculated from logistic regression models: the ORs (95% CI are 0.77 (0.60–0.97, 0.79 (0.62–1.01, 1.18 (0.92–1.53, and 0.51 (0.35–0.76 for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12 supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.

  7. Metabolic consequences of decreased nitric oxide synthesis in the hearth

    International Nuclear Information System (INIS)

    Pechanova, O.; Bernatova, I.; Pelouch, V.

    1998-01-01

    The aim of the present study was to determine long-term effect of NO-synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on concentrations of cyclic nucleotides, nucleic acids and of collagenous proteins in the left ventricle. Male Wistar rats were investigated. NO-synthase activity in the homogenates of left ventricle was determined by measuring the formation of 3 H]-L-citrulline from [ 3 H]-L-arginine. Cyclic GMP and cAMP concentrations were determined by using radioimmunoassay procedures and commercial cGMP and cAMP 125 I scintillation proximity assay systems.Significantly more remarkable decrease of NO-synthase activity was recorded in the group with higher dose (40 mg/kg/day) of L-NAME. The changes in metabolic parameters corresponded well with the dose-depend decrease of NO-synthase activity. (authors)

  8. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

    Science.gov (United States)

    Lee, Jieun; Wolfgang, Michael J

    2012-10-25

    Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  9. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jieun

    2012-10-01

    Full Text Available Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. Results In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT and CPT1c knockout (KO mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Conclusions Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  10. Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

    Science.gov (United States)

    Melnyk, Stepan; Fuchs, George J.; Schulz, Eldon; Lopez, Maya; Kahler, Stephen G.; Fussell, Jill J.; Bellando, Jayne; Pavliv, Oleksandra; Rose, Shannon; Seidel, Lisa; Gaylor, David W.

    2012-01-01

    Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism. PMID:21519954

  11. 14C-carbaril metabolism in soils modified by organic matter oxidation and addition of glucose

    International Nuclear Information System (INIS)

    Hirata, R.; Ruegg, E.F.

    1984-01-01

    Carbaril behaviour is studied in samples of Brunizen and Dark Red Latosol soils from Parana, using radiometric techniques, with the objective of determining the role of oxidation fo its organic components, and enrichment with glucose, in the metabolism of the insecticide. Lots of autoclaved soils, oxidized and with no previous treatment, with and without glucose addition, are incubated with 14 C-carbaril and analysed during eight weeks. Its was noted that, as a result of oxidation both soils showed a marked improvement in the metabolism of the agrochemical while addition of glucose exerted litlle influence on the degrading processes. Three metabolites were detected with R sub(f) 0.23, 0.40 and 0.70. (Author) [pt

  12. Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress.

    Science.gov (United States)

    Belba, Arben; Cortelazzo, Alessio; Andrea, Giansanti; Durante, Jacopo; Nigi, Laura; Dotta, Francesco; Timperio, Anna Maria; Zolla, Lello; Leoncini, Roberto; Guerranti, Roberto; Ponchietti, Roberto

    2016-01-01

    To test the hypothesis that exists an association of non-diabetic and diabetic patients suffering from erectile dysfunction (ED) with lipid metabolism and oxidative stress. Clinical and laboratory characteristics in non-diabetic (n = 30, middle age range: 41–55.5 years; n = 25, old age range: 55.5–73), diabetic ED patients (n = 30, age range: 55.5–75 years) and diabetic patients (n = 25, age range: 56–73.25), were investigated. Proteomic analysis was performed to identify differentially expressed plasma proteins and to evaluate their oxidative posttranslational modifications. A decreased level of high-density lipoproteins in all ED patients (P < 0.001, C.I. 0.046–0.10), was detected by routine laboratory tests. Proteomic analysis showed a significant decreased expression (P < 0.05) of 5 apolipoproteins (i.e. apolipoprotein H, apolipoprotein A4, apolipoprotein J, apolipoprotein E and apolipoprotein A1) and zinc-alpha-2-glycoprotein, 50% of which are more oxidized proteins. Exclusively for diabetic ED patients, oxidative posttranslational modifications for prealbumin, serum albumin, serum transferrin and haptoglobin markedly increased. Showing evidence for decreased expression of apolipoproteins in ED and the remarkable enhancement of oxidative posttranslational modifications in diabetes-associated ED, considering type 2 diabetes mellitus and age as independent risk factors involved in the ED pathogenesis, lipid metabolism and oxidative stress appear to exert a complex interplay in the disease.

  13. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

    International Nuclear Information System (INIS)

    Aw, Tak Yee

    2005-01-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium

  14. Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Diana Luque-Contreras

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

  15. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Full Text Available Objective: Plasma levels of branched-chain amino acids (BCAA are consistently elevated in obesity and type 2 diabetes (T2D and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

  16. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography

    International Nuclear Information System (INIS)

    Brown, M.A.; Myears, D.W.; Bergmann, S.R.

    1988-01-01

    Noninvasive quantification of regional myocardial metabolism would be highly desirable to evaluate pathogenetic mechanisms of heart disease and their response to therapy. It was previously demonstrated that the metabolism of radiolabeled acetate, a readily utilized myocardial substrate predominantly metabolized to carbon dioxide (CO2) by way of the tricarboxylic acid cycle, provides a good index of oxidative metabolism in isolated perfused rabbit hearts because of tight coupling between the tricarboxylic acid cycle and oxidative phosphorylation. In the present study, in a prelude to human studies, the relation between myocardial clearance of carbon-11 (11C)-labeled acetate and myocardial oxygen consumption was characterized in eight intact dogs using positron emission tomography. Anesthetized dogs were studied during baseline conditions and again during either high or low work states induced pharmacologically. High myocardial extraction and rapid blood clearance of tracer yielded myocardial images of excellent quality. The turnover (clearance) of 11C radioactivity from the myocardium was biexponential with the mean half-time of the dominant rapid phase averaging 5.4 +/- 2.2, 2.8 +/- 1.3 and 11.1 +/- 1.3 min in control, high and low work load studies, respectively. No significant difference was found between the rate of clearance of 11C radioactivity from the myocardium measured noninvasively with positron emission tomography and the myocardial efflux of 11CO2 measured directly from the coronary sinus. The rate of clearance of the 11C radioactivity from the heart correlated closely with myocardial oxygen consumption (r = 0.90, p less than 0.001) as well as with the rate-pressure product (r = 0.95, p less than 0.001). Hence, the rate of oxidation of 11C-acetate can be determined noninvasively with positron emission tomography, providing a quantitative index of oxidative metabolism under diverse conditions

  17. Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiological modeling approaches

    International Nuclear Information System (INIS)

    McMullin, Tami S.; Hanneman, William H.; Cranmer, Brian K.; Tessari, John D.; Andersen, Melvin E.

    2007-01-01

    Atrazine (ATRA) is metabolized by cytochrome P450s to the chlorinated metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1, 3, 5-triazine (ISO), and diaminochlorotriazine (DACT). Here, we develop a set of physiologically based pharmacokinetic (PBPK) models that describe the influence of oral absorption and oxidative metabolism on the blood time course curves of individual chlorotriazines (Cl-TRIs) in rat after oral dosing of ATRA. These models first incorporated in vitro metabolic parameters to describe time course plasma concentrations of DACT, ETHYL, and ISO after dosing with each compound. Parameters from each individual model were linked together into a final composite model in order to describe the time course of all 4 Cl-TRIs after ATRA dosing. Oral administration of ISO, ETHYL and ATRA produced double peaks of the compounds in plasma time courses that were described by multiple absorption phases from gut. An adequate description of the uptake and bioavailability of absorbed ATRA also required inclusion of additional oxidative metabolic clearance of ATRA to the mono-dealkylated metabolites occurring in GI a tract compartment. These complex processes regulating tissue dosimetry of atrazine and its chlorinated metabolites likely reflect limited compound solubility in the gut from dosing with an emulsion, and sequential absorption and metabolism along the GI tract at these high oral doses

  18. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  19. Unveiling the oxidative metabolism of Achatina fulica (Mollusca: Gastropoda) experimentally infected to Angiostrongylus cantonensis (Nematoda: Metastrongylidae).

    Science.gov (United States)

    Tunholi-Alves, Vinícius Menezes; Tunholi, Victor Menezes; Garcia, Juberlan; Mota, Esther Maria; Castro, Rosane Nora; Pontes, Emerson Guedes; Pinheiro, Jairo

    2018-06-01

    For the first time, alterations in the oxidative metabolism of Achatina fulica experimentally infected with different parasite loads of Angiostrongylus cantonensis were determined. For this, the hemolymph activities of lactate dehydrogenase (LDH) and hexokinase and the glucose concentrations in the hemolymph, as well as the polysaccharide reserves in the digestive gland and cephalopedal mass, were assessed. Additionally, the contents of some carboxylic acids in the hemolymph of infected and uninfected snails were determined by high-performance liquid chromatography (HPLC), permitting a better understanding of the alterations related to the host's oxidative metabolism. As the main results, activation of oxidative pathways, such as the glycolytic pathway, was demonstrated in response to the increase in the activity of hexokinase. This tendency was confirmed by the decrease in the contents of glucose in the hemolymph of parasitized snails, indicating that the infection by A. cantonensis alters the host's metabolism, and that these changes are strongly influenced by the parasite load. This metabolic scenario was accompanied by activation of the anaerobic fermentative metabolism, indicated not only by an increase in the activity of (LDH), but also by a reduction of the content of pyruvic acid and accumulation of lactic acid in the hemolymph of parasitized snails. In this circumstance, maintenance of the host's redox balance occurs through activation of the fermentative pathways, and LDH plays a central role in this process. Together, the results indicate that A. cantonensis infection induces activation of the anaerobic metabolism of A. fulica, characterized not only by the accumulation of lactic acid, but also by a reduction in the pyruvic acid and oxalic acid contents in the hemolymph of the infected snails.

  20. Oxidative metabolism of 5-o-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria.

    Science.gov (United States)

    dos Santos, Michel D; Martins, Patrícia R; dos Santos, Pierre A; Bortocan, Renato; Iamamoto, Y; Lopes, Norberto P

    2005-09-01

    Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research.

  1. Vascular affection in relation to oxidative DNA damage in metabolic syndrome.

    Science.gov (United States)

    Abd El Aziz, Rokayaa; Fawzy, Mary Wadie; Khalil, Noha; Abdel Atty, Sahar; Sabra, Zainab

    2018-02-01

    Obesity has become an important issue affecting both males and females. Obesity is now regarded as an independent risk factor for atherosclerosis-related diseases. Metabolic syndrome is associated with increased risk for development of cardiovascular disease. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentration has been used to express oxidation status. Twenty-seven obese patients with metabolic syndrome, 25 obese patients without metabolic syndrome and 31 healthy subjects were included in our study. They were subjected to full history and clinical examination; fasting blood sugar (FBS), 2 hour post prandial blood sugar (2HPP), lipid profile, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and carotid duplex, A/B index and tibial diameters were all assessed. There was a statistically significant difference ( p = 0.027) in diameter of the right anterior tibial artery among the studied groups, with decreased diameter of the right anterior tibial artery in obese patients with metabolic syndrome compared to those without metabolic syndrome; the ankle brachial index revealed a lower index in obese patients with metabolic syndrome compared to those without metabolic syndrome. There was a statistically insignificant difference ( p = 0.668) in the 8-oxodG in the studied groups. In obese patients with metabolic syndrome there was a positive correlation between 8-oxodG and total cholesterol and LDL. Urinary 8-oxodG is correlated to total cholesterol and LDL in obese patients with metabolic syndrome; signifying its role in the mechanism of dyslipidemia in those patients. Our study highlights the importance of anterior tibial artery diameter measurement and ankle brachial index as an early marker of atherosclerosis, and how it may be an earlier marker than carotid intima-media thickness.

  2. Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats.

    Science.gov (United States)

    Bartnik-Olson, Brenda L; Oyoyo, Udochukwu; Hovda, David A; Sutton, Richard L

    2010-12-01

    Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1. In contrast, enrichment of glutamine in astrocytes from acetate was not significantly decreased at day 1. At day 5 the ¹³C enrichment of glutamate and glutamine from glucose in the injured hemisphere of FPI rats did not differ from sham levels, but glutamine derived from acetate metabolism in astrocytes was significantly increased. The ¹³C glucose enrichment of the C3 position of glutamate (C3) in neurons was significantly decreased ipsilateral to FPI at day 14, whereas the enrichment of glutamine in astrocytes had returned to sham levels at this time point. These findings indicate that the oxidative metabolism of glucose is reduced to a greater extent in neurons compared to astrocytes following a FPI. The increased utilization of acetate to synthesize glutamine, and the acetate enrichment of glutamate via the glutamate-glutamine cycle, suggests an integral protective role for astrocytes in maintaining metabolic function following TBI-induced impairments in glucose metabolism.

  3. Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

    2011-01-21

    Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

  4. Role of NAD, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Musthafa Mohamed Essa

    2013-01-01

    Full Text Available Autism spectrum disorder (ASD is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD + , NADH, ATP, pyruvate, and lactate, are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD.

  5. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  6. Native T-1 reference values for nonischemic cardiomyopathies and populations with increased cardiovascular risk : A systematic review and meta-analysis

    NARCIS (Netherlands)

    van den Boomen, Maaike; Slart, Riemer H J A; Hulleman, Enzo V; Dierckx, Rudi A J O; Velthuis, Birgitta K; van der Harst, Pim; Sosnovik, David E; Borra, Ronald J H; Prakken, Niek H J

    BACKGROUND: Although cardiac MR and T1 mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T1 values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem

  7. Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet.

    Science.gov (United States)

    Auberval, Nathalie; Dal, Stéphanie; Bietiger, William; Pinget, Michel; Jeandidier, Nathalie; Maillard-Pedracini, Elisa; Schini-Kerth, Valérie; Sigrist, Séverine

    2014-01-01

    Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress. Metabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared to rats fed a normal diet (ND) for 2 months. Metabolic control was determined by measuring body weight, blood glucose, triglycerides, lipid peroxidation and protein carbonylation in plasma. Insulinemia was evaluated through the measure of C-peptide. Histological analysis was performed on the pancreas, liver and blood vessels. After 2 months, the HFD induced an increase in body weight, insulin and triglycerides. Liver steatosis was also observed in the HFD group, which was associated with an increase in glycogen storage. In the pancreas, the HFD induced islet hyperplasia. Tissue oxidative stress was also increased in the liver, pancreas and blood vessels, but plasma oxidative stress remained unchanged. This paper reports the development of a fast and easy model of rat metabolic syndrome associated with tissue oxidative stress. This model may be a good tool for the biological validation of drugs or antioxidants to limit or prevent the complications of metabolic syndrome.

  8. Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude

    DEFF Research Database (Denmark)

    Møller, Kirsten; Paulson, Olaf B; Hornbein, Thomas F.

    2002-01-01

    The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level....... At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery...... and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow...

  9. The role of oxidative stress on the pathophysiology of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fabiane Valentini Francisqueti

    Full Text Available Summary Metabolic syndrome (MetS has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

  10. Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

    Science.gov (United States)

    Sadek, Km; Saleh, Ea

    2014-12-01

    Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

  11. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  12. Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

    Directory of Open Access Journals (Sweden)

    Erich B Tahara

    Full Text Available Calorie restriction (CR is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0 S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0 cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

  13. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

    Directory of Open Access Journals (Sweden)

    Anne Abot

    2018-04-01

    Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

  14. Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase Is Not Sufficient to Promote Oxidative Metabolism*

    Science.gov (United States)

    Frederick, David W.; Davis, James G.; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A.; Nakamaru-Ogiso, Eiko; Baur, Joseph A.

    2015-01-01

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. PMID:25411251

  15. A novel strategy involved in [corrected] anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network.

    Directory of Open Access Journals (Sweden)

    Ranji Singh

    Full Text Available The reduced nicotinamide adenine dinucleotide phosphate (NADPH is pivotal to the cellular anti-oxidative defence strategies in most organisms. Although its production mediated by different enzyme systems has been relatively well-studied, metabolic networks dedicated to the biogenesis of NADPH have not been fully characterized. In this report, a metabolic pathway that promotes the conversion of reduced nicotinamide adenine dinucleotide (NADH, a pro-oxidant into NADPH has been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes such as pyruvate carboxylase (PC, malic enzyme (ME, malate dehydrogenase (MDH, malate synthase (MS, and isocitrate lyase (ICL that are involved in disparate metabolic modules, converged to create a metabolic network aimed at the transformation of NADH into NADPH. The downregulation of phosphoenol carboxykinase (PEPCK and the upregulation of pyruvate kinase (PK ensured that this metabolic cycle fixed NADH into NADPH to combat the oxidative stress triggered by the menadione insult. This is the first demonstration of a metabolic network invoked to generate NADPH from NADH, a process that may be very effective in combating oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant.

  16. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  17. The effect of ICD programming on inappropriate and appropriate ICD Therapies in ischemic and nonischemic cardiomyopathy: the MADIT-RIT trial.

    Science.gov (United States)

    Sedláček, Kamil; Ruwald, Anne-Christine; Kutyifa, Valentina; McNitt, Scott; Thomsen, Poul Erik Bloch; Klein, Helmut; Stockburger, Martin; Wichterle, Dan; Merkely, Bela; DE LA Concha, Joaquin Fernandez; Swissa, Moshe; Zareba, Wojciech; Moss, Arthur J; Kautzner, Josef; Ruwald, Martin H

    2015-04-01

    The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy. © 2014 Wiley Periodicals, Inc.

  18. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  19. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  20. Ivabradine Improves Heart Rate Variability in Patients with Nonischemic Dilated Cardiomyopathy

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    Ertugrul Kurtoglu

    2014-10-01

    Full Text Available Background: Ivabradine is a novel specific heart rate (HR-lowering agent that improves event-free survival in patients with heart failure (HF. Objectives: We aimed to evaluate the effect of ivabradine on time domain indices of heart rate variability (HRV in patients with HF. Methods: Forty-eight patients with compensated HF of nonischemic origin were included. Ivabradine treatment was initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter recording was obtained from each patient before and after 8 weeks of treatment with ivabradine. Results: The mean RR interval, standard deviation of all normal to normal RR intervals (SDNN, the standard deviation of 5-min mean RR intervals (SDANN, the mean of the standard deviation of all normal-to-normal RR intervals for all 5-min segments (SDNN index, the percentage of successive normal RR intervals exceeding 50 ms (pNN50, and the square root of the mean of the squares of the differences between successive normal to normal RR intervals (RMSSD were low at baseline before treatment with ivabradine. After 8 weeks of treatment with ivabradine, the mean HR (83.6 ± 8.0 and 64.6 ± 5.8, p < 0.0001, mean RR interval (713 ± 74 and 943 ± 101 ms, p < 0.0001, SDNN (56.2 ± 15.7 and 87.9 ± 19.4 ms, p < 0.0001, SDANN (49.5 ± 14.7 and 76.4 ± 19.5 ms, p < 0.0001, SDNN index (24.7 ± 8.8 and 38.3 ± 13.1 ms, p < 0.0001, pNN50 (2.4 ± 1.6 and 3.2 ± 2.2 %, p < 0.0001, and RMSSD (13.5 ± 4.6 and 17.8 ± 5.4 ms, p < 0.0001 substantially improved, which sustained during both when awake and while asleep. Conclusion: Our findings suggest that treatment with ivabradine improves HRV in nonischemic patients with HF.

  1. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

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    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  2. Multicenter Experience with Nonischemic Multiport Laparoscopic and Laparoendoscopic Single-Site Partial Nephrectomy Utilizing Bipolar Radiofrequency Ablation Coagulator

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    Wassim M. Bazzi

    2011-01-01

    Full Text Available Objective. To investigate feasibility of multiport and laparoendoscopic single-site (LESS nonischemic laparoscopic partial nephrectomy (NI-LPN utilizing bipolar radiofrequency coagulator. Methods. Multicenter retrospective review of 60 patients (46 multiport/14 LESS undergoing NI-LPN between 4/2006 and 9/2009. Multiport and LESS NI-LPN utilized Habib 4X bipolar radiofrequency coagulator to form a hemostatic zone followed by nonischemic tumor excision and renorrhaphy. Demographics, tumor/perioperative characteristics, and outcomes were analyzed. Results. 59/60 (98.3% successfully underwent NI-LPN. Mean tumor size was 2.35 cm. Mean operative time was 160.0 minutes. Mean estimated blood loss was 131.4 mL. Preoperative/postoperative creatinine (mg/dL was 1.02/1.07 (=.471. All had negative margins. 12 (20% patients developed complications. 3 (5% developed urine leaks. No differences between multiport and LESS-PN were noted as regards demographics, tumor size, outcomes, and complications. Conclusion. Initial experience demonstrates that nonischemic multiport and LESS-PN is safe and efficacious, with excellent short-term preservation of renal function. Long-term data are needed to confirm oncological efficacy.

  3. Role of ring oxidation in the metabolic activation of 1-nitropyrene.

    Science.gov (United States)

    Beland, F A

    1991-12-01

    Nitrated polycyclic aromatic hydrocarbons are wide-spread environmental pollutants that have been detected in photocopier toners, airborne particulates, coal fly ash, and diesel engine exhaust emissions. 1-Nitropyrene, a representative nitropolycyclic aromatic hydrocarbon present in diesel particulates, is a mutagen in Salmonella typhimurium and a tumorigen in laboratory animals. The activation of 1-nitropyrene to a bacterial mutagen has been attributed to nitroreduction; however, the metabolic pathways involved in its metabolism to a tumorigen are not known, but may involve nitroreduction, ring oxidation, or a combination of the two. In these experiments, we examined the importance of ring oxidation in the activation of 1-nitropyrene (99.85 to 99.98 percent 1-nitropyrene, 0.15 to 0.02 percent 1,3-, 1,6-, and 1,8-dinitropyrene by mass spectral analyses) to a mammalian-cell mutagen and carcinogen. Chinese hamster ovary cells were used to assess the mutagenicity of ring-oxidized 1-nitropyrene metabolites. In the absence of a rat liver 9,000 x g supernatant, 6-hydroxy-1-nitropyrene, 1-nitropyrene-9,10-oxide, and pyrene-4,5-oxide were the most mutagenic compounds tested. 3-Hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 1-nitropyrene-4,5-oxide were weaker mutagens, whereas pyrene and 1-nitropyrene were essentially nonmutagenic. The order of mutagenic potency with S9 was: 1-nitropyrene-4,5-oxide greater than 6-hydroxy-1-nitropyrene approximately 1-nitropyrene-9,10-oxide greater than 1-nitropyrene approximately 3-hydroxy-1-nitropyrene approximately 8-hydroxy-1-nitropyrene greater than pyrene approximately pyrene-4,5-oxide, with the last two compounds being nearly nonmutagenic. The epoxide hydrase inhibitor 1,2-epoxy-3,3,3-trichloropropane increased the mutation frequency fivefold. In addition, guinea pig liver microsomes and Aroclor-induced rat liver microsomes, which increased the formation of 1-nitropyrene-4,5-oxide and 1-nitropyrene-9,10-oxide, increased the

  4. Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.

    Science.gov (United States)

    Bañuls, C; Rovira-Llopis, S; Lopez-Domenech, S; Diaz-Morales, N; Blas-Garcia, A; Veses, S; Morillas, C; Victor, V M; Rocha, M; Hernandez-Mijares, A

    2017-10-01

    Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6). The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels. Our findings support the

  5. CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48.

    Science.gov (United States)

    Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

    2015-09-01

    Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.

  6. Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.

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    Sofi G Julien

    2017-02-01

    Full Text Available Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls, attenuates diet-induced obesity (DIO in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.

  7. Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance

    Science.gov (United States)

    This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baselin...

  8. The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism.

    Science.gov (United States)

    Cisternas, Pedro; Silva-Alvarez, Carmen; Martínez, Fernando; Fernandez, Emilio; Ferrada, Luciano; Oyarce, Karina; Salazar, Katterine; Bolaños, Juan P; Nualart, Francisco

    2014-05-01

    Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes. © 2014 International Society for Neurochemistry.

  9. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...... to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males....... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...

  10. Metatranscriptomic and metagenomic description of the bacterial nitrogen metabolism in waste water wet oxidation effluents

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    Julien Crovadore

    2017-10-01

    Full Text Available Anaerobic digestion is a common method for reducing the amount of sludge solids in used waters and enabling biogas production. The wet oxidation process (WOX improves anaerobic digestion by converting carbon into methane through oxidation of organic compounds. WOX produces effluents rich in ammonia, which must be removed to maintain the activity of methanogens. Ammonia removal from WOX could be biologically operated by aerobic granules. To this end, granulation experiments were conducted in 2 bioreactors containing an activated sludge (AS. For the first time, the dynamics of the microbial community structure and the expression levels of 7 enzymes of the nitrogen metabolism in such active microbial communities were followed in regard to time by metagenomics and metatranscriptomics. It was shown that bacterial communities adapt to the wet oxidation effluent by increasing the expression level of the nitrogen metabolism, suggesting that these biological activities could be a less costly alternative for the elimination of ammonia, resulting in a reduction of the use of chemicals and energy consumption in sewage plants. This study reached a strong sequencing depth (from 4.4 to 7.6 Gb and enlightened a yet unknown diversity of the microorganisms involved in the nitrogen pathway. Moreover, this approach revealed the abundance and expression levels of specialised enzymes involved in nitrification, denitrification, ammonification, dissimilatory nitrate reduction to ammonium (DNRA and nitrogen fixation processes in AS. Keywords: Applied sciences, Biological sciences, Environmental science, Genetics, Microbiology

  11. Hormonal enhancement of insecticide efficacy in Tribolium castaneum: oxidative stress and metabolic aspects.

    Science.gov (United States)

    Plavšin, Ivana; Stašková, Tereza; Šerý, Michal; Smýkal, Vlastimil; Hackenberger, Branimir K; Kodrík, Dalibor

    2015-04-01

    Insect anti-stress responses, including those induced by insecticides, are controlled by adipokinetic hormones (AKHs). We examined the physiological consequences of Pyrap-AKH application on Tribolium castaneum adults (AKH-normal and AKH-deficient prepared by the RNAi technique) treated by two insecticides, pirimiphos-methyl and deltamethrin. Co-application of pirimiphos-methyl and/or deltamethrin with AKH significantly increased beetle mortality compared with application of the insecticides alone. This co-treatment was accompanied by substantial stimulation of general metabolism, as monitored by carbon dioxide production. Further, the insecticide treatment alone affected some basic markers of oxidative stress: it lowered total antioxidative capacity as well as the activity of superoxide dismutase in the beetle body; in addition, it enhanced the activity of catalase and glutathione-S-transferase. However, these discrepancies in oxidative stress markers were eliminated/reduced by co-application with Pyrap-AKH. We suggest that the elevation of metabolism, which is probably accompanied with faster turnover of toxins, might be responsible for the higher mortality that results after AKH and insecticide co-application. Changes in oxidative stress markers are probably not included in the mechanisms responsible for increased mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation.

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-06-10

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.

  13. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

    2016-01-01

    , circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...... in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were...

  14. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

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    Javed K. Manesia

    2015-11-01

    Full Text Available Hematopoietic stem cells (HSCs in the fetal liver (FL unlike adult bone marrow (BM proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos and the citric acid cycle (TCA. We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (genotoxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

  15. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    International Nuclear Information System (INIS)

    Algotsson, L.; Messeter, K.; Rosen, I.; Holmin. T.

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo 2 ), and quantified electroencephalography (EEG) under two sets of conditions: 1) 1.7% end-tidal concentration of isoflurane in air/oxygen: 2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N 2 O)/oxygen. The object was to study the effects of N 2 O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N 2 O in the anaesthetic gas mixture caused a 43% (P 2 was not significantly altered by N 2 O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N 2 O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au)

  16. An unknown oxidative metabolism substantially contributes to soil CO2 emissions

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    T. Shahzad

    2013-02-01

    Full Text Available The respiratory release of CO2 from soils is a major determinant of the global carbon cycle. It is traditionally considered that this respiration is an intracellular metabolism consisting of complex biochemical reactions carried out by numerous enzymes and co-factors. Here we show that the endoenzymes released from dead organisms are stabilised in soils and have access to suitable substrates and co-factors to permit function. These enzymes reconstitute an extracellular oxidative metabolism (EXOMET that may substantially contribute to soil respiration (16 to 48% of CO2 released from soils in the present study. EXOMET and respiration from living organisms should be considered separately when studying effects of environmental factors on the C cycle because EXOMET shows specific properties such as resistance to high temperature and toxic compounds.

  17. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    Science.gov (United States)

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  18. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  19. Positron emission tomography with [11C]-acetate for evaluation of myocardial oxidative metabolism. Clinical use

    International Nuclear Information System (INIS)

    Litvinova, I.S.; Litvinov, M.M.; Rozhkova, G.G.; Leont'eva, I.V.; Sebeleva, I.A.; Tumanyan, M.R.; Koledinskij, D.G.; Sukhorukov, V.S.

    2001-01-01

    The diagnostic potentials of positron emission tomography (PET) with [ 11 C]-acetate as applied to mitochondrial disorders in children with cardiomyopathies (CMP) are evaluated. PET examinations are performed in 17 patients of the mean age of 7.5 ± 3.1 years with CMP. A dynamic study with [ 11 C]-acetate is conducted to evaluate the Krebs cycle activity. The experiments have indicated to a fewer accumulation of [ 11 C]-acetate and to its slower clearance in the ischemic zone as compared with the normal myocardium. The Krebs cycle activity has been reduced. By means of PET with [ 11 C]-acetate the oxidation rate constant of the Krebs cycle and the [ 11 C]-acetate-activity clearance half-time can be quantified. This makes possible to assess the extent of oxidative metabolism malfunction, including the case of perfusion reduction [ru

  20. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

    Science.gov (United States)

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

  1. High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

    Science.gov (United States)

    Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

    2014-05-01

    Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

  2. Nitric oxide metabolism and indole acetic acid biosynthesis cross-talk in Azospirillum brasilense SM.

    Science.gov (United States)

    Koul, Vatsala; Tripathi, Chandrakant; Adholeya, Alok; Kochar, Mandira

    2015-04-01

    Production of nitric oxide (NO) and the presence of NO metabolism genes, nitrous oxide reductase (nosZ), nitrous oxide reductase regulator (nosR) and nitric oxide reductase (norB) were identified in the plant-associated bacterium (PAB) Azospirillum brasilense SM. NO presence was confirmed in all overexpressing strains, while improvement in the plant growth response of these strains was mediated by increased NO and indole-3-acetic acid (IAA) levels in the strains. Electron microscopy showed random distribution to biofilm, with surface colonization of pleiomorphic Azospirilla. Quantitative IAA estimation highlighted a crucial role of nosR and norBC in regulating IAA biosynthesis. The NO quencher and donor reduced/blocked IAA biosynthesis by all strains, indicating their common regulatory role in IAA biosynthesis. Tryptophan (Trp) and l-Arginine (Arg) showed higher expression of NO genes tested, while in the case of ipdC, only Trp and IAA increased expression, while Arg had no significant effect. The highest nosR expression in SMnosR in the presence of IAA and Trp, along with its 2-fold IAA level, confirmed the relationship of nosR overexpression with Trp in increasing IAA. These results indicate a strong correlation between IAA and NO in A. brasilense SM and suggest the existence of cross-talk or shared signaling mechanisms in these two growth regulators. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. Simulation of the oxidative metabolism of diclofenac by electrochemistry/(liquid chromatography/)mass spectrometry.

    Science.gov (United States)

    Faber, Helene; Melles, Daniel; Brauckmann, Christine; Wehe, Christoph Alexander; Wentker, Kristina; Karst, Uwe

    2012-04-01

    Diclofenac is a frequently prescribed drug for rheumatic diseases and muscle pain. In rare cases, it may be associated with a severe hepatotoxicity. In literature, it is discussed whether this toxicity is related to the oxidative phase I metabolism, resulting in electrophilic quinone imines, which can subsequently react with nucleophiles present in the liver in form of glutathione or proteins. In this work, electrochemistry coupled to mass spectrometry is used as a tool for the simulation of the oxidative pathway of diclofenac. Using this purely instrumental approach, diclofenac was oxidized in a thin layer cell equipped with a boron doped diamond working electrode. Sum formulae of generated oxidation products were calculated based on accurate mass measurements with deviations below 2 ppm. Quinone imines from diclofenac were detected using this approach. It could be shown for the first time that these quinone imines do not react with glutathione exclusively but also with larger molecules such as the model protein β-lactoglobulin A. A tryptic digest of the generated drug-protein adduct confirms that the protein is modified at the only free thiol-containing peptide. This simple and purely instrumental set-up offers the possibility of generating reactive metabolites of diclofenac and to assess their reactivity rapidly and easily.

  4. Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.

    Science.gov (United States)

    Bhattacharyya, Sudip; Sinha, Krishnendu; Sil, Parames C

    2014-01-01

    Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches. CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible. Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity. Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.

  5. Discrimination of acute ischemic stroke from nonischemic vertigo in patients presenting with only imbalance.

    Science.gov (United States)

    Honda, Shoji; Inatomi, Yuichiro; Yonehara, Toshiro; Hashimoto, Yoichiro; Hirano, Teruyuki; Ando, Yukio; Uchino, Makoto

    2014-01-01

    Some patients who present with an acute feeling of imbalance are experiencing an ischemic stroke that is not evident on computed tomography (CT) scans. The aim of this study was to compare ischemic stroke and nonischemic vertigo patient groups and to investigate independent factors associated with ischemic stroke. We examined 332 consecutive patients with an acute feeling of imbalance who showed no neurologic findings or responsible lesions on CT scan at the hyperacute phase. We examined their clinical backgrounds, physical findings, and laboratory examinations, with ischemic stroke diagnosed by later CT and/or magnetic resonance imaging (MRI). We identified 41 (12.3%) ischemic stroke patients. Atrial fibrillation (odds ratio 4.1; 95% confidence interval 1.4-11.5), white blood cell count (10(3)/μL, 1.4; 1.2-1.6), head and/or neck pain (4.6; 2.1-10.3), first attack of imbalance feeling (3.3; 1.1-12.2), and dizziness (3.7; 1.7-8.3) were significant and independent factors associated with ischemic stroke among patients with an acute feeling of imbalance. We used these factors to calculate an "imbalance score"; 1 point was given for the presence of each factor and a score of 3-5 points was independently associated with ischemic stroke. An awareness of these factors may indicate that further examinations including MRI are necessary to rule out ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. The Impact of Rapid Weight Loss on Oxidative Stress Markers and the Expression of the Metabolic Syndrome in Obese Individuals

    Directory of Open Access Journals (Sweden)

    Eva Tumova

    2013-01-01

    Full Text Available Objective. Obesity is linked with a state of increased oxidative stress, which plays an important role in the etiology of atherosclerosis and type 2 diabetes mellitus. The aim of our study was to evaluate the effect of rapid weight loss on oxidative stress markers in obese individuals with metabolic syndrome (MetS. Design and Methods. We measured oxidative stress markers in 40 obese subjects with metabolic syndrome (MetS+, 40 obese subjects without metabolic syndrome (MetS−, and 20 lean controls (LC at baseline and after three months of very low caloric diet. Results. Oxidized low density lipoprotein (ox-LDL levels decreased by 12% in MetS+ subjects, associated with a reduction in total cholesterol (TC, even after adjustment for age and sex. Lipoprotein associated phospholipase A2 (Lp-PLA2 activity decreased by 4.7% in MetS+ subjects, associated with a drop in LDL-cholesterol (LDL-C, TC, and insulin levels. Multivariate logistic regression analysis showed that a model including ox-LDL, LpPLA2 activity, and myeloperoxidase (MPO improved prediction of MetS status among obese individuals compared to each oxidative stress marker alone. Conclusions. Oxidative stress markers were predictive of MetS in obese subjects, suggesting a higher oxidative stress. Rapid weight loss resulted in a decline in oxidative stress markers, especially in MetS+ patients.

  7. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

    Science.gov (United States)

    Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

    2017-11-01

    Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

  8. Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS.

    Science.gov (United States)

    Bañuls, Celia; Rovira-Llopis, Susana; Martinez de Marañon, Aranzazu; Veses, Silvia; Jover, Ana; Gomez, Marcelino; Rocha, Milagros; Hernandez-Mijares, Antonio; Victor, Victor M

    2017-06-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined. Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (pPCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (pPCOS and PCOS+MetS groups vs their respective controls (pPCOS groups (pPCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (pPCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; pPCOS, all of which are related to vascular complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Scar Homogenization Versus Limited-Substrate Ablation in Patients With Nonischemic Cardiomyopathy and Ventricular Tachycardia.

    Science.gov (United States)

    Gökoğlan, Yalçın; Mohanty, Sanghamitra; Gianni, Carola; Santangeli, Pasquale; Trivedi, Chintan; Güneş, Mahmut F; Bai, Rong; Al-Ahmad, Amin; Gallinghouse, G Joseph; Horton, Rodney; Hranitzky, Patrick M; Sanchez, Javier E; Beheiry, Salwa; Hongo, Richard; Lakkireddy, Dhanunjaya; Reddy, Madhu; Schweikert, Robert A; Dello Russo, Antonio; Casella, Michela; Tondo, Claudio; Burkhardt, J David; Themistoclakis, Sakis; Di Biase, Luigi; Natale, Andrea

    2016-11-01

    Scar homogenization improves long-term ventricular arrhythmia-free survival compared with standard limited-substrate ablation in patients with post-infarction ventricular tachycardia (VT). Whether such benefit extends to patients with nonischemic cardiomyopathy and scar-related VT is unclear. The aim of this study was to assess the long-term efficacy of an endoepicardial scar homogenization approach compared with standard ablation in this population. Consecutive patients with dilated nonischemic cardiomyopathy (n = 93), scar-related VTs, and evidence of low-voltage regions on the basis of pre-defined criteria on electroanatomic mapping (i.e., bipolar voltage homogenization and standard ablation, respectively (p = 0.01). During a mean follow-up period of 14 ± 2 months, single-procedure success rates were 63.9% after scar homogenization and 38.6% after standard ablation (p = 0.031). After multivariate analysis, scar homogenization and left ventricular ejection fraction were predictors of long-term success. During follow-up, the rehospitalization rate was significantly lower in the scar homogenization group (p = 0.035). In patients with dilated nonischemic cardiomyopathy, scar-related VT, and evidence of low-voltage regions on electroanatomic mapping, endoepicardial homogenization of the scar significantly increased freedom from any recurrent ventricular arrhythmia compared with a standard limited-substrate ablation. However, the success rate with this approach appeared to be lower than previously reported with ischemic cardiomyopathy, presumably because of the septal and midmyocardial distribution of the scar in some patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Metabolic engineering of β-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.

    Science.gov (United States)

    Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

    2012-07-01

    Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. A role for PPARα in the regulation of arginine metabolism and nitric oxide synthesis.

    Science.gov (United States)

    Guelzim, Najoua; Mariotti, François; Martin, Pascal G P; Lasserre, Frédéric; Pineau, Thierry; Hermier, Dominique

    2011-10-01

    The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets containing either saturated fatty acids (COCO diet) or 18:3 n-3 (LIN diet). Metabolic markers of arginine metabolism were assayed in urine and plasma. mRNA levels of arginases and NOS were determined in liver. Whole-body NO synthesis and the conversion of systemic arginine into urea were assessed by using (15)N(2)-guanido-arginine and measuring urinary (15)NO(3) and [(15)N]-urea. PPARα deficiency resulted in a markedly lower whole-body NO synthesis, whereas the conversion of systemic arginine into urea remained unaffected. PPARα deficiency also increased plasma arginine and decreased citrulline concentration in plasma. These changes could not be ascribed to a direct effect on hepatic target genes, since NOS mRNA levels were unaffected, and arginase mRNA levels decreased in KO mice. Despite the low level in the diet, the nature of the fatty acids modulated some effects of PPARα deficiency, including plasma arginine and urea, which increased more in KO mice fed the LIN diet than in those fed the COCO diet. In conclusion, PPARα is largely involved in normal whole-body NO synthesis. This warrants further study on the potential of PPARα activation to maintain NO synthesis in the initiation of the metabolic syndrome.

  13. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  14. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  15. The effect of increasing body mass index on cardio-metabolic risk and biomarkers of oxidative stress and inflammation in nascent metabolic syndrome.

    Science.gov (United States)

    Pahwa, Roma; Adams-Huet, Beverley; Jialal, Ishwarlal

    2017-05-01

    The effect of BMI defined obesity on cardio-metabolic features and biomarkers of oxidative stress and inflammation in patients with nascent metabolic Syndrome (MetS) is poorly defined. Hence the aim of this study was to examine the effect of increasing obesity on the cardio metabolic risk profile, pro-oxidant state and pro-inflammatory features in nascent MetS patients without Diabetes or CVD. MetS was diagnosed by ATPIII criteria using waist circumference (WC) as the measure of adiposity. Patients (n=58) were stratified into overweight, obese and extreme obesity groups using BMI cut offs of 25-29.9, 30-39.9kg/m 2 and ≥40kg/m 2 and cardio-metabolic features, circulating and cellular biomarkers of oxidative stress and inflammation were determined and correlated with BMI. None of the main cardio-metabolic features including blood pressure, blood glucose, HDL-cholesterol, triglycerides, HOMA-IR, free fatty acids were increased with increasing BMI. Also none of the biomarkers of oxidative stress (ox-LDL, nitrotyrosine and monocyte superoxide anion release) were increased with increasing BMI. However, significant increase in hsCRP, the soluble TNFR1 and sTNFR2 and leptin, were observed with increasing adiposity. Other inflammatory bio-mediators (IL-1β, IL-6, IL-8, MCP-1, Toll-like receptors 2-4), endotoxin, LBP, sCD14 and HMGB1, adiponectin, and chemerin did not show significant increases with increasing BMI. Leptin, hsCRP, sTNFR1, and sTNFR2 correlated significantly with BMI. In conclusion, capturing the cardio-metabolic cluster of MetS that predisposed to both increased risk of diabetes and CVD, using waist circumference, as one of the 5 diagnostic criteria is sufficient and BMI does not appear to afford any major incremental benefit on the cardio-metabolic risk factors, increased oxidative stress and the majority of both cellular and circulating biomarkers of inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P Hibiscus extract. Overall, aqueous extract of H. sabdariffa palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  17. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  18. Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.

    Science.gov (United States)

    Sil, Rajarshi; Chakraborti, Abhay Sankar

    2016-09-01

    Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    International Nuclear Information System (INIS)

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  20. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Energy Technology Data Exchange (ETDEWEB)

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  1. Exposure to lead in water and cysteine non-oxidative metabolism in Pelophylax ridibundus tissues

    International Nuclear Information System (INIS)

    Kaczor, Marta; Sura, Piotr; Bronowicka-Adamska, Patrycja; Wróbel, Maria

    2013-01-01

    Chronic, low-level exposure to metals is an increasing global problem. Lead is an environmentally persistent toxin that causes many lead-related pathologies, directly affects tissues and cellular components or exerts an effect of the generation of reactive oxygen species causing a diminished level of available sulfhydryl antioxidant reserves. Cysteine is one of substrates in the synthesis of glutathione – the most important cellular antioxidant, and it may also undergo non-oxidative desulfuration that produces compounds containing sulfane sulfur atoms. The aim of the experiment was to examine changes of the non-oxidative metabolism of cysteine and the levels of cysteine and glutathione in the kidneys, heart, brain, liver and muscle of Marsh frogs (Pelophylax ridibundus) exposed to 28 mg/L Pb(NO 3 ) 2 for 10 days. The activities of sulfurtransferases, enzymes related to the sulfane sulfur metabolism – 3-mercaptopyruvate sulfurtransfearse, γ-cystathionase and rhodanese – were detected in tissue homogenates. The activity of sulfurtransferases was much higher in the kidneys of frogs exposed to lead in comparison to control frogs, not exposed to lead. The level of sulfane sulfur remained unchanged. Similarly, the total level of cysteine did not change significantly. The total levels of glutathione and the cysteine/cystine and GSH/GSSG ratios were elevated. Thus, it seems that the exposure to lead intensified the metabolism of sulfane sulfur and glutathione synthesis in the kidneys. The results presented in this work not only confirm the participation of GSH in the detoxification of lead ions and/or products appearing in response to their presence, such as reactive oxygen species, but also indicate the involvement of sulfane sulfur and rhodanese in this process (e.g. brain). As long as the expression of enzymatic proteins (rhodanese, MPST and CST) is not examined, no answer will be provided to the question whether changes in their activity are due to differences

  2. Exposure to lead in water and cysteine non-oxidative metabolism in Pelophylax ridibundus tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kaczor, Marta [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Sura, Piotr [Department of Human Developmental Biology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Bronowicka-Adamska, Patrycja [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Wrobel, Maria, E-mail: mbwrobel@cyf-kr.edu.pl [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland)

    2013-02-15

    Chronic, low-level exposure to metals is an increasing global problem. Lead is an environmentally persistent toxin that causes many lead-related pathologies, directly affects tissues and cellular components or exerts an effect of the generation of reactive oxygen species causing a diminished level of available sulfhydryl antioxidant reserves. Cysteine is one of substrates in the synthesis of glutathione - the most important cellular antioxidant, and it may also undergo non-oxidative desulfuration that produces compounds containing sulfane sulfur atoms. The aim of the experiment was to examine changes of the non-oxidative metabolism of cysteine and the levels of cysteine and glutathione in the kidneys, heart, brain, liver and muscle of Marsh frogs (Pelophylax ridibundus) exposed to 28 mg/L Pb(NO{sub 3}){sub 2} for 10 days. The activities of sulfurtransferases, enzymes related to the sulfane sulfur metabolism - 3-mercaptopyruvate sulfurtransfearse, {gamma}-cystathionase and rhodanese - were detected in tissue homogenates. The activity of sulfurtransferases was much higher in the kidneys of frogs exposed to lead in comparison to control frogs, not exposed to lead. The level of sulfane sulfur remained unchanged. Similarly, the total level of cysteine did not change significantly. The total levels of glutathione and the cysteine/cystine and GSH/GSSG ratios were elevated. Thus, it seems that the exposure to lead intensified the metabolism of sulfane sulfur and glutathione synthesis in the kidneys. The results presented in this work not only confirm the participation of GSH in the detoxification of lead ions and/or products appearing in response to their presence, such as reactive oxygen species, but also indicate the involvement of sulfane sulfur and rhodanese in this process (e.g. brain). As long as the expression of enzymatic proteins (rhodanese, MPST and CST) is not examined, no answer will be provided to the question whether changes in their activity are due to

  3. Correlation between right ventricular T1 mapping and right ventricular dysfunction in non-ischemic cardiomyopathy.

    Science.gov (United States)

    Jellis, Christine L; Yingchoncharoen, Teerapat; Gai, Neville; Kusunose, Kenya; Popović, Zoran B; Flamm, Scott; Kwon, Deborah

    2018-01-01

    Right ventricular (RV) fibrosis is increasingly recognized as the underlying pathological substrate in a variety of clinical conditions. We sought to employ cardiac magnetic resonance (CMR) techniques of strain imaging and longitudinal relaxation time (T 1 ) mapping to better examine the relationship between RV function and structure. Our aim was to initially evaluate the feasibility of these techniques to evaluate the right ventricle. We then sought to explore the relationship between RV function and underlying fibrosis, along with examining the evolution of RV remodeling according to the amount of baseline fibrosis. Echocardiography was performed in 102 subjects with non-ischemic cardiomyopathy. Right ventricular parameters were assessed including: fractional area change (FAC) and longitudinal strain. The same cohort underwent CMR. Post-contrast T 1 mapping was performed as a marker of fibrosis with a Look-Locker technique using inversion recovery imaging. Mid-ventricular post-contrast T 1 values of the RV free wall, RV septum and lateral LV were calculated using prototype analysis software. Biventricular volumetric data including ejection fraction was measured by CMR using a cine short axis stack. CMR strain analysis was also performed to assess 2D RV longitudinal and radial strain. Simultaneous biochemical and anthropometric data were recorded. Subjects were followed over a median time of 29 months (IQR 20-37 months) with echocardiography to evaluate temporal change in RV FAC according to baseline post-contrast T 1 values. Longitudinal data analysis was performed to adjust for patient loss during follow-up. Subjects (62% men, 51 ± 15 years) had mild to moderately impaired global RV systolic function (RVEF = 39 ± 15%; RVEDV = 187 ± 69 ml; RVESV = 119 ± 68 ml) and moderate left ventricular dysfunction at baseline (LVEF 30 ± 17%). Good correlation was observed between mean LV and RV post-contrast T 1 values (r = 0.652, p

  4. Anesthesia with halothane and nitrous oxide alters protein and amino acid metabolism in dogs

    International Nuclear Information System (INIS)

    Horber, F.F.; Krayer, S.; Rehder, K.; Haymond, M.W.

    1988-01-01

    General anesthesia in combination with surgery is known to result in negative nitrogen balance. To determine whether general anesthesia without concomitant surgery decreases whole body protein synthesis and/or increases whole body protein breakdown, two groups of dogs were studied: Group 1 (n = 6) in the conscious state and Group 2 (n = 8) during general anesthesia employing halothane (1.5 MAC) in 50% nitrous oxide and oxygen. Changes in protein metabolism were estimated by isotope dilution techniques employing simultaneous infusions of [4,53H]leucine and alpha-[1-14C]-ketoisocaproate (KIC). Total leucine carbon flux was unchanged or slightly increased in the anesthetized animals when compared to the conscious controls, indicating only a slight increase in the rate of proteolysis. However, leucine oxidation was increased (P less than 0.001) by more than 80% in the anesthetized animals when compared with their conscious controls, whereas whole body nonoxidative leucine disappearance, an indicator of whole body protein synthesis, was decreased. The ratio of leucine oxidation to the nonoxidative rate of leucine disappearance, which provides an index of the catabolism of at least one essential amino acid in the postabsorptive state, was more than twofold increased (P less than 0.001) in the anesthetized animals regardless of the tracer employed. These studies suggest that the administration of anesthesia alone, without concomitant surgery, is associated with a decreased rate of whole body protein synthesis and increased leucine oxidation, resulting in increased leucine and protein catabolism, which may be underlying or initiating some of the protein wasting known to occur in patients undergoing surgery

  5. Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Bacterial response to nitric oxide (NO is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR, and NnrR; two-component systems NarXL and NarQP; NO-responsive activator NorR; and nitrite-sensitive repressor NsrR. Using comparative genomics approaches, we predict DNA-binding motifs for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA recognition motif. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria, including Clostridia, Thermotogales, and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides' metabolism, not only in most gamma- and beta-proteobacteria (including well-studied species such as Escherichia coli, but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding motif. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon also includes two nitrite-responsive loci, nipAB (hcp-hcr and nipC (dnrN, thus confirming the identity of the effector, i.e. nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include

  6. Dissimilatory Metabolism of Nitrogen Oxides in Bacteria:Comparative Reconstruction of Transcriptional Networks

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A.; Dubchak, Inna L.; Arkin, Adam P.; Alm, EricJ.; Gelfand, Mikhail S.

    2005-09-01

    Bacterial response to nitric oxide (NO) is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR and NnrR, two-component systems NarXL and NarQP, NO-responsive activator NorR, and nitrite sensitive repressor NsrR. Using comparative genomics approaches we predict DNA-binding signals for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA signal. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria including Clostridia, Thermotogales and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides metabolism not only in most gamma- and beta-proteobacteria (including well-studied species like Escherichia coli), but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding signal. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon includes also two nitrite-responsive loci, nipAB (hcp-hcr) and nipC(dnrN), thus confirming the identity of the effector, i.e., nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include denitrification genes. As the

  7. ROLE OF POTASSIUM IN THE OXIDATIVE METABOLISM OF MICROCOCCUS SODONENSIS1

    Science.gov (United States)

    Perry, Jerome J.; Evans, James B.

    1961-01-01

    Perry, Jerome J. (The University of Chicago, Chicago, Ill.), and James B. Evans. Role of potassium in the oxidative metabolism of Micrococcus sodonensis. J. Bacteriol. 82:551–555. 1961.—An absolute potassium requirement has been established for the growth of Micrococcus sodonensis with lactate or pyruvate as substrate. Potassium at 0.67 × 10−2m concentration was necessary for maximal growth. Resting cell and cell-free preparations from cells grown on minimal levels of potassium were stimulated by potassium but, due to residual or bound cation, did not show an absolute requirement. Rubidium and cesium replaced potassium in these cells although cesium is much less effective. PMID:14485577

  8. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    Science.gov (United States)

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver. © 2016 Poultry Science Association Inc.

  9. Imitation of phase I oxidative metabolism of anabolic steroids by titanium dioxide photocatalysis.

    Science.gov (United States)

    Ruokolainen, Miina; Valkonen, Minna; Sikanen, Tiina; Kotiaho, Tapio; Kostiainen, Risto

    2014-12-18

    The aim of this study was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for oxidation of anabolic steroids and for imitation of their phase I metabolism. The photocatalytic reaction products of five anabolic steroids were compared to their phase I in vitro metabolites produced by human liver microsomes (HLM). The same main reaction types - hydroxylation, dehydrogenation and combination of these two - were observed both in TiO2 photocatalysis and in microsomal incubations. Several isomers of each product type were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO2 photocatalytic reactions. However, products characteristic to only either one of the systems were also formed. In conclusion, TiO2 photocatalysis is a rapid, simple and inexpensive method for imitation of phase I metabolism of anabolic steroids and production of metabolite standards. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Energy Technology Data Exchange (ETDEWEB)

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  11. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  12. Oxidative Stress and Metabolic Perturbations in Wooden Breast Disorder in Chickens.

    Directory of Open Access Journals (Sweden)

    Behnam Abasht

    Full Text Available This study was conducted to characterize metabolic features of the breast muscle (pectoralis major in chickens affected with the Wooden Breast myopathy. Live birds from two purebred chicken lines and one crossbred commercial broiler population were clinically examined by manual palpation of the breast muscle (pectoralis major at 47-48 days of age. Metabolite abundance was determined by gas chromatography/mass spectrometry (GC/MS and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS using breast muscle tissue samples from 16 affected and 16 unaffected chickens. Muscle glycogen content was also quantified in breast muscle tissue samples from affected and unaffected chickens. In total, levels of 140 biochemicals were significantly different (FDR1.3 or <0.77 between affected and unaffected chickens. Glycogen content measurements were considerably lower (1.7-fold in samples taken from Wooden Breast affected birds when compared with samples from unaffected birds. Affected tissues exhibited biomarkers related to increased oxidative stress, elevated protein levels, muscle degradation, and altered glucose utilization. Affected muscle also showed elevated levels of hypoxanthine, xanthine, and urate molecules, the generation of which can contribute to altered redox homeostasis. In conclusion, our findings show that Wooden Breast affected tissues possess a unique metabolic signature. This unique profile may identify candidate biomarkers for diagnostic utilization and provide mechanistic insight into altered biochemical processes contributing to tissue hardening associated with the Wooden Breast myopathy in commercial chickens.

  13. Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.

    Science.gov (United States)

    Scheit, Katrin; Bauer, Georg

    2014-10-01

    Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Poungrat Pakdeechote

    2014-01-01

    Full Text Available Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS induced by a high-carbohydrate, high-fat (HCHF diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α levels (p < 0.05. Plasma nitrate and nitrite (NOx were markedly high with upregulation of inducible nitric oxide synthase (iNOS expression, but dowregulation of endothelial nitric oxide synthase (eNOS expression (p < 0.05. Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05. In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  15. Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

    Science.gov (United States)

    Max, S. R.; Rance, N.

    1983-01-01

    The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

  16. Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

    Science.gov (United States)

    Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

  17. Association of Inflammatory and Oxidative Stress Markers with Metabolic Syndrome in Asian Indians in India

    Directory of Open Access Journals (Sweden)

    Veena S. Rao

    2011-01-01

    Full Text Available Metabolic syndrome (MetS is a primary risk factor for cardiovascular disease and is associated with a proinflammatory state. Here, we assessed the contribution of inflammatory and oxidative stress markers towards prediction of MetS. A total of 2316 individuals were recruited in Phase I of the Indian Atherosclerosis Research Study (IARS. Modified ATPIII guidelines were used for classification of subjects with MetS. Among the inflammatory and oxidative stress markers studied, levels of hsCRP (P<.0001, Neopterin (P=.036, and oxLDL (P<.0001 were significantly higher among subjects with MetS. Among the markers we tested, oxLDL stood out as a robust predictor of MetS in the IARS population (OR 4.956 95% CI 2.504–9.810; P<.0001 followed by hsCRP (OR 1.324 95% CI 1.070–1.638; P=.010. In conclusion, oxLDL is a candidate predictor for MetS in the Asian Indian population.

  18. Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Eunice Molinar-Toribio

    Full Text Available SHROB rats have been suggested as a model for metabolic syndrome (MetS as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA or proteins (carbonylation. We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.

  19. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Directory of Open Access Journals (Sweden)

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  20. Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.

    Science.gov (United States)

    Christenson, Stuart D; Chareonthaitawee, Panithaya; Burnes, John E; Hill, Michael R S; Kemp, Brad J; Khandheria, Bijoy K; Hayes, David L; Gibbons, Raymond J

    2008-02-01

    Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.

  1. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

    NARCIS (Netherlands)

    Bakker, G.C.M.; Erk, M.J. van; Pellis, L.; Wopereis, S.; Rubingh, C.M.; Cnubben, N.H.P.; Kooistra, T.; Ommen, B. van; Hendriks, H.F.J.

    2010-01-01

    Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products

  2. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

    NARCIS (Netherlands)

    Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

    2012-01-01

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+)

  3. Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians

    DEFF Research Database (Denmark)

    Skjelbo, E; Mutabingwa, T K; Bygbjerg, Ib Christian

    1996-01-01

    S-Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 tanzanians. The mephenytoin S/R ratio in urine ranged from 0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation b...

  4. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  5. Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

    Science.gov (United States)

    Mancini, Antonio; Martorana, Giuseppe Ettore; Magini, Marinella; Festa, Roberto; Raimondo, Sebastiano; Silvestrini, Andrea; Nicolotti, Nicola; Mordente, Alvaro; Mele, Maria Cristina; Miggiano, Giacinto Abele Donato; Meucci, Elisabetta

    2015-04-01

    Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m 2 ), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H 2 O 2 -metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated

  6. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Directory of Open Access Journals (Sweden)

    Elizabeth Moreno-Arriola

    2014-01-01

    Full Text Available Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

  7. The nucleic acid metabolism in rat liver after single and long-term administration of tritium oxide

    International Nuclear Information System (INIS)

    Shorokhova, V.B.

    1984-01-01

    It was shown that after a single administration of tritiUm oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesjs rate increased dUring a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleac acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months)

  8. A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

    Science.gov (United States)

    Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

    2011-01-01

    The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

  9. Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronisation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, Juhani; Naum, Alexandru; Stolen, Kira Q.; Kalliokoski, Riikka [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Sundell, Jan [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Engblom, Erik; Koistinen, Juhani; Airaksinen, K.E. Juhani [University of Turku, Department of Medicine, Turku (Finland); Ylitalo, Antti [Satakunta Central Hospital, Department of Medicine, Pori (Finland); Nekolla, Stephan G. [Klinikum rechts der Isar der Technischen Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Bax, K.E. Jeroen J. [Leiden University, Department of Cardiology, Leiden (Netherlands)

    2004-12-01

    Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronisation therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8{+-}5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [{sup 11}C]acetate positron emission tomography (K{sub mono}). The measurements were performed at rest and during dobutamine-induced stress (5 {mu}g/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. CRT had no effect on RV K{sub mono} at rest (ON: 0.052{+-}0.014, OFF: 0.047{+-}0.018, NS). Dobutamine-induced stress increased RV K{sub mono} significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076{+-}0.026 vs 0.065{+-}0.027, p=0.003). CRT shortened interventricular delay significantly (45{+-}33 vs 19{+-}35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV K{sub mono} and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV K{sub mono} with CRT OFF was significantly lower

  10. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II-oxidizer

    Directory of Open Access Journals (Sweden)

    Jennyfer eMIOT

    2015-09-01

    Full Text Available Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is however thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had however never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry (NanoSIMS. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidences of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasm encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a strategy of survival in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern

  11. Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

    Science.gov (United States)

    Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

    2017-11-01

    Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  12. Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

    Science.gov (United States)

    Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

    2011-01-01

    Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

  13. Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

    Directory of Open Access Journals (Sweden)

    Jiwon Kim

    Full Text Available Non-ischemic fibrosis (NIF on cardiac magnetic resonance (CMR has been linked to poor prognosis, but its association with adverse right ventricular (RV remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.The population comprised patients with RV dysfunction (EF 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001.Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

  14. Short communication: Characterizing metabolic and oxidant status of pastured dairy cows postpartum in an automatic milking system.

    Science.gov (United States)

    Elischer, M F; Sordillo, L M; Siegford, J M; Karcher, E L

    2015-10-01

    The periparturient period represents a stressful time for dairy cows as they transition from late gestation to early lactation. Undesirable fluctuations in metabolites and impaired immune defense mechanisms near parturition can severely affect cow health and have residual effects on performance and longevity. Metabolic and oxidative stress profiles of multiparous and primiparous dairy cows in traditional parlor and feeding systems are well characterized, but status of these profiles in alternative management systems, such as grazing cows managed with an automatic milking system (AMS), are poorly characterized. Therefore, the objective of this case study was to characterize the metabolic and oxidant status of pastured cows milked with an AMS. It was hypothesized that primiparous and multiparous cows milked with an AMS would experience changes in oxidative and metabolic status after parturition; however, these changes would not impair cow health or production. Blood was collected from 14 multiparous and 8 primiparous Friesian-cross dairy cows at 1, 7, 14, and 21 d relative to calving for concentrations of insulin, glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate, reduced glutathione, oxidized glutathione, and antioxidant potential. Milk production and milking frequency data were collected postpartum. Milk production differed on d 7 and 14 between primiparous and multiparous cows and frequency was not affected by parity. Primiparous cows had higher levels of glucose than multiparous cows. No differences in insulin, NEFA, or β-hydroxybutyrate concentrations were noted between multiparous and primiparous cows postpartum, though days relative to calving significantly affected insulin and NEFA. Primiparous cows also had higher antioxidant potential than multiparous cows during the postpartum period. Results from this study show that, although responses were within expected ranges, periparturient multiparous cows responded differently than periparturient

  15. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes.

    Science.gov (United States)

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano; Corrado, Domenico

    2016-07-01

    The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. We compared 35 athletes (80% men, age: 14-48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. © 2016 The Authors.

  16. Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

    Science.gov (United States)

    Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

    2014-02-01

    The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig.

    Science.gov (United States)

    Witkamp, R F; Nijmeijer, S M; Csikó, G; van Miert, A S

    1994-08-01

    The simultaneous use of the antibiotic tiamulin with certain ionophoric antibiotics (monensin, salinomycin) may give rise to a toxic interaction in pigs and poultry. In the present study, effects of tiamulin on hepatic cytochrome P450 activities in vitro were studied using pig liver microsomes. When tiamulin was added to the incubation medium the N-demethylation rate of ethylmorphine and the hydroxylation of testosterone at the 6 beta- and 11 alpha-positions was strongly inhibited. Tiamulin inhibited these activities more than SKF525A or cimetidine, but less than ketoconazole. The microsomal N-demethylation rate of erythromycin and the hydroxylation of testosterone at the 2 beta-position were inhibited to a lesser degree, whereas the ethoxyresorufin-O-deethylation, aniline hydroxylation and testosterone hydroxylations at the 15 alpha- and 15 beta-positions were not affected by tiamulin. No in vitro complexation by tiamulin of cytochrome P450 resulting in a loss of CO-binding capacity could be demonstrated. Results from the present study suggest a selective inhibition of cytochrome P450 enzymes in pigs, probably belonging to the P4503A subfamily. The mechanism of this interaction is still unclear. However, interactions between tiamulin and those veterinary drugs or endogenous compounds which undergo oxidative metabolism by P450 enzymes must be considered. More research is needed to reveal which of the P450 enzymes are affected by tiamulin in order to improve the understanding and probably the predictability of this interaction.

  18. Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

    Science.gov (United States)

    Kuhn, Viktoria; Diederich, Lukas; Keller, T.C. Stevenson; Kramer, Christian M.; Lückstädt, Wiebke; Panknin, Christina; Suvorava, Tatsiana; Isakson, Brant E.; Kelm, Malte

    2017-01-01

    Abstract Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified. Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia. Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far. Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742. PMID:27889956

  19. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Gregorio Caimi

    2014-01-01

    Full Text Available Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS, nitric oxide metabolites (nitrite + nitrate expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS. In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS and nondiabetic (NDMS and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

  20. Effects of Hormone Therapy on Oxidative Stress in Postmenopausal Women with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Martha A. Sánchez-Rodríguez

    2016-08-01

    Full Text Available The aim of this study was to determine the effect of oral hormone therapy (HT on oxidative stress (OS in postmenopausal women with metabolic syndrome (MetS. A randomized, double blind, placebo-controlled trial was carried out. We formed four groups of 25 women each; healthy (HW and MetS women (MSW were assigned to HT (1 mg/day of estradiol valerate plus 5 mg/10 day of medroxiprogesterone or placebo. We measured plasma lipoperoxides, erythrocyte superoxide dismutase and glutathione peroxidase, total plasma antioxidant status and uric acid, as OS markers. Alternative cut-off values of each parameter were defined and a stress score (SS ranging from 0 to 7 was used as total OS. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII criteria. Participants were seen at baseline, 3 and 6 months. After 6 months, MetS decreased in MSW-HT (48%, their triglycerides and high-density lipoprotein cholesterol (HDL-c improved; in the other groups no difference was found. SS in MSW-HT decreased (3.8 ± 0.3 to 1.7 ± 0.3, p < 0.05 and OS was also reduced (44%, this effect was evident since 3 mo. HW-HT with high OS also decreased (40%. In placebo groups there was no change. Our findings suggest that HT improve lipids and OS associated to MetS in postmenopausal women.

  1. Metabolic responses of Beauveria bassiana to hydrogen peroxide-induced oxidative stress using an LC-MS-based metabolomics approach.

    Science.gov (United States)

    Zhang, Chen; Wang, Wei; Lu, Ruili; Jin, Song; Chen, Yihui; Fan, Meizhen; Huang, Bo; Li, Zengzhi; Hu, Fenglin

    2016-06-01

    The entomopathogenic fungus, Beauveria bassiana, is commonly used as a biological agent for pest control. Environmental and biological factors expose the fungus to oxidative stress; as a result, B. bassiana has adopted a number of anti-oxidant mechanisms. In this study, we investigated metabolites of B. bassiana that are formed in response to oxidative stress from hydrogen peroxide (H2O2) by using a liquid chromatography mass spectrometry (LC-MS) approach. Partial least-squares discriminant analysis (PLS-DA) revealed differences between the control and the H2O2-treated groups. Hierarchical cluster analysis (HCA) showed 18 up-regulated metabolites and 25 down-regulated metabolites in the H2O2-treated fungus. Pathway analysis indicated that B. bassiana may be able to alleviate oxidative stress by enhancing lipid catabolism and glycometabolism, thus decreasing membrane polarity and preventing polar H2O2 or ROS from permeating into fungal cells and protecting cells against oxidative injury. Meanwhile, most of the unsaturated fatty acids that are derived from glycerophospholipids hydrolysis can convert into oxylipins through autoxidation, which can prevent the reactive oxygen of H2O2 from attacking important macromolecules of the fungus. Results showed also that H2O2 treatment can enhance mycotoxins production which implies that oxidative stress may be able to increase the virulence of the fungus. In comparison to the control group, citric acid and UDP-N-acetylglucosamine were down-regulated, which suggested that metabolic flux was occurring to the TCA cycle and enhancing carbohydrate metabolism. The findings from this study will contribute to the understanding of how the molecular mechanisms of fungus respond to environmental and biological stress factors as well as how the manipulation of such metabolisms may lead to selection of more effective fungal strains for pest control. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

    Science.gov (United States)

    Nunes, Ana R; Alves, Marco G; Tomás, Gonçalo D; Conde, Vanessa R; Cristóvão, Ana C; Moreira, Paula I; Oliveira, Pedro F; Silva, Branca M

    2015-03-14

    Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

  3. Solar photocatalytic oxidation of recalcitrant natural metabolic by-products of amoxicillin biodegradation

    OpenAIRE

    João Pereira; Ana Reis; Vera Homem; José Silva; Arminda Alves; Maria Teresa Borges; Rui Boaventura; Vítor Vilar; Olga Pastor Nunes

    2014-01-01

    The contamination of the aquatic environment by non-metabolized and metabolized antibiotic residues has brought the necessity of alternative treatment steps to current water decontamination technologies. This work assessed the feasibility of using a multi-stage treatment system for amoxicillin (AMX) spiked solutions combining: i) a biological treatment process using an enriched culture to metabolize AMX, with ii) a solar photocatalytic system to achieve the removal of the metabolized transfor...

  4. Weekend ethanol consumption and high-sucrose diet: resveratrol effects on energy expenditure, substrate oxidation, lipid profile, oxidative stress and hepatic energy metabolism.

    Science.gov (United States)

    Rocha, Katiucha Karolina Honório Ribeiro; Souza, Gisele Aparecida; Seiva, Fábio Rodrigues Ferreira; Ebaid, Geovana Xavier; Novelli, Ethel Lourenzi Barbosa

    2011-01-01

    The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, 3,5,4'-trans-trihydroxystilbene) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle. Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week. After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats. The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

  5. The effect of right ventricular pacing on myocardial oxidative metabolism and efficiency: relation with left ventricular dyssynchrony

    Energy Technology Data Exchange (ETDEWEB)

    Ukkonen, Heikki; Saraste, Antti; Koistinen, Juhani [Turku University Hospital, Department of Medicine, P.O. Box 52, Turku (Finland); Tops, Laurens; Bax, Jeroen [Leiden University Medical Center, Leiden (Netherlands); Naum, Alexander [University of Turku, Turku PET Centre, Turku (Finland); Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Turku University Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland)

    2009-12-15

    Right ventricular (RV) apical pacing induces dyssynchrony by a left bundle branch block type electrical activation sequence in the heart and may impair left ventricular (LV) function. Whether these functional changes are accompanied by changes in myocardial perfusion, oxidative metabolism and efficiency, and the relation with the induction of LV dyssynchrony are unknown. Our study was designed to investigate the acute effects of RV pacing on these parameters. Ten patients with normal LV ejection fraction and VVI/DDD pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing-OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [{sup 15}O]water and [{sup 11}C]acetate positron emission tomography was used to measure perfusion and oxidative metabolism (k{sub mono}) of the LV. An echocardiographic examination was used to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of forward work was calculated as systolic blood pressure x cardiac output/LV mass/k{sub mono}. RV pacing decreased SV in all subjects (mean decrease 13%, from 76 {+-} 7 to 66 {+-} 7 ml, p = 0.004), but global perfusion and k{sub mono} were unchanged. The efficiency tended to be lower with pacing-ON (70 {+-} 20 vs 81 {+-} 21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6) efficiency decreased by 23% (from 78 {+-} 25 to 60 {+-} 14 mmHg l/g, p = 0.02), but in patients without dyssynchrony no change in efficiency was detected. Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was detected during pacing in patients with dyssynchrony but not in those without dyssynchrony. RV pacing resulted in a significant decrease in SV. However, deleterious effects on LV oxidative metabolism and efficiency were observed only in patients with dyssynchrony during RV pacing. (orig.)

  6. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Science.gov (United States)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  7. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  8. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  9. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  10. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    Science.gov (United States)

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  11. Effect of Tiaoxin Recipe (调心方) on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimer's Disease Rats

    Institute of Scientific and Technical Information of China (English)

    邱宏; 金国琴; 赵伟康; 张学礼

    2003-01-01

    Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO)ⅡmRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COⅡmRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.

  12. Assessment of nitric oxide (NO) redox reactions contribution to nitrous oxide (N2 O) formation during nitrification using a multispecies metabolic network model.

    Science.gov (United States)

    Perez-Garcia, Octavio; Chandran, Kartik; Villas-Boas, Silas G; Singhal, Naresh

    2016-05-01

    Over the coming decades nitrous oxide (N2O) is expected to become a dominant greenhouse gas and atmospheric ozone depleting substance. In wastewater treatment systems, N2O is majorly produced by nitrifying microbes through biochemical reduction of nitrite (NO2(-)) and nitric oxide (NO). However it is unknown if the amount of N2O formed is affected by alternative NO redox reactions catalyzed by oxidative nitrite oxidoreductase (NirK), cytochromes (i.e., P460 [CytP460] and 554 [Cyt554 ]) and flavohemoglobins (Hmp) in ammonia- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In this study, a mathematical model is developed to assess how N2O formation is affected by such alternative nitrogen redox transformations. The developed multispecies metabolic network model captures the nitrogen respiratory pathways inferred from genomes of eight AOB and NOB species. The performance of model variants, obtained as different combinations of active NO redox reactions, was assessed against nine experimental datasets for nitrifying cultures producing N2O at different concentration of electron donor and acceptor. Model predicted metabolic fluxes show that only variants that included NO oxidation to NO2(-) by CytP460 and Hmp in AOB gave statistically similar estimates to observed production rates of N2O, NO, NO2(-) and nitrate (NO3(-)), together with fractions of AOB and NOB species in biomass. Simulations showed that NO oxidation to NO2(-) decreased N2O formation by 60% without changing culture's NO2(-) production rate. Model variants including NO reduction to N2O by Cyt554 and cNor in NOB did not improve the accuracy of experimental datasets estimates, suggesting null N2O production by NOB during nitrification. Finally, the analysis shows that in nitrifying cultures transitioning from dissolved oxygen levels above 3.8 ± 0.38 to <1.5 ± 0.8 mg/L, NOB cells can oxidize the NO produced by AOB through reactions catalyzed by oxidative NirK. © 2015 Wiley Periodicals, Inc.

  13. Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

    Science.gov (United States)

    Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-09-01

    Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  14. NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation

    International Nuclear Information System (INIS)

    Pan, Tao; Zhang, Mei; Zhang, Fang; Yan, Guang; Ru, Yi; Wang, Qinhao; Zhang, Yao; Wei, Xuehui; Xu, Xinyuan; Shen, Lan; Zhang, Jian; Wu, Kaichun; Yao, Libo; Li, Xia

    2017-01-01

    Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation. - Highlights: • NDRG2 overexpression reduces the tolerance of hepatoma cells to glucose limitation. • NDRG2 overexpression aggravates energy imbalance and oxidative stress under glucose deprivation. • NDRG2 overexpression disturbs the activation of FAO in hepatoma cells under glucose limitation. • NDRG2 overexpression inhibits the activation of AMPK/ACC pathway in hepatoma cells during glucose starvation.

  15. Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

    Directory of Open Access Journals (Sweden)

    Vučeljić Marina

    2006-01-01

    Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

  16. Investigation of cytokines, oxidative stress, metabolic, and inflammatory biomarkers after orange juice consumption by normal and overweight subjects

    Directory of Open Access Journals (Sweden)

    Grace K. Z. S. Dourado

    2015-10-01

    Full Text Available Background: Abdominal adiposity has been linked to metabolic abnormalities, including dyslipidemia, oxidative stress, and low-grade inflammation. Objective: To test the hypothesis that consumption of 100% orange juice (OJ would improve metabolic, oxidative, and inflammatory biomarkers and cytokine levels in normal and overweight subjects with increased waist circumference. Design: Subjects were divided into two groups in accordance with their body mass index: normal and overweight. Both groups of individuals consumed 750 mL of OJ daily for 8 weeks. Body composition (weight, height, percentage of fat mass, and waist circumference; metabolic biomarkers (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triglycerides, glucose, insulin, HOMA-IR, and glycated hemoglobin; oxidative biomarkers (malondialdehyde and DPPH•; inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP]; cytokines (IL-4, IL-10, IL-12, TNF-α, and IFN-γ; and diet were evaluated before and after consumption of OJ for 8 weeks. Results: The major findings of this study were: 1 no alteration in body composition in either group; 2 improvement of the lipid profile, evidenced by a reduction in total cholesterol and LDL-C; 3 a potential stimulation of the immune response due to increase in IL-12; 4 anti-inflammatory effect as a result of a marked reduction in hsCRP; and 5 antioxidant action by the enhancement of total antioxidant capacity and the reduction of lipid peroxidation, in both normal and overweight subjects. Conclusions: OJ consumption has a positive effect on important biomarkers of health status in normal and overweight subjects, thereby supporting evidence that OJ acts as functional food and could be consumed as part of a healthy diet to prevent metabolic and chronic diseases.

  17. Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

    Directory of Open Access Journals (Sweden)

    Ullmann Cris

    2006-06-01

    Full Text Available Abstract Background Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation. Methods White male New Zealand rabbits were treated with doxorubicine (3 mg/kg/week; 6 weeks to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC and injected 1.5–2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect β1- and β2-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping. Results In doxorubicine-treated animals β-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less β-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity. Conclusion BMSC transplantation improves sympathoadrenal dysregualtion in non-ischemic heart failure.

  18. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

    Science.gov (United States)

    Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

    2017-03-15

    Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of Feeding Oxidized Soybean Oil against Antioxidant role of Pomegranate Seed on Physiology and Metabolism of Periparturient Saanen Goats

    Directory of Open Access Journals (Sweden)

    Seyyed Ehsan Ghiasi

    2016-08-01

    Full Text Available Introduction Oxidative stress is metabolic and physiologic status caused by imbalance between free radical production and antioxidant defense of body. In some physiological status such as rapid growth, parturition, disease and high production rate that imbalance would occur. High producing dairy animals are suspected to oxidative stress and require to antioxidant supplementation. Negative energy balance in early lactation force the nutrition specialist to apply oil and high NFC diet to exceed the requirement of high producing dairy animals such as Holstein cows and Saanen goats. In recent years, the attention to the use of herbal or organic antioxidant in animal nutrition has increased. This study was carried out to investigate the effects of feeding oxidized soybean oil (OSO plus pomegranate seed (PS as a natural antioxidant, on metabolism and physiology of Preparturient Saanen Goats. Materials and Methods Eighteen Saanen dairy goats with initial body weight of 47 ± 9 kg were assigned to three dietary treatments in a completely randomized design with repeated measurements for 21 days before anticipated parturition. Experimental treatments including: 1 base diet and 4% fresh soybean oil (FSO, 2 base diet and 4% oxidized soybean oil (DM basis respectively, and 3 base diet plus 4% OSO and 8% Pomegranate seed (OSO-PS. After 2 weeks of feeding trial diets, goats were sampled for blood, rumen liquor, faeces and urine for measuring parameters of blood glucose, BHBA, lipid and nitrogen profile, rumen liquor ammonia nitrogen, urine pH and volume, faeces qualitative and quantitative variables and other responses such as nutrients digestibility. The GLM procedure of SAS software v.9.2 were used for statistical analysis. Initial body weight and metabolic variables were used as covariate in the model. Results and discussion All nutrients digestibility, Ruminal ammonia nitrogen and voluntary feed intake were decreased by OSO (p

  20. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  1. Age-Specific Determinants of Pulse Wave Velocity among Metabolic Syndrome Components, Inflammatory Markers, and Oxidative Stress.

    Science.gov (United States)

    Kim, Minkyung; Kim, Minjoo; Yoo, Hye Jin; Lee, Seung Yeon; Lee, Sang-Hyun; Lee, Jong Ho

    2018-02-01

    Pulse wave velocity (PWV) is thought to have different relationships with metabolic syndrome (MS) components, inflammatory markers, and oxidative stress, according to age. However, age-specific determinants of PWV have not yet been studied. We investigated age-dependent relationships among PWV and MS components, inflammatory markers, and oxidative stress. A total of 4,318 subjects were divided into 4 groups: 19-34 y (n=687), 35-44 y (n=1,413), 45-54 y (n=1,384), and 55-79 y (n=834). MS components, brachial-ankle PWV (baPWV), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress markers were measured. There were age-related increases in MS, body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic BP (DBP), triglycerides, glucose, hs-CRP, oxidized low-density lipoprotein (LDL), 8-epi-prostaglandin F 2α (8-epi-PGF 2α ), and baPWV. BaPWV was significantly associated with sex and elevated BP in the 19-34 y group; with age, sex, BMI, elevated BP and triglycerides in the 35-44 y group; with age, sex, elevated BP, fasting glucose, hs-CRP and oxidized LDL in the 45-54 y group; and with age, BMI, elevated BP, fasting glucose and oxidized LDL in the 55-79 y group. Our results show that age-related increases in baPWV are associated with age-related changes in MS components, inflammatory markers, and oxidative stress. However, each of these factors has an age-specific, different impact on arterial stiffness. In particular, oxidative stress may be independently associated with arterial stiffness in individuals older than 45 y.

  2. Effects of glucose metabolism pathways on sperm motility and oxidative status during long-term liquid storage of goat semen.

    Science.gov (United States)

    Qiu, Jian-Hua; Li, You-Wei; Xie, Hong-Li; Li, Qing; Dong, Hai-Bo; Sun, Ming-Ju; Gao, Wei-Qiang; Tan, Jing-He

    2016-08-01

    Although great efforts were made to prolong the fertility of liquid-stored semen, limited improvements have been achieved in different species. Although it is expected that energy supply and the redox potential will play an essential role in sperm function, there are few reports on the impact of specific energy substrates on spermatozoa during liquid semen storage. Furthermore, although it is accepted that glucose metabolism through glycolysis provides energy, roles of pentose phosphate pathway (PPP) and tricarboxylic acid cycle remain to be unequivocally found in spermatozoa. We have studied the pathways by which spermatozoa metabolize glucose during long-term liquid storage of goat semen. The results indicated that among the substrates tested, glucose and pyruvate were better than lactate in maintaining goat sperm motility. Although both glycolysis and PPP were essential, PPP was more important than glycolysis to maintain sperm motility. Pentose phosphate pathway reduced oxidative stress and provided glycolysis with more intermediate products such as fructose-6-phosphate. Pyruvate entered goat spermatozoa through monocarboxylate transporters and was oxidized by the tricarboxylic acid cycle and electron transfer to sustain sperm motility. Long-term liquid semen storage can be used as a good model to study sperm glucose metabolism. The data are important for an optimal control of sperm survival during semen handling and preservation not only in the goat but also in other species. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

    Science.gov (United States)

    Kavitha, S; Chandra, T S

    2014-11-01

    Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

  4. A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl

    2014-01-01

    Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...

  5. Role of nitric oxide synthase uncoupling at rostral ventrolateral medulla in redox-sensitive hypertension associated with metabolic syndrome.

    Science.gov (United States)

    Wu, Kay L H; Chao, Yung-Mei; Tsay, Shiow-Jen; Chen, Chen Hsiu; Chan, Samuel H H; Dovinova, Ima; Chan, Julie Y H

    2014-10-01

    Metabolic syndrome (MetS), which is rapidly becoming prevalent worldwide, is long known to be associated with hypertension and recently with oxidative stress. Of note is that oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, contributes to sympathoexcitation and hypertension. This study sought to identify the source of tissue oxidative stress in RVLM and their roles in neural mechanism of hypertension associated with MetS. Adult normotensive rats subjected to a high-fructose diet for 8 weeks developed metabolic traits of MetS, alongside increases in sympathetic vasomotor activity and blood pressure. In RVLM of these MetS rats, the tissue level of reactive oxygen species was increased, nitric oxide (NO) was decreased, and mitochondrial electron transport capacity was reduced. Whereas the protein expression of neuronal NO synthase (nNOS) or protein inhibitor of nNOS was increased, the ratio of nNOS dimer/monomer was significantly decreased. Oral intake of pioglitazone or intracisternal infusion of tempol or coenzyme Q10 significantly abrogated all those molecular events in high-fructose diet-fed rats and ameliorated sympathoexcitation and hypertension. Gene silencing of protein inhibitor of nNOS mRNA in RVLM using lentivirus carrying small hairpin RNA inhibited protein inhibitor of nNOS expression, increased the ratio of nNOS dimer/monomer, restored NO content, and alleviated oxidative stress in RVLM of high-fructose diet-fed rats, alongside significantly reduced sympathoexcitation and hypertension. These results suggest that redox-sensitive and protein inhibitor of nNOS-mediated nNOS uncoupling is engaged in a vicious cycle that sustains the production of reactive oxygen species in RVLM, resulting in sympathoexcitation and hypertension associated with MetS. © 2014 American Heart Association, Inc.

  6. A Metagenomics-Based Metabolic Model of Nitrate-Dependent Anaerobic Oxidation of Methane by Methanoperedens-Like Archaea

    Science.gov (United States)

    Arshad, Arslan; Speth, Daan R.; de Graaf, Rob M.; Op den Camp, Huub J. M.; Jetten, Mike S. M.; Welte, Cornelia U.

    2015-01-01

    Methane oxidation is an important process to mitigate the emission of the greenhouse gas methane and further exacerbating of climate forcing. Both aerobic and anaerobic microorganisms have been reported to catalyze methane oxidation with only a few possible electron acceptors. Recently, new microorganisms were identified that could couple the oxidation of methane to nitrate or nitrite reduction. Here we investigated such an enrichment culture at the (meta) genomic level to establish a metabolic model of nitrate-driven anaerobic oxidation of methane (nitrate-AOM). Nitrate-AOM is catalyzed by an archaeon closely related to (reverse) methanogens that belongs to the ANME-2d clade, tentatively named Methanoperedens nitroreducens. Methane may be activated by methyl-CoM reductase and subsequently undergo full oxidation to carbon dioxide via reverse methanogenesis. All enzymes of this pathway were present and expressed in the investigated culture. The genome of the archaeal enrichment culture encoded a variety of enzymes involved in an electron transport chain similar to those found in Methanosarcina species with additional features not previously found in methane-converting archaea. Nitrate reduction to nitrite seems to be located in the pseudoperiplasm and may be catalyzed by an unusual Nar-like protein complex. A small part of the resulting nitrite is reduced to ammonium which may be catalyzed by a Nrf-type nitrite reductase. One of the key questions is how electrons from cytoplasmically located reverse methanogenesis reach the nitrate reductase in the pseudoperiplasm. Electron transport in M. nitroreducens probably involves cofactor F420 in the cytoplasm, quinones in the cytoplasmic membrane and cytochrome c in the pseudoperiplasm. The membrane-bound electron transport chain includes F420H2 dehydrogenase and an unusual Rieske/cytochrome b complex. Based on genome and transcriptome studies a tentative model of how central energy metabolism of nitrate-AOM could work is

  7. Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

    Science.gov (United States)

    Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

    2014-04-01

    Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    Directory of Open Access Journals (Sweden)

    Oluwafeyisetan O. Adebiyi

    2015-12-01

    Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

  9. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

    Directory of Open Access Journals (Sweden)

    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  10. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

    International Nuclear Information System (INIS)

    Luethy, P.C.; Chatelain, P.; Papageorgiou, I.; Schubiger, A.; Lerch, R.A.

    1988-01-01

    Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs

  11. Effects of extra virgin olive oil and fish oil on lipid profile and oxidative stress in patients with metabolic syndrome.

    Science.gov (United States)

    Venturini, Danielle; Simão, Andréa Name Colado; Urbano, Mariana Ragassi; Dichi, Isaias

    2015-06-01

    The aim of this study was to verify if extra virgin olive oil and fish oil have a synergistic effect on lipid and oxidative stress parameters in patients with metabolic syndrome (MetS). This intervention study included 102 patients (81 women and 21 men) with MetS (mean age 51.45 ± 8.27 y) from the ambulatory center of the University Hospital of Londrina, Paraná, Brazil. Patients were randomly assigned to one of four groups: Patients in the control group (CG) were instructed to maintain their usual diet; the second group (fish oil group [FO]) received 3 g/d of fish oil ω-3 fatty acids (10 capsules); the third group (extra virgin olive oil group [OO]) received 10 mL/d of extra virgin olive oil at lunch and dinner; and the fourth group (fish oil and extra virgin olive oil group [FOO]) received 3 g/d of fish oil ω-3 fatty acids and 10 mL/d of extra virgin olive oil. MetS related markers and oxidative stress were measured at baseline and after 90 d. Differences across treatment groups showed a statistically significant decrease (P virgin olive oil have beneficial synergistic effects on lipid metabolism and oxidative stress in patients with MetS. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Formation of quinones by one-electron oxidation in the metabolism of benzo[a]pyrene and 6-fluorobenzo[a]pyrene

    International Nuclear Information System (INIS)

    Cavalieri, E.; Wong, A.; Cremonesi, P.; Warner, C.; Rogan, E.

    1986-01-01

    Metabolic activation of polycyclic aromatic hydrocarbons (PAH), as well as other chemical carcinogens, occurs by two major pathways: One-electron oxidation and two-electron oxidation, or monooxygenation. One-electron oxidation generates radical cations or radicals, depending on the molecule in which the oxidation occurs, whereas two-electron oxidation produces oxygenated metabolites. Radical cations of PAH are ultimate electrophilic metabolites capable of binding to cellular macromolecules to initiate the tumor process. In this paper the authors will provide evidence that one-electron oxidation is involved not only in PAH carcinogenesis, but also in the formation of certain metabolites. Metabolism of benzo[a]pyrene (BP) by cytochrome P-450 monooxygenase yields three classes of products: phenols, dihydrodiols and the quinones, 1,6-, 3,6- and 6,12- dione

  13. Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.

    Science.gov (United States)

    Lozoya, Oswaldo A; Martinez-Reyes, Inmaculada; Wang, Tianyuan; Grenet, Dagoberto; Bushel, Pierre; Li, Jianying; Chandel, Navdeep; Woychik, Richard P; Santos, Janine H

    2018-04-18

    Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.

  14. Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy.

    Directory of Open Access Journals (Sweden)

    Maria Vinaixa

    Full Text Available Polycystic ovary syndrome (PCOS is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.

  15. Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Atsushi Fukushima

    2017-08-01

    Full Text Available Plants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1 and plants overexpressing the gene encoding γ-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditions—oxidative stress elicited by methyl viologen and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. As a common oxidative stress response, several flavonoids that we assessed showed overaccumulation, whereas the mild phosphate stress resulted in increased levels of specific kaempferol- and quercetin-glycosides. Remarkably, in addition to a significant increased level of sugar, osmolytes, and lipids as mild oxidative stress-responsive metabolites, short-chain aliphatic glucosinolates over-accumulated in the mutants, whereas the level of long-chain aliphatic glucosinolates and specific lipids decreased. Coordinated gene expressions related to glucosinolate and

  16. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo

    2009-01-01

    In catalyzing the reversible hydration of CO2 to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2 transport, in acid-base balance, and in linking local acidosis to O2 unloading from hemoglobin. Considering the structural similarity between...... bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  17. [The role of oxidative metabolism disturbance in the development of NO-related endothelial dysfunction during chronic hearth failure].

    Science.gov (United States)

    Goishvili, N; Kakauridze, N; Sanikidze, T

    2005-05-01

    The aim of the work was to establish the oxidative metabolism changes and NO data in Chronic Hearth Failure (HF). 52 patients were included in the investigation, among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA) and 17 without it (control group). For revealing of organism redox-status (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic centers was studied by electron paramagnetic resonance method. For revealing of blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the oxidative process intensification and organism compensate reaction reduction with low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of erythrocytes membranes adrenergic receptors were revealed. In chronic HF the accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote with following decreases of blood free NO and develop the endothelial dysfunction.

  18. Genetically Determined Insulin Resistance is Characterized by Down-Regulation of Mitochondrial Oxidative Metabolism in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Wojtaszewski, Jørgen

    2010-01-01

    Transcriptional profiling of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated a co-ordinated down-regulation of oxidative phosphorylation (OxPhos) genes, suggesting a link between insulin resistance and mitochondrial dysfunction. However, whether...... mitochondrial dysfunction is a cause or consequence of insulin resistance remains to be clarified. In the present study, we tested the hypothesis that mitochondrial oxidative metabolism was down-regulated in skeletal muscle of patients with genetically determined insulin resistance. Skeletal muscle biopsies.......02), and complex V (ATP5B; p=0.005). Our data demonstrate that genetically determined insulin resistance is associated with a co-ordinated down-regulation of OxPhos components both at the transcriptional and translational level. These findings suggest that an impaired biological response to insulin in skeletal...

  19. Metabolic alkene labeling and in vitro detection of histone acylation via the aqueous oxidative Heck reaction

    NARCIS (Netherlands)

    Ourailidou, Maria E; Dockerty, Paul; Witte, Martin; Poelarends, Gerrit J; Dekker, Frank J

    2015-01-01

    The detection of protein lysine acylations remains a challenge due to lack of specific antibodies for acylations with various chain lengths. This problem can be addressed by metabolic labeling techniques using carboxylates with reactive functionalities. Subsequent chemoselective reactions with a

  20. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    Science.gov (United States)

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (pglucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

  1. CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48

    OpenAIRE

    Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

    2015-01-01

    Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine rec...

  2. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    OpenAIRE

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p

  3. Effects of a Physical Activity Program on Markers of Endothelial Dysfunction, Oxidative Stress, and Metabolic Status in Adolescents with Metabolic Syndrome

    Science.gov (United States)

    Camarillo-Romero, Eneida; Dominguez-Garcia, Ma Victoria; Amaya-Chavez, Araceli; Camarillo-Romero, Maria del Socorro; Talavera-Piña, Juan; Huitron-Bravo, Gerardo; Majluf-Cruz, Abraham

    2012-01-01

    The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration. PMID:22888450

  4. Coping with Salt Water Habitats: Metabolic and Oxidative Responses to Salt Intake in the Rufous-Collared Sparrow

    Directory of Open Access Journals (Sweden)

    Pablo Sabat

    2017-09-01

    Full Text Available Many physiological adjustments occur in response to salt intake in several marine taxa, which manifest at different scales from changes in the concentration of individual molecules to physical traits of whole organisms. Little is known about the influence of salinity on the distribution, physiological performance, and ecology of passerines; specifically, the impact of drinking water salinity on the oxidative status of birds has been largely ignored. In this study, we evaluated whether experimental variations in the salt intake of a widely-distributed passerine (Zontotrichia capensis could generate differences in basal (BMR and maximum metabolic rates (Msum, as well as affect metabolic enzyme activity and oxidative status. We measured rates of energy expenditure of birds after 30-d acclimation to drink salt (SW or tap (fresh water (TW and assessed changes in the activity of mitochondrial enzymes (cytochrome c oxidase and citrate synthase in skeletal muscle, heart, and kidney. Finally, we evaluated the oxidative status of bird tissues by means of total antioxidant capacity (TAC and superoxide dismutase activities and lipid oxidative damage (Malondialdehyde, MDA. The results revealed a significant increase in BMR but not Msum, which resulted in a reduction in factorial aerobic scope in SW- vs. TW-acclimated birds. These changes were paralleled with increased kidney and intestine masses and catabolic activities in tissues, especially in pectoralis muscle. We also found that TAC and MDA concentrations were ~120 and ~400% higher, respectively in the liver of animals acclimated to the SW- vs. TW-treatment. Our study is the first to document changes in the oxidative status in birds that persistently drink saltwater, and shows that they undergo several physiological adjustments that range that range in scale from biochemical capacities (e.g., TAC and MDA to whole organism traits (e.g., metabolic rates. We propose that the physiological changes observed

  5. Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake

    DEFF Research Database (Denmark)

    Hall, Ulrika Andersson; Pettersson, Stefan; Edin, Fredrik

    2018-01-01

    : Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate...

  6. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco

    2007-01-01

    ), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  7. Metabolism of styrene-7,8-oxide in human liver in vitro: interindividual variation and stereochemistry

    NARCIS (Netherlands)

    Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

    2000-01-01

    Styrene is an industrial solvent which is mainly oxidized by cytochrome P450 to an electrophilic, chiral epoxide metabolite: styrene-7,8-oxide (SO). SO has cytotoxic and genotoxic properties; the (R)-enantiomer is more mutagenic to Salmonella typhimurium TA 100 in the Ames test than the

  8. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility

    Directory of Open Access Journals (Sweden)

    Anna Gvozdjáková

    2015-01-01

    Full Text Available Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ10-TOTAL, γ, and α-tocopherols, and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp. and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ10-TOTAL (ubiquinone + ubiquinol and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ10-TOTAL, and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

  9. The Oxidative Metabolism of Fossil Hydrocarbons and Sulfide Minerals by the Lithobiontic Microbial Community Inhabiting Deep Subterrestrial Kupferschiefer Black Shale

    Directory of Open Access Journals (Sweden)

    Agnieszka Włodarczyk

    2018-05-01

    Full Text Available Black shales are one of the largest reservoirs of fossil organic carbon and inorganic reduced sulfur on Earth. It is assumed that microorganisms play an important role in the transformations of these sedimentary rocks and contribute to the return of organic carbon and inorganic sulfur to the global geochemical cycles. An outcrop of deep subterrestrial ~256-million-year-old Kupferschiefer black shale was studied to define the metabolic processes of the deep biosphere important in transformations of organic carbon and inorganic reduced sulfur compounds. This outcrop was created during mining activity 12 years ago and since then it has been exposed to the activity of oxygen and microorganisms. The microbial processes were described based on metagenome and metaproteome studies as well as on the geochemistry of the rock. The microorganisms inhabiting the subterrestrial black shale were dominated by bacterial genera such as Pseudomonas, Limnobacter, Yonghaparkia, Thiobacillus, Bradyrhizobium, and Sulfuricaulis. This study on black shale was the first to detect archaea and fungi, represented by Nitrososphaera and Aspergillus genera, respectively. The enzymatic oxidation of fossil aliphatic and aromatic hydrocarbons was mediated mostly by chemoorganotrophic bacteria, but also by archaea and fungi. The dissimilative enzymatic oxidation of primary reduced sulfur compounds was performed by chemolithotrophic bacteria. The geochemical consequences of microbial activity were the oxidation and dehydrogenation of kerogen, as well as oxidation of sulfide minerals.

  10. Sodium acetate induces a metabolic alkalosis but not the increase in fatty acid oxidation observed following bicarbonate ingestion in humans.

    Science.gov (United States)

    Smith, Gordon I; Jeukendrup, Asker E; Ball, Derek

    2007-07-01

    We conducted this study to quantify the oxidation of exogenous acetate and to determine the effect of increased acetate availability upon fat and carbohydrate utilization in humans at rest. Eight healthy volunteers (6 males and 2 females) completed 2 separate trials, 7 d apart in a single-blind, randomized, crossover design. On each occasion, respiratory gas and arterialized venous blood samples were taken before and during 180 min following consumption of a drink containing either sodium acetate (NaAc) or NaHCO3 at a dose of 2 mmol/kg body mass. Labeled [1,2 -13C] NaAc was added to the NaAc drink to quantify acetate oxidation. Both sodium salts induced a mild metabolic alkalosis and increased energy expenditure (P < 0.05) to a similar magnitude. NaHCO3 ingestion increased fat utilization from 587 +/- 83 kJ/180 min to 693 +/- 101 kJ/180 min (P = 0.01) with no change in carbohydrate utilization. Following ingestion of NaAc, the amount of fat and carbohydrate utilized did not differ from the preingestion values. However, oxidation of the exogenous acetate almost entirely (90%) replaced the additional fat that had been oxidized during the bicarbonate trial. We determined that 80.1 +/- 2.3% of an exogenous source of acetate is oxidized in humans at rest. Whereas NaHCO3 ingestion increased fat oxidation, a similar response did not occur following NaAc ingestion despite the fact both sodium salts induced a similar increase in energy expenditure and shift in acid-base balance.

  11. Oxidative Stress and Antioxidant Defense Mechanisms Linked to Exercise During Cardiopulmonary and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kelsey Fisher-Wellman

    2009-01-01

    Full Text Available Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS, evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary “signal” for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.

  12. Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome.

    Science.gov (United States)

    Pilar, Bruna; Güllich, Angélica; Oliveira, Patrícia; Ströher, Deise; Piccoli, Jacqueline; Manfredini, Vanusa

    2017-12-01

    This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components

  13. Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia

    Directory of Open Access Journals (Sweden)

    Richard T. Jaspers

    2014-07-01

    Full Text Available Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH (10% air/90%N2 saturated water. We analyzed cross-sectional area (CSA, succinate dehydrogenase (SDH activity, capillarization, myonuclear density, myoglobin (Mb concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P<0.001. Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P<0.001. In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.

  14. Foliar-applied urea modulates nitric oxide synthesis metabolism and glycinebetaine accumulation in drought-stressed maize

    International Nuclear Information System (INIS)

    Zhang, L.; Tian, L.; Lai, J.; Zheng, P.; Liang, Z.; Alva, A

    2014-01-01

    Foliar urea has been proved to play a better positive role in enhancing accumulation of nitric oxide (NO) and glycinebetaine (GB) in maize (Zea mays L.) under drought stress (DS). However, it is unclear how foliar urea affects biosynthetic metabolism of NO and its relationship with GB accumulation. This study was on investigating the effect of foliar- applied urea on seedlings of maize cultivar Zhengdan 958 grown in a hydroponic medium under DS or No DS. Contents of NO and GB and nitric oxide synthase (NOS) activity increased and peaked 12 h after the treatment. Nitrate reductase activity (NRA) followed the similar pattern 6h after the treatment. Under DS foliar urea application increased NR and NOS activity and, thereby, increased NO formation. Therefore, enhancement in activities of both NRA and NOS resulted in an increase of NO accumulation. Foliar- applied urea could induce an increased NO burst by enhanced NO synthesis metabolism as a nitrogen signal, possibly resulting in GB accumulation under DS. (author)

  15. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Directory of Open Access Journals (Sweden)

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  16. Expanded metabolic versatility of ubiquitous nitrite-oxidizing bacteria from the genus Nitrospira

    DEFF Research Database (Denmark)

    Koch, Hanna; Lücker, Sebastian; Albertsen, Mads

    2015-01-01

    , we identified ecophysiological traits that contribute to the ecological success of Nitrospira. Unexpectedly, N. moscoviensis possesses genes coding for a urease and cleaves urea to ammonia and CO2. Ureolysis was not observed yet in nitrite oxidizers and enables N. moscoviensis to supply ammonia...... oxidizers lacking urease with ammonia from urea, which is fully nitrified by this consortium through reciprocal feeding. The presence of highly similar urease genes in Nitrospira lenta from activated sludge, in metagenomes from soils and freshwater habitats, and of other ureases in marine nitrite oxidizers...

  17. Tryptophan Oxidative Metabolism Catalyzed by : A Thermophile Isolated from Kuwait Soil Contaminated with Petroleum Hydrocarbons

    Directory of Open Access Journals (Sweden)

    Jassim M. Al-Hassan

    2011-01-01

    Full Text Available Tryptophan metabolism has been extensively studied in humans as well as in soil. Its metabolism takes place mainly through kynurenine pathway yielding hydroxylated, deaminated and many other products of physiological significance. However, tryptophan metabolism has not been studied in an isolated thermophilic bacterium. Geobacillus stearothermophilus is a local thermophile isolated from Kuwait desert soil contaminated with petroleum hydrocarbons. The bacterium grows well at 65 °C in 0.05 M phosphate buffer (pH 7, when supplied with organic compounds as a carbon source and has a good potential for transformation of steroids and related molecules. In the present study, we used tryptophan ethyl ester as a carbon source for the bacterium to study the catabolism of the amino acid at pH 5 and pH 7. In this endeavor, we have resolved twenty one transformation products of tryptophan by GC/LC and have identified them through their mass spectral fragmentation.

  18. Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

    Science.gov (United States)

    Masha, A; Martina, V

    2014-01-01

    Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

  19. Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

    International Nuclear Information System (INIS)

    Balasubramanian, A.; Ramakrishnan, S.

    1980-01-01

    The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

  20. A personalized BEST: characterization of latent clinical classes of nonischemic heart failure that predict outcomes and response to bucindolol.

    Directory of Open Access Journals (Sweden)

    David P Kao

    Full Text Available Heart failure patients with reduced ejection fraction (HFREF are heterogenous, and our ability to identify patients likely to respond to therapy is limited. We present a method of identifying disease subtypes using high-dimensional clinical phenotyping and latent class analysis that may be useful in personalizing prognosis and treatment in HFREF.A total of 1121 patients with nonischemic HFREF from the β-blocker Evaluation of Survival Trial were categorized according to 27 clinical features. Latent class analysis was used to generate two latent class models, LCM A and B, to identify HFREF subtypes. LCM A consisted of features associated with HF pathogenesis, whereas LCM B consisted of markers of HF progression and severity. The Seattle Heart Failure Model (SHFM Score was also calculated for all patients. Mortality, improvement in left ventricular ejection fraction (LVEF defined as an increase in LVEF ≥5% and a final LVEF of 35% after 12 months, and effect of bucindolol on both outcomes were compared across HFREF subtypes. Performance of models that included a combination of LCM subtypes and SHFM scores towards predicting mortality and LVEF response was estimated and subsequently validated using leave-one-out cross-validation and data from the Multicenter Oral Carvedilol Heart Failure Assessment Trial.A total of 6 subtypes were identified using LCM A and 5 subtypes using LCM B. Several subtypes resembled familiar clinical phenotypes. Prognosis, improvement in LVEF, and the effect of bucindolol treatment differed significantly between subtypes. Prediction improved with addition of both latent class models to SHFM for both 1-year mortality and LVEF response outcomes.The combination of high-dimensional phenotyping and latent class analysis identifies subtypes of HFREF with implications for prognosis and response to specific therapies that may provide insight into mechanisms of disease. These subtypes may facilitate development of personalized

  1. Linear relationship between in distribution of thallium-201 and blood flow in ischemic and nonischemic myocardium during exercise

    International Nuclear Information System (INIS)

    Nielsen, A.P.; Morris, K.G.; Murdock, R.; Bruno, F.P.; Cobb, F.R.

    1980-01-01

    The purpose of this study was to compare the myocardial distribution of thallium-201 and regional myocrdial blood flow during ischemia and the physiologic stress of exercise. Studies were carried out in six dogs with chronically implanted catheters in the atrium and aorta and a snare on the circumflex coronary artery distal to the first marginal branch. Regional myocardial blood flow was measured during quiet, resting conditions using 7 to 10 ] of radioisotope-labeled microspheres. Each dog was then exercised on a treadmill at speeds of 5 to 9 mph at a 5/sup o/ incline. (After 1 minute of exercise the cirumflex coronary artery was occluded and thallium-201 and a second label of microspheres were injected. Exercise was continued for 5 minutes. The dogs were then sacrificed and the left ventricle was sectioned into approximately 80 1-2-g samples to compare thallium-201 activity and regional myocardial blood flow. The maximum increase in blood flow ranged from 3.3 to 7.2 times resting control values. Each dog had myocardial samples in which blood flow was markedly reduced, to less than 0.10 ml/min/g. In each dog there was a close linear relationship between thallium-201 distribution and direct measurements of regional myocardial blood flow. Linear regression analyses demonstrated a correlation coefficient of 0.98 or greater in each dog. These data indicate that during the physiologic stress of exercise, the myocardial distribution of thallium activity is linearly related to regional myocardial blood flow in both the ischemic and nonischemic regions

  2. Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway.

    Science.gov (United States)

    Tieu, Elaine W; Tang, Edith K Y; Tuckey, Robert C

    2014-07-01

    CYP24A1 is the multicatalytic cytochrome P450 responsible for the catabolism of vitamin D via the C23- and C24-oxidation pathways. We successfully expressed the labile human enzyme in Escherichia coli and partially purified it in an active state that permitted detailed characterization of its metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] and the intermediates of the C24-oxidation pathway in a phospholipid-vesicle reconstituted system. The C24-oxidation pathway intermediates, 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, 24-oxo-1,23,25-trihydroxyvitamin D3 and tetranor-1,23-dihydroxyvitamin D3, were enzymatically produced from 1,25(OH)2 D3 using rat CYP24A1. Both 1,25(OH)2 D3 and 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 were found to partition strongly into the phospholipid bilayer when in aqueous medium. Changes to the phospholipid concentration did not affect the kinetic parameters for the metabolism of 1,25(OH)2 D3 by CYP24A1, indicating that it is the concentration of substrates in the membrane phase (mol substrate·mol phospholipid(-1) ) that determines their rate of metabolism. CYP24A1 exhibited Km values for the different C24-intermediates ranging from 0.34 to 15 mmol·mol phospholipid(-1) , with 24-oxo-1,23,25-trihydroxyvitamin D3 [24-oxo-1,23,25(OH)3 D3] displaying the lowest and 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3 D3] displaying the highest. The kcat values varied by up to 3.8-fold, with 1,24,25(OH)3 D3 displaying the highest kcat (34 min(-1) ) and 24-oxo-1,23,25(OH)3 D3 the lowest. The data show that the cleavage of the side chain of 24-oxo-1,23,25(OH)3 D3 occurs with the highest catalytic efficiency (kcat /Km ) and produces 1-hydroxy-23-oxo-24,25,26,27-tetranorvitamin D3 and not 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, as the primary product. These kinetic analyses also show that intermediates of the C24-oxidation pathway effectively compete with precursor substrates for binding to the active site of the

  3. Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats

    Directory of Open Access Journals (Sweden)

    Chien-Chun Li

    2018-01-01

    Full Text Available The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg and 400 LO (400 mg/kg and its major component, citral (240 mg/kg, on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(PH:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5′-diphospho (UDP glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen.

  4. Foliar urea application affects nitric oxide burst and glycine betaine metabolism in two maize cultivars under drought

    International Nuclear Information System (INIS)

    Zhang, L.; Zhang, X.; Wang, K.; Zhao, Y.; Zhai, Y.; Gao, M.

    2011-01-01

    Foliar urea has been proved to act a better role in alleviation of the negative effects of drought stress (DS). However, the modulation mechanism of foliar urea are not conclusive in view of nitric oxide (NO) burst and glycine betaine metabolism and their relationship. Two maize ( Zea mays L.) cultivars (Zhengdan 958, JD958, Jundan 20, ZD20) were grown in hydroponic medium, which were treated with spraying of urea concentration of 15 g L/sup -1/ and two water regimes (non-stress and DS simulated by the addition of polyethylene glycol (PEG, 15% w/v, MW 6000). The ten-day DS treatment increased betaine aldehyde dehydrogenase (BADH) activity, choline content and nitric oxide (NO) content acted as the key enzyme, initial substrate and a nitrogenous signal substance respectively in GB synthesis metabolism, thus, induced to great GB accumulation. The accumulation of NO reached the summit earlier than that of GB. The more positive/less negative responses were recorded in JD958 as compared with ZD20 to DS. Addition of foliar ur ea could increase accumulation of choline and BADH activity as well as NO content, thereby, increase GB accumulation under DS. These positive effects of urea applying foliarly on all parameters measured were more pronounced in cultivar JD20 than those in ZD958 under drought. It is, therefore, concluded that increases of both BADH activity and choline content possibly resulted in enhancement of GB accumulation. Foliar urea application could provoke better GB accumulation by modulation of GB metabolism, possibly mediating by NO burst as a signal molecule during drought, especially in the drought sensitive maize cultivar. (author)

  5. Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats.

    Science.gov (United States)

    Li, Chien-Chun; Yu, Hsiang-Fu; Chang, Chun-Hua; Liu, Yun-Ta; Yao, Hsien-Tsung

    2018-01-01

    The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO)] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg) and 400 LO (400 mg/kg) and its major component, citral (240 mg/kg), on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(P)H:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5'-diphospho (UDP) glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen. Copyright © 2017. Published by Elsevier B.V.

  6. β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels.

    Science.gov (United States)

    Chen, Chuck T; Bazinet, Richard P

    2015-01-01

    The brain has a unique polyunsaturated fatty acid composition, with high levels of arachidonic and docosahexaenoic acids (DHA) while levels of eicosapentaenoic acid (EPA) are several orders of magnitude lower. As evidence accumulated that fatty acid entry into the brain was not selective and, in fact, that DHA and EPA enter the brain at similar rates, new mechanisms were required to explain their large concentration differences in the brain. Here we summarize recent research demonstrating that EPA is rapidly and extensively β-oxidized upon entry into the brain. Although the ATP generated from the β-oxidation of EPA is low compared to the use of glucose, fatty acid β-oxidation may serve to regulate brain fatty acid levels in the absence of selective transportation. Furthermore, when β-oxidation of EPA is blocked, desaturation of EPA increases and Land׳s recycling decreases to maintain low EPA levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Oxidation kinetics of model compounds of metabolic waste in supercritical water

    Science.gov (United States)

    Webley, Paul A.; Holgate, Henry R.; Stevenson, David M.; Tester, Jefferson W.

    1990-01-01

    In this NASA-funded study, the oxidation kinetics of methanol and ammonia in supercritical water have been experimentally determined in an isothermal plug flow reactor. Theoretical studies have also been carried out to characterize key reaction pathways. Methanol oxidation rates were found to be proportional to the first power of methanol concentration and independent of oxygen concentration and were highly activated with an activation energy of approximately 98 kcal/mole over the temperature range 480 to 540 C at 246 bar. The oxidation of ammonia was found to be catalytic with an activation energy of 38 kcal/mole over temperatures ranging from 640 to 700 C. An elementary reaction model for methanol oxidation was applied after correction for the effect of high pressure on the rate constants. The conversion of methanol predicted by the model was in good agreement with experimental data.

  8. Mechanisms and evolution of oxidative sulfur metabolism in green sulfur bacteria

    DEFF Research Database (Denmark)

    Gregersen, Lea Haarup; Bryant, Donald A.; Frigaard, Niels-Ulrik

    2011-01-01

    Green sulfur bacteria (GSB) constitute a closely related group of photoautotrophic and thiotrophic bacteria with limited phenotypic variation. They typically oxidize sulfide and thiosulfate to sulfate with sulfur globules as an intermediate. Based on genome sequence information from 15 strains...... product is further oxidized to sulfite by the dissimilatory sulfite reductase (DSR) system. This system consists of components horizontally acquired partly from sulfide-oxidizing and partly from sulfate-reducing bacteria. Depending on the strain, the sulfite is probably oxidized to sulfate by one of two...... in sulfate formation in other bacteria has been replaced by the DSR system in GSB. Sequence analyses suggested that the conserved soxJXYZAKBW gene cluster was horizontally acquired by Chlorobium phaeovibrioides DSM 265 from the Chlorobaculum lineage and that this acquisition was mediated by a mobile genetic...

  9. Nitrous oxide metabolism in nitrate-reducing bacteria: Physiology and regulatory mechanisms

    OpenAIRE

    Torres, Maria; Simon, Jorg; Rowley, Gary; Bedmar, Eulogio; Richardson, David; Gates, Andrew; Delgado, Maria

    2016-01-01

    Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nit- ric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the appli- cation of synthetic nitrogen-containing fertilizers. Thus, mitigation stra...

  10. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2014-01-01

    Accumulation of damaged macromolecules, including irreversibly oxidized proteins, is a hallmark of cellular and organismal ageing. Failure of protein homesotasis is a major contributor to the age-related accumulation of damaged proteins. In skeletal muscle, tissue maintenance and regeneration...... phenotype. In addition, these findings highlight the molecular mechanisms implicated in satellite cells dysfunction during ageing, paving the road for future therapeutic interventions aimed at preventing oxidative modifications of proteins and/or stimulating their elimination....

  11. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75

    OpenAIRE

    Cáceres, Lucía; Necakov, Aleksandar S.; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J.H.; Krause, Henry M.

    2011-01-01

    Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer part...

  12. Role of glutathione metabolism status in the definition of some cellular parameters and oxidative stress tolerance of Saccharomyces cerevisiae cells growing as biofilms.

    Science.gov (United States)

    Gales, Grégoire; Penninckx, Michel; Block, Jean-Claude; Leroy, Pierre

    2008-08-01

    The resistance of Saccharomyces cerevisiae to oxidative stress (H(2)O(2) and Cd(2+)) was compared in biofilms and planktonic cells, with the help of yeast mutants deleted of genes related to glutathione metabolism and oxidative stress. Biofilm-forming cells were found predominantly in the G1 stage of the cell cycle. This might explain their higher tolerance to oxidative stress and the young replicative age of these cells in an old culture. The reduced glutathione status of S. cerevisiae was affected by the growth phase and apparently plays an important role in oxidative stress tolerance in cells growing as a biofilm.

  13. Interpretation of metabolic memory phenomenon using a physiological systems model: What drives oxidative stress following glucose normalization?

    Science.gov (United States)

    Voronova, Veronika; Zhudenkov, Kirill; Helmlinger, Gabriel; Peskov, Kirill

    2017-01-01

    Hyperglycemia is generally associated with oxidative stress, which plays a key role in diabetes-related complications. A complex, quantitative relationship has been established between glucose levels and oxidative stress, both in vitro and in vivo. For example, oxidative stress is known to persist after glucose normalization, a phenomenon described as metabolic memory. Also, uncontrolled glucose levels appear to be more detrimental to patients with diabetes (non-constant glucose levels) vs. patients with high, constant glucose levels. The objective of the current study was to delineate the mechanisms underlying such behaviors, using a mechanistic physiological systems modeling approach that captures and integrates essential underlying pathophysiological processes. The proposed model was based on a system of ordinary differential equations. It describes the interplay between reactive oxygen species production potential (ROS), ROS-induced cell alterations, and subsequent adaptation mechanisms. Model parameters were calibrated using different sources of experimental information, including ROS production in cell cultures exposed to various concentration profiles of constant and oscillating glucose levels. The model adequately reproduced the ROS excess generation after glucose normalization. Such behavior appeared to be driven by positive feedback regulations between ROS and ROS-induced cell alterations. The further oxidative stress-related detrimental effect as induced by unstable glucose levels can be explained by inability of cells to adapt to dynamic environment. Cell adaptation to instable high glucose declines during glucose normalization phases, and further glucose increase promotes similar or higher oxidative stress. In contrast, gradual ROS production potential decrease, driven by adaptation, is observed in cells exposed to constant high glucose.

  14. Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.

    Science.gov (United States)

    Wegman, Martin P; Guo, Michael H; Bennion, Douglas M; Shankar, Meena N; Chrzanowski, Stephen M; Goldberg, Leslie A; Xu, Jinze; Williams, Tiffany A; Lu, Xiaomin; Hsu, Stephen I; Anton, Stephen D; Leeuwenburgh, Christiaan; Brantly, Mark L

    2015-04-01

    Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.

  15. Positive effect of combined exercise training in a model of metabolic syndrome and menopause: autonomic, inflammatory, and oxidative stress evaluations.

    Science.gov (United States)

    Conti, Filipe Fernandes; Brito, Janaina de Oliveira; Bernardes, Nathalia; Dias, Danielle da Silva; Malfitano, Christiane; Morris, Mariana; Llesuy, Susana Francisca; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2015-12-15

    It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions. Copyright © 2015 the American Physiological Society.

  16. Enhanced metabolic versatility of planktonic sulfur-oxidizing γ-proteobacteria in an oxygen-deficient coastal ecosystem

    Directory of Open Access Journals (Sweden)

    Alejandro A. Murillo

    2014-07-01

    Full Text Available Sulfur-oxidizing Gamma-proteobacteria are abundant in marine oxygen-deficient waters, and appear to play a key role in a previously unrecognized cryptic sulfur cycle. Metagenomic analyses of members of the uncultured SUP05 lineage in the Canadian seasonally anoxic fjord Saanich Inlet (SI, hydrothermal plumes in the Guaymas Basin (GB and single cell genomics analysis of two ARCTIC96BD-19 representatives from the South Atlantic Sub-Tropical Gyre (SASG have shown them to be metabolically versatile. However, SI and GB SUP05 bacteria seem to be obligate chemolithoautotrophs, whereas ARCTIC96BD-19 has the genetic potential for aerobic respiration. Here, we present results of a metagenomic analysis of sulfur-oxidizing Gamma-proteobacteria (GSO, closely related to the SUP05/ARCTIC96BD-19 clade, from a coastal ecosystem in the eastern South Pacific (ESP. This ecosystem experiences seasonal anoxia and accumulation of nitrite and ammonium at depth, with a corresponding increase in the abundance of GSO representatives. The ESP-GSOs appear to have a significantly different gene complement than those from Saanich Inlet, Guaymas Basin and SASG. Genomic analyses of de novo assembled contigs indicate the presence of a complete aerobic respiratory complex based on the cytochrome bc1 oxidase. Furthermore, they appear to encode a complete TCA cycle and several transporters for dissolved organic carbon species, suggesting a mixotrophic lifestyle. Thus, the success of sulfur-oxidizing Gamma-proteobacteria in oxygen-deficient marine ecosystems appears due not only to their previously recognized anaerobic metabolic versatility, but also to their capacity to function under aerobic conditions using different carbon sources. Finally, members of ESP-GSO cluster also have the genetic potential for reducing nitrate to ammonium based on the nirBD genes, and may therefore facilitate a tighter coupling of the nitrogen and sulfur cycles in oxygen-deficient waters.

  17. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  18. Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

    Science.gov (United States)

    Eraslan, G; Kanbur, M; Karabacak, M; Arslan, K; Siliğ, Y; Soyer Sarica, Z; Tekeli, M Y; Taş, A

    2017-01-01

    A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg -1 body weight (b.w.); acute stage), at a dose of 7.5 g kg -1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg -1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

  19. Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect

    NARCIS (Netherlands)

    Rosewich, H.; Waterham, H. R.; Wanders, R. J. A.; Ferdinandusse, S.; Henneke, M.; Hunneman, D.; Gärtner, J.

    2006-01-01

    We present a rare case of peroxisomal acyl-CoA oxidase deficiency that was not detected by the common metabolic screening program for peroxisomal disorders. The patient presented with a typical MRI pattern showing pachygyria, perisylvian polymicrogyria, cerebral and cerebellar white matter

  20. Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

    DEFF Research Database (Denmark)

    Hohnholt, Michaela C; Andersen, Vibe H; Andersen, Jens V

    2017-01-01

    by glutamate was significantly lower in brain mitochondria from GDH KO mice and synaptosomes were not able to increase their respiration upon an elevated energy demand. The role of GDH for metabolism of glutamine and the respiratory capacity underscore the importance of GDH for neurons particularly during...

  1. Metabolic evidence of diminished lipid oxidation in women with polycystic ovary syndrome

    Science.gov (United States)

    Complex diseases, such as polycystic ovary syndrome (PCOS), are not limited to specific genes, pathogens, toxicoses, or identifiable environmental influences. PCOS still remains a diagnosis of exclusion despite being the most common female endocrinopathy and the leading cause of metabolic syndrome, ...

  2. C1 Metabolism in Corynebacterium glutamicum: an Endogenous Pathway for Oxidation of Methanol to Carbon Dioxide

    Science.gov (United States)

    Witthoff, Sabrina; Mühlroth, Alice

    2013-01-01

    Methanol is considered an interesting carbon source in “bio-based” microbial production processes. Since Corynebacterium glutamicum is an important host in industrial biotechnology, in particular for amino acid production, we performed studies of the response of this organism to methanol. The C. glutamicum wild type was able to convert 13C-labeled methanol to 13CO2. Analysis of global gene expression in the presence of methanol revealed several genes of ethanol catabolism to be upregulated, indicating that some of the corresponding enzymes are involved in methanol oxidation. Indeed, a mutant lacking the alcohol dehydrogenase gene adhA showed a 62% reduced methanol consumption rate, indicating that AdhA is mainly responsible for methanol oxidation to formaldehyde. Further studies revealed that oxidation of formaldehyde to formate is catalyzed predominantly by two enzymes, the acetaldehyde dehydrogenase Ald and the mycothiol-dependent formaldehyde dehydrogenase AdhE. The Δald ΔadhE and Δald ΔmshC deletion mutants were severely impaired in their ability to oxidize formaldehyde, but residual methanol oxidation to CO2 was still possible. The oxidation of formate to CO2 is catalyzed by the formate dehydrogenase FdhF, recently identified by us. Similar to the case with ethanol, methanol catabolism is subject to carbon catabolite repression in the presence of glucose and is dependent on the transcriptional regulator RamA, which was previously shown to be essential for expression of adhA and ald. In conclusion, we were able to show that C. glutamicum possesses an endogenous pathway for methanol oxidation to CO2 and to identify the enzymes and a transcriptional regulator involved in this pathway. PMID:24014532

  3. Solar photocatalytic oxidation of recalcitrant natural metabolic by-products of amoxicillin biodegradation.

    Science.gov (United States)

    Pereira, João H O S; Reis, Ana C; Homem, Vera; Silva, José A; Alves, Arminda; Borges, Maria T; Boaventura, Rui A R; Vilar, Vítor J P; Nunes, Olga C

    2014-11-15

    The contamination of the aquatic environment by non-metabolized and metabolized antibiotic residues has brought the necessity of alternative treatment steps to current water decontamination technologies. This work assessed the feasibility of using a multistage treatment system for amoxicillin (AMX) spiked solutions combining: i) a biological treatment process using an enriched culture to metabolize AMX, with ii) a solar photocatalytic system to achieve the removal of the metabolized transformation products (TPs) identified via LC-MS, recalcitrant to further biological degradation. Firstly, a mixed culture (MC) was obtained through the enrichment of an activated sludge sample collected in an urban wastewater treatment plant (WWTP). Secondly, different aqueous matrices spiked with AMX were treated with the MC and the metabolic transformation products were identified. Thirdly, the efficiency of two solar assisted photocatalytic processes (TiO2/UV or Fe(3+)/Oxalate/H2O2/UV-Vis) was assessed in the degradation of the obtained TPs using a lab-scale prototype photoreactor equipped with a compound parabolic collector (CPC). Highest AMX specific biodegradation rates were obtained in buffer and urban wastewater (WW) media (0.10 ± 0.01 and 0.13 ± 0.07 g(AMX) g(biomass)(-1) h(-1), respectively). The resulting TPs, which no longer presented antibacterial activity, were identified as amoxicilloic acid (m/z = 384). The performance of the Fe(3+)/Oxalate/H2O2/UV-Vis system in the removal of the TPs from WW medium was superior to the TiO2/UV process (TPs no longer detected after 40 min (QUV = 2.6 kJ L(-1)), against incomplete TPs removal after 240 min (QUV = 14.9 kJ L(-1)), respectively). Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Oxidative stress and homocyteine metabolism following coronary artery grafting by on pump and off pump CABG techniques

    International Nuclear Information System (INIS)

    Parvizi, R.; Noubar, R.; Salmasi, H.S.

    2007-01-01

    To compare the effect of on-pump and off-pump CABG on the induction of the oxidative stress and the metabolism of homocysteine, which is involved in the synthesis of glutathione. This retrospective study was performed in Shahid Madani Heart Hospital in Tabriz, Iran in 2004 using a questionnaire. Plasma homocysteine, folate total antioxidant capacity (TAC) and malonedialdehyde (MDA) were determined on blood samples obtained from 40 patients undergoing CABG, preoperatively and at 0,12,48,120 hours and 6 months after surgery. The patients were divided into two matched groups, one off-pump and the other on-pump CABG. A marked reduction of homocysteine, folate and significant elevation of MDA were noticed at 0, 12, 48 hours after operation in the both groups (P<0.05). A negative and marked correlation between homocysteine and TAC but a positive and significant between homocysteinc and MDA were observed (P<0.05 in the both groups). In CABG operation because of oxidative stress and consumption of GSH immediate reduction in the plasma levels of homocyticine occurs in the both techniques. However using off pump CABG induction of oxidative stress and changes in plasma levels of homocysteine are not as high as on- pump CABG. (author)

  5. The possible influences of dietary oil supplementation in ameliorating metabolic disturbances and oxidative stress in Alloxan injected rats

    International Nuclear Information System (INIS)

    Farag, M.F.S.; Osman, N.N.; Darwish, M.M.

    2005-01-01

    Diabetes mellitus (DM) is a multifactor disease that is associated with a number of different metabolic abnormalities. Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with DM. The present work was conducted to examine the protective or treating effects of two different dietary oils rich in medium chain fatty acids (MCFA) as coconut oil (CO) or omega-3-polyunsaturated fatty acids (ω-3-PUFAs)as flaxseed oil (FO) on the severity of DM induced experimentally by alloxan injection. Wistar strain albino rats (17 Og) were fed commercial rat chow diet supplemented with either CO or FO for four weeks. A single dose of alloxan (150 mg/kg) resulted in hyperglycemia, decreases in serum insulin, thyroxine (T 4 ), and high density lipoprotein-cholesterol levels, elevated triglycerides, total cholesterol and low density lipoprotein-cholesterol concentrations. Concurrent with those changes, an increased liver malonaldehyde (MDA) level was observed. This oxidative stress was related to decreases in superoxide dismutase (SOD) activity and glutathione (GSH) content in the liver of alloxan diabetic rats. Oils supplementation after diabetes induction ameliorated hyperglycemia, increased insulin and thyroxine hormone levels, improved lipid profiles, blunted the increase in MDA, modulated the levels of hepatic SOD activity and GSH content of alloxan treated rats. It could be suggested that each of CO or FO could be used as antidiabetic complement in case of DM. This may be related to their anti oxidative properties

  6. Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Juliana Alves Parente-Rocha

    Full Text Available Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD, thioredoxins (THX and cytochrome c peroxidase (CCP. Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection.

  7. Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

    Science.gov (United States)

    dos Santos, Rafael S; Donadio, Márcio V F; da Silva, Gabriela V; Blattner, Clarissa N; Melo, Denizar A S; Nunes, Fernanda B; Dias, Fernando S; Squizani, Eamim D; Pedrazza, Leonardo; Gadegast, Isabella; de Oliveira, Jarbas R

    2014-09-01

    Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors stress were evaluated before and 15 min after physiotherapy. Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. Copyright © 2014 by Daedalus Enterprises.

  8. Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells.

    Science.gov (United States)

    Kim, Yong-Dae; Lantz-McPeak, Susan M; Ali, Syed F; Kleinman, Michael T; Choi, Young-Sook; Kim, Heon

    2014-05-01

    A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO(2)) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO(2) levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid......), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  10. Metabolism of clebopride in vitro. Identification of N-oxidized products.

    Science.gov (United States)

    Huizing, G; Beckett, A H

    1980-01-01

    1. N-(1'-Benzyl-4'-piperidyl-N-oxide)-4-amino-5-chloro-2-methoxybenzamide, N-(4'-(N-hydroxylpiperidyl)-4-amino-5-chloro-2-methoxybenzamide and N-(4'-(delta 1'-piperidyl-N-oxide))-4-amino-5-chloro-2-methoxybenzamide were obtained from chloroform extracts of incubation mixtures of clebopride or desbenzyl clebopride with 9000 g supernatant of liver homogenates of male NZW rabbits. 2. These metabolites were identified using electron impact (low and high resolution) and field desorption mass spectrometry, and computer averaged time proton magnetic resonance spectroscopy.

  11. Deuterium oxide as a tool for the study of amino acid metabolism

    International Nuclear Information System (INIS)

    Mitra, R.; Burton, J.; Varner, J.E.

    1976-01-01

    We have used deuterium oxide in nontoxic concentrations to study, in intact seedlings, the biosynthesis of amino acids. The extent and pattern of deuteration, as determined by a gas--liquid chromatograph--mass spectrometer system, permits conclusions about the biosynthesis of individual amino acids and also about their exposure to transaminases and other enzymes that might introduce deuterium into specific positions of the amino acid by exchange. This method could be used to study amino acid biogenesis in any organism that can tolerate 20 to 40 percent deuterium oxide for a period of a few hours to a few days

  12. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.

    Science.gov (United States)

    Cáceres, Lucía; Necakov, Aleksandar S; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J H; Krause, Henry M

    2011-07-15

    Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.

  13. Acute effect of glucose on cerebral blood flow, blood oxygenation, and oxidative metabolism.

    Science.gov (United States)

    Xu, Feng; Liu, Peiying; Pascual, Juan M; Xiao, Guanghua; Huang, Hao; Lu, Hanzhang

    2015-02-01

    While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose-sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole-brain metabolism is not completely understood. Several recent reports have elucidated the long-term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O2 (CMRO2 ) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO2 was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post-ingestion, the amount of CMRO2 reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO2 , CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. © 2014 Wiley Periodicals, Inc.

  14. In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism.

    Science.gov (United States)

    Gao, Jianjun; Kashfi, Khosrow; Rigas, Basil

    2005-03-01

    NO-donating aspirin (NO-ASA) is a potentially important chemopreventive agent against cancer. Since positional isomerism affects strongly its potency in inhibiting colon cancer cell growth, we studied the metabolic transformations of its ortho-, meta-, and para-isomers in rat liver and colon cytosolic, microsomal, and mitochondrial fractions as well as in intact HT-29 human colon cancer cells. NO-ASA and metabolites were determined by high-performance liquid chromatography and products identified by mass spectroscopy, as required. For all three isomers, the acetyl group on the ASA moiety was hydrolyzed rapidly. This was followed by hydrolysis of the ester bond linking the salicylate anion to the spacer. The ortho- and para-isomers produced salicylic acid and a putative intermediate consisting of the remainder of the molecule, which via a rapid step generated nitrate, (hydroxymethyl)phenol, and a conjugate of spacer with glutathione. The meta-isomer, in contrast, generated salicylic acid and (nitroxymethyl)phenol, the latter leading to (hydroxymethyl)phenol and the glutathione-spacer conjugate. This metabolic pathway takes place in its entirety only in the cytosolic fraction of the tissues tested and in intact human colon cancer cells, perhaps reflecting exposure to the cytosolic glutathione S-transferase, which catalyzes the formation of the spacer-glutathione conjugate. Thus, the three positional isomers of NO-ASA differ in their metabolism and these differences correlate with their differential effects on cancer cell growth, underscoring the importance of positional isomerism in modulating drug effects.

  15. COPPER AND COPPER-CONTAINING PESTICIDES: METABOLISM, TOXICITY AND OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Viktor Husak

    2015-05-01

    Full Text Available The purpose of this paper is to provide a brief review of the current knowledge regarding metabolism and toxicity of copper and copper-based pesticides in living organisms. Copper is an essential trace element in all living organisms (bacteria, fungi, plants, and animals, because it participates in different metabolic processes and maintain functions of organisms. The transport and metabolism of copper in living organisms is currently the subject of many studies. Copper is absorbed, transported, distributed, stored, and excreted in the body via the complex of homeostatic processes, which provide organisms with a needed constant level of this micronutrient and avoid excessive amounts. Many aspects of copper homeostasis were studied at the molecular level. Copper based-pesticides, in particularly fungicides, bacteriocides and herbicides, are widely used in agricultural practice throughout the world. Copper is an integral part of antioxidant enzymes, particularly copper-zinc superoxide dismutase (Cu,Zn-SOD, and plays prominent roles in iron homeostasis. On the other hand, excess of copper in organism has deleterious effect, because it stimulates free radical production in the cell, induces lipid peroxidation, and disturbs the total antioxidant capacity of the body. The mechanisms of copper toxicity are discussed in this review also.

  16. Unveiling the oxidative metabolism of Rhipicephalus microplus (Acari: Ixodidae) experimentally exposed to entomopathogenic fungi.

    Science.gov (United States)

    Tunholi-Alves, Vinícius Menezes; Tunholi Alves, Victor Menezes; da Silva, Jairo Pinheiro; Nora Castro, Rosane; Salgueiro, Fernanda Barbosa; Perinotto, Wendell Marcelo de Souza; Gôlo, Patrícia Silva; Camargo, Mariana Guedes; Angelo, Isabele da Costa; Bittencourt, Vânia Rita Elias Pinheiro

    2016-10-01

    Rhipicephalus microplus is an important tick in tropical regions due to the high economic losses caused by its parasitism. Metarhizium anisopliae and Beauveria bassiana are well-known entomopathogenic fungi that can afflict R. microplus ticks. The development of new targets and strategies to control this parasite can be driven by studies of this tick's physiology. Recently, it was reported that when exposed to adverse physiological conditions, ticks can activate fermentative pathways, indicating transition from aerobic to anaerobic metabolism. Nevertheless, the precise mechanism by which entomopathogenic fungi influence R. microplus metabolism has not been clarified, limiting understanding of the tick-fungus association. Thus, the present study aimed to evaluate the effect of infection of ticks by M. anisopliae and B. bassiana on the amount of selected carboxylic acids present in the hemolymph, enabling increased understanding of changes previously reported. The results showed preservation in the concentrations of oxalic, lactic, and pyruvic acids in the hemolymph 24 and 48 h after dropping from cattle; while there were variations in the concentration of these carboxylic acids after infection of female ticks to M. anisopliae and B. bassiana. Significant increases were observed in the concentration of oxalic and lactic acids and significant reduction of pyruvic acid for both observation times (24 and 48 h) after infection by entomopathogenic fungi. These results indicate that B. bassiana and M. anisopliae infection alters the basal metabolism of R. microplus females, resulting in the activation of fermentative pathways.

  17. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  18. Oxidative stress status, antioxidant metabolism and polypeptide patterns in Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon (Portugal).

    Science.gov (United States)

    Anjum, Naser A; Duarte, Armando C; Pereira, Eduarda; Ahmad, Iqbal

    2014-05-01

    This study assessed the oxidative stress status, antioxidant metabolism and polypeptide patterns in salt marsh macrophyte Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon at reference and the sites with highest, moderate and the lowest mercury contamination. In order to achieve these goals, shoot-mercury burden and the responses of representative oxidative stress indices, and the components of both non-glutathione- and glutathione-based H2O2-metabolizing systems were analyzed and cross-talked with shoot-polypeptide patterns. Compared to the reference site, significant elevations in J. maritimus shoot mercury and the oxidative stress indices such as H2O2, lipid peroxidation, electrolyte leakage and reactive carbonyls were maximum at the site with highest followed by moderate and the lowest mercury contamination. Significantly elevated activity of non-glutathione-based H2O2-metabolizing enzymes such as ascorbate peroxidase and catalase accompanied the studied damage-endpoint responses, whereas the activity of glutathione-based H2O2-scavenging enzymes glutathione peroxidase and glutathione sulfo-transferase was inhibited. Concomitantly, significantly enhanced glutathione reductase activity and the contents of both reduced and oxidized glutathione were perceptible in high mercury-exhibiting shoots. It is inferred that high mercury-accrued elevations in oxidative stress indices were obvious, where non-glutathione-based H2O2-decomposing enzyme system was dominant over the glutathione-based H2O2-scavenging enzyme system. In particular, the glutathione-based H2O2-scavenging system failed to coordinate with elevated glutathione reductase which in turn resulted into increased pool of oxidized glutathione and the ratio of oxidized glutathione-to-reduced glutathione. The substantiation of the studied oxidative stress indices and antioxidant metabolism with approximately 53-kDa polypeptide warrants further studies.

  19. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome

    NARCIS (Netherlands)

    Schreurs, M.; Kuipers, F.; van der Leij, F. R.

    P>Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial beta-oxidation and is inhibited by malonyl-CoA, the product of acetyl-CoA carboxylase (ACC). The adenosine

  20. Ripening, storage temperature, ethylene action, and oxidative stress alter apple peel phytosterol metabolism

    Science.gov (United States)

    The chilling conditions of apple cold storage can provoke an economically significant necrotic peel disorder called superficial scald (scald) in susceptible cultivars. Disorder development can be reduced by inhibiting ethylene action or oxidative stress. We found previously that scald is preceded b...

  1. Establishment of oxidative D-xylose metabolism in Pseudomonas putida S12

    NARCIS (Netherlands)

    Meijnen, J.P.; Winde, J.H. de; Ruijssenaars, H.J.

    2009-01-01

    The oxidative D-xylose catabolic pathway of Caulobacter crescentus, encoded by the xylXABCD operon, was expressed in the gram-negative bacterium Pseudomonas putida S12. This engineered transformant strain was able to grow on D-xylose as a sole carbon source with a biomass yield of 53% (based on g

  2. Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

    Background. The PNA (protein equivalent of nitrogen appearance) is used to calculate protein intake from urea kinetics. One of the essential assumptions in the calculation of PNA is that urea accumulation in haemodialysis (HD) patients is equivalent to amino acid oxidation. However, urea is

  3. Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martín A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2016-01-01

    Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging are not...

  4. Free Radical Oxidation Induced by Iron Metabolism Disorder in Femoral and Pelvic Fractures and Potential for Its Correction

    Directory of Open Access Journals (Sweden)

    Y. P. Orlov

    2016-01-01

    Full Text Available Objective: To determine the pathogenic significance of iron ions in the activation of free radical oxidation in trau matic disease and valuate the efficacy of Desferal in the complex therapy of patients with femoral and pelvic fractions.Materials and methods. Iron metabolism and the intensity of free radical oxidation have been studed in 30 patients with traumas. The patients were randomized into two groups by gender, age and the severity of injury. Group I (n=15 included the injured patients who received the standard intensive therapy. Group II (n=15 included the patients who were treated with Desferal of 8 mg/kg twice daily in 12 hours along with the intensive therapy. The control group comprized of 10 healthy individuals of the same age. The concentration of total and free hemoglobine, serum iron, transferrin, total antioxidant activity of blood serum, the intensity of free radical oxida tion by the Fe2+induced chemiluminescence and hemostatic parameters were studied on admittance as well as on 3rd and 5th day of hospitalization. The parameters of sistemic hemodyamics were checked by integral rheovasog raphy. Statistical processing of data was carried out using Biostat and MS Excel software. The results were pre sented as a mean and standart deviation (M±δ. The Student’s (t and MannWhitney tests were used to prove the hypotheses. The critical level of significance was P=0.05.Results. It was determined that the disorders of iron metabolism in patients with traumatic disease were accompanied by intra and extravascular hemolysis, the excess off reduced iron ions catalizing the free radical oxidation, and failure of antioxidant system and disorders of hemostatic system and central hemodynamics. Desferal lowered the level of reduced iron in blood serum, diminished the intensity of free radical oxidation and eliminated the disorders in hemostasis and systemic hemodynamics.Conclusion. Data confirm the pathogenic role of iron ions in the

  5. Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Mady Charles

    2007-09-01

    Full Text Available Abstract Background In patients with advanced non-ischemic cardiomyopathy (NIC, right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA flow pattern and flow reserve (CFR are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire data was obtained in RCA and left anterior descendent coronary artery (LAD before and after adenosine. Resting RCA phasic pattern (diastolic/systolic was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 ± 3.5 % and 69.4 ± 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS; RCA vs. LAD was 1.35 vs. 2.85 (p Conclusion In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or

  6. Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.

    Science.gov (United States)

    Mayevsky, A; Nioka, S; Subramanian, V H; Chance, B

    1988-04-01

    The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

    Science.gov (United States)

    Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

    2009-01-01

    Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

  8. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    Science.gov (United States)

    Feng, Jianghua; Zhao, Jing; Hao, Fuhua; Chen, Chang; Bhakoo, Kishore; Tang, Huiru

    2011-05-01

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  9. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    International Nuclear Information System (INIS)

    Feng Jianghua; Zhao Jing; Hao Fuhua; Chen Chang; Bhakoo, Kishore; Tang, Huiru

    2011-01-01

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  10. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ...

  11. Nitrous Oxide Metabolism in Nitrate-Reducing Bacteria: Physiology and Regulatory Mechanisms.

    Science.gov (United States)

    Torres, M J; Simon, J; Rowley, G; Bedmar, E J; Richardson, D J; Gates, A J; Delgado, M J

    2016-01-01

    Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nitric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the application of synthetic nitrogen-containing fertilizers. Thus, mitigation strategies must be developed which increase (or at least do not negatively impact) on agricultural efficiency whilst decrease the levels of N2O released. This aim is particularly important in the context of the ever expanding population and subsequent increased burden on the food chain. More than two-thirds of N2O emissions from soils can be attributed to bacterial and fungal denitrification and nitrification processes. In ammonia-oxidizing bacteria, N2O is formed through the oxidation of hydroxylamine to nitrite. In denitrifiers, nitrate is reduced to N2 via nitrite, NO and N2O production. In addition to denitrification, respiratory nitrate ammonification (also termed dissimilatory nitrate reduction to ammonium) is another important nitrate-reducing mechanism in soil, responsible for the loss of nitrate and production of N2O from reduction of NO that is formed as a by-product of the reduction process. This review will synthesize our current understanding of the environmental, regulatory and biochemical control of N2O emissions by nitrate-reducing bacteria and point to new solutions for agricultural GHG mitigation. © 2016 Elsevier Ltd. All rights reserved.

  12. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    OpenAIRE

    Lee, Jieun; Wolfgang, Michael J

    2012-01-01

    Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to...

  13. Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

    DEFF Research Database (Denmark)

    Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne

    2015-01-01

    BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate...... that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. METHODS: Cerebral energy metabolism was monitored in 15 patients with severe...... community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

  14. Enhanced sulfamethoxazole degradation through ammonia oxidizing bacteria co-metabolism and fate of transformation products.

    Science.gov (United States)

    Kassotaki, Elissavet; Buttiglieri, Gianluigi; Ferrando-Climent, Laura; Rodriguez-Roda, Ignasi; Pijuan, Maite

    2016-05-01

    The occurrence of the widely-used antibiotic sulfamethoxazole (SFX) in wastewaters and surface waters has been reported in a large number of studies. However, the results obtained up-to-date have pointed out disparities in its removal. This manuscript explores the enhanced biodegradation potential of an enriched culture of Ammonia Oxidizing Bacteria (AOB) towards SFX. Several sets of batch tests were conducted to establish a link between SFX degradation and specific ammonia oxidation rate. The occurrence, degradation and generation of SFX and some of its transformation products (4-Nitro SFX, Desamino-SFX and N(4)-Acetyl-SFX) was also monitored. A clear link between the degradation of SFX and the nitrification rate was found, resulting in an increased SFX removal at higher specific ammonia oxidation rates. Moreover, experiments conducted under the presence of allylthiourea (ATU) did not present any removal of SFX, suggesting a connection between the AMO enzyme and SFX degradation. Long term experiments (up to 10 weeks) were also conducted adding two different concentrations (10 and 100 μg/L) of SFX in the influent of a partial nitrification sequencing batch reactor, resulting in up to 98% removal. Finally, the formation of transformation products during SFX degradation represented up to 32%, being 4-Nitro-SFX the most abundant. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Effects of Ropivacaine and Bupivacaine on Rabbit Myocardial Energetic Metabolism and Mitochondria Oxidation

    Institute of Scientific and Technical Information of China (English)

    张诗海; 姚尚龙; 李晴

    2003-01-01

    Summary: To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigatethe mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into controlgroup (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawnout rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropiva-caine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution.Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chro-matogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine wasdetected with Clark electrode. Our results showed that myocardial ATP and ADP decreased signifi-cantly (P<0. 05) in group R and most significantly (P<0. 01) in group B as compared with groupC. Myocardial ATP and ADP decreased most significantly (P<0. 01) in group B as compared withgroup R. The changes of myocardial AMP revealed significant difference among three groups. Thechanges of pyruvate oxidation exibited no significant difference among the three groups. Palmitoyl-carnitine oxidation decreased markedly (P<0. 05) in group R and most significantly (P<0. 01) ingroup B as compared with group C. The present study indicated that the inhibition of lipid substrateoxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The car-diotoxicity induced by ropivacaine is far more less than bupivacaine.

  16. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  17. Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

    Science.gov (United States)

    Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

    2018-05-01

    Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

  18. MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

    Science.gov (United States)

    Sahoo, Anupama; Lee, Bongyong; Boniface, Katia; Seneschal, Julien; Sahoo, Sanjaya K; Seki, Tatsuya; Wang, Chunyan; Das, Soumen; Han, Xianlin; Steppie, Michael; Seal, Sudipta; Taieb, Alain; Perera, Ranjan J

    2017-09-01

    Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    Science.gov (United States)

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-05

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

  20. The effects of resveratrol on hepatic oxidative stress in metabolic syndrome model induced by high fructose diet.

    Science.gov (United States)

    Yilmaz Demirtas, C; Bircan, F S; Pasaoglu, O T; Turkozkan, N

    2018-01-01

    The purpose of this study was to evaluate probable protective effects of resveratrol treatment on hepatic oxidative events in a rat model of metabolic syndrome (MetS). Thirty-two male adult rats were randomly divided into 4 groups: control, fructose, resveratrol, and fructose plus resveratrol. To induce MetS, fructose solution (20 % in drinking water) was used. Resveratrol (10 mg/kg/day) was given by oral gavage. All treatments were given for 8 weeks. Serum lipid profile, glucose and insulin levels, liver total oxidant status (TOS) levels and paraoxonase (PON), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were analyzed. Fructose-fed rats displayed statistically significant increases in TOS levels, and decreases in PON activity compared to the control group. Resveratrol treatment moderately prevented the decrease in liver PON activity caused by fructose. On the other hand, resveratrol, alone or in combination with fructose, did not change the TOS levels when compared to the fructose group. The SOD and CAT activities in all groups did not change. In this experimental design, high-fructose consumption led to elevated TOS levels and low PON activities. The resveratrol therapy shown beneficial effects on PON activity. However, it was found to behave like a prooxidant when administered together with fructose and alone in some parameters. Our results can inspire the development of new clinical therapy in patients with MetS (Tab. 2, Ref. 34).

  1. The Effects Of Two Fitness Programs With Different Metabolic Demands On Oxidative Stress In The Blood Of Young Females

    Directory of Open Access Journals (Sweden)

    Djordjevic Dusica

    2015-06-01

    Full Text Available The aim of the present study was to assess the effects of two metabolically different exercise programs on the redox state of women who were physically inactive before the beginning of the study. For this purpose, participants (women 25±5 years old chose one of two popular fitness programs, Pilates or Tae Bo, and attended it 3 times a week for 12 weeks. At the beginning and end of the study, body composition analysis and venous blood sampling were performed. The levels of superoxide anion radical, hydrogen peroxide, nitric oxide and lipid peroxidation were measured in plasma, and the levels of reduced glutathione and the activity of superoxide dismutase and catalase were measured in erythrocytes. Only the Tae Bo program induced changes (positive in body composition, whereas both exercise programs induced slight oxidative stress in exercisers. In the Tae Bo group, the levels of hydrogen peroxide were significantly increased, whereas the levels of reduced glutathione were decreased after three months of training. In the Pilates group, hydrogen peroxide and catalase activity were increased, and nitrites decreased. However, at the end of the study, those two groups had no significantly different values for any pro/antioxidant compared with the subjects who served as controls. This finding suggests that moderate physical activity, such as recreational fitness programs, may induce the increased production of reactive oxygen species but do not lead to a serious disturbance of the redox homeostasis of exercisers.

  2. Low density lipoprotein for oxidation and metabolic studies. Isolation from small volumes of plasma using a tabletop ultracentrifuge.

    Science.gov (United States)

    Himber, J; Bühler, E; Moll, D; Moser, U K

    1995-01-01

    A rapid method is described for the isolation of small volumes of plasma low density lipoprotein (LDL) free of plasma protein contaminants using the TL-100 Tabletop Ultracentrifuge (Beckman). The isolation of LDL was achieved by a 25 min discontinuous gradient density centrifugation between the density range of 1.006 and 1.21 g/ml, recovery of LDL by tube slicing followed by a 90 min flotation step (d = 1.12 g/ml). The purity of LDL and apolipoprotein B100 (apo B100) were monitored by agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), radial immunodiffusion and micropreparative fast protein liquid chromatography (FPLC). The ability of LDL oxidation was assessed by following absorbance at 234 nm after addition of copper ions. The functional integrity of the isolated LDL was checked by clearance kinetics after injection of [125I]-labelled LDL in estrogen-treated rats. The additional purification step led to LDL fractions free of protein contamination and left apo B100, alpha-tocopherol and beta-carotene intact. The LDL prepared in this way was free of albumin, as evident from analytic tests and from its enhanced oxidative modification by copper ions. Used for analytical purposes, this method allows LDL preparations from plasma volumes up to 570 microliters. This method is also convenient for metabolic studies in small animals, especially those relating to the determination of kinetic parameters of LDL in which LDL-apo B100 has to be specifically radiolabelled.

  3. The incidences of oxidative –stress occurrence following two metabolic support measures in critically ill patients

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    Mojtaba Mojtahedzadeh

    2013-02-01

    Full Text Available Background: A high percentage of patients admitted to the intensive care unit (ICU have systemic inflammatory response syndrome (SIRS criteria. Free radicals play an important role in initiation and development of SIRS. The purpose of this study was to assess and compare the molecular changes of cellular antioxidant power in patients with SIRS who received enteral nutrition (EN or EN combined with parenteral nutrition (PN. Methods: Two groups of 10 patients were enrolled in this randomized, controlled clinical trial. Those in the treatment group received EN+PN and the control group received only EN. Venous blood samples were taken just prior to initiation of nutritional support and then 24, 48 and 72 hours following entry into the study for examination of antioxidant parameters including total thiol, total antioxidant capacity and lipid peroxidation. Results: The two supportive regimens had different affects on total antioxidant capacity (P=0.005. In the EN group the amount of total antioxidant capacity was not significantly different in different days (P>0.05, but in the EN+PN group it was significantly different on third and forth days as compared to the first day. The two other parameters had no significant differences between the two groups. Conclusion: These results are suggesting that an increase in oxidative stress bio-markers are not necessarily related to the route of pharmaconutrition and may occur independently during metabolic support measures. Keywords: Parenteral Nutrition, Enteral Nitrition, Systemic Inflammatory Response Syndrome, Oxidative stress

  4. Oxidative and nonoxidative metabolism of polycyclic aromatic hydrocarbons in rabbit and chicken aortas and in human fetal smooth-muscle cells

    International Nuclear Information System (INIS)

    Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

    1980-01-01

    A description of the various enzyme systems in aortas of rabbits and chickens and in human fetal smooth muscle cells in culture which are responsible overall for the metabolism of F, 12-dimethylbenz(a)anthracene and benzo(a)pyrene-4, 5-oxide are provided

  5. Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung.

    Science.gov (United States)

    Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

    2017-02-20

    Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

  6. Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

    DEFF Research Database (Denmark)

    Petersson, Stine J; Christensen, Louise L; Kristensen, Jonas M

    2014-01-01

    therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. METHODS: Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13......) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative......: The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable...

  7. Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

    Science.gov (United States)

    Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

    2017-11-01

    Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

  8. Paraquat administration in Drosophila for use in metabolic studies of oxidative stress.

    Science.gov (United States)

    Rzezniczak, T Z; Douglas, L A; Watterson, J H; Merritt, T J S

    2011-12-15

    Paraquat (PQ) is widely used in the laboratory to induce in vivo oxidative stress, particularly in the fruit fly, Drosophila melanogaster. PQ administration to the fly traditionally involves feeding in a 1% sucrose solution; however, a diet high in sucrose can itself be stressful. We examined a novel method of PQ administration: incorporation into the fly's standard cornmeal-sucrose-yeast diet. This method successfully delivers PQ to the fly at concentrations similar to those of the traditional method but with fewer possibly confounding complications. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Propolis Supplementation and the Changes in the Oxidative Metabolism of Blood Platelets Exposed to Electromagnetic Radiation

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    Henrykowska Gabriela

    2015-03-01

    Full Text Available Introduction. Electromagnetic radiation (EMR that has an effect on living organisms may be a source of oxidative stress. A lack of proper compensation by antioxidant defences on the part of proteins leading to an uncontrolled growth of reactive forms of oxygen, which may give rise to numerous health conditions. Various scientific studies have indicated that propolis has multiple valuable medicinal properties: antibacterial, anti-inflammatory, antioxidant, protective - in relation to liver parenchyma, as well as anti-cancer. Nonetheless, the results of studies concerned with its antioxidant capabilities are not explicit and require further tests and analyses.

  10. Effect of metabolic gases and water vapor, perfluorocarbon emulsions, and nitric oxide on tissue bubbles during decompression sickness.

    Science.gov (United States)

    Randsøe, Thomas

    2016-05-01

    In aviation and diving, fast decrease in ambient pressure, such as during accidental loss of cabin pressure or when a diver decompresses too fast to sea level, may cause nitrogen (N2) bubble formation in blood and tissue resulting in decompression sickness (DCS). Conventional treatment of DCS is oxygen (O2) breathing combined with recompression.  However, bubble kinetic models suggest, that metabolic gases, i.e. O2 and carbon dioxide (CO2), and water vapor contribute significantly to DCS bubble volume and growth at hypobaric altitude exposures. Further, perfluorocarbon emulsions (PFC) and nitric oxide (NO) donors have, on an experimental basis, demonstrated therapeutic properties both as treatment and prophylactic intervention against DCS. The effect was ascribed to solubility of respiratory gases in PFC, plausible NO elicited nuclei demise and/or N2 washout through enhanced blood flow rate. Accordingly, by means of monitoring injected bubbles in exposed adipose tissue or measurements of spinal evoked potentials (SEPs) in anaesthetized rats, the aim of this study was to: 1) evaluate the contribution of metabolic gases and water vapor to bubble volume at different barometrical altitude exposures, 2) clarify the O2 contribution and N2 solubility from bubbles during administration of PFC at normo- and hypobaric conditions and, 3) test the effect of different NO donors on SEPs during DCS upon a hyperbaric air dive and, to study the influence of  NO on tissue bubbles at high altitude exposures. The results support the bubble kinetic models and indicate that metabolic gases and water vapor contribute significantly to bubble volume at 25 kPa (~10,376 m above sea level) and constitute a threshold for bubble stabilization or decay at the interval of 47-36 kPa (~6,036 and ~7,920 m above sea level). The effect of the metabolic gases and water vapor seemed to compromise the therapeutic properties of both PFC and NO at altitude, while PFC significantly increased bubble

  11. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

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    Nady Braidy

    2011-04-01

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

  12. The effects of vitamin-E on oxidative stress and metabolic imbalance induced by acute unilateral ureteral obstruction in anaesthetized rats

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    Shirazi M

    2008-12-01

    Full Text Available "nBackground: Obstructive nephropathy has been associated with disorders in metabolism state and oxidative balance of kidney. Stress oxidative play a key role in the pathophysiological processes of renal diseases. The objective of this study was to investigate effects of vitamin-E, as a powerful antioxidant, on renal oxidative stress and metabolism defect induced by 24-hr unilateral ureteral obstruction (UUO. "nMethods: Anesthetized male Sprague-Dawley rats (n=10 in each group were sterilely operated to occlude the left ureter. In UUO+NS, we had a single dose normal saline injection and in UUO+VitE and UUO+OO groups, D-α-tocopherol (50 mg/kg, the main component of vitamin-E, and its vehicle (Olive Oil, respectively, were twicely infused I.P. before and after UUO-induction. There were also sham-operated and control groups. 24-hr after of UUO-induction, both kidneys were removed and stored in -70°C. To determine metabolism condition, the levels of ATP and ADP; and to evaluate redox state, the levels of malondialdehyde (MDA and ferric reducing/antioxidant power (FRAP of kidneys were assessed. "nResults: The comparisons between UUO+NS and sham groups indicated that UUO increased MDA (p<0.001 and ADP (p<0.05, but decreased FRAP, and ATP/ADP ratio in obstructed kidney (all p<0.001. In UUO+VitE group, MDA and FRAP were equal to their levels in sham group, while ATP, ADP and ATP/ADP ratio were not different from those of UUO+NS group in obstructed kidney. "nConclusion: Twenty four hour of UUO caused renal reduction in oxidative metabolism and elevations in reactive oxygen species; and administration of vitamin-E, although considerably ameliorated the oxidative stress, could not improve the defected metabolism.

  13. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Science.gov (United States)

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  14. Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

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    Antonietta Messina

    2018-03-01

    Full Text Available Autism spectrum disorders (ASD is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012. Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR, heart rate variability (HRV, body temperature, and galvanic skin response (GSR, may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.

  15. Mechanistic aspects of ingested chlorine dioxide on thyroid function: impact of oxidants on iodide metabolism

    International Nuclear Information System (INIS)

    Bercz, J.P.; Jones, L.L.; Harrington, R.M.; Bawa, R.; Condie, L.

    1986-01-01

    Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO 2 ) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO 2 ingestion, it seems that ClO 2 does not cause iodide deficiency of sufficient magnitude to account for the decease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrient, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen

  16. Oxidative effects, nutrients and metabolic changes in aquatic macrophyte, Elodea nuttallii, following exposure to lanthanum.

    Science.gov (United States)

    Zhang, Jingjing; Zhang, Tingting; Lu, Qianqian; Cai, Sanjuan; Chu, Weiyue; Qiu, Han; Xu, Ting; Li, Feifei; Xu, Qinsong

    2015-05-01

    We investigated the phytoremediation potential of Elodea nuttallii to remove rare earth metals from contaminated water. The laboratory experiments were designed to assess the responses induced by lanthanum (5-20mgL(-1)) in E. nuttallii over a period of 7 days. The results showed that most La (approximately 85%) was associated with the cell wall. The addition of La to the culture medium reduced the concentration of K, Ca, Cu, Mg, and Mn. However, O2(·-) levels increased with a concomitant increase in the malondialdehyde (MDA) concentration as the La concentration increased, which indicated that the cells were under oxidative stress. Significant reductions in the levels of chlorophyll (Chl) a, b, and carotenoids (Car) were observed in a concentration-dependent manner. However, the levels of reduced glutathione (GSH), total non-protein thiols (TNP-SH) and phytochelatins (PCs) increased for all La concentrations. The results suggested that La was toxic to E. nuttallii because it induced oxidative stress and disturbed mineral uptake. However, E. nuttallii was able to combat La induced damage via an immobilization mechanism, which involved the cell wall and the activation of non-enzymatic antioxidant. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation.

    Science.gov (United States)

    Gupta, Sonam; Verma, Dinesh Kumar; Biswas, Joyshree; Rama Raju, K Siva; Joshi, Neeraj; Wahajuddin; Singh, Sarika

    2014-08-01

    This study was performed to investigate the involvement of mitochondrion-specific endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown the antiapoptotic effects of piracetam but the mechanism of action of piracetam is still an enigma. To assess the involvement of endonuclease G in piracetam-induced protective effects, astrocyte glial cells were treated with lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation, and DNA fragmentation, which were attenuated by piracetam cotreatment. Cotreatment of astrocytes with piracetam showed its significantly time-dependent absorption as observed with high-performance liquid chromatography. Astrocytes treated with piracetam alone showed enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS-treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of the terminal executor of the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment attenuated the LPS-induced endonuclease G translocation. In conclusion this study indicates that LPS treatment of astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and translocation of endonuclease G to the nucleus, which was inhibited by piracetam cotreatment, confirming that the mitochondrion-specific endonuclease G is one of the factors involved in piracetam-induced protective mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

    Science.gov (United States)

    Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

    1992-04-01

    Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

  19. The Role of Propolis in Oxidative Stress and Lipid Metabolism: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Verónica Mujica

    2017-01-01

    Full Text Available Although there is evidence of the benefits of propolis on human health, the vast majority of studies have been conducted using animal models. The present study includes the chemical characterization and clinical evaluation of the effects of the oral administration of propolis solution on the oxidative status and modulation of lipids in a human population in Talca, Chile. Chemical characterization of propolis, total phenol, flavonoids, and total antioxidant capacity were determined by ORAC. Identification of phenols and flavonoids in propolis was assessed by HPLC-DAD. A double-blind, placebo-controlled clinical trial was conducted. Subjects provided informed consent form and the Bioethics Committee of the Universidad de Talca approved protocol. Eligible subjects (n=67 were randomized in two groups: propolis (n=35 and placebo (n=32. All subjects were evaluated at 0 (baseline, 45, and 90 days. In the propolis group, we observed that increases in HDL-c went from 53.9 ± 11.9 to 65.8 ± 16.7 mg/dL (p<0.001 from baseline to 90 days. Compared to placebo subjects, consumption of propolis induced a net increase in GSH levels (p<0.0001 and a decrease (p<0.001 in TBARS levels for the propolis group. Our findings indicate potential benefits of propolis use in human health. The use of propolis appears to have positive effects on oxidative status and improvement of HDL-c, both of which contribute to a reduced risk of cardiovascular disease.

  20. Effects of mercury and selenium on glutathione metabolism and oxidative stress in mallard ducks

    Science.gov (United States)

    Hoffman, D.J.; Heinz, G.H.

    1998-01-01

    Earlier studies reported on the toxicity and related oxidative stress of different forms of Se, including seleno-D,L-methionine, in mallards (Anas platyrhynchos). This study compares the effects of Se (seleno-D,L-methionine) and Hg (methylmercury chloride) separately and in combination. Mallard drakes received one of the following diets: untreated feed (controls), or feed containing 10 ppm Se, 10 ppm Hg, or 10 ppm Se in combination with 10 ppm Hg. After 10 weeks, blood, liver, and brain samples were collected for biochemical assays. The following clinical and biochemical alterations occurred in response to mercury exposure: hematocrit and hemoglobin concentrations decreased; activities of the enzymes glutathione (GSH) peroxidase (plasma and liver), glutathione-S-transferase (liver), and glucose-6-phosphate dehydrogenase (G-6-PDH) (liver and brain) decreased; hepatic oxidized glutathione (GSSG) concentration increased relative to reduced glutathione (GSH); and lipid peroxidation in the brain was evident as detected by increased thiobarbituric reactive substances (TBARS). Effects of Se alone included increased hepatic GSSG reductase activity and brain TBARS concentration. Se in combination with Hg partially or totally alleviated effects of Hg on GSH peroxidase, G-6-PDH, and GSSG. These findings are compared in relation to field observations for diving ducks and other aquatic birds. It is concluded that since both Hg and excess Se can affect thiol status, measurement of associated enzymes in conjunction with thiol status may be a useful bioindicator to discriminate between Hg and Se effects. The ability of Se to restore the activities of G-6-PDH, GSH peroxidase, and glutathione status involved in antioxidative defense mechanisms may be crucial to biological protection from the toxic effects of methyl mercury.

  1. Role of ultraviolet irradiation and oxidative stress in cataract formation-medical prevention by nutritional antioxidants and metabolic agonists.

    Science.gov (United States)

    Varma, Shambhu D; Kovtun, Svitlana; Hegde, Kavita R

    2011-07-01

    Cataract is a significant cause of visual disability with relatively high incidence. It has been proposed that such high incidence is related to oxidative stress induced by continued intraocular penetration of light and consequent photochemical generation of reactive oxygen species, such as superoxide and singlet oxygen and their derivatization to other oxidants, such as hydrogen peroxide and hydroxyl radical. The latter two can also interact to generate singlet oxygen by Haber-Weiss reaction. It has been proposed that in addition to the endogenous enzymatic antioxidant enzymes, the process can be inhibited by many nutritional and metabolic oxyradical scavengers, such as ascorbate, vitamin E, pyruvate, and xanthine alkaloids, such as caffeine. Initial verification of the hypothesis has been done primarily by rat and mouse lens organ culture studies under ambient as well as ultraviolet (UV) light irradiation and determining the effect of such irradiation on its physiology in terms of its efficiency of active membrane transport activity and the levels of certain metabolites such as glutathione and adenosine triphosphate as well as in terms of apoptotic cell death. In vivo studies on the possible prevention of oxidative stress and cataract formation have been conducted by administering pyruvate and caffeine orally in drinking water and by their topical application using diabetic and galactosemic animal models. Photosensitized damage to lens caused by exposure to visible light and UVA has been found to be significantly prevented by ascorbate and pyruvate. Caffeine has been found be effective against UVA and UVB. Oral or topical application of pyruvate has been found to inhibit the formation of cataracts induced by diabetes and galactosemia. Caffeine has also been found to inhibit cataract induced by sodium selenite and high levels of galactose. Studies with diabetes are in progress. Various in vitro and in vivo studies summarized in this review strongly support the

  2. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    Directory of Open Access Journals (Sweden)

    Ana Carolina eAriza

    2012-02-01

    Full Text Available The succinate receptor (also known as GPR91 is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: The succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  3. Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress.

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M

    2010-12-26

    The myocardium adapts to ischemic insults in a variety of ways. One adaptation is the phenomenon of acute preconditioning, which can greatly ameliorate ischemic damage. However, this effect wanes within a few hours and does not confer chronic protection. A more chronic adaptation is the so-called second window of preconditioning, which enables protection for a few days. The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart, angiogenesis and arteriogenesis (collateral growth), which prevent the development of ischemia by enabling flow to a jeopardized region of the heart. This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart. The concept of a redox window, which is an optimal redox state for vascular growth, is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion. Finally, the review discusses of some of the pathologies, especially the metabolic syndrome, that negatively affect collateral growth through the corruption of redox signaling processes.

  4. Study on oxidative metabolism of S180 cells induced by meretrix glycopeptide

    Science.gov (United States)

    Wu, Jielian; Wang, Ping; Kang, Huizhu

    2017-03-01

    Previous in vitro researches have showed that MGP0501, a natural glycopeptide isolated from Meretrix meretrix, can inhibit proliferation or induce apoptosis in human gastric carcinoma, lung cance (A549), Leukemia K562, mouse melanoma B16, hepatoma or breast cancer cells (MDA-MB-231). In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of MGP0501 on xenografted sarcoma 180 (S180) in mice. Results revealed that the inhibition rates of S180 on solid tumors were 69.72%, with a concentration of 6 mg/kg MGP0501,which was significantly higher than that of CTX. In addition, the biochemical metabolism analysis showed that MGP0501 could enhance the activities of glutathione tablets (GSH-Px) and catalase (CAT) and supersxide dismutase (SOD) in liver of mice. The content of malondialdehyde (MDA) in liver, on the contrary, was decreased. The promotion to antioxidation and the elimination of free radical in liver also attribute the antitumor activity of MGP0501. These results indicated that in vivo antitumor activity is associated with enhanced antioxidant capacity in S180 xenografts-bearing mice.

  5. Effect of Conbercept injection and macular grid pattern photocoagulation in treating macular edema after non-ischemic branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Jiang Zhu

    2018-06-01

    Full Text Available AIM: To investigate the effects and safety of intravitreal injection of Conbercept combined with macular grid pattern photocoagulation for macular edema secondary to non-ischemic branch retinal vein occlusion(BRVO. METHODS: A total of 38 patients(38 eyes with macular edema following non-ischemic BRVO were retrospectively analyzed. All patients were given best corrected visual acuity(BCVA, intraocular pressure, slit lamp with preset lens, optic coherent tomography(OCTand fluorescence fundus angiography(FFAexamination. The BCVA and central macular thickness(CMTwere observed before and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment. The change in pre-treatment and post-treatment were compared, and the related complications were recorded. RESULTS:BCVA before treatment and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment were 0.89±0.62, 0.64±0.59, 0.55±0.62, 0.46±0.43, 0.53±0.67, 0.43±0.38, 0.42±0.29, 0.40±0.30, the difference was statistically significant between that before and after treatment(PP>0.05. CMT were 683.25±236.47, 298.65±116.12, 276.89±107.28, 281.55±99.62, 251.41±119.47, 240.58±88.62, 231.74±75.36, 209.51±84.68μm, the difference was statistically significant between that before and after treatment(PP>0.05. There were 11 eyes received one injection, 18 eyes with two injections, 2 eyes with 3, 3 eyes with 4, and 4 eyes more than 4, the average injection was 2.01±1.42. The CMT decreased after every injection. The intraocular hypertension and other complications were not seen after treatment. CONCLUSION: Intravitreal injection of conbercept combined with macular grid pattern photocoagulation for macular edema to non-ischemic BRVO can reduce the macular edema and improve BCVA, which is effective and safety.

  6. Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

    Science.gov (United States)

    Long, Yue; Dong, Xin; Yuan, Yawei; Huang, Jinqiang; Song, Jiangang; Sun, Yumin; Lu, Zhijie; Yang, Liqun; Yu, Weifeng

    2015-07-01

    The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.

  7. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  8. The Modulatory Role of Vitis vinifera in Oxidative Stress and Carbohydrate Metabolism of Irradiated Rats

    International Nuclear Information System (INIS)

    El Tahawy, N.A.; Salama, S.F.; Ashry, O.M.

    2008-01-01

    Proanthocyanidins are naturally occurring antioxidants found in grape seed extract (GSPE) of Vitis vinifera. The present study aims at assessing the protective effects of GSPI against free radicals induced by ionizing radiation on the antioxidant status, the process of carbohydrate metabolism, and some hematological parameters in adult rats. Catalase (CAT) activity and reduced glutathione (GSH) concentration along with lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) were determined in liver and muscle tissues, The activity of glucose-6)-phosphatase was determined in liver tissues and glucose level in serum. Erythrocytes count (RBCs), hemoglobin content (Hb) and haematocrit value (Hct %) were also determined. Rats received daily GSPE by gavage in concentration of 100 mg/Kg body weight for 15 consecutive days before exposure to 5 Gy dose of whole body gamma irradiation. The experimental investigations were carried out on the second and third weeks post irradiation.The results indicate that ingestion of GSPE is safe and had no significant effect on the levels of the parameters studied. Exposure to radiation produced a significant decrease in CAT activity and GSH content along with significant increase of TEARS levels in liver and muscle tissues. Liver glucose-6-phosphatase activity increased 2 and 3 weeks post irradiation concomitant with a significant increase of serum glucose level. Blood RBCs, Hb and Hct levels were significantly depressed. Administration of GSPE ameliorated the severity of changes in all the parameters measured. It could be concluded that proanthocyanidins might play a considerable role in ameliorating the radiation induced changes in antioxidant status and carbohydrate metabolites

  9. Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: the RESMENA project.

    Science.gov (United States)

    Perez-Cornago, Aurora; Lopez-Legarrea, Patricia; de la Iglesia, Rocio; Lahortiga, Francisca; Martinez, J Alfredo; Zulet, M Angeles

    2014-12-01

    Metabolic syndrome and depression seem to share some common underlying mechanisms, although less is known about the impact of metabolic syndrome dietary treatments on depression. This study examined the association between a hypocaloric treatment designed to reduce metabolic syndrome features in self-perceived depression and the potential involvement of dietary components and oxidative stress changes. Analyses were based on volunteers (n = 55) with metabolic syndrome (age 50 ± 1 y.o.; 38M/17F), where depressive symptoms were assessed using the Beck Depression Inventory. Participants followed two hypocaloric diets (control diet and RESMENA diet) with the same energy restriction (-30% TCV) for six months. Depressive symptoms, dietary records, anthropometrical measurements, biochemical parameters and oxidative stress levels were analysed. Both diets improved self-perceived depression similarly (p = 0.528). Participants with lower depressive symptoms at baseline reported a significantly higher intake of omega-3 polyunsaturated fatty acids (p trend = 0.002). Interestingly, after adjusting for potential confounders, the increase in folate consumption (p = 0.011) and the decrease in plasma malondialdehyde levels (p = 0.012) throughout the intervention, were associated with the improvement in depressive symptoms. A higher intake of folate and a decline in malondialdehyde plasma levels during a weight loss intervention, were related to improvements in manifestations of depression (www.clinicaltrials.gov; NCT01087086). Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis

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    Ling-Yu Wang

    2016-09-01

    Full Text Available The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer.

  11. Effects of methylmercury exposure on glutathione metabolism, oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks

    International Nuclear Information System (INIS)

    Kenow, Kevin P.; Hoffman, David J.; Hines, Randy K.; Meyer, Michael W.; Bickham, John W.; Matson, Cole W.; Stebbins, Katie R.; Montagna, Paul; Elfessi, Abdulaziz

    2008-01-01

    We quantified the level of dietary mercury (Hg), delivered as methylmercury chloride (CH 3 HgCl), associated with negative effects on organ and plasma biochemistries related to glutathione (GSH) metabolism and oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks reared from hatch to 105 days. Mercury-associated effects related to oxidative stress and altered glutathione metabolism occurred at 1.2 μg Hg/g and 0.4 μg Hg/g, an ecologically relevant dietary mercury level, but not at 0.08 μg Hg/g. Among the variables that contributed most to dissimilarities in tissue chemistries between control and treatment groups were increased levels of oxidized glutathione (GSSG), GSH peroxidase, and the ratio of GSSG to GSH in brain tissue; increased levels of hepatic GSH; and decreased levels of hepatic glucose-6-phosphate dehydrogenase (G-6-PDH). Our results also suggest that chronic exposure to environmentally relevant dietary Hg levels did not result in statistically significant somatic chromosomal damage in common loon chicks. - Oxidative stress and altered glutathione metabolism were evident in common loon chicks exposed to ≥0.4 μg Hg as CH 3 HgCl per gram wet food intake

  12. Effects of methylmercury exposure on glutathione metabolism, oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks

    Energy Technology Data Exchange (ETDEWEB)

    Kenow, Kevin P. [U.S. Geological Survey, Upper Midwest Environmental Sciences Center, 2630 Fanta Reed Road, La Crosse, WI 54603 (United States)], E-mail: kkenow@usgs.gov; Hoffman, David J. [U.S. Geological Survey, Patuxent Wildlife Research Center, 10300 Baltimore Avenue, Beltsville, MD 20705 (United States)], E-mail: djhoffman@usgs.gov; Hines, Randy K. [U.S. Geological Survey, Upper Midwest Environmental Sciences Center, 2630 Fanta Reed Road, La Crosse, WI 54603 (United States)], E-mail: rkhines@usgs.gov; Meyer, Michael W. [Wisconsin Department of Natural Resources, 107 Sutliff Avenue, Rhinelander, WI 54501 (United States)], E-mail: michael.meyer@dnr.state.wi.us; Bickham, John W. [Center for the Environment and Department of Forestry and Natural Resources, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: bickham@purdue.edu; Matson, Cole W. [Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC 27708 (United States)], E-mail: matson@duke.edu; Stebbins, Katie R. [U.S. Geological Survey, Patuxent Wildlife Research Center, 10300 Baltimore Avenue, Beltsville, MD 20705 (United States); Montagna, Paul [Texas A and M University-Corpus Christi, Harte Research Institute, Corpus Christi, TX (United States)], E-mail: paul.montagna@tamucc.edu; Elfessi, Abdulaziz [University of Wisconsin-La Crosse, La Crosse, WI 54601 (United States)], E-mail: elfessi.abdu@uwlax.edu

    2008-12-15

    We quantified the level of dietary mercury (Hg), delivered as methylmercury chloride (CH{sub 3}HgCl), associated with negative effects on organ and plasma biochemistries related to glutathione (GSH) metabolism and oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks reared from hatch to 105 days. Mercury-associated effects related to oxidative stress and altered glutathione metabolism occurred at 1.2 {mu}g Hg/g and 0.4 {mu}g Hg/g, an ecologically relevant dietary mercury level, but not at 0.08 {mu}g Hg/g. Among the variables that contributed most to dissimilarities in tissue chemistries between control and treatment groups were increased levels of oxidized glutathione (GSSG), GSH peroxidase, and the ratio of GSSG to GSH in brain tissue; increased levels of hepatic GSH; and decreased levels of hepatic glucose-6-phosphate dehydrogenase (G-6-PDH). Our results also suggest that chronic exposure to environmentally relevant dietary Hg levels did not result in statistically significant somatic chromosomal damage in common loon chicks. - Oxidative stress and altered glutathione metabolism were evident in common loon chicks exposed to {>=}0.4 {mu}g Hg as CH{sub 3}HgCl per gram wet food intake.

  13. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO 2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [ 3 H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of 13 C and 14 C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO 2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488. © 2016 Wiley Periodicals, Inc.

  14. Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

    Science.gov (United States)

    Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

    2017-01-23

    Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice.

  15. Water addition regulates the metabolic activity of ammonia oxidizers responding to environmental perturbations in dry subhumid ecosystems.

    Science.gov (United States)

    Hu, Hang-Wei; Macdonald, Catriona A; Trivedi, Pankaj; Holmes, Bronwyn; Bodrossy, Levente; He, Ji-Zheng; Singh, Brajesh K

    2015-02-01

    Terrestrial arid and semi-arid ecosystems (drylands) constitute about 41% of the Earth's land surface and are predicted to experience increasing fluctuations in water and nitrogen availability. Mounting evidence has confirmed the significant importance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in nitrification, plant nitrogen availability and atmospheric N2 O emissions, but their responses to environmental perturbations in drylands remain largely unknown. Here we evaluate how the factorial combinations of irrigation and fertilization in forests and land-use change from grassland to forest affects the dynamics of AOA and AOB following a 6-year dryland field study. Potential nitrification rates and AOA and AOB abundances were significantly higher in the irrigated plots, accompanied by considerable changes in community compositions, but their responses to fertilization alone were not significant. DNA-stable isotope probing results showed increased (13) CO2 incorporation into the amoA gene of AOA, but not of AOB, in plots receiving water addition, coupled with significantly higher net mineralization and nitrification rates. High-throughput microarray analysis revealed that active AOA assemblages belonging to Nitrosopumilus and Nitrosotalea were increasingly labelled by (13) CO2 following irrigation. However, no obvious effects of land-use changes on nitrification rates or metabolic activity of AOA and AOB could be observed under dry conditions. We provide evidence that water addition had more important roles than nitrogen fertilization in influencing the autotrophic nitrification in dryland ecosystems, and AOA are increasingly involved in ammonia oxidation when dry soils become wetted. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery

    Directory of Open Access Journals (Sweden)

    An-Jun Cao

    2017-11-01

    Full Text Available Objective: To discuss the effect of 毩 -lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery. Methods: A total of 110 patients with femoral fracture who received surgical treatment in the hospital between January 2015 and January 2017 were collected and divided into the control group (n=55 and study group (n=55 by random number table. Control group received postoperative nerve growth factor therapy, and study group received postoperative 毩 -lipoic acid combined with nerve growth factor therapy. The differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were not statistically significant between the two groups. After treatment, serum bone metabolism indexes BGP and PⅠNP contents of study group were higher than those of control group while CTX-Ⅰ and TRAP contents were lower than those of control group; serum oxidative stress indexes TAC, CAT and SOD contents of study group were higher than those of control group while MDA content was lower than that of control group; limb nerve conduction velocity SCV and MCV levels of study group were higher than those of control group. Conclusion: 毩 -lipoic acid combined with nerve growth factor therapy after femoral fracture surgery can effectively balance osteoblast/ osteoclast activity, reduce oxidative stress and improve limb nerve conduction velocity.

  17. Possible effect of pentoxifylline on oxidative stress and certain metabolic disorders in gamma irradiated rats

    International Nuclear Information System (INIS)

    Ashry, O.M.; Salama, S.F.; El Tahawy, N.A.

    2007-01-01

    Pentoxifylline (PTX) is a methylxanthine derivative and phospho-di esterase inhibitor used to treat cerebral, diabetic or functional disorders of vascular system. It lowers blood viscosity and improves erythrocyte flexibility and it has anti-oxidant properties and anti-inflammatory activity. In this study, PTX effects on antioxidant status of cerebral cortex and certain organ functions in rats subjected to 2 fractionated irradiation doses 4 and 8 Gy were investigated. Animals were divided into 4 groups: Group 1: which served as a control. Group 2: in which PTX was administered (1200 mg/ L daily for 6 rats) in drinking water for 8 and 16 days. Group 3: which was irradiated with fractionated irradiation at dose levels of 4 and 8 Gy (2 Gy every 4 days) for 8 and 16 days. Group 4: in which PTX was administered together with fractionated irradiation 4 and 8 Gy for 8 and 16 days. The cerebral cortex levels of reduced glutathione (GSH) and malonaldehyde (MDA) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities, were determined. Serum ALT and AST activities and contents of glucose, uric acid and liver glycogen were also measured. Fractionated irradiation of 4 and 8 Gy significantly elevated GSH and MDA contents and SOD activity in cerebral cortex, while CAT activity was depressed. Exposure to fractionated dose level of 8 Gy caused significant elevation of serum ALT and AST activities, as well as liver glycogen contents and depressed uric acid level. PTX depressed MDA level and elevated the activity of antioxidant enzymes in cerebral cortex. ALT, AST activities and levels of uric acid and liver glycogen were lowered by PTX administration. Serum glucose was significantly decreased by all treatments applied. PTX might hold promise, as a useful therapeutic intervention, reducing late radiation injury via antioxidant pathway

  18. Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

    Science.gov (United States)

    Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

    2016-08-01

    Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

  19. Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

    Directory of Open Access Journals (Sweden)

    A.N.C. Simão

    2011-07-01

    Full Text Available Metabolic syndrome (MS is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx levels in MS patients. Fifty patients with MS (4 males/46 females and 50 controls (3 males/47 females were studied. Compared to control (Mann-Whitney test, MS patients presented higher serum levels (P < 0.05 of fibrinogen: 314 (185-489 vs 262 (188-314 mg/dL, C-reactive protein (CRP: 7.80 (1.10-46.50 vs 0.70 (0.16-5.20 mg/dL, interleukin-6: 3.96 (3.04-28.18 vs 3.33 (2.55-9.63 pg/mL, uric acid: 5.45 (3.15-9.65 vs 3.81 (2.70-5.90 mg/dL, and hydroperoxides: 20,689 (19,076-67,182 vs 18,636 (15,926-19,731 cpm. In contrast, they presented lower (P < 0.05 adiponectin: 7.11 (3.19-18.22 vs 12.31 (9.11-27.27 µg/mL, and NOx levels: 5.69 (2.36-8.18 vs 6.72 (5.14-12.43 µM. NOx was inversely associated (Spearman’s rank correlation with body mass index (r = -0.2858, P = 0.0191, insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315, CRP (r = -0.2843, P = 0.0171 and fibrinogen (r = -0.2464, P = 0.0413, and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408. In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

  20. Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Meng-Xi; Jin, Lei; Sun, Si-Jia; Liu, Peng; Feng, Xu; Cheng, Zhou-Li; Liu, Wei-Ren; Guan, Kun-Liang; Shi, Ying-Hong; Yuan, Hai-Xin; Xiong, Yue

    2018-03-01

    Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.

  1. Benign Effect of Extremely Low-Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Natalia Cichoń

    2017-01-01

    Full Text Available Nitric oxide (NO is one of the most important signal molecules, involved in both physiological and pathological processes. As a neurotransmitter in the central nervous system, NO regulates cerebral blood flow, neurogenesis, and synaptic plasticity. The aim of our study was to investigate the effect of the extremely low-frequency electromagnetic field (ELF-EMF on generation and metabolism of NO, as a neurotransmitter, in the rehabilitation of poststroke patients. Forty-eight patients were divided into two groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week rehabilitation program. Additionally, the ELF-EMF group was exposed to an extremely low-frequency electromagnetic field of 40 Hz, 7 mT, for 15 min/day. Levels of 3-nitrotyrosine, nitrate/nitrite, and TNFα in plasma samples were measured, and NOS2 expression was determined in whole blood samples. Functional status was evaluated before and after a series of treatments, using the Activity Daily Living, Geriatric Depression Scale, and Mini-Mental State Examination. We observed that application of ELF-EMF significantly increased 3-nitrotyrosine and nitrate/nitrite levels, while expression of NOS2 was insignificantly decreased in both groups. The results also show that ELF-EMF treatments improved functional and mental status. We conclude that ELF-EMF therapy is capable of promoting recovery in poststroke patients.

  2. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    Science.gov (United States)

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  3. Statins attenuate but do not eliminate the reverse epidemiology of total serum cholesterol in patients with non-ischemic chronic heart failure.

    Science.gov (United States)

    Fröhlich, Hanna; Raman, Nandita; Täger, Tobias; Schellberg, Dieter; Goode, Kevin M; Kazmi, Syed; Grundtvig, Morten; Hole, Torstein; Cleland, John G F; Katus, Hugo A; Agewall, Stefan; Clark, Andrew L; Atar, Dan; Frankenstein, Lutz

    2017-07-01

    In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Beneficial Effects of the RESMENA Dietary Pattern on Oxidative Stress in Patients Suffering from Metabolic Syndrome with Hyperglycemia Are Associated to Dietary TAC and Fruit Consumption

    Directory of Open Access Journals (Sweden)

    J. Alfredo Martinez

    2013-03-01

    Full Text Available Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS, whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (−30% Energy: the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates, which was characterized by an increase of the meal frequency (seven-times/day, low glycemic load, high antioxidant capacity (TAC and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI, waist circumference, fat mass and triacilglyceride (TG levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

  5. Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients suffering from metabolic syndrome with hyperglycemia are associated to dietary TAC and fruit consumption.

    Science.gov (United States)

    de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Celada, Paloma; Sánchez-Muniz, Francisco J; Martinez, J Alfredo; Zulet, M Angeles

    2013-03-27

    Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS), whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (-30% Energy): the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates), which was characterized by an increase of the meal frequency (seven-times/day), low glycemic load, high antioxidant capacity (TAC) and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra) diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL) values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI), waist circumference, fat mass and triacilglyceride (TG) levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

  6. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2007-01-01

    Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

  7. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows

    Science.gov (United States)

    Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows. PMID:25938406

  8. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Science.gov (United States)

    Lamp, Ole; Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd; Kuhla, Björn

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  9. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Directory of Open Access Journals (Sweden)

    Ole Lamp

    Full Text Available High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS and one pair-fed (PF at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1, cows were challenged for 6 days (P2 by heat stress (temperature humidity index (THI = 76 or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  10. The Role of ?786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome

    OpenAIRE

    Misiak, Blazej; Krolik, Marta; Kukowka, Anna; Lewera, Anna; Leszczynski, Przemyslaw; Stankiewicz-Olczyk, Joanna; Slezak, Ryszard

    2011-01-01

    Background. Extensive evidence, arising from models of endothelial nitric oxide synthase gene (NOS3)-knockout mice supports the role of endothelial malfunction in the pathogenesis of the metabolic syndrome (MS). Aims. The aim of this study was to evaluate the role of −786T/C polymorphism in the etiology of MS and assess previously reported interaction with cigarette smoking. Methods. Based on International Diabetes Federation 2005 criteria, we recruited randomly 152 subjects with MS and 75 su...

  11. Enzymatic oxidation of 2-phenylethylamine to phenylacetic acid and 2-phenylethanol with special reference to the metabolism of its intermediate phenylacetaldehyde.

    Science.gov (United States)

    Panoutsopoulos, Georgios I; Kouretas, Demetrios; Gounaris, Elias G; Beedham, Christine

    2004-12-01

    2-phenylethylamine is an endogenous constituent of the human brain and is implicated in cerebral transmission. This bioactive amine is also present in certain foodstuffs such as chocolate, cheese and wine and may cause undesirable side effects in susceptible individuals. Metabolism of 2-phenylethylamine to phenylacetaldehyde is catalysed by monoamine oxidase B but the oxidation to its acid is usually ascribed to aldehyde dehydrogenase and the contribution of aldehyde oxidase and xanthine oxidase, if any, is ignored. The objective of this study was to elucidate the role of the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, in the metabolism of phenylacetaldehyde derived from its parent biogenic amine. Treatments of 2-phenylethylamine with monoamine oxidase were carried out for the production of phenylacetaldehyde, as well as treatments of synthetic or enzymatic-generated phenylacetaldehyde with aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase. The results indicated that phenylacetaldehyde is metabolised mainly to phenylacetic acid with lower concentrations of 2-phenylethanol by all three oxidising enzymes. Aldehyde dehydrogenase was the predominant enzyme involved in phenylacetaldehyde oxidation and thus it has a major role in 2-phenylethylamine metabolism with aldehyde oxidase playing a less prominent role. Xanthine oxidase does not contribute to the oxidation of phenylacetaldehyde due to low amounts being present in guinea pig. Thus aldehyde dehydrogenase is not the only enzyme oxidising xenobiotic and endobiotic aldehydes and the role of aldehyde oxidase in such reactions should not be ignored.

  12. Effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with GDM

    Directory of Open Access Journals (Sweden)

    Liu Jie

    2017-05-01

    Full Text Available Objective: To study the effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with gestational diabetes mellitus (GDM. Methods: Patients with GDM who received insulin therapy between March 2013 and May 2016 were selected as the research subjects and randomly divided into multiple subcutaneous insulin injection (MSII group and continuous subcutaneous insulin pump infusion (CSII group. Before and after treatment, serum glucolipid metabolism as well as inflammation and oxidative stress inexes in placenta were determined respectively. Results: 2 weeks and 4 weeks after treatment, FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of both groups of patients were significantly lower than those before treatment and FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of CSII group were significantly lower than those of MSII group; after delivery, TNF-α, IL-6, ROS and AGEs levels in placenta of CSII group were significantly lower than those of MSII group. Conclusion: Continuous subcutaneous insulin infusion can more effectively improve the glucolipid metabolism and inhibit the inflammation and oxidative stress in placenta of patients with GDM than multiple subcutaneous insulin injection.

  13. Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

    Science.gov (United States)

    Ajiboye, T O; Aliyu, H; Tanimu, M A; Muhammad, R M; Ibitoye, O B

    2016-11-04

    extract. Data generated in this study further laid credence to the hypoglycemic activity of aqueous leaf extract of D. cumminsii as evident from the reversal of hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  15. D-Serine exposure resulted in gene expression changes indicative of activation of fibrogenic pathways and down-regulation of energy metabolism and oxidative stress response

    International Nuclear Information System (INIS)

    Soto, Armando; DelRaso, Nicholas J.; Schlager, John J.; Chan, Victor T.

    2008-01-01

    , metabolism and transport, inflammatory response, proteasome-mediated degradation of oxidatively damaged cytosolic proteins, Ras protein signal transduction, TGF-beta signaling pathway and mRNA transcription, processing, splicing and transport. On the other hand, major metabolic pathways, which include carbohydrate metabolism, TCA cycle, oxidative phosphorylation, ATP synthesis coupled electron transport, amino acid metabolism and transport, lipid metabolism, nucleotide metabolism, and vitamin metabolism, and oxidative stress response including induction of antioxidant genes and glutathione metabolism are down-regulated. As tubular epithelia have strong energy demand for normal functions, down-regulation of energy metabolism after D-serine treatment may be related to the mechanism of its nephrotoxicity. In addition, hydrogen peroxide, a reactive oxygen species, is produced as a byproduct of the metabolism of D-serine by D-amino acid oxidase in the peroxisomes of the tubular epithelia. Down-regulation of pathways for antioxidant genes induction and glutathione metabolism will likely exacerbate the cytotoxicity of this reactive oxygen species. The observation that the genes involved in apoptosis, DNA repair, proteasome pathway for the degradation of oxidatively damaged cytosolic proteins were up-regulated lends some supports to this premise. Up-regulation of pathways of cell proliferation cycle, DNA replication and gene expression process, including mRNA transcription, processing, splicing, transport, translation initiation, and protein transport along with protein complex assembly, suggests ongoing tissue repair and regeneration. Consistent with the fibrogenic function of the TGF-beta signaling pathway in various experimental renal diseases, genes encoding major extracellular matrix components such as collagens, laminins, fibronectin 1 and tenascins are also strongly up-regulated. Taken together, the results of this study provide important insights into the molecular mechanism

  16. Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

    Directory of Open Access Journals (Sweden)

    Ojaimi Caroline

    2010-08-01

    Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

  17. Nitric Oxide Mediates the Hormonal Control of Crassulacean Acid Metabolism Expression in Young Pineapple Plants1[W][OA

    Science.gov (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Domingues, Douglas Silva; Purgatto, Eduardo; Van Sluys, Marie-Anne; Magalhaes, Jose Ronaldo; Kaiser, Werner M.; Mercier, Helenice

    2010-01-01

    Genotypic, developmental, and environmental factors converge to determine the degree of Crassulacean acid metabolism (CAM) expression. To characterize the signaling events controlling CAM expression in young pineapple (Ananas comosus) plants, this photosynthetic pathway was modulated through manipulations in water availability. Rapid, intense, and completely reversible up-regulation in CAM expression was triggered by water deficit, as indicated by the rise in nocturnal malate accumulation and in the expression and activity of important CAM enzymes. During both up- and down-regulation of CAM, the degree of CAM expression was positively and negatively correlated with the endogenous levels of abscisic acid (ABA) and cytokinins, respectively. When exogenously applied, ABA stimulated and cytokinins repressed the expression of CAM. However, inhibition of water deficit-induced ABA accumulation did not block the up-regulation of CAM, suggesting that a parallel, non-ABA-dependent signaling route was also operating. Moreover, strong evidence revealed that nitric oxide (NO) may fulfill an important role during CAM signaling. Up-regulation of CAM was clearly observed in NO-treated plants, and a conspicuous temporal and spatial correlation was also evident between NO production and CAM expression. Removal of NO from the tissues either by adding NO scavenger or by inhibiting NO production significantly impaired ABA-induced up-regulation of CAM, indicating that NO likely acts as a key downstream component in the ABA-dependent signaling pathway. Finally, tungstate or glutamine inhibition of the NO-generating enzyme nitrate reductase completely blocked NO production during ABA-induced up-regulation of CAM, characterizing this enzyme as responsible for NO synthesis during CAM signaling in pineapple plants. PMID:20147491

  18. The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

    Science.gov (United States)

    Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

    2012-03-01

    Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

  19. EXPERIMENTAL WORK AND RESEARCH Effect of Tiaoxin Recipe(调心方)on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimers Disease Rats

    Institute of Scientific and Technical Information of China (English)

    QIUHong; ZHAOWei-kang; 等

    2003-01-01

    Objective:To observe the effect of Tiaoxin Recipe(TXR) on the spatial memory,brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease(AD) rats,and to explore the mechanism of TXR in treating AD.Methods:Eighty-eight SD rats were randomly divided into five groups (normal group,operative group,“AD”model group,TXR group and Aricept group).An oxygen free rad-ical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate,DHF-FeCl3-ADP)was used to create oxidation injured rat models mimic to AD; spatial learning and memeory impairment (Morris water maze method),the activity of Succinate-oxidase,NADH-oxidase,CytC-oxidase(Clark ox-ygen electrode method)and the expression of cytochrome oxidase(CO)ⅡmRNA(in situ hybridization method)were observed.Results:Compared with the normal group,the spatial memory,activity of CytC-oxidase and COⅡmRNA expression of oxidation injured“AD”rats were obviously decreased;TXR,how-ever,could improve these functions in “AD”rat models obviously.Conclusion:The mechanism of the ac-tion of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mi-tochondrial energy metabolism.

  20. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo

    International Nuclear Information System (INIS)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; Hoff, Joerg van den

    2004-01-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ( 18 F) by conjugation with N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [ 18 F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [ 18 F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo

  1. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

    Science.gov (United States)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; van den Hoff, Joerg

    2004-11-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

  2. PGC-1α mRNA Level and Oxidative Capacity of the Plantaris Muscle in Rats with Metabolic Syndrome, Hypertension, and Type 2 Diabetes

    International Nuclear Information System (INIS)

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Gu, Ning; Takeda, Isao; Ishioka, Noriaki; Tsuda, Kinsuke; Ishihara, Akihiko

    2011-01-01

    We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA

  3. Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

    Science.gov (United States)

    Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

    2013-01-01

    Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

  4. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  5. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  6. Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis.

    Science.gov (United States)

    Chen, Yanmei; Hoehenwarter, Wolfgang

    2015-12-01

    Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K(+) and Na(+) transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

  7. The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

    Science.gov (United States)

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

    2012-03-01

    Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

  8. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K; Farmer, Stephen R; Goodyear, Laurie; Doria, Alessandro; Blüher, Matthias; Hsu, Stephen I-Hong; Kulkarni, Rohit N

    2013-02-01

    Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2-null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia.

  9. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

    Science.gov (United States)

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K; Farmer, Stephen R; Goodyear, Laurie; Doria, Alessandro; Blüher, Matthias; Hsu, Stephen I-Hong; Kulkarni, Rohit N

    2012-01-01

    SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher energy expenditure due to increased adipocyte thermogenesis and oxidative metabolism by up-regulating key enzymes in respective processes. Our data show for the first time that a cell cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data together with the observation that TRIP-BR2 expression is selectively elevated in visceral fat in obese humans suggests that this transcriptional co-regulator is a novel therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia. PMID:23291629

  10. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Ni, Xunjun; Wang, Haiyan

    2016-01-01

    Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

  11. Dietary phenolic acids reverse insulin resistance, hyperglycaemia, dyslipidaemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

    Science.gov (United States)

    Ibitoye, Oluwayemisi B; Ajiboye, Taofeek O

    2017-12-20

    This study investigated the influence of caffeic, ferulic, gallic and protocatechuic acids on high-fructose diet-induced metabolic syndrome in rats. Oral administration of the phenolic acids significantly reversed high-fructose diet-mediated increase in body mass index and blood glucose. Furthermore, phenolic acids restored high-fructose diet-mediated alterations in metabolic hormones (insulin, leptin and adiponectin). Similarly, elevated tumour necrosis factor-α, interleukin-6 and -8 were significantly lowered. Administration of phenolic acids restored High-fructose diet-mediated increase in the levels of lipid parameters and indices of atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated decrease in activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione, lipid peroxidation products, protein oxidation and fragmented DNA) were significantly restored by the phenolic acids. The result of this study shows protective influence of caffeic acid, ferulic acid, gallic acid and protocatechuic acid in high-fructose diet-induced metabolic syndrome.

  12. Atorvastatin improves cardiac function and remodeling in chronic non-ischemic heart failure: A clinical and pre-clinical study

    Directory of Open Access Journals (Sweden)

    Ibrahim Elmadbouh

    2015-12-01

    Conclusions: Atorvastatin with standard CHF therapy improved cardiac function and remodeling. Cardio-protective “pleiotropic” actions of atorvastatin are anti-inflammatory, anti-fibrotic and anti-oxidative. Thus, atorvastatin has a potential therapeutic value in the management of CHF patients.

  13. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation

    NARCIS (Netherlands)

    Feige, Jérôme N.; Lagouge, Marie; Canto, Carles; Strehle, Axelle; Houten, Sander M.; Milne, Jill C.; Lambert, Philip D.; Mataki, Chikage; Elliott, Peter J.; Auwerx, Johan

    2008-01-01

    The NAD(+)-dependent deacetylase SIRT1 controls metabolic processes in response to low nutrient availability. We report the metabolic phenotype of mice treated with SRT1720, a specific and potent synthetic activator of SIRT1 that is devoid of direct action on AMPK. SRT1720 administration robustly

  14. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders

    Directory of Open Access Journals (Sweden)

    Zhimin Chen

    2017-08-01

    Conclusions: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD in patients.

  15. The control of short-term feed intake by metabolic oxidation in late-pregnant and early lactating dairy cows exposed to high ambient temperatures.

    Science.gov (United States)

    Eslamizad, Mehdi; Lamp, Ole; Derno, Michael; Kuhla, Björn

    2015-06-01

    The objective of the present study was to integrate the dynamics of feed intake and metabolic oxidation in late pregnant and early lactating Holstein cows under heat stress conditions. On day 21 before parturition and again on day 20 after parturition, seven Holstein cows were kept for 7days at thermoneutral (TN) conditions (15°C; temperature-humidity-index (THI)=60) followed by a 7day heat stress (HS) period at 28°C (THI=76). On the last day of each temperature condition, gas exchange, feed intake and water intake were recorded every 6min in a respiration chamber. Pre- and post-partum cows responded to HS by decreasing feed intake. The reduction in feed intake in pre-partum cows was achieved through decreased meal size, meal duration, eating rate and daily eating time with no change in meal frequency, while post-partum cows kept under HS conditions showed variable responses in feeding behavior. In both pre- and post-partum cows exposed to heat stress, daily and resting metabolic heat production decreased while the periprandial respiratory quotient (RQ) increased. The prolonged time between meal and the postprandial minimum in fat oxidation and the postprandial RQ maximum, respectively, revealed that HS as compared to TN early-lactating cows have slower postprandial fat oxidation, longer feed digestion, and thereby showing a shift from fat to glucose utilization. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats

    Directory of Open Access Journals (Sweden)

    Raffaella Crescenzo

    2018-04-01

    Full Text Available The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism. Therefore, the aim of this study was to compare the metabolic changes induced by the fructose-rich diet in rats of different age, i.e., young (30 days old and adult (90 days old rats. The fructose-rich diet increased whole body lipid content in adult, but not in young rats. The analysis of liver markers of inflammation suggests that different mechanisms depending on the age might be activated after the fructose-rich diet. In fact, a pro-inflammatory gene-expression analysis showed just a minor activation of macrophages in young rats compared to adult rats, while other markers of low-grade metabolic inflammation (TNF-alpha, myeloperoxidase, lipocalin, haptoglobin significantly increased. Inflammation was associated with oxidative damage to hepatic lipids in young and adult rats, while increased levels of hepatic nitrotyrosine and ceramides were detected only in young rats. Interestingly, fructose-induced hepatic insulin resistance was evident in young but not in adult rats, while whole body insulin sensitivity decreased both in fructose-fed young and adult rats. Taken together, the present data indicate that young rats do not increase their body lipids but are exposed to metabolic perturbations, such as hepatic insulin resistance and hepatic oxidative stress, in line with the finding that increased fructose intake may be an important predictor of metabolic risk in young people, independently of weight status. These results indicate the need of corrective

  17. Development of an updated PBPK model for trichloroethylene and metabolites in mice, and its application to discern the role of oxidative metabolism in TCE-induced hepatomegaly.

    Science.gov (United States)

    Evans, M V; Chiu, W A; Okino, M S; Caldwell, J C

    2009-05-01

    Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term exposure. An integrated dataset for gavage and inhalation TCE exposure and oral data for exposure to two of its oxidative metabolites (TCA and DCA) was used, in combination with an updated and more accurate physiologically-based pharmacokinetic (PBPK) model, to examine the question as to whether the presence of TCA in the liver is responsible for TCE-induced hepatomegaly in mice. The updated PBPK model was used to help discern the quantitative contribution of metabolites to this effect. The update of the model was based on a detailed evaluation of predictions from previously published models and additional preliminary analyses based on gas uptake inhalation data in mice. The parameters of the updated model were calibrated using Bayesian methods with an expanded pharmacokinetic database consisting of oral, inhalation, and iv studies of TCE administration as well as studies of TCE metabolites in mice. The dose-response relationships for hepatomegaly derived from the multi-study database showed that the proportionality of dose to response for TCE- and DCA-induced hepatomegaly is not observed for administered doses of TCA in the studied range. The updated PBPK model was used to make a quantitative comparison of internal dose of metabolized and administered TCA. While the internal dose of TCA predicted by modeling of TCE exposure (i.e., mg TCA/kg-d) showed a linear relationship with hepatomegaly, the slope of the relationship was much greater than that for directly administered TCA. Thus, the degree of hepatomegaly induced per unit of TCA produced through TCE oxidation is greater than that expected per unit of TCA

  18. Development of an updated PBPK model for trichloroethylene and metabolites in mice, and its application to discern the role of oxidative metabolism in TCE-induced hepatomegaly

    International Nuclear Information System (INIS)

    Evans, M.V.; Chiu, W.A.; Okino, M.S.; Caldwell, J.C.

    2009-01-01

    Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term exposure. An integrated dataset for gavage and inhalation TCE exposure and oral data for exposure to two of its oxidative metabolites (TCA and DCA) was used, in combination with an updated and more accurate physiologically-based pharmacokinetic (PBPK) model, to examine the question as to whether the presence of TCA in the liver is responsible for TCE-induced hepatomegaly in mice. The updated PBPK model was used to help discern the quantitative contribution of metabolites to this effect. The update of the model was based on a detailed evaluation of predictions from previously published models and additional preliminary analyses based on gas uptake inhalation data in mice. The parameters of the updated model were calibrated using Bayesian methods with an expanded pharmacokinetic database consisting of oral, inhalation, and iv studies of TCE administration as well as studies of TCE metabolites in mice. The dose-response relationships for hepatomegaly derived from the multi-study database showed that the proportionality of dose to response for TCE- and DCA-induced hepatomegaly is not observed for administered doses of TCA in the studied range. The updated PBPK model was used to make a quantitative comparison of internal dose of metabolized and administered TCA. While the internal dose of TCA predicted by modeling of TCE exposure (i.e., mg TCA/kg-d) showed a linear relationship with hepatomegaly, the slope of the relationship was much greater than that for directly administered TCA. Thus, the degree of hepatomegaly induced per unit of TCA produced through TCE oxidation is greater than that expected per unit of TCA

  19. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

    Science.gov (United States)

    Leke, Renata; Bak, Lasse K; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-04-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

  20. Structured lifestyle intervention in patients with the metabolic syndrome mitigates oxidative stress but fails to improve measures of cardiovascular autonomic neuropathy.

    Science.gov (United States)

    Pennathur, Subramaniam; Jaiswal, Mamta; Vivekanandan-Giri, Anuradha; White, Elizabeth A; Ang, Lynn; Raffel, David M; Rubenfire, Melvyn; Pop-Busui, Rodica

    2017-09-01

    To assess the role of oxidative stress in mediating adverse outcomes in metabolic syndrome (MetS) and resultant cardiovascular autonomic neuropathy (CAN), and to evaluate the effects of lifestyle interventions on measures of oxidative stress and CAN in subjects with MetS. Pilot study in 25 non-diabetic subjects with MetS (age 49±10years, 76% females) participating in a 24-week lifestyle intervention (supervised aerobic exercise/Mediterranean diet), and 25 age-matched healthy controls. CAN was assessed by cardiovascular reflex tests, heart rate variability (HRV) and PET imaging with sympathetic analog [ 11 C] meta-hydroxyephedrine ([ 11 C]HED). Specific oxidative fingerprints were measured by liquid-chromatography/mass-spectrometry (LC/MS). At baseline, MetS subjects had significantly higher oxidative stress markers [3-nitrotyrosine (234±158 vs. 54±47μmol/mol tyrosine), ortho-tyrosine (59±38 vs. 18±10μmol/molphenylalanine, all P<0.0001], and impaired HRV at rest and during deep breathing (P=0.039 and P=0.021 respectively) compared to controls. Twenty-four-week lifestyle intervention significantly reduced all oxidative stress markers (all P<0.01) but did not change any of the CAN measures. Subjects with MetS present with signs of CAN and increased oxidative stress in the absence of diabetes. The 24-week lifestyle intervention was effective in ameliorating oxidative stress, but did not improve measures of CAN. Larger clinical trials with longer duration are required to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of adrenergic agents on intracellular ca(2+) homeostasis and metabolism of glucose in astrocytes with an emphasis on pyruvate carboxylation, oxidative decarboxylation and recycling

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Andersen, Karen M H; Bak, Lasse Kristoffer

    2012-01-01

    and oxidative decarboxylation in astrocytic glucose metabolism. Importantly, pyruvate carboxylation was best visualized at 10 min of incubation. The abundance and pattern of labeling in lactate and alanine indicated not only an extensive activity of malic enzyme (initial step for pyruvate recycling) but also...... a high degree of compartmentalization of the pyruvate pool. Stimulating with 1 µM NE had no effect on labeling patterns and glycogen metabolism, whereas 100 µM NE increased glutamate labeling and decreased labeling in alanine, the latter supposedly due to dilution from degradation of non-labeled glycogen....... It is suggested that further experiments uncovering the correlation between adrenergic and glutamatergic pathways should be performed in order to gain further insight into the role of astrocytes in brain function and dysfunction, the latter including excitotoxicity....

  2. Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts.

    Science.gov (United States)

    Najafipour, Hamid; Joukar, Siyavash; Malekpour-Afshar, Reza; Mirzaeipour, Fateme; Nasri, Hamid Reza

    2010-02-03

    To scientifically test a traditionally belief of some Asian countries residents that opium may prevent or have ameliorating effects on cardiovascular diseases (CVD) we investigated the effect of passive opium smoking (POS) on plasma lipids and some cardiovascular parameters in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. 40 rabbits were fed for 2 weeks with cholesterol-enriched diet and divided to control (CTL), short-term opium (SO) and long-term opium (LO) groups. SO and LO groups were exposed to POS for 3 days and 4 weeks respectively. ECG, blood pressure (BP) and left ventricular pressure recorded and serum lipid and cardiac troponin I levels were measured. Isoproterenol (ISO) injected for induction of cardiac ischemia and after 4h the above variables were measured along with cardiac histopathology assessment. HDL cholesterol decreased significantly in LO compared to CTL group (35+/-5 vs 53+/-5mg/dl). Groups treated with ISO showed significantly higher increments in troponin I level (POpium exposure caused a trend of increase in blood pressure, LDL cholesterol and ECG disturbances, attenuated ISO induced myonecrosis but augmented tissue congestion and hemorrhage. POS can be considered as a CVD risk factor. Opium does not reduce BP or cholesterol level, as is anticipated by its users. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  3. The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis.

    Science.gov (United States)

    Becker, Marthe A J; Cornel, Jan H; van de Ven, Peter M; van Rossum, Albert C; Allaart, Cornelis P; Germans, Tjeerd

    2018-04-13

    This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM). Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events. PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling. Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36). The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Contrast-enhanced T1 mapping-based extracellular volume fraction independently predicts clinical outcome in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Jong-Chan [Hallym University College of Medicine, Division of Cardiology, Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of); Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of); Hong, Yoo Jin; Lee, Hye-Jeong; Han, Kyunghwa; Suh, Young Joo; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Shim, Chi Young; Hong, Geu-Ru; Kang, Seok-Min [Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of)

    2017-09-15

    We aimed to evaluate the prognostic role of cardiac magnetic resonance imaging (CMR)-based extracellular volume fraction (ECV) in patients with non-ischemic dilated cardiomyopathy (NIDCM) and compare it with late gadolinium enhancement (LGE) parameters. This was a single-center, prospective, cohort study of 117 NIDCM patients (71 men, 51.9 ± 16.7 years) who underwent clinical 3.0-T CMR. Myocardial ECV and LGE were quantified on the left ventricular myocardium. The presence of midwall LGE was also detected. Nineteen healthy subjects served as controls. The primary end points were cardiovascular (CV) events defined by CV death, rehospitalization due to heart failure, and heart transplantation. During the follow-up period (median duration, 11.2 months; 25{sup th}-75{sup th} percentile, 7.8-21.9 months), the primary end points occurred in 19 patients (16.2%). The ECV (per 3% and 1% increase) was associated with a hazard ratio of 1.80 and 1.22 (95% confidence interval [CI], 1.48-2.20 and 1.14-1.30, respectively; p < 0.001) for the CV events. Multivariable analysis also indicated that ECV was an independent prognostic factor and had a higher prognostic value (Harrell's c statistic, 0.88) than LGE quantification values (0.77) or midwall LGE (0.80). CMR-based ECV independently predicts the clinical outcome in NIDCM patients. (orig.)

  5. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats.

    Directory of Open Access Journals (Sweden)

    Ichiro Tokubuchi

    Full Text Available Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats.In human studies, metformin (1500mg/day was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old.Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE did not change, baseline respiratory quotient (RQ was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.From the results obtained, beneficial effects of metformin on visceral fat reduction has been

  6. Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.

    Science.gov (United States)

    Briley-Saebo, Karen C; Johansson, Lars O; Hustvedt, Svein Olaf; Haldorsen, Anita G; Bjørnerud, Atle; Fayad, Zahi A; Ahlstrom, Haakan K

    2006-07-01

    We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

  7. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw

    2017-01-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1...... and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation...

  8. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

    DEFF Research Database (Denmark)

    Magnussen, Line V; Glintborg, Dorte; Hermann, Pernille

    2016-01-01

    . MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels mass (LBM......), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect......AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy...

  9. Pericytopathy: Oxidative Stress and Impaired Cellular Longevity in the Pancreas and Skeletal Muscle in Metabolic Syndrome and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Melvin R. Hayden

    2010-01-01

    early pharmacotherapy in addition to lifestyle changes targeted to maintaining pericyte integrity. In conclusion, we have provided a review of current knowledge regarding the pericyte and novel ultrastructural findings regarding its role in metabolic syndrome and T2DM.

  10. Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism

    Directory of Open Access Journals (Sweden)

    Timothy R. H. Regnault

    2010-01-01

    Full Text Available PPAR-α, PPAR-β, and PPAR-γ, and RXR in conjunction with PGC-1α and SIRT1, activate oxidative metabolism genes determining insulin sensitivity. In utero, hypoxia is commonly observed in Intrauterine Growth Restriction (IUGR, and reduced insulin sensitivity is often observed in these infants as adults. We sought to investigate how changes in oxygen tension might directly impact muscle PPAR regulation of oxidative genes. Following eight days in culture at 1% oxygen, C2C12 muscle myoblasts displayed a reduction of PGC-1α, PPAR-α, and RXR-α mRNA, as well as CPT-1b and UCP-2 mRNA. SIRT1 and PGC-1α protein was reduced, and PPAR-γ protein increased. The addition of a PPAR-β agonist (L165,041 for the final 24 hours of 1% treatment resulted in increased levels of UCP-2 mRNA and protein whereas Rosiglitazone induced SIRT1, PGC-1α, RXR-α, PPAR-α, CPT-1b, and UCP-2 mRNA and SIRT1 protein. Under hypoxia, Resveratrol induced SIRT1, RXR-α, PPAR-α mRNA, and PPAR-γ and UCP-2 protein. These findings demonstrate that hypoxia alters the components of the PPAR pathway involved in muscle fatty acid oxidative gene transcription and translation. These results have implications for understanding selective hypoxia adaptation and how it might impact long-term muscle oxidative metabolism and insulin sensitivity.

  11. Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer.

    Science.gov (United States)

    Zuikov, S A; Borzenko, B G; Shatova, O P; Bakurova, E M; Polunin, G E

    2014-06-01

    To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer stage -III---IV, aged 40 to 79 years. Increase of pro-oxidant system of erythrocytes with the age against decrease in level of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of pro-ducts of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzymatic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient with colorectal cancer was determined. Obtained results have demonstrated the imbalance in the antioxidant system of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing.

  12. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.

    Science.gov (United States)

    Becattini, Barbara; Zani, Fabio; Breasson, Ludovic; Sardi, Claudia; D'Agostino, Vito Giuseppe; Choo, Min-Kyung; Provenzani, Alessandro; Park, Jin Mo; Solinas, Giovanni

    2016-09-01

    Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on glucose homeostasis and oxidative stress in obese mice were investigated for the first time. Mice lacking JNK1 (JNK1(-/-)) were fed an obesogenic high-fat diet (HFD) for a long period. JNK1(-/-) mice fed an HFD for the long term had reduced expression of antioxidant genes in their skin, more skin oxidative damage, and increased epidermal thickness and inflammation compared with the effects in control wild-type mice. However, we also observed that the protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, conferred by JNK1 ablation, was sustained over a long period and was paralleled by decreased oxidative damage in fat and liver. We conclude that compounds targeting JNK1 activity in brain and adipose tissue, which do not accumulate in the skin, may be safer and most effective.-Becattini, B., Zani, F., Breasson, L., Sardi, C., D'Agostino, V. G., Choo, M.-K., Provenzani, A., Park, J. M., Solinas, G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage. © FASEB.

  13. Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8.

    Directory of Open Access Journals (Sweden)

    Tiago B Rodrigues

    Full Text Available Mutations of the monocarboxylate transporter 8 (MCT8 cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3 transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13C glucose and brain extracts prepared and analyzed by (13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

  14. Xanthine Oxidase Activity Is Associated with Risk Factors for Cardiovascular Disease and Inflammatory and Oxidative Status Markers in Metabolic Syndrome: Effects of a Single Exercise Session

    Directory of Open Access Journals (Sweden)

    Ana Maria Pandolfo Feoli

    2014-01-01

    Full Text Available Objective. The main goal of the present study was to investigate the xanthine oxidase (XO activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. Materials/Methods. A case-control study (9 healthy and 8 MS volunteers was performed to measure XO, superoxide dismutase (SOD, glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Results. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Conclusions. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

  15. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

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    Matias Russo

    2016-07-01

    Full Text Available The purpose of this study was to determine whether the administration of the feruloyl esterase (FE-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group, CR diet Group (CR Group and CR diet plus L. fermentum Group (CR-Lf Group. CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020 than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025, total cholesterol (p = 0.005 and glucose (p < 0.0001 levels and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006 parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

  16. Effects of dietary cold-pressed turnip rapeseed oil and butter on serum lipids, oxidized LDL and arterial elasticity in men with metabolic syndrome

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    Wallenius Marja

    2010-12-01

    Full Text Available Abstract Background Rapeseed oil is the principal dietary source of monounsaturated and n-3 polyunsaturated fatty acids in the Northern Europe. However, the effect of rapeseed oil on the markers of subclinical atherosclerosis is not known. The purpose of this study was to compare the effects of dietary intake of cold-pressed turnip rapeseed oil (CPTRO and butter on serum lipids, oxidized LDL and arterial elasticity in men with metabolic syndrome. Methods Thirty-seven men with metabolic syndrome completed an open and balanced crossover study. Treatment periods lasted for 6 to 8 weeks and they were separated from each other with an eight-week washout period. Subjects maintained their normal dietary habits and physical activity without major variations. The daily fat adjunct consisted either of 37.5 grams of butter or 35 mL of VirginoR CPTRO. Participants were asked to spread butter on bread on the butter period and to drink CPTRO on the oil period. The fat adjunct was used as such without heating or frying. Results Compared to butter, administration of CPTRO was followed by a reduction of total cholesterol by 8% (p Conclusion Cold-pressed turnip rapeseed oil had favourable effects on circulating LDL cholesterol and oxidized LDL, which may be important in the management of patients at high cardiovascular risk. Trial registration ClinicalTrial.gov NCT01119690

  17. Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

    Science.gov (United States)

    Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

    2018-02-14

    Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

  18. Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport.

    Science.gov (United States)

    Reuter, Tanja Y; Medhurst, Annette L; Waisfisz, Quinten; Zhi, Yu; Herterich, Sabine; Hoehn, Holger; Gross, Hans J; Joenje, Hans; Hoatlin, Maureen E; Mathew, Christopher G; Huber, Pia A J

    2003-10-01

    Mutations in one of at least eight different genes cause bone marrow failure, chromosome instability, and predisposition to cancer associated with the rare genetic syndrome Fanconi anemia (FA). The cloning of seven genes has provided the tools to study the molecular pathway disrupted in Fanconi anemia patients. The structure of the genes and their gene products provided few clues to their functional role. We report here the use of 3 FA proteins, FANCA, FANCC, and FANCG, as "baits" in the hunt for interactors to obtain clues for FA protein functions. Using five different human cDNA libraries we screened 36.5x10(6) clones with the technique of the yeast two-hybrid system. We identified 69 proteins which have not previously been linked to the FA pathway as direct interactors of FANCA, FANCC, or FANCG. Most of these proteins are associated with four functional classes including transcription regulation (21 proteins), signaling (13 proteins), oxidative metabolism (10 proteins), and intracellular transport (11 proteins). Interaction with 6 proteins, DAXX, Ran, IkappaBgamma, USP14, and the previously reported SNX5 and FAZF, was additionally confirmed by coimmunoprecipitation and/or colocalization studies. Taken together, our data strongly support the hypothesis that FA proteins are functionally involved in several complex cellular pathways including transcription regulation, cell signaling, oxidative metabolism, and cellular transport.

  19. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells.

    Science.gov (United States)

    Bajbouj, Khuloud; Shafarin, Jasmin; Abdalla, Maher Y; Ahmad, Iman M; Hamad, Mawieh

    2017-10-01

    It is well established that several forms of cancer associate with significant iron overload. Recent studies have suggested that estrogen (E2) disrupts intracellular iron homeostasis by reducing hepcidin synthesis and maintaining ferroportin integrity. Here, the ability of E2 to alter intracellular iron status and cell growth potential was investigated in MCF-7 cells treated with increasing concentrations of E2. Treated cells were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, oxidative stress, cell survival, growth, and apoptosis. E2 treatment resulted in a significant reduction in hepcidin expression and a significant increase in hypoxia-inducible factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a transient decrease in labile iron pool; and a significant increase in total intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also showed increased total glutathione and oxidized glutathione levels, increased superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth (0.35/1 migration rate) and decreased cell survival (iron metabolism and precipitates adverse effects concerning cell viability, membrane integrity, and growth potential.

  20. Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress.

    Science.gov (United States)

    Rahimi, Zohreh; Ahmadi, Reza; Vaisi-Raygani, Asad; Rahimi, Ziba; Bahrehmand, Fariborz; Parsian, Abbas

    2013-11-01

    To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women. In a case-control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively. The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE ε3ε4 compared to ε3ε3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level. Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.

  1. Xanthine oxidase activity is associated with risk factors for cardiovascular disease and inflammatory and oxidative status markers in metabolic syndrome: effects of a single exercise session.

    Science.gov (United States)

    Feoli, Ana Maria Pandolfo; Macagnan, Fabrício Edler; Piovesan, Carla Haas; Bodanese, Luiz Carlos; Siqueira, Ionara Rodrigues

    2014-01-01

    The main goal of the present study was to investigate the xanthine oxidase (XO) activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. A case-control study (9 healthy and 8 MS volunteers) was performed to measure XO, superoxide dismutase (SOD), glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP) content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

  2. Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.

    Science.gov (United States)

    Liu, Yong; He, Yizhou; Jin, Aiwen; Tikunov, Andrey P; Zhou, Lishi; Tollini, Laura A; Leslie, Patrick; Kim, Tae-Hyung; Li, Lei O; Coleman, Rosalind A; Gu, Zhennan; Chen, Yong Q; Macdonald, Jeffrey M; Graves, Lee M; Zhang, Yanping

    2014-06-10

    The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.

  3. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Directory of Open Access Journals (Sweden)

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  4. Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate-glutamine cycle in the tree shrew visual cortex.

    Science.gov (United States)

    Sonnay, Sarah; Poirot, Jordan; Just, Nathalie; Clerc, Anne-Catherine; Gruetter, Rolf; Rainer, Gregor; Duarte, João M N

    2018-03-01

    Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (V NT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1 H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a reduction of glucose concentration by -0.34 ± 0.09 µmol/g (p glucose infusion was employed to measure fluxes of energy metabolism. Stimulation of glutamatergic activity, as indicated by a 20% increase of V NT , resulted in increased TCA cycle rates in neurons by 12% ( VTCAn, p glucose oxidation and to mitochondrial metabolism in both neurons and astrocytes. © 2017 Wiley Periodicals, Inc.

  5. Activation of the oxidative stress regulator PpYap1 through conserved cysteine residues during methanol metabolism in the yeast Pichia pastoris.

    Science.gov (United States)

    Yano, Taisuke; Yurimoto, Hiroya; Sakai, Yasuyoshi

    2009-06-01

    The methylotrophic yeast Pichia pastoris can grow on methanol as sole source of carbon and energy. The first reaction in yeast methanol metabolism, catalyzed by an abundant peroxisomal enzyme, alcohol oxidase, generates high levels of H(2)O(2), but the oxidative stress response during methanol metabolism has not been elucidated. In this study, we isolated the Yap1 homolog of P. pastoris (PpYap1) and analyzed the properties of a PpYAP1-disruption strain. The PpYap1 transcription factor is activated after exposure to various reactive agents, and therefore functions as a regulator of the redox system in P. pastoris. We have also identified PpGPX1, the unique glutathione peroxidase-encoding gene in P. pastoris whose expression is induced by PpYap1. PpGpx1, but not the ScTsa1 or SpTpx1 homolog PpTsa1, functions as a H(2)O(2) sensor and activates PpYap1. This study is the first demonstration of a yeast Yap1 family protein activated during conventional metabolism.

  6. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

    Directory of Open Access Journals (Sweden)

    Zeba Farooqui

    Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

  7. Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

    Science.gov (United States)

    Pathak, Kaveri; Soares, Mario J; Zhao, Yun; James, Anthony P; Sherriff, Jillian L; Newsholme, Philip

    2017-05-01

    Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 10 4 /(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. Higher vitamin D status, but not FGF21, was associated with greater postprandial

  8. Characterization of γ-aminobutyric acid metabolism and oxidative damage in wheat (Triticum aestivum L.) seedlings under salt and osmotic stress.

    Science.gov (United States)

    Al-Quraan, Nisreen A; Sartawe, Fatima Al-Batool; Qaryouti, Muien M

    2013-07-15

    The molecular response of plants to abiotic stresses has been considered a process mainly involved in the modulation of transcriptional activity of stress-related genes. Nevertheless, recent findings have suggested new layers of regulation and complexity. Upstream molecular mechanisms are involved in the plant response to abiotic stress. Plants gain resistance to abiotic stress by reprogramming metabolism and gene expression. GABA is proposed to be a signaling molecule involved in nitrogen metabolism, regulating the cytosolic pH, and protection against oxidative damage in response to various abiotic stresses. The aim of our study was to examine the role of the GABA shunt pathway-specific response in five wheat (Triticum aestivum L.) cultivars (Hurani 75, Sham I, Acsad 65, Um Qayes and Nodsieh) to salt and osmotic stress in terms of seed germination, seedling growth, oxidative damage (malondialdehyde (MDA) accumulation), and characterization of the glutamate decarboxylse gene (GAD) m-RNA level were determined using RT-PCR techniques. Our data showed a marked increase in GABA, MDA and GAD m-RNA levels under salt and osmotic stress in the five wheat cultivars. Um Qayes cultivar showed the highest germination percentage, GABA accumulation, and MDA level under salt and osmotic stresses. The marked increase in GAD gene expression explains the high accumulation of the GABA level under both stresses. Our results indicated that the GABA shunt is a key signaling and metabolic pathway that allows wheat to adapt to salt and osmotic stress. Based on our data, the Um Qayes wheat cultivar is the cultivar most recommended to be grown in soil with high salt and osmotic contents. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

    Science.gov (United States)

    Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

    2014-01-21

    Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

  10. Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells.

    Science.gov (United States)

    Fresta, Claudia G; Chakraborty, Aishik; Wijesinghe, Manjula B; Amorini, Angela M; Lazzarino, Giacomo; Lazzarino, Giuseppe; Tavazzi, Barbara; Lunte, Susan M; Caraci, Filippo; Dhar, Prajnaparamita; Caruso, Giuseppe

    2018-02-14

    Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism. Particularly, we initially measured decrease in cell viability as a function of increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 µg/mL causing decrease in cell number < 5%) we determined NO and ROS production, and measured the concentrations of compounds related to energy metabolism, mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We found that in both cell lines non-cytotoxic ECN concentrations increased NO and ROS production with sustained oxidative/nitrosative stress, and caused energy metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes) and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results underline the importance to deeply investigate the molecular and biochemical changes occurring upon the interaction of ECNs (and nanoparticles in general) with living cells, even at apparently non-toxic concentration. Since the use of ECNs in biomedical field is attracting increasing attention the complete evaluation of their biosafety, toxicity and/or possible side effects both in vitro and in vivo is mandatory before these highly promising tools might find the correct application.

  11. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Cahová, M.; Chrastina, P.; Hansíková, H.; Drahota, Zdeněk; Trnovská, J.; Škop, V.; Spáčilová, J.; Malínská, H.; Oliyarnyk, O.; Papáčková, Z.; Páleníčková, E.; Kazdová, L.

    2015-01-01

    Roč. 40, č. 3 (2015), s. 280-291 ISSN 1715-5312 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : metabolic syndrome * insulin resistance * antioxidant * liver steatosis * mass spectrometry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.910, year: 2015

  12. The Prevalence, Correlates, and Impact on Cardiac Mortality of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy.

    Science.gov (United States)

    Pueschner, Andreas; Chattranukulchai, Pairoj; Heitner, John F; Shah, Dipan J; Hayes, Brenda; Rehwald, Wolfgang; Parker, Michele A; Kim, Han W; Judd, Robert M; Kim, Raymond J; Klem, Igor

    2017-10-01

    This study sought to determine the prevalence, correlates, and impact on cardiac mortality of right ventricular (RV) dysfunction in nonischemic cardiomyopathy. Current heart failure guidelines place little emphasis on RV assessment due to limited available data on determinants of RV function, mechanisms leading to its failure, and relation to outcomes. We prospectively studied 423 patients with cardiac magnetic resonance (CMR). The pre-specified study endpoint was cardiac mortality. In 100 patients, right heart catheterization was performed as clinically indicated. During a median follow-up time of 6.2 years (interquartile range: 2.9 to 7.6 years), 101 patients (24%) died of cardiac causes. CMR right ventricular ejection fraction (RVEF) was a strong independent predictor of cardiac mortality after adjustment for age, heart failure-functional class, blood pressure, heart rate, serum sodium, serum creatinine, myocardial scar, and left ventricular ejection fraction (LVEF). Patients with the lowest quintile of RVEF had a nearly 5-fold higher cardiac mortality risk than did patients with the highest quintile (hazard ratio: 4.68; 95% confidence interval [CI]: 2.43 to 9.02; p right atrial pressure (r = -0.32; p = 0.001), pulmonary artery pressure (r = -0.34; p = 0.0005), transpulmonary gradient (r = -0.28; p = 0.006) but not with pulmonary wedge pressure (r = -0.15; p = 0.13). In multivariable logistic regression analysis of CMR, clinical, and hemodynamic data the strongest predictors of right ventricular dysfunction were LVEF (odds ratio [OR]: 0.85; 95% CI: 0.78 to 0.92; p Right ventricular dysfunction is strongly associated with both indices of intrinsic myocardial contractility and increased afterload from pulmonary vascular dysfunction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

    Science.gov (United States)

    Arenja, Nisha; Riffel, Johannes H; Fritz, Thomas; André, Florian; Aus dem Siepen, Fabian; Mueller-Hennessen, Matthias; Giannitsis, Evangelos; Katus, Hugo A; Friedrich, Matthias G; Buss, Sebastian J

    2017-06-01

    Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental

  14. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

    Science.gov (United States)

    Smits, Loek P; Kootte, Ruud S; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G; Wang, Zeneng; Levison, Bruce S; Cleophas, Maartje C P; Kemper, E Marleen; Dallinga-Thie, Geesje M; Groen, Albert K; Joosten, Leo A B; Netea, Mihai G; Stroes, Erik S G; de Vos, Willem M; Hazen, Stanley L; Nieuwdorp, Max

    2018-03-26

    Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. URL: http://www.trialregister.nl. Unique identifier: NTR 4338. © 2018 The Authors. Published on

  15. Effect of diet on expression of genes involved in lipid metabolism, oxidative stress, and inflammation in mouse liver-insights into mechanisms of hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Helen J Renaud

    Full Text Available Nutritional intake is a fundamental determinant of health. Many studies have correlated excess caloric intake, as well as a high ratio of n-6:n-3 fatty acids, with detrimental health outcomes, such as the metabolic syndrome. In contrast, low-calorie diets have beneficial health effects. Despite these associations, our understanding of the causal relationship between diet and health remains largely elusive. The present study examined the molecular changes elicited by nine diets with varying fat, sugar, cholesterol, omega-3 fatty acids, omega-6 fatty acids, and calories in C57BL/6 male mice. Microarray analyses were conducted on liver samples from three mice per diet and detected 20,449 genes of which 3,734 were responsive to changes in dietary components. Principal component analysis showed that diet restriction correlated the least with the other diets and also affected more genes than any other diet. Interestingly, Gene Set Enrichment Analysis (GSEA identified gene sets involved in glutathione metabolism, immune response, fatty acid metabolism, cholesterol metabolism, ABC transporters, and oxidative phosphorylation as being highly responsive to changes in diet composition. On the gene level, this study reveals novel findings such as the induction of the drug efflux pump Abcb1a (p-glycoprotein by diet restriction and an atherogenic diet, as well as the suppression of the rate limiting step of bile acid synthesis, Cyp7a1, by a high fructose diet. This study provides considerable insight into the molecular changes incurred by a variety of diets and furthers our understanding of the causal relationships between diet and health.

  16. Effect of Diet on Expression of Genes Involved in Lipid Metabolism, Oxidative Stress, and Inflammation in Mouse Liver–Insights into Mechanisms of Hepatic Steatosis

    Science.gov (United States)

    Renaud, Helen J.; Cui, Julia Y.; Lu, Hong; Klaassen, Curtis D.

    2014-01-01

    Nutritional intake is a fundamental determinant of health. Many studies have correlated excess caloric intake, as well as a high ratio of n-6:n-3 fatty acids, with detrimental health outcomes, such as the metabolic syndrome. In contrast, low-calorie diets have beneficial health effects. Despite these associations, our understanding of the causal relationship between diet and health remains largely elusive. The present study examined the molecular changes elicited by nine diets with varying fat, sugar, cholesterol, omega-3 fatty acids, omega-6 fatty acids, and calories in C57BL/6 male mice. Microarray analyses were conducted on liver samples from three mice per diet and detected 20,449 genes of which 3,734 were responsive to changes in dietary components. Principal component analysis showed that diet restriction correlated the least with the other diets and also affected more genes than any other diet. Interestingly, Gene Set Enrichment Analysis (GSEA) identified gene sets involved in glutathione metabolism, immune response, fatty acid metabolism, cholesterol metabolism, ABC transporters, and oxidative phosphorylation as being highly responsive to changes in diet composition. On the gene level, this study reveals novel findings such as the induction of the drug efflux pump Abcb1a (p-glycoprotein) by diet restriction and an atherogenic diet, as well as the suppression of the rate limiting step of bile acid synthesis, Cyp7a1, by a high fructose diet. This study provides considerable insight into the molecular changes incurred by a variety of diets and furthers our understanding of the causal relationships between diet and health. PMID:24551121

  17. Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

    Directory of Open Access Journals (Sweden)

    Kennedy Hugh

    2008-10-01

    Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

  18. Metabolism in the Uncultivated Giant Sulfide-Oxidizing Bacterium Thiomargarita Namibiensis Assayed Using a Redox-Sensitive Dye

    Science.gov (United States)

    Bailey, J.; Flood, B.; Ricci, E.

    2014-12-01

    The colorless sulfur bacteria are non-photosynthetic chemolithotrophs that live at interfaces between nitrate, or oxygen, and hydrogen sulfide. In sulfidic settings such as cold seeps and oxygen minimum zones, these bacteria are thought to constitute a critical node in the geochemical cycling of carbon, sulfur, nitrogen, and phosphorous. Many of these bacteria remain uncultivated and their metabolisms and physiologies are incompletely understood. Thiomargarita namibiensis is the largest of these sulfur bacteria, with individual cells reaching millimetric diameters. Despite the current inability to maintain a Thiomargarita culture in the lab, their large size allows for individual cells to be followed in time course experiments. Here we report on the novel use of a tetrazolium-based dye that measures the flux of NADH production from catabolic pathways via a colorimetric response. Staining with this dye allows for metabolism to be detected, even in the absence of observable cell division. When coupled to microscopy, this approach also allows for metabolism in Thiomargaritato be differentiated from that of epibionts or contaminants in xenic samples. The results of our tetrazolium dye-based assay suggests that Thiomargarita is the most metabolically versatile under anoxic conditions where it appears capable of using acetate, succinate, formate, thiosulfate, citrate, thiotaurine, hydrogen sulfide, and perhaps hydrogen as electron donors. Under hypoxic conditions, staining results suggest the utilization of acetate, citrate, and hydrogen sulfide. Cells incubated under oxic conditions showed the weakest tetrazolium staining response, and then only to hydrogen sulfide and questionably succinate. These initial results using a redox sensitive dye suggest that Thiomargarita is most metabolically versatile under anaerobic and hypoxic conditions. The results of this assay can be further evaluated using molecular approaches such as transcriptomics, as well as provide cultivation

  19. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pietzsch, Jens [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Bergmann, Ralf [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Rode, Katrin [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Hultsch, Christina [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Pawelke, Beate [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Wuest, Frank [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany); Hoff, Joerg van den [PET-Center, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Center Rossendorf Dresden, P.O. Box 51 01 19, D-01314 Dresden (Germany)

    2004-11-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ({sup 18}F) by conjugation with N-succinimidyl-4-[{sup 18}F]fluorobenzoate ([{sup 18}F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [{sup 18}F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [{sup 18}F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

  20. Nitric oxide in acute brain injury: a pilot study of NO(x) concentrations in human brain microdialysates and their relationship with energy metabolism.

    Science.gov (United States)

    Carpenter, Keri L H; Timofeev, Ivan; Al-Rawi, Pippa G; Menon, David K; Pickard, John D; Hutchinson, Peter J

    2008-01-01

    This pilot microdialysis study in acute brain injury patients assessed the relationship between nitric oxide products (total nitrite plus nitrate, termed NO(x)) and energy-related molecules: glucose, lactate, pyruvate, glutamate and glycerol. Twelve patients (11 major head-injury and one subarachnoid haemorrhage) were studied, 11 of which had single catheters and one had two catheters, in the cerebral cortex. Catheters were perfused at 0.3 microL/min with CNS perfusion fluid. Collection vials were changed hourly. Microdialysates were analysed for energy-related molecules on a CMA600 or ISCUS analyser, and for NO(x) using a purge vessel (VCl3 plus HCl at 95 degrees C, purged with nitrogen) connected to a Sievers NOA 280i analyser. The mean of mean NO(x) concentration (+/- SD) for the 13 catheters was 32.7 +/- 16.8 micromol/L, and the lactate/ pyruvate ratio was 38.6 +/- 20.1. Increasing NO(x) concentrations correlated significantly with decreasing lactate/ pyruvate ratio (Spearman r = -0.79, p = 0.0065), with decreasing lactate concentration (r = -0.59, p = 0.042), and with increasing glucose concentration (r = 0.71, p = 0.018). These pilot data suggest that in injured brains, higher concentrations of nitric oxide are associated with more favourable metabolism. Nitric oxide may act beneficially by increasing blood flow and delivery of oxygen and glucose. Further patients are being recruited.

  1. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  2. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    International Nuclear Information System (INIS)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

    2014-01-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  3. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

    DEFF Research Database (Denmark)

    Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D

    2011-01-01

    Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout...... mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species......, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle....

  4. Novel mode of microbial energy metabolism: organic carbon oxidation coupled to dissimilatory reduction of iron or manganese.

    Science.gov (United States)

    Lovley, D R; Phillips, E J

    1988-06-01

    A dissimilatory Fe(III)- and Mn(IV)-reducing microorganism was isolated from freshwater sediments of the Potomac River, Maryland. The isolate, designated GS-15, grew in defined anaerobic medium with acetate as the sole electron donor and Fe(III), Mn(IV), or nitrate as the sole electron acceptor. GS-15 oxidized acetate to carbon dioxide with the concomitant reduction of amorphic Fe(III) oxide to magnetite (Fe(3)O(4)). When Fe(III) citrate replaced amorphic Fe(III) oxide as the electron acceptor, GS-15 grew faster and reduced all of the added Fe(III) to Fe(II). GS-15 reduced a natural amorphic Fe(III) oxide but did not significantly reduce highly crystalline Fe(III) forms. Fe(III) was reduced optimally at pH 6.7 to 7 and at 30 to 35 degrees C. Ethanol, butyrate, and propionate could also serve as electron donors for Fe(III) reduction. A variety of other organic compounds and hydrogen could not. MnO(2) was completely reduced to Mn(II), which precipitated as rhodochrosite (MnCO(3)). Nitrate was reduced to ammonia. Oxygen could not serve as an electron acceptor, and it inhibited growth with the other electron acceptors. This is the first demonstration that microorganisms can completely oxidize organic compounds with Fe(III) or Mn(IV) as the sole electron acceptor and that oxidation of organic matter coupled to dissimilatory Fe(III) or Mn(IV) reduction can yield energy for microbial growth. GS-15 provides a model for how enzymatically catalyzed reactions can be quantitatively significant mechanisms for the reduction of iron and manganese in anaerobic environments.

  5. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Science.gov (United States)

    Popławski, Piotr; Wiśniewski, Jacek R; Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef; Piekiełko-Witkowska, Agnieszka

    2017-01-01

    Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3'-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression and changes

  6. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Directory of Open Access Journals (Sweden)

    Piotr Popławski

    Full Text Available Type 1 iodothyronine deiodinase (DIO1 contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4 yielding of 3,5,3'-triiodothyronine (T3, a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2 that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2, enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2, sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10. DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression

  7. Pioglitazone enhances expression of genes involved in mitochondrial oxidative metabolism in skeletal muscle of women with polycystic ovary syndrome (PCOS)

    DEFF Research Database (Denmark)

    Skov, Vibe

    Aims                Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women and is associated with insulin resistance increasing the risk for developing type 2 diabetes mellitus. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS...... patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity. Methods Using the HG-U133 2.0 Plus expression array from Affymetrix, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene...... expression in skeletal muscle of 10 obese women with PCOS (dataset 1). Furthermore, evaluation of gene expression changes between PCOS patients before treatment and control subjects were performed (dataset 2). All subjects were metabolically characterised by a euglycemic-hyperinsulinemic clamp combined...

  8. CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48

    DEFF Research Database (Denmark)

    Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

    2015-01-01

    the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared...

  9. Females Are Protected From Iron?Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress

    OpenAIRE

    Das, Subhash K.; Patel, Vaibhav B.; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y.

    2017-01-01

    Background Sex?related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron?overload cardiomyopathy is poorly understood. Methods and Results Male and female wild?type and hemojuvelin?null mice were injected and fed with a high?iron diet, respectively, to develop secondary iron overload and geneti...

  10. Role of lecithin-cholesterol acyltransferase in the metabolism of oxidized phospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma.

    Science.gov (United States)

    Subramanian, V S; Goyal, J; Miwa, M; Sugatami, J; Akiyama, M; Liu, M; Subbaiah, P V

    1999-07-09

    To determine the relative importance of platelet-activating factor-acetylhydrolase (PAF-AH) and lecithin-cholesterol acyltransferase (LCAT) in the hydrolysis of oxidized phosphatidylcholines (OXPCs) to lyso-phosphatidylcholine (lyso-PC), we studied the formation and metabolism of OXPCs in the plasma of normal and PAF-AH-deficient subjects. Whereas the loss of PC following oxidation was similar in the deficient and normal plasmas, the formation of lyso-PC was significantly lower, and the accumulation of OXPC was higher in the deficient plasma. Isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation, and stimulated adhesion molecule synthesis in endothelial cells, more than the normal LDL. Oxidation of 16:0-[1-14C]-18:2 PC, equilibrated with plasma PC, resulted in the accumulation of labeled short- and long-chain OXPCs, in addition to the labeled aqueous products. The formation of the aqueous products decreased by 80%, and the accumulation of short-chain OXPC increased by 110% in the deficient plasma, compared to the normal plasma, showing that PAF-AH is predominantly involved in the hydrolysis of the truncated OXPCs. Labeled sn-2-acyl group from the long-chain OXPC was not only hydrolyzed to free fatty acid, but was preferentially transferred to diacylglycerol, in both the normal and deficient plasmas. In contrast, the acyl group from unoxidized PC was transferred only to cholesterol, showing that the specificity of LCAT is altered by OXPC. It is concluded that, while PAF-AH carries out the hydrolysis of mainly truncated OXPCs, LCAT hydrolyzes and transesterifies the long-chain OXPCs.

  11. Human systemic exposure to [14C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment

    NARCIS (Netherlands)

    Nohynek, G.J.; Skare, J.A.; Meuling, W.J.A.; Wehmeyer, K.R.; Bie, A.T.H.J. de; Vaes, W.H.J.; Dufour, E.K.; Fautz, R.; Steiling, W.; Bramante, M.; Toutain, H.

    2015-01-01

    Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [14C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [14C] was measured in all

  12. Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

    Science.gov (United States)

    He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

    2017-01-01

    Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.

    Science.gov (United States)

    da Costa, Rafael M; da Silva, Josiane F; Alves, Juliano V; Dias, Thiago B; Rassi, Diane M; Garcia, Luis V; Lobato, Núbia de Souza; Tostes, Rita C

    2018-01-01

    Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility. This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia. The O -linked β-N-acetylglucosamine ( O -GlcNAc) modification of proteins ( O -GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity. Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O -GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions. We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O -GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects. Therefore, the current study was devised to determine whether a high-sugar diet increases O -GlcNAcylation in the PVAT and how increased O -GlcNAc interferes with PVAT vasorelaxant function. To assess molecular mechanisms by which O -GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks. Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O -GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect. PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O -GlcNAcylation of eNOS. High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT. Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O -GlcNAc-modified proteins, increased ROS

  14. Effects of aging and exercise training on leg hemodynamics and oxidative metabolism in the transition from rest to steady state exercise

    DEFF Research Database (Denmark)

    Piil, Peter Bergmann; Jørgensen, Tue Smith; Egelund, Jon

    2018-01-01

    hemodynamics and oxidative metabolism in the transition from rest to steady state exercise engaging the knee-extensor muscles in young (n=15, 25{plus minus}1 years) and older (n=15, 72{plus minus}1 years) subjects before and after a period of aerobic high-intensity exercise training. To enhance cGMP signaling....... The rate of increase in leg VO2 was, however, similar in the two groups as a result of higher ( PGMP signaling did not affect the rate of increase in blood flow or VO2 in either group. Exercise training augmented ( P.... A lower blood flow response in aging does not appear to be a result of reduced cGMP signaling....

  15. E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

    Science.gov (United States)

    Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

    2012-09-01

    E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

  16. Energy Metabolism in the Liver

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

  17. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

    Science.gov (United States)

    Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

    2012-02-01

    The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

  18. Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

    Science.gov (United States)

    Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

    2016-07-01

    Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

    Science.gov (United States)

    Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

    2009-07-01

    Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

  20. The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

    Science.gov (United States)

    Ghazimoradi, Maryam; Saberi-Karimian, Maryam; Mohammadi, Farzane; Sahebkar, Amirhossein; Tavallaie, Shima; Safarian, Hamideh; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Moohebati, Mohsen; Esmaeili, Habibollah; Ahmadinejad, Malihe

    2017-11-01

    Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Moderate chronic administration of Vineatrol-enriched red wines improves metabolic, oxidative, and inflammatory markers in hamsters fed a high-fat diet.

    Science.gov (United States)

    Romain, Cindy; Bresciani, Letizia; Gaillet, Sylvie; Feillet-Coudray, Christine; Calani, Luca; Bonafos, Béatrice; Vidé, Joris; Rugani, Nathalie; Ramos, Jeanne; Del Rio, Daniele; Cristol, Jean-Paul; Rouanet, Jean-Max

    2014-06-01

    High-fat (HF) diets contribute to the development of cardiovascular diseases and the metabolic syndrome. This study was undertaken to investigate the beneficial effects of Vineatrol®-enriched red wines on blood lipids, oxidative stress and inflammation, and the role of some metabolic pathway regulatory proteins. Golden Syrian hamsters received an HF diet for 13 wk, in the presence or absence of red wines supplemented with Vineatrol® (RWV) or not. The HF diet increased plasma cholesterol, triglycerides, glucose, and insulin, which were attenuated by RWV treatment. RWV protected against the HF-induced increase in liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and spared antioxidant enzyme activities. RWV did not reduce either liver steatosis or increased plasma leptin due to the HF diet, but greatly improved adiponectinemia. In the liver, RWV affected the inflammatory response by decreasing polymorphonuclear cell number and lowering TNF-α and IL-6 levels. Moreover, the increase in NF-κB activity in the HF group liver was prevented by RWV. Finally, RWV partially corrected low SIRT1 levels due to the HF diet but had no influence on SIRT3 or p-AMPK protein levels. Our studies suggest that RWV is capable of reversing the atherogenic process induced by an HF diet in hamster tissues. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Ocean Warming Enhances Malformations, Premature Hatching, Metabolic Suppression and Oxidative Stress in the Early Life Stages of a Keystone Squid

    Science.gov (United States)

    Rosa, Rui; Pimentel, Marta S.; Boavida-Portugal, Joana; Teixeira, Tatiana; Trübenbach, Katja; Diniz, Mário

    2012-01-01

    Background The knowledge about the capacity of organisms’ early life stages to adapt to elevated temperatures is very limited but crucial to understand how marine biota will respond to global warming. Here we provide a comprehensive and integrated view of biological responses to future warming during the early ontogeny of a keystone invertebrate, the squid Loligo vulgaris. Methodology/Principal Findings Recently-spawned egg masses were collected and reared until hatching at present day and projected near future (+2°C) temperatures, to investigate the ability of early stages to undergo thermal acclimation, namely phenotypic altering of morphological, behavioural, biochemical and physiological features. Our findings showed that under the projected near-future warming, the abiotic conditions inside the eggs promoted metabolic suppression, which was followed by premature hatching. Concomitantly, the less developed newborns showed greater incidence of malformations. After hatching, the metabolic burst associated with the transition from an encapsulated embryo to a planktonic stage increased linearly with temperature. However, the greater exposure to environmental stress by the hatchlings seemed to be compensated by physiological mechanisms that reduce the negative effects on fitness. Heat shock proteins (HSP70/HSC70) and antioxidant enzymes activities constituted an integrated stress response to ocean warming in hatchlings (but not in embryos). Conclusions/Significance The stressful abiotic conditions inside eggs are expected to be aggravated under the projected near-future ocean warming, with deleterious effects on embryo survival and growth. Greater feeding challenges and the lower thermal tolerance limits of the hatchlings are strictly connected to high metabolic demands associated with the planktonic life strategy. Yet, we found some evidence that, in the future, the early stages might support higher energy demands by adjusting some cellular functional properties

  3. Contribution of polyamines metabolism and GABA shunt to chilling tolerance induced by nitric oxide in cold-stored banana fruit.

    Science.gov (United States)

    Wang, Yansheng; Luo, Zisheng; Mao, Linchun; Ying, Tiejin

    2016-04-15

    Effect of exogenous nitric oxide (NO) on polyamines (PAs) catabolism, γ-aminobutyric acid (GABA) shunt, proline accumulation and chilling injury of banana fruit under cold storage was investigated. Banana fruit treated with NO sustained lower chilling injury index than the control. Notably elevated nitric oxide synthetase activity and endogenous NO level were observed in NO-treated banana fruit. PAs contents in treated fruit were significantly higher than control fruit, due to the elevated activities of arginine decarboxylase and ornithine decarboxylase. NO treatment increased the activities of diamine oxidase, polyamine oxidase and glutamate decarboxylase, while reduced GABA transaminase activity to lower levels compared with control fruit, which resulted the accumulation of GABA. Besides, NO treatment upregulated proline content and significantly enhanced the ornithine aminotransferase activity. These results indicated that the chilling tolerance induced by NO treatment might be ascribed to the enhanced catabolism of PAs, GABA and proline. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress

    Czech Academy of Sciences Publication Activity Database

    Maya-Mendoza, A.; Ostrakova, J.; Košař, Martin; Hall, A.; Duskova, P.; Mistrik, M.; Merchut-Maya, J.M.; Hodný, Zdeněk; Bartkova, J.; Christensen, C.; Bartek, Jiří

    2015-01-01

    Roč. 9, č. 3 (2015), s. 601-616 ISSN 1574-7891 R&D Projects: GA ČR GA13-17555S; GA MŠk(CZ) LO1304 Grant - others:Danish Council for Independent Research(DK) DFF- 1331-00262; Lundbeck Foundation(DK) R93-A8990 Institutional support: RVO:68378050 Keywords : Myc * Ras * Replication stress * DNA fork progression * Energy metabolism * DNA damage response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.367, year: 2015

  5. The uptake and excretion of partially oxidized sulfur expands the repertoire of energy resources metabolized by hydrothermal vent symbioses.

    Science.gov (United States)

    Beinart, R A; Gartman, A; Sanders, J G; Luther, G W; Girguis, P R

    2015-05-07

    Symbiotic associations between animals and chemoautotrophic bacteria crowd around hydrothermal vents. In these associations, symbiotic bacteria use chemical reductants from venting fluid for the energy to support autotrophy, providing primary nutrition for the host. At vents along the Eastern Lau Spreading Center, the partially oxidized sulfur compounds (POSCs) thiosulfate and polysulfide have been detected in and around animal communities but away from venting fluid. The use of POSCs for autotrophy, as an alternative to the chemical substrates in venting fluid, could mitigate competition in these communities. To determine whether ESLC symbioses could use thiosulfate to support carbon fixation or produce POSCs during sulfide oxidation, we used high-pressure, flow-through incubations to assess the productivity of three symbiotic mollusc genera-the snails Alviniconcha spp. and Ifremeria nautilei, and the mussel Bathymodiolus brevior-when oxidizing sulfide and thiosulfate. Via the incorporation of isotopically labelled inorganic carbon, we found that the symbionts of all three genera supported autotrophy while oxidizing both sulfide and thiosulfate, though at different rates. Additionally, by concurrently measuring their effect on sulfur compounds in the aquaria with voltammetric microelectrodes, we showed that these symbioses excreted POSCs under highly sulfidic conditions, illustrating that these symbioses could represent a source for POSCs in their habitat. Furthermore, we revealed spatial disparity in the rates of carbon fixation among the animals in our incubations, which might have implications for the variability of productivity in situ. Together, these results re-shape our thinking about sulfur cycling and productivity by vent symbioses, demonstrating that thiosulfate may be an ecologically important energy source for vent symbioses and that they also likely impact the local geochemical regime through the excretion of POSCs.

  6. Role of wheat germ oil in radiation-induced oxidative stress and alteration in energy metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shedid, S M.E. [National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

    2008-07-01

    The liver is essential in keeping the body functioning properly while muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage liver and muscle tissues. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the efficacy of wheat germ oil, on radiation induced oxidative damage in rat's liver and skeletal muscle. Wheat germ oil was supplemented orally via gavage to rats at a dose of 54 mg/ kg body weight for 14 successive days pre- and 7 days post-exposure to 5 Gy (single dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma irradiation of rats induces oxidative stress in liver and skeletal muscles obvious by significant elevation in the levels of xanthine oxidase and thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione, as well as decreases in xanthine dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase activities. Irradiated rats showed also significant decreases in creatine phosphokinase, glutamate dehydrogenase and glucose-6- phosphate dehydrogenase activities while lactate dehydrogenase were significantly increased. Total iron, total copper and total calcium levels significantly increased in the liver and skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation-induced oxidative stress might play a role in maintaining liver and skeletal muscle

  7. Role of wheat germ oil in radiation-induced oxidative stress and alteration in energy metabolism in rats

    International Nuclear Information System (INIS)

    Shedid, S.M.E.

    2008-01-01

    The liver is essential in keeping the body functioning properly while muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage liver and muscle tissues. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the efficacy of wheat germ oil, on radiation induced oxidative damage in rat's liver and skeletal muscle. Wheat germ oil was supplemented orally via gavage to rats at a dose of 54 mg/ kg body weight for 14 successive days pre- and 7 days post-exposure to 5 Gy (single dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma irradiation of rats induces oxidative stress in liver and skeletal muscles obvious by significant elevation in the levels of xanthine oxidase and thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione, as well as decreases in xanthine dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase activities. Irradiated rats showed also significant decreases in creatine phosphokinase, glutamate dehydrogenase and glucose-6- phosphate dehydrogenase activities while lactate dehydrogenase were significantly increased. Total iron, total copper and total calcium levels significantly increased in the liver and skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation-induced oxidative stress might play a role in maintaining liver and skeletal muscle

  8. Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers

    International Nuclear Information System (INIS)

    Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Janusz; Ostałowska, Alina; Zalejska-Fiolka, Jolanta; Birkner, Ewa

    2014-01-01

    The aim of this study was to determ