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Sample records for metabolic oxidative stress

  1. Fipronil insecticide toxicology: oxidative stress and metabolism.

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    Wang, Xu; Martínez, María Aránzazu; Wu, Qinghua; Ares, Irma; Martínez-Larrañaga, María Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-11-01

    Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates. In the last decade, oxidative stress has been suggested to be involved in the various toxicities induced by FIP. To date, few reviews have addressed the toxicity of FIP in relation to oxidative stress. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a possible mechanism for FIP-induced toxicity as well as metabolism. The present review reports that studies have been conducted to reveal the generation of reactive oxygen species (ROS) and oxidative stress as a result of FIP treatment and have correlated them with various types of toxicity. Furthermore, the metabolism of FIP was also reviewed, and during this process, various CYP450 enzymes were involved and oxidative stress might occur. The roles of various compounds in protecting against FIP-induced toxicity based on their anti-oxidative effects were also summarized to further understand the role of oxidative stress in FIP-induced toxicity.

  2. Oxidative stress in metabolic syndrome

    OpenAIRE

    Sharma, Praveen; Mishra, Sandhya; Ajmera, Peeyush; Mathur, Sandeep

    2005-01-01

    As antioxidants play a protective role in the pathophysiology of diabetes and cardiovascular diseases, understanding the physiological status of antioxidant concentration among people at high risk for developing these conditions, such as Metabolic Syndrome, is of interest. In present study out of 187 first degree non-diabetic relatives and 192 non-diabetic spouses, 33.1% and 19.7% were found to have metabolic syndrome respectively. Subjects with metabolic syndrome (≥3 risk factors) had poor a...

  3. Metabolic syndrome and oxidative stress.

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    Ando, Katsuyuki; Fujita, Toshiro

    2009-08-01

    Metabolic syndrome is an obesity-associated collection of disorders, each of which contributes to cardiovascular risk. Metabolic syndrome is also associated with overproduction of reactive oxygen species (ROS). ROS contribute to the interrelationship between metabolic syndrome and salt-sensitive hypertension, which are both caused by obesity and excess salt consumption and are major threats to health in developed countries. ROS can induce insulin resistance, which is indispensable for the progression of metabolic syndrome, and salt-sensitive hypertension stimulates ROS production, thereby promoting the development of metabolic syndrome. Moreover, ROS activate mineralocorticoid receptors (MRs) and the sympathetic nervous system, which can contribute to the development of metabolic syndrome and salt-sensitive hypertension. Salt-induced progression of cardiovascular disease (CVD) is also accelerated in animal models with metabolic syndrome, probably owing to further stimulation of ROS overproduction and subsequent ROS-induced MR activation and sympathetic excitation. Therefore, ROS contribute to the progression of the metabolic syndrome itself and to the CVD accompanying it, particularly in conjunction with excessive salt consumption.

  4. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.

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    Rani, Vibha; Deep, Gagan; Singh, Rakesh K; Palle, Komaraiah; Yadav, Umesh C S

    2016-03-01

    Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy.

  5. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response.

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    Busch, Andrea W U; Montgomery, Beronda L

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. Copyright © 2015 The Authprs. Published by Elsevier B.V. All rights reserved.

  6. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response

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    Andrea W.U. Busch

    2015-04-01

    Full Text Available Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms.

  7. Oxidant stress and skeletal muscle microvasculopathy in the metabolic syndrome.

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    Goodwill, Adam G; Frisbee, Jefferson C

    2012-01-01

    The evolution of the metabolic syndrome in afflicted individuals is, in part, characterized by the development of a severely pro-oxidant state within the vasculature. It has been previously demonstrated by many investigators that this increasingly pro-oxidant state can have severe negative implications for many relevant processes within the vasculature, including the coordination of dilator/constrictor tone or reactivity, the structural adaptations of the vascular wall or distal networks, as well as the integrated regulation of perfusion resistance across and throughout the vascular networks. The purpose of this review article is to present the different sources of oxidant stress within the setting of the metabolic syndrome, the available mechanism for attempts at regulation and the vascular outcomes associated with this condition. It is anticipated that this overview will help readers and investigators to more effectively design experiments and interpret their results within the extremely complicated setting of metabolic syndrome.

  8. Oxidative stress and DNA methylation regulation in the metabolic syndrome.

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    Yara, Sabrina; Lavoie, Jean-Claude; Levy, Emile

    2015-01-01

    DNA methylation is implicated in tissue-specific gene expression and genomic imprinting. It is modulated by environmental factors, especially nutrition. Modified DNA methylation patterns may contribute to health problems and susceptibility to complex diseases. Current advances have suggested that the metabolic syndrome (MS) is a programmable disease, which is characterized by epigenetic modifications of vital genes when exposed to oxidative stress. Therefore, the main objective of this paper is to critically review the central context of MS while presenting the most recent knowledge related to epigenetic alterations that are promoted by oxidative stress. Potential pro-oxidant mechanisms that orchestrate changes in methylation profiling and are related to obesity, diabetes and hypertension are discussed. It is anticipated that the identification and understanding of the role of DNA methylation marks could be used to uncover early predictors and define drugs or diet-related treatments able to delay or reverse epigenetic changes, thereby combating MS burden.

  9. Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress

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    2013-01-01

    Background A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. In order to characterize the extent of tumor cell metabolic adaptations to acidosis, we employed stable isotope tracers to examine how acidosis impacts glucose, glutamine, and palmitate metabolism in breast cancer cells exposed to extracellular acidosis. Results Acidosis increased both glutaminolysis and fatty acid β-oxidation, which contribute metabolic intermediates to drive the tricarboxylic acid cycle (TCA cycle) and ATP generation. Acidosis also led to a decoupling of glutaminolysis and novel glutathione (GSH) synthesis by repressing GCLC/GCLM expression. We further found that acidosis redirects glucose away from lactate production and towards the oxidative branch of the pentose phosphate pathway (PPP). These changes all serve to increase nicotinamide adenine dinucleotide phosphate (NADPH) production and counter the increase in reactive oxygen species (ROS) present under acidosis. The reduced novel GSH synthesis under acidosis may explain the increased demand for NADPH to recycle existing pools of GSH. Interestingly, acidosis also disconnected novel ribose synthesis from the oxidative PPP, seemingly to reroute PPP metabolites to the TCA cycle. Finally, we found that acidosis activates p53, which contributes to both the enhanced PPP and increased glutaminolysis, at least in part, through the induction of G6PD and GLS2 genes. Conclusions Acidosis alters the cellular metabolism of several major metabolites, which induces a significant degree of metabolic inflexibility. Cells exposed to acidosis largely rely upon mitochondrial metabolism for energy generation to the extent that metabolic intermediates are

  10. Oxidative stress and an altered methionine metabolism in alcoholism.

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    Bleich, S; Spilker, K; Kurth, C; Degner, D; Quintela-Schneider, M; Javaheripour, K; Rüther, E; Kornhuber, J; Wiltfang, J

    2000-11-03

    The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (Pbrain shrinkage.

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

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    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.

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

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    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.

  13. Metabolic effects of melatonin on oxidative stress and diabetes mellitus.

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    Nishida, Shigeru

    2005-07-01

    Melatonin, which is synthesized in the pineal gland and other tissues, has a variety of physiological, immunological, and biochemical functions. It is a direct scavenger of free radicals and has indirect antioxidant effects due to its stimulation of the expression and activity of antioxidative enzymes such as glutathione peroxidase, superoxide dismutase and catalase, and NO synthase, in mammalian cells. Melatonin also reduces serum lipid levels in mammalian species, and helps to prevent oxidative stress in diabetic subjects. Long-term melatonin administration to diabetic rats reduced their hyperlipidemia and hyperinsulinemia, and restored their altered ratios of polyunsaturated fatty acid in serum and tissues. It was recently reported that melatonin enhanced insulin-receptor kinase and IRS-1 phosphorylation, suggesting the potential existence of signaling pathway cross-talk between melatonin and insulin. Because TNF-alpha has been shown to impair insulin action by suppressing insulin receptor-tyrosine kinase activity and its IRS-1 tyrosine phosphorylation in peripheral tissues such as skeletal muscle cells, it was speculated that melatonin might counteract TNF-alpha-associated insulin resistance in type 2 diabetes. This review will focus on the physiological and metabolic effects of melatonin and highlight its potential use for the treatment of cholesterol/lipid and carbohydrate disorders.

  14. Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View

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    Soazig Le Lay

    2014-01-01

    Full Text Available Oxidative stress plays a pathological role in the development of various diseases including diabetes, atherosclerosis, or cancer. Systemic oxidative stress results from an imbalance between oxidants derivatives production and antioxidants defenses. Reactive oxygen species (ROS are generally considered to be detrimental for health. However, evidences have been provided that they can act as second messengers in adaptative responses to stress. Obesity represents a major risk factor for deleterious associated pathologies such as type 2 diabetes, liver, and coronary heart diseases. Many evidences regarding obesity-induced oxidative stress accumulated over the past few years based on established correlations of biomarkers or end-products of free-radical-mediated oxidative stress with body mass index. The hypothesis that oxidative stress plays a significant role in the development of metabolic disorders, especially insulin-resistance state, is supported by several studies where treatments reducing ROS production reverse metabolic alterations, notably through improvement of insulin sensitivity, hyperlipidemia, or hepatic steatosis. In this review, we will develop the mechanistic links between oxidative stress generated by adipose tissue in the context of obesity and its impact on metabolic complications development. We will also attempt to discuss potential therapeutic approaches targeting obesity-associated oxidative stress in order to prevent associated-metabolic complications.

  15. Prevalence of Oxidative Stress and Metabolic Syndrome in Adults with Paraplegia and Tetraplegia

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    Objectives: To investigate the extent of oxidative stress and metabolic syndrome (MetS) in people with spinal cord injuries (SCI) and to identify the major factors associated with oxidative stress and MetS in this population. Methods: 24 subjects with paraplegia (PARA), 26 subjects with tetraplegia ...

  16. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

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    Justin D Crane

    Full Text Available Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  17. Permethrin-induced oxidative stress and toxicity and metabolism. A review.

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    Wang, Xu; Martínez, María-Aránzazu; Dai, Menghong; Chen, Dongmei; Ares, Irma; Romero, Alejandro; Castellano, Victor; Martínez, Marta; Rodríguez, José Luis; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-08-01

    Permethrin (PER), the most frequently used synthetic Type I pyrethroid insecticide, is widely used in the world because of its high activity as an insecticide and its low mammalian toxicity. It was originally believed that PER exhibited low toxicity on untargeted animals. However, as its use became more extensive worldwide, increasing evidence suggested that PER might have a variety of toxic effects on animals and humans alike, such as neurotoxicity, immunotoxicity, cardiotoxicity, hepatotoxicity, reproductive, genotoxic, and haematotoxic effects, digestive system toxicity, and cytotoxicity. A growing number of studies indicate that oxidative stress played critical roles in the various toxicities associated with PER. To date, almost no review has addressed the toxicity of PER correlated with oxidative stress. The focus of this article is primarily to summarise advances in the research associated with oxidative stress as a potential mechanism for PER-induced toxicity as well as its metabolism. This review summarises the research conducted over the past decade into the reactive oxygen species (ROS) generation and oxidative stress as a consequence of PER treatments, and ultimately their correlation with the toxicity and the metabolism of PER. The metabolism of PER involves various CYP450 enzymes, alcohol or aldehyde dehydrogenases for oxidation and the carboxylesterases for hydrolysis, through which oxidative stress might occur, and such metabolic factors are also reviewed. The protection of a variety of antioxidants against PER-induced toxicity is also discussed, in order to further understand the role of oxidative stress in PER-induced toxicity. This review will throw new light on the critical roles of oxidative stress in PER-induced toxicity, as well as on the blind spots that still exist in the understanding of PER metabolism, the cellular effects in terms of apoptosis and cell signaling pathways, and finally strategies to help to protect against its oxidative

  18. Metabolic characteristics and oxidative damage to skeletal muscle in broiler chickens exposed to chronic heat stress.

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    Azad, M A K; Kikusato, M; Maekawa, T; Shirakawa, H; Toyomizu, M

    2010-03-01

    Emerging evidence has shown that acute heat exposure affects metabolic characteristics and causes oxidative damage to skeletal muscle in birds. Little is known, however, about such phenomena under chronic heat stress conditions. To address this, we designed the present study to determine the influence of cyclic (32 to 24 to 32 degrees C: 32 degrees C for 8 h/d, 32-24-32HS ), and constant (32 and 34 degrees C, 32HS and 34HS, respectively) heat exposure on the metabolic and peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat stress, particularly in the 32HS and 34HS groups, depressed feed intake and growth, while cyclic high temperature gave rise to a less severe stress response in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were enhanced (Pstress model. The 3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS (citrate synthase) enzyme activities were lowered (Pchickens. On exposure to chronic heat stress, GPx activity remained relatively constant, though a temperature-dependent elevation in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was disturbed by the chronic stress condition. From these results it can be concluded that chronic heat stress did not induce oxidative damage to a major extent. This may probably be due to a decrease in metabolic oxidation capacity or due to a self-propagating scavenging system, though the system was not fully activated.

  19. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway.

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    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A; Ralser, Markus

    2016-04-01

    Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway.

  20. A redox-resistant sirtuin-1 mutant protects against hepatic metabolic and oxidant stress.

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    Shao, Di; Fry, Jessica L; Han, Jingyan; Hou, Xiuyun; Pimentel, David R; Matsui, Reiko; Cohen, Richard A; Bachschmid, Markus M

    2014-03-14

    Sirtuin-1 (SirT1), a member of the NAD(+)-dependent class III histone deacetylase family, is inactivated in vitro by oxidation of critical cysteine thiols. In a model of metabolic syndrome, SirT1 activation attenuated apoptosis of hepatocytes and improved liver function including lipid metabolism. We show in SirT1-overexpressing HepG2 cells that oxidants (nitrosocysteine and hydrogen peroxide) or metabolic stress (high palmitate and high glucose) inactivated SirT1 by reversible oxidative post-translational modifications (OPTMs) on three cysteines. Mutating these oxidation-sensitive cysteines to serine preserved SirT1 activity and abolished reversible OPTMs. Overexpressed mutant SirT1 maintained deacetylase activity and attenuated proapoptotic signaling, whereas overexpressed wild type SirT1 was less protective in metabolically or oxidant-stressed cells. To prove that OPTMs of SirT1 are glutathione (GSH) adducts, glutaredoxin-1 was overexpressed to remove this modification. Glutaredoxin-1 overexpression maintained endogenous SirT1 activity and prevented proapoptotic signaling in metabolically stressed HepG2 cells. The in vivo significance of oxidative inactivation of SirT1 was investigated in livers of high fat diet-fed C57/B6J mice. SirT1 deacetylase activity was decreased in the absence of changes in SirT1 expression and associated with a marked increase in OPTMs. These results indicate that glutathione adducts on specific SirT1 thiols may be responsible for dysfunctional SirT1 associated with liver disease in metabolic syndrome.

  1. Interrelation between compensation of carbohydrate metabolism and severity of manifestations of oxidative stress in type II diabetes mellitus.

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    Nedosugova, L V; Lankin, V Z; Balabolkin, M I; Konovalova, G G; Lisina, M O; Antonova, K V; Tikhaze, A K; Belenkov, Yu N

    2003-08-01

    Glycosylation end-products formed during diabetes mellitus promoted atherogenic oxidative modification of low-density lipoproteins. We evaluated the effects of compensation of carbohydrate metabolism and therapy with antioxidant probucol on parameters of free radical oxidation in patients with type II diabetes mellitus. Compensation of carbohydrate metabolism reduced manifestations of oxidative stress, which was manifested in accelerated enzymatic utilization of reactive oxygen species and lipid peroxides and decreased content of free radical oxidation products in low-density lipoproteins. In patients with type II diabetes mellitus combination therapy with antioxidant probucol decreased the severity of oxidative stress and stabilized carbohydrate metabolism without increasing the dose of hypoglycemic preparations.

  2. 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.

  3. Lipid mobilisation and oxidative stress as metabolic adaptation processes in dairy heifers during transition period.

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    Turk, R; Podpečan, O; Mrkun, J; Kosec, M; Flegar-Meštrić, Z; Perkov, S; Starič, J; Robić, M; Belić, M; Zrimšek, P

    2013-10-01

    The objective of this study was to evaluate metabolic disorders and oxidative stress in dairy heifers during the transition period. Possible relationships between lipid mobilisation indicators and oxidative stress markers were investigated as well. Nineteen dairy heifers were included in the study. Blood samples were collected at the time of estrus synchronisation in heifers, at insemination, three weeks after insemination, one week before calving, at calving and 1, 2, 4 and 8 weeks postpartum. Common metabolic parameters, beta-hydroxybutyrate (BHB), free fatty acids (FFA), paraoxonase-1 (PON1) activity and total antioxidative status (TAS) were analysed. Around insemination, no significant difference was observed in the majority of tested parameters (P>0.05). However, the transition period markedly affected the concentration of triglycerides, total cholesterol, HDL-C, BHB, FFA, TAS and PON1activity. Positive correlations between PON1 activity and total cholesterol, HDL-C and triglycerides were noted but inverse correlations with FFA, BHB and bilirubin were found indicating that PON1 activity changed with lipid metabolism and was influenced by negative energy balance. These findings suggest that lipid mobilisation and oxidative stress are part of a complex metabolic adaptation to low energy balance which reaches equilibrium later in advanced lactation.

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

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    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.

  5. Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome.

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    Roul, David; Recchia, Fabio A

    2015-06-10

    Several authors have proposed a link between altered cardiac energy substrate metabolism and reactive oxygen species (ROS) generation. A cogent evidence of this association has been found in diabetic cardiomyopathy (dCM); however, experimental findings in animal models of heart failure (HF) and in human myocardium also seem to support the coexistence of the two alterations in HF. Two important questions remain open: whether pathological changes in metabolism play an important role in enhancing oxidative stress and whether there is a common pathway linking altered substrate utilization and activation of ROS-generating enzymes, independently of the underlying cardiac pathology. In this regard, the comparison between dCM and HF is intriguing, in that these pathological conditions display very different cardiac metabolic phenotypes. Our literature review on this topic indicates that a vast body of knowledge is now available documenting the relationship between the metabolism of energy substrates and ROS generation in dCM. In some cases, biochemical mechanisms have been identified. On the other hand, only a few and relatively recent studies have explored this phenomenon in HF and their conclusions are not consistent. Better methods of investigation, especially in vivo, will be necessary to test whether the metabolic fate of certain substrates is causally linked to ROS production. If successful, these studies will place a new emphasis on the potential clinical relevance of metabolic modulators, which might indirectly mitigate cardiac oxidative stress in dCM, HF, and, possibly, in other pathological conditions.

  6. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

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    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  7. Purine metabolism and oxidative stress in children with autistic spectrum disorders

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    Faisal Gh. Al-Rubaye

    2013-08-01

    Results: Serum ADA and SOD were significantly lower in boys with autism accompanied by significant higher serum MDA levels when compared with controls. Conclusion: Patients with ASD have impaired purine metabolism and increased oxidative stress which was supported by low levels of ADA and SOD, and high level of MDA. Further biochemical or genetic studies are required to explore the nature of autism. [J Exp Integr Med 2013; 3(4.000: 293-297

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

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    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.

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

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    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.

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    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. Antioxidant defenses and metabolic depression. The hypothesis of preparation for oxidative stress in land snails.

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    Hermes-Lima, M; Storey, J M; Storey, K B

    1998-07-01

    The roles of enzymatic antioxidant defenses in the natural tolerance of environmental stresses that impose changes in oxygen availability and oxygen consumption on animals is discussed with a particular focus on the biochemistry of estivation and metabolic depression in pulmonate land snails. Despite reduced oxygen consumption and PO2 during estivation, which should also mean reduced production of oxyradicals, the activities of antioxidant enzymes, such as superoxide dismutase and catalase, increased in 30 day-estivating snails. This appears to be an adaptation that allows the snails to deal with oxidative stress that takes place during arousal when PO2 and oxygen consumption rise rapidly. Indeed, oxidative stress was indicated by increased levels of lipid peroxidation damage products accumulating in hepatopancreas within minutes after arousal was initiated. The various metabolic sites responsible for free radical generation during arousal are still unknown but it seems unlikely that the enzyme xanthine oxidase plays any substantial role in this despite being implicated in oxidative stress in mammalian models of ischemia/reperfusion. We propose that the activation of antioxidant defenses in the organs of Otala lactea during estivation is a preparative mechanism against oxidative stress during arousal. Increased activities of antioxidant enzymes have also observed under other stress situations in which the actual production of oxyradicals should decrease. For example, antioxidant defenses are enhanced during anoxia exposure in garter snakes Thamnophis sirtalis parietalis (10 h at 5 degrees C) and leopard frogs Rana pipiens (30 h at 5 degrees C) and during freezing exposure (an ischemic condition due to plasma freezing) in T. sirtalis parietalis and wood frogs Rana sylvatica. It seems that enhancement of antioxidant enzymes during either anoxia or freezing is used as a preparatory mechanism to deal with a physiological oxidative stress that occurs rapidly within the

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

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    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.

  13. Metabolic changes, hypothalamo-pituitary-adrenal axis and oxidative stress after short-term starvation in healthy pregnant women

    OpenAIRE

    Schraag, Sabrina; Mandach, Ursula von; Schweer, Horst; Beinder, Ernst

    2017-01-01

    Aim: To compare metabolic effects and oxidative stress in pregnant and non-pregnant women after 12h of fasting. Methods: Twenty-six healthy women with uncomplicated singleton pregnancies between the 24th and 28th gestational week were recruited. After an overnight fast, venous blood samples and urine samples were tested for metabolic parameters characteristic for starvation, cortisol and oxidative stress products. Healthy non-pregnant women matched by age, body mass index and length of fastin...

  14. Coupling of transcriptional response to oxidative stress and secondary metabolism regulation in filamentous fungi.

    Science.gov (United States)

    Montibus, Mathilde; Pinson-Gadais, Laëtitia; Richard-Forget, Florence; Barreau, Christian; Ponts, Nadia

    2015-01-01

    To survive sudden and potentially lethal changes in their environment, filamentous fungi must sense and respond to a vast array of stresses, including oxidative stresses. The generation of reactive oxygen species, or ROS, is an inevitable aspect of existence under aerobic conditions. In addition, in the case of fungi with pathogenic lifestyles, ROS are produced by the infected hosts and serve as defense weapons via direct toxicity, as well as effectors in fungal cell death mechanisms. Filamentous fungi have thus developed complex and sophisticated responses to evade oxidative killing. Several steps are determinant in these responses, including the activation of transcriptional regulators involved in the control of the antioxidant machinery. Gathering and integrating the most recent advances in knowledge of oxidative stress responses in fungi are the main objectives of this review. Most of the knowledge coming from two models, the yeast Saccharomyces cerevisiae and fungi of the genus Aspergillus, is summarized. Nonetheless, recent information on various other fungi is delivered when available. Finally, special attention is given on the potential link between the functional interaction between oxidative stress and secondary metabolism that has been suggested in recent reports, including the production of mycotoxins.

  15. Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: role of oxidative stress.

    Science.gov (United States)

    Castro, María C; Francini, Flavio; Gagliardino, Juan J; Massa, María L

    2014-03-01

    Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes. Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35mg/kg, i.p.) (control+L and fructose+L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration. Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91(phox) and p22(phox)) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration. Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration. Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Functional changes of the coronary microvasculature with aging regarding glucose tolerance, energy metabolism, and oxidative stress.

    Science.gov (United States)

    Mourmoura, Evangelia; Couturier, Karine; Hininger-Favier, Isabelle; Malpuech-Brugère, Corinne; Azarnoush, Kasra; Richardson, Melanie; Demaison, Luc

    2014-01-01

    This study was aimed at characterizing the functional progression of the endothelial (ECs) and smooth muscle cells (SMCs) of the coronary microvasculature between youth and old age, as well as at determining the mechanisms of the observed changes on the basis of the glucose tolerance, mitochondrial energy metabolism, and oxidative stress. Male rats were divided into four age groups (3, 6, 11, and 17 months for the young (Y), young adult (YA), middle-aged (MA), and old (O) animals). The cardiac mechanical function, endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the coronary microvasculature were determined in a Langendorff preparation. The mitochondrial respiration and H2O2 production were evaluated and completed by ex vivo measurements of oxidative stress. EDD progressively decreased from youth to old age. The relaxation properties of the SMCs, although high in the Y rats, decreased drastically between youth and young adulthood and stabilized thereafter, paralleling the reduction of mitochondrial oxidative phosphorylation. The ECs dilatation activity, low at youth, was stimulated in YA animals and returned to their initial level at middle age. That parameter followed faithfully the progression of the amount of active cardiac endothelial nitric oxide synthase and whole body glucose intolerance. In conclusion, the progressive decrease in EDD occurring with aging is due to different functional behaviors of the ECs and SMCs, which appear to be associated with the systemic glucose intolerance and cardiac energy metabolism.

  17. Obesity and oxidative stress: potential roles of melatonin as antioxidant and metabolic regulator.

    Science.gov (United States)

    Bonnefont-Rousselot, Dominique

    2014-01-01

    Obesity is associated with an oxidative stress status, defined as an excessive production of reactive oxygen species (ROS) compared to the level of antioxidants acting in the natural defence systems. Several sources of ROS can be identified in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could contribute to the pathogenesis of obesity. Indeed, these conditions favour the development of insulin resistance and metabolic syndrome through deregulation of adipokines and pro-inflammatory cytokines, so that it could be of interest to associate antioxidant therapeutic strategies with strategies of weight loss. Among antioxidants, melatonin holds a special place, on the one hand for its antioxidant and anti-inflammatory properties, and on the other hand for its role as a metabolic regulator. As melatonin modulates several processes involved in obesity and its related metabolic alterations, it could have a therapeutic interest in the treatment of obesity.

  18. Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.

    Science.gov (United States)

    Ferreira, Andréa G K; da Cunha, Aline A; Machado, Fernanda R; Pederzolli, Carolina D; Dalazen, Giovana R; de Assis, Adriano M; Lamers, Marcelo L; dos Santos, Marinilce F; Dutra-Filho, Carlos S; Wyse, Angela T S

    2012-01-01

    The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. Copyright © 2011 Wiley Periodicals, Inc.

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

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    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.

  20. 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.

  1. The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress.

    Science.gov (United States)

    Aldarini, Nohaiah; Alhasawi, Azhar A; Thomas, Sean C; Appanna, Vasu D

    2017-01-17

    Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls. The enhanced activities of such enzymes as acetate kinase, adenylate kinase and nucleotide diphosphate kinase ensured the efficacy of this ATP producing-machine by transferring the high energy phosphate. The elevated amounts of phosphoenol pyruvate carboxylase and pyruvate orthophosphate dikinase recorded in the H2O2 exposed cells provided another route to ATP independent of the reduction of O2. This is the first demonstration of a metabolic pathway involving GS dedicated to ATP synthesis. The phospho-transfer network that is pivotal to the survival of the microorganism under oxidative stress may reveal therapeutic targets against infectious microbes reliant on glutamine for their proliferation.

  2. Chronic oxidative-nitrosative stress impairs coronary vasodilation in metabolic syndrome model rats.

    Science.gov (United States)

    Kagota, Satomi; Maruyama, Kana; Tada, Yukari; Fukushima, Kazuhito; Umetani, Keiji; Wakuda, Hirokazu; Shinozuka, Kazumasa

    2013-07-01

    Metabolic syndrome (MetS) is a combination of clinical disorders that together increase the risk for cardiovascular disease and diabetes. SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with MetS show impaired nitric oxide-mediated relaxation in coronary and mesenteric arteries, and angiotensin II receptor type 1 blockers protect against dysfunction and oxidative-nitrosative stress independently of metabolic effects. We hypothesize that superoxide contributes to functional deterioration in SHRSP.ZF rats. To test our hypothesis, we studied effects of treatment with tempol, a membrane-permeable radical scavenger, on impaired vasodilation in SHRSP.ZF rats. Tempol did not alter body weight, high blood pressure, or metabolic abnormalities, but prevented impairment of acetylcholine-induced and nitroprusside-induced vasodilation in the coronary and mesenteric arteries. Furthermore, tempol reduced the levels of serum thiobarbituric acid reactive substance (TBARS) and 3-nitrotyrosine content in mesenteric arteries. Systemic administration of tempol elevated the expression of soluble guanylate cyclase (sGC) above basal levels in mesenteric arteries of SHRSP.ZF rats. However, acute treatment with tempol or ebselen, a peroxynitrite scavenger, did not ameliorate impaired relaxation of isolated mesenteric arteries. No nitration of tyrosine residues in sGC was observed; however, sGC mRNA expression levels in the arteries of SHRSP.ZF rats were lower than those in the arteries of Wistar-Kyoto rats. Levels of Thr(496)- and Ser(1177)-phosphorylated endothelial nitric oxide synthase (eNOS) were lower in arteries of SHRSP.ZF rats, and acetylcholine decreased Thr(496)-phosphorylated eNOS levels. These results indicated that prolonged superoxide production, leading to oxidative-nitrosative stress, was associated with impaired vasodilation in SHRSP.ZF rats with MetS. Down-regulated sGC expression may be linked to dysfunction, while reduced NO bioavailability/eNOS activity and modified s

  3. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Osredkar Joško

    2012-05-01

    Full Text Available The human organism is exposed to the influence of various forms of stress, either physical, psychological or chemical, which all have in common that they may adversely affect our body. A certain amount of stress is always present and somehow directs, promotes or inhibits the functioning of the human body. Unfortunately, we are now too many and too often exposed to excessive stress, which certainly has adverse consequences. This is especially true for a particular type of stress, called oxidative stress. All aerobic organisms are exposed to this type of stress because they produce energy by using oxygen. For this type of stress you could say that it is rather imperceptibly involved in our lives, as it becomes apparent only at the outbreak of certain diseases. Today we are well aware of the adverse impact of radicals, whose surplus is the main cause of oxidative stress. However, the key problem remains the detection of oxidative stress, which would allow us to undertake timely action and prevent outbreak of many diseases of our time. There are many factors that promote oxidative stress, among them are certainly a fast lifestyle and environmental pollution. The increase in oxidative stress can also trigger intense physical activity that is directly associated with an increased oxygen consumption and the resulting formation of free radicals. Considering generally positive attitude to physical activity, this fact may seem at first glance contradictory, but the finding has been confimed by several studies in active athletes. Training of a top athlete daily demands great physical effort, which is also reflected in the oxidative state of the organism. However, it should be noted that the top athletes in comparison with normal individuals have a different defense system, which can counteract the negative effects of oxidative stress. Quite the opposite is true for irregular or excessive physical activity to which the body is not adapted.

  4. Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress.

    Science.gov (United States)

    Lee, Yoon-Mi; Lee, Gibok; Oh, Taek-In; Kim, Byeong Mo; Shim, Do-Wan; Lee, Kwang-Ho; Kim, Young Jun; Lim, Beong Ou; Lim, Ji-Hong

    2016-01-01

    Recent studies have shown anticancer activity of apigenin by suppressing glucose transporter 1 (GLUT1) expression in cultured cancer cells; however, it is not clear whether apigenin can suppress glucose metabolism in lung cancer cells or sensitize them to inhibition of glutamine utilization-mediated apoptosis through metabolic and oxidative stress. We show that apigenin significantly decreases GLUT1 expression in mice. Furthermore, we demonstrate that apigenin induces growth retardation and apoptosis through metabolic and oxidative stress caused by suppression of glucose utilization in lung cancer cells. The underlying mechanisms were defined that the anticancer effects of apigenin were reversed by ectopic GLUT1 overexpression and galactose supplementation, through activation of pentose phosphate pathway-mediated NADPH generation. Importantly, we showed that severe metabolic stress using a glutaminase inhibitor, compound 968, was involved in the mechanism of sensitization by apigenin. Taken together, the combination of apigenin with inhibitors of glutamine metabolism may provide a promising therapeutic strategy for cancer treatment.

  5. 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

  6. Relation of Oxidative Stress and Impaired Fibrinolysis with HDL Biogenesis in Indonesian Men with Metabolic Syndrome

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    Ida Paulina Sormin

    2010-04-01

    Full Text Available BACKGROUND: Biogenesis of HDL involves factors that regulate the synthesis, intravascular remodeling, and catabolism of HDL. Disturbance of these factors can lead to low concentration of HDL-C. Metabolic syndrome (MetS is characterized by low concentration of high-density lipoprotein cholesterol (HDL-C. In MetS occur several pathological conditions including oxidative stress and impaired fibrinolysis, which contribute to the risk of atherosclerosis process. The correlation between oxidative stress and impaired fibrinolysis with HDL biogenesis dysfunction and its correlation with low concentration of HDL-C has not been well understood and therefore needs to be further investigated. METHODS: This study was an observational study with crosssectional design, involving 163 adult men, aged 25-60 years with metabolic syndrome. Concentration of apoA-1, prebeta-1 HDL, CETP, F2-isoprostan, PAI-1, and HDL-C were measured. The apo A1/HDL ratio indicated HDL maturation, whereas the CETP/HDL-C and CETP/TG ratios indicated HDL catabolism. RESULTS: The study showed that there were a positive correlation between PAI-1 with apoA1/HDL-C ratios (r=0.226, p=0.005 and a negative correlation with the CETP/TG ratios (r=-0.215, p=0.007, whereas F2-isoprostan did not have correlation with HDL biogenesis factors. CONCLUSIONS: We concluded that there was correlation between impaired fibrinolysis with decreased HDL maturation and there was increased HDL catabolism leading to low HDL-C concentration in men with metabolic syndrome. KEYWORDS: F2-isoprostan, PAI-1, apoA-1, prebeta-1 HDL, CETP, metabolic syndrome.

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

    Science.gov (United States)

    Sekler, Alejandra; Jiménez, José M; Rojo, Leonel; Pastene, Edgard; Fuentes, Patricio; Slachevsky, Andrea; Maccioni, Ricardo B

    2008-01-01

    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 patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis. PMID:19043515

  8. Cognitive impairment and Alzheimer's disease: Links with oxidative stress and cholesterol metabolism.

    Science.gov (United States)

    Sekler, Alejandra; Jiménez, José M; Rojo, Leonel; Pastene, Edgard; Fuentes, Patricio; Slachevsky, Andrea; Maccioni, Ricardo B

    2008-08-01

    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 patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis.

  9. Differential response of oxidative stress and thiol metabolism in contrasting rice genotypes for arsenic tolerance.

    Science.gov (United States)

    Tripathi, Preeti; Mishra, Aradhana; Dwivedi, Sanjay; Chakrabarty, Debasis; Trivedi, Prabodh K; Singh, Rana Pratap; Tripathi, Rudra Deo

    2012-05-01

    The mechanism of arsenic (As) tolerance was investigated on two contrasting rice (Oryza sativa L.) genotypes, selected for As tolerance and accumulation. One tolerant (Triguna) and one sensitive (IET-4786) variety were exposed to various arsenate (0-50 μM) levels for 7 d for biochemical analyses. Arsenic induced oxidative stress was more pronounced in IET-4786 than Triguna especially in terms of reactive oxygen species, lipid peroxidation, EC and pro-oxidant enzymes (NADPH oxidase and ascorbate oxidase). However, Triguna tolerated As stress through the enhanced enzymes activities particularly pertaining to thiol metabolism such as serine acetyl transferase (SAT), cysteine synthase (CS), γ-glutamyl cysteine synthase (γ-ECS), γ-glutamyl transpeptidase (γ-GT), and glutathione-S-transferase (GST) as well as arsenate reductase (AR). Besides maintaining the ratio of redox couples GSH/GSSG and ASC/DHA, the level of phytochelatins (PCs) and phytochelatin synthase (PCS) activity were more pronounced in Triguna, in which harmonized responses of thiol metabolism was responsible for As tolerance in contrast to IET-4786 showing its susceptible nature towards As exposure.

  10. Mitochondrial function and energy metabolism in neuronal HT22 cells resistant to oxidative stress

    Science.gov (United States)

    Pfeiffer, Annika; Jaeckel, Martin; Lewerenz, Jan; Noack, Rebecca; Pouya, Alireza; Schacht, Teresa; Hoffmann, Christina; Winter, Jennifer; Schweiger, Susann; Schäfer, Michael K E; Methner, Axel

    2014-01-01

    Background and Purpose The hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Extracellular glutamate depletes cellular glutathione by blocking the glutamate/cystine antiporter system xc−. Glutathione depletion induces a well-defined programme of cell death characterized by an increase in reactive oxygen species and mitochondrial dysfunction. Experimental Approach We compared the mitochondrial shape, the abundance of mitochondrial complexes and the mitochondrial respiration of HT22 cells, selected based on their resistance to glutamate, with those of the glutamate-sensitive parental cell line. Key Results Glutamate-resistant mitochondria were less fragmented and displayed seemingly contradictory features: mitochondrial calcium and superoxide were increased while high-resolution respirometry suggested a reduction in mitochondrial respiration. This was interpreted as a reverse activity of the ATP synthase under oxidative stress, leading to hydrolysis of ATP to maintain or even elevate the mitochondrial membrane potential, suggesting these cells endure ineffective energy metabolism to protect their membrane potential. Glutamate-resistant cells were also resistant to oligomycin, an inhibitor of the ATP synthase, but sensitive to deoxyglucose, an inhibitor of hexokinases. Exchanging glucose with galactose rendered resistant cells 1000-fold more sensitive to oligomycin. These results, together with a strong increase in cytosolic hexokinase 1 and 2, a reduced lactate production and an increased activity of glucose-6-phosphate dehydrogenase, suggest that glutamate-resistant HT22 cells shuttle most available glucose towards the hexose monophosphate shunt to increase glutathione recovery. Conclusions and Implications These results indicate that mitochondrial and metabolic adaptations play an important role in the resistance of cells to oxidative stress. Linked Articles This article is part of a themed issue on

  11. 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

  12. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    DEFF Research Database (Denmark)

    Assies, Johanna; Mocking, Roel J T; Lok, Christianne A

    2014-01-01

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive...... affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine...... membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. Conclusion: While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co...

  13. 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

  14. The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions.

    Science.gov (United States)

    Piedrafita, Gabriel; Keller, Markus A; Ralser, Markus

    2015-09-10

    Cellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalyzed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of metabolites and unspecific enzyme function give rise to a number of side products that are not part of canonical metabolic pathways. It is increasingly acknowledged that these molecules are important for the evolution of metabolism, affect metabolic efficiency, and that they play a potential role in human disease-age-related disorders and cancer in particular. In this review we discuss the impact of oxidative and other cellular stressors on the formation of metabolic side products, which originate as a consequence of: (i) chemical reactivity or modification of regular metabolites; (ii) through modifications in substrate specificity of damaged enzymes; and (iii) through altered metabolic flux that protects cells in stress conditions. In particular, oxidative and heat stress conditions are causative of metabolite and enzymatic damage and thus promote the non-canonical metabolic activity of the cells through an increased repertoire of side products. On the basis of selected examples, we discuss the consequences of non-canonical metabolic reactivity on evolution, function and repair of the metabolic network.

  15. Manganese Complexes: Diverse Metabolic Routes to Oxidative Stress Resistance in Prokaryotes and Yeast

    Science.gov (United States)

    2013-01-01

    Abstract Significance: Antioxidant enzymes are thought to provide critical protection to cells against reactive oxygen species (ROS). However, many organisms can fully compensate for the loss of such enzymatic defenses by accumulating metabolites and Mn2+, which can form catalytic Mn-antioxidants. Accumulated metabolites can direct reactivity of Mn2+ with superoxide and specifically shield proteins from oxidative damage. Recent Advances: There is mounting evidence that Mn-Pi (orthophosphate) complexes act as potent scavengers of superoxide in all three branches of life. Moreover, it is evident that Mn2+ in complexes with carbonates, peptides, nucleosides, and organic acids can also form catalytic Mn-antioxidants, pointing to diverse metabolic routes to oxidative stress resistance. Critical Issues: What conditions favor utility of Mn-metabolites versus enzymatic means for removing ROS? Mn2+-metabolite defenses are critical for preserving the activity of repair enzymes in Deinococcus radiodurans exposed to intense radiation stress, and in Lactobacillus plantarum, which lacks antioxidant enzymes. In other microorganisms, Mn-antioxidants can serve as an auxiliary protection when enzymatic antioxidants are insufficient or fail. These findings of a critical role of Mn-antioxidants in the survival of prokaryotes under oxidative stress parallel the trends developing for the simple eukaryote Saccharomyces cerevisiae. Future Directions: Phosphates, peptides and organic acids are just a snapshot of the types of anionic metabolites that promote such reactivity of Mn2+. Their probable roles in pathogen defense against the host immune response and in ROS-mediated signaling pathways are also areas that are worthy of serious investigation. Moreover, it is clear that these protective chemical processes can be harnessed for practical purposes. Antioxid. Redox Signal. 19, 933–944. PMID:23249283

  16. 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.

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

    Science.gov (United States)

    Moreno-Arriola, Elizabeth; Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Carmona-Aparicio, Liliana; Ortega-Cuellar, Daniel

    2014-01-01

    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. PMID:24955209

  18. 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.

  19. Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.

    Science.gov (United States)

    Shen, Tie; Rui, Bin; Zhou, Hong; Zhang, Ximing; Yi, Yin; Wen, Han; Zheng, Haoran; Wu, Jihui; Shi, Yunyu

    2013-01-27

    The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E

  20. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R.J.; Lok, A.; Ruhe, H.G.; Pouwer, F.; Schene, A.H.

    2014-01-01

    OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  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. 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

  3. Metabolic changes, hypothalamo-pituitary-adrenal axis and oxidative stress after short-term starvation in healthy pregnant women.

    Science.gov (United States)

    Schraag, Sabrina; Mandach, Ursula von; Schweer, Horst; Beinder, Ernst

    2007-01-01

    To compare metabolic effects and oxidative stress in pregnant and non-pregnant women after 12 h of fasting. Twenty-six healthy women with uncomplicated singleton pregnancies between the 24(th) and 28(th) gestational week were recruited. After an overnight fast, venous blood samples and urine samples were tested for metabolic parameters characteristic for starvation, cortisol and oxidative stress products. Healthy non-pregnant women matched by age, body mass index and length of fasting comprised the control group. The metabolic parameters beta-hydroxybutyrate and free fatty acids in blood and ketones in urine showed no differences in pregnant and non-pregnant women. However, the oxidative stress parameters, 8,12-iso-iPF(2alpha)-VI, isoprostanes and malondialdehyde were significantly higher in pregnant subjects, as was cortisol. Healthy pregnant women are exposed to oxidative stress and activation of the hypothalamo-pituitary-adrenal axis, but not to metabolic changes resembling starvation during short fasting periods in comparison to non-pregnant healthy women.

  4. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R. J. T.; Lok, A.; Ruhe, H. G.; Pouwer, F.; Schene, A. H.

    2014-01-01

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  5. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R.J.; Lok, A.; Ruhe, H.G.; Pouwer, F.; Schene, A.H.

    2014-01-01

    OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive

  6. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R. J. T.; Lok, A.; Ruhe, H. G.; Pouwer, F.; Schene, A. H.

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive

  7. Correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Wei-Xia Gu; Zhi-Qing Zhuang; Mo-Lan Wang; Jun Zhu

    2016-01-01

    Objective:To analyze the correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease.Methods:A total of 58 patients with Parkinson's disease and 67 normal human beings were included in the study, levels of plasma homocysteine (Hcy) as well as superoxide dismutase (SOD), GSH, malondialdehyde (MDA) and other oxidative stress indexes were detected, and common peroneal nerve motor conduction velocity (MCV), latent period (LP) and amplitude (Amp) were determined.Results: Serum Hcy level of observation group was higher than that of control group while folic acid and vitamin B6 levels were lower than those of control group; serum oxidative indexes LHP, H2O2, AOPP and MDA levels were higher than those of control group while antioxidant indexes SOD T, SOD Mn, SOD Cu-Zn, GSH-PX, T-AOC and CAT levels were lower than those of control group; common peroneal nerve MCV and Amp values were lower than those of control group while LP value was higher than that of control group. Peripheral nerve damage parameter values in patients with Parkinson's disease were directly correlated with serum levels of Hcy metabolism indexes and oxidative stress indexes. Conclusions: Peripheral nerve damage in patients with Parkinson's disease is associated with hyperhomocysteinemia and oxidative stress disorder, and intervention in serum levels of Hcy and oxidative stress indexes is expected to become a new way for treatment of Parkinson's disease.

  8. Effects of the Crotalus durissus terrificus snake venom on hepatic metabolism and oxidative stress.

    Science.gov (United States)

    da Silva, Jonas Golart; da Silva Soley, Bruna; Gris, Vanessa; do Rocio Andrade Pires, Amanda; Caderia, Silvia Maria Suter Correia; Eler, Gabrielle Jackin; Hermoso, Aparecida Pinto Munhos; Bracht, Adelar; Dalsenter, Paulo Roberto; Acco, Alexandra

    2011-01-01

    Snake venoms present different action mechanisms because of their complex composition, represented mainly by toxins and enzymes. This work aimed to investigate the effects of the Crotalus durissus terrificus(Cdt) venom in the liver. Wistar rats were inoculated intraperitoneally with saline (control) or Cdt venom. After 3, 4, or 6 h, the following parameters were analyzed: (a) hepatic function, (b) oxidative stress parameters, and (c) the metabolism of alanine in the isolated perfused liver. Plasma activities of alanine aminotransferase and aspartate aminotransferase and hepatic glutathione S-transferase and catalase presented significant elevation in rats inoculated with 300 μg ⋅ kg(-1) Cdt venom. Liver lipoperoxidation was enormously increased by venom doses of 100, 200, and 300 μg ⋅kg(-1) , whereas glutathione S-transferase was not changed. Perfused livers from rats inoculated with 1500 μg ⋅kg(-1) venom showed increased production of lactate, pyruvate, and ammonia when alanine was the metabolic substrate. These results demonstrate that the Cdt venom can produce several changes in hepatocytes. The causes of the changes are possibly related to the disequilibrium in the redox homeostasis but also to specific needs of the poisoned organism, for example, an increased supply of lactate and pyruvate in response to an increased activity of the Cori cycle. Copyright © 2010 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Abasht, Behnam; Mutryn, Marie F; Michalek, Ryan D; Lee, William R

    2016-01-01

    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 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.

  10. Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    2014-01-01

    Full Text Available Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3 of the ethanol extract (CAE of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties.

  11. 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.

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

    Science.gov (United States)

    Sánchez-Rodríguez, Martha A.; Zacarías-Flores, Mariano; Castrejón-Delgado, Lizett; Ruiz-Rodríguez, Ana Karen; Mendoza-Núñez, Víctor Manuel

    2016-01-01

    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. PMID:27563883

  13. 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.

  14. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.

    Science.gov (United States)

    Fletcher, Marianne E; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C; Smolenski, Ryszard T; Kirkham, Paul A; Adcock, Ian M; Barton, Paul J; Takata, Masao; Marczin, Nandor

    2015-06-15

    Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.

  15. The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo.

    Science.gov (United States)

    Wang, Xu; Martínez, María-Aránzazu; Cheng, Guyue; Liu, Zhaoying; Huang, Lingli; Dai, Menghong; Chen, Dongmei; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-05-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) have been widely used as growth promoters and antibacterial agents. Carbadox (CBX), olaquindox (OLA), quinocetone (QCT), cyadox (CYA) and mequindox (MEQ) are the classical members of QdNOs. Some members of QdNOs are known to cause a variety of toxic effects. To date, however, almost no review has addressed the toxicity and metabolism of QdNOs in relation to oxidative stress. This review focused on the research progress associated with oxidative stress as a plausible mechanism for QdNO-induced toxicity and metabolism. The present review documented that the studies were performed over the past 10 years to interpret the generation of reactive oxygen species (ROS) and oxidative stress as the results of QdNO treatment and have correlated them with various types of QdNO toxicity, suggesting that oxidative stress plays critical roles in their toxicities. The major metabolic pathways of QdNOs are N→O group reduction and hydroxylation. Xanthine oxidoreductase (XOR), aldehyde oxidase (SsAOX1), carbonyl reductase (CBR1) and cytochrome P450 (CYP) enzymes were involved in the QdNOs metabolism. Further understanding the role of oxidative stress in QdNOs-induced toxicity will throw new light onto the use of antioxidants and scavengers of ROS as well as onto the blind spots of metabolism and the metabolizing enzymes of QdNOs. The present review might contribute to revealing the QdNOs toxicity, protecting against oxidative damage and helping to improve the rational use of concurrent drugs, while developing novel QdNO compounds with more efficient potentials and less toxic effects.

  16. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2012-01-01

    Full Text Available The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others. There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others, a series of disorders is developed that are jointly called „oxidative stress.“ The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. [Projekat Ministarstva nauke Republike Srbije, br. 173034, br. 175061 i br. 31085

  17. 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.

  18. Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Pan; Shao-Zhen He; Hong-Zhi Xu; Xiao-Juan Zhan; Xiao-Ning Yang; Hong-Min Xiao; Hua-Xiu Shi; Jian-Lin Ren

    2008-01-01

    AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury.METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT-PCR).RESULTS: The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and the exposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol.CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.

  19. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    Science.gov (United States)

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

  20. Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease.

    Science.gov (United States)

    Hartl, Daniela; Schuldt, Victoria; Forler, Stephanie; Zabel, Claus; Klose, Joachim; Rohe, Michael

    2012-06-01

    Glucose hypometabolism is the earliest symptom observed in the brains of Alzheimer disease (AD) patients. In a former study, we analyzed the cortical proteome of the APP23 mouse model of AD at presymptomatic age (1 month) using a 2-D electrophoresis-based approach. Interestingly, long before amyloidosis can be observed in APP23 mice, proteins associated with energy metabolism were predominantly altered in transgenic as compared to wild-type mice indicating presymptomatic changes in energy metabolism. In the study presented here, we analyzed whether the observed changes were associated with oxidative stress and confirmed our previous findings in primary cortical neurons, which exhibited altered ADP/ATP levels if transgenic APP was expressed. Reactive oxygen species produced during energy metabolism have important roles in cell signaling and homeostasis as they modify proteins. We observed an overall up-regulation of protein oxidation status as shown by increased protein carbonylation in the cortex of presymptomatic APP23 mice. Interestingly, many carbonylated proteins, such as Vilip1 and Syntaxin were associated to synaptic plasticity. This demonstrates an important link between energy metabolism and synaptic function, which is altered in AD. In summary, we demonstrate that changes in cortical energy metabolism and increased protein oxidation precede the amyloidogenic phenotype in a mouse model for AD. These changes might contribute to synaptic failure observed in later disease stages, as synaptic transmission is particularly dependent on energy metabolism.

  1. Metabolic correlation between polyol and energy-storing carbohydrate under osmotic and oxidative stress condition in Moniliella megachiliensis.

    Science.gov (United States)

    Kobayashi, Yosuke; Iwata, Hisashi; Yoshida, Junjiro; Ogihara, Jun; Kato, Jun; Kasumi, Takafumi

    2015-10-01

    Moniliella megachiliensis, the osmo-tolerant basidiomycetous yeast was found to accumulate intracellularly energy-storing carbohydrates (trehalose and glycogen) along with polyols (glycerol and erythritol) up to stationary growth phase. In trehalose-loaded cell, osmotic-stress resulted in the rapid generation of glycerol, and oxidative stress with menadione resulted in the rapid generation of erythritol. Under either of these conditions, the levels of the energy-storing carbohydrates were depleted, while little glucose uptake was observed. These results suggested that the intracellular pools of trehalose and glycogen were rapidly converted to glycerol in response to osmotic stress, and to erythritol in response to oxidative stress and altered redox balance. Expression of tps1 encoding trehalose synthetic enzymes paralleled trehalose accumulation in the cell during the culture in 2% glucose, in contrast, expression of tpp1 or tpp2 encoding trehalose-6-phosphate phosphatase was little increased under the same condition. Expression of tre (tre1/tre2) encoding trehalose hydrolase (trehalase) increased with time associated with depletion of trehalose during oxidative stress. From these results, we concluded that glycerol and erythritol, the compatible solutes in M. megachiliensis were metabolically interrelated to energy-storing carbohydrates such as trehalose or glycogen during conditions of osmotic or oxidative stress. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  2. 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

  3. 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.

  4. 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.

  5. 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

    2016-01-01

    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. PMID:27767182

  6. Butyl hydroxytoluene (BHT)-induced oxidative stress: effects on serum lipids and cardiac energy metabolism in rats.

    Science.gov (United States)

    Faine, L A; Rodrigues, H G; Galhardi, C M; Ebaid, G M X; Diniz, Y S; Fernandes, A A H; Novelli, E L B

    2006-01-01

    Recent lines of evidences indicate that several pathological conditions, as cardiovascular diseases, are associated with oxidative stress. In order to validate a butylated hydroxytoluene (BHT)-induced experimental model of oxidative stress in the cardiac tissue and serum lipids, 12 Wistar rats were divided into two groups, a control group and the BHT group, which received BHT i.p. twice a week (1500 mg/kg body weight) during 30 days. BHT group presented lower body weight gain and heart weight. BHT induced toxic effects on serum through increased triacylglycerols (TG), VLDL and LDL-cholesterol concentrations. The heart of BHT animals showed alteration of antioxidant defenses and increased concentrations of lipid hydroperoxides, indicating elevated lipoperoxidation. TG concentrations and lactate dehydrogenase activities were elevated in the cardiac muscle of BHT animals. Thus, long-term administration of BHT is capable to induce oxidative and metabolic alterations similarly to some pathological disorders, constituting an efficient experimental model to health scientific research.

  7. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.

    Science.gov (United States)

    Liu, Dong; Chan, Sic L; de Souza-Pinto, Nadja C; Slevin, John R; Wersto, Robert P; Zhan, Ming; Mustafa, Khadija; de Cabo, Rafael; Mattson, Mark P

    2006-01-01

    The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (Deltapsim) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased Deltapsim, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of Deltapsim to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.

  8. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress.

    Science.gov (United States)

    Maya-Mendoza, Apolinar; Ostrakova, Jitka; Kosar, Martin; Hall, Arnaldur; Duskova, Pavlina; Mistrik, Martin; Merchut-Maya, Joanna Maria; Hodny, Zdenek; Bartkova, Jirina; Christensen, Claus; Bartek, Jiri

    2015-03-01

    Both Myc and Ras oncogenes impact cellular metabolism, deregulate redox homeostasis and trigger DNA replication stress (RS) that compromises genomic integrity. However, how are such oncogene-induced effects evoked and temporally related, to what extent are these kinetic parameters shared by Myc and Ras, and how are these cellular changes linked with oncogene-induced cellular senescence in different cell context(s) remain poorly understood. Here, we addressed the above-mentioned open questions by multifaceted comparative analyses of human cellular models with inducible expression of c-Myc and H-RasV12 (Ras), two commonly deregulated oncoproteins operating in a functionally connected signaling network. Our study of DNA replication parameters using the DNA fiber approach and time-course assessment of perturbations in glycolytic flux, oxygen consumption and production of reactive oxygen species (ROS) revealed the following results. First, overabundance of nuclear Myc triggered RS promptly, already after one day of Myc induction, causing slow replication fork progression and fork asymmetry, even before any metabolic changes occurred. In contrast, Ras overexpression initially induced a burst of cell proliferation and increased the speed of replication fork progression. However, after several days of induction Ras caused bioenergetic metabolic changes that correlated with slower DNA replication fork progression and the ensuing cell cycle arrest, gradually leading to senescence. Second, the observed oncogene-induced RS and metabolic alterations were cell-type/context dependent, as shown by comparative analyses of normal human BJ fibroblasts versus U2-OS sarcoma cells. Third, the energy metabolic reprogramming triggered by Ras was more robust compared to impact of Myc. Fourth, the detected oncogene-induced oxidative stress was due to ROS (superoxide) of non-mitochondrial origin and mitochondrial OXPHOS was reduced (Crabtree effect). Overall, our study provides novel

  9. Oxidative stress and metabolic perturbations in Escherichia coli exposed to sublethal levels of 2,4-dichlorophenoxyacetic acid.

    Science.gov (United States)

    Bhat, Supriya V; Booth, Sean C; Vantomme, Erik A N; Afroj, Shirin; Yost, Christopher K; Dahms, Tanya E S

    2015-09-01

    The chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used extensively worldwide despite its known toxicity and our limited understanding of how it affects non-target organisms. Escherichia coli is a suitable model organism to investigate toxicity and adaptation mechanisms in bacteria exposed to xenobiotic chemicals. We developed a methodical platform that uses atomic force microscopy, metabolomics and biochemical assays to quantify the response of E. coli exposed to sublethal levels of 2,4-D. This herbicide induced a filamentous phenotype in E. coli BL21 and a similar phenotype was observed in a selection of genotypically diverse E. coli strains (A0, A1, B1, and D) isolated from the environment. The filamentous phenotype was observed at concentrations 1000 times below field levels and was reversible upon supplementation with polyamines. Cells treated with 2,4-D had more compliant envelopes, significantly remodeled surfaces that were rougher and altered vital metabolic pathways including oxidative phosphorylation, the ABC transport system, peptidoglycan biosynthesis, amino acid, nucleotide and sugar metabolism. Most of the observed effects could be attributed to oxidative stress, consistent with increases in reactive oxygen species as a function of 2,4-D exposure. This study provides direct evidence that 2,4-D at sublethal levels induces oxidative stress and identifies the associated metabolic changes in E. coli.

  10. 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 olive oil have beneficial synergistic effects on lipid metabolism and oxidative stress in patients with MetS. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

  12. Mechanism of Anesthetic Toxicity: Metabolism, Reactive Oxygen Species, Oxidative Stress, and Electron Transfer

    OpenAIRE

    2011-01-01

    There is much literature on the toxic effects of anesthetics. This paper deals with both the volatiles and locals. Adverse effects appear to be multifaceted, with the focus on radicals, oxidative stress (OS), and electron transfer (ET). ET functionalities involved are quinone, iminoquinone, conjugated iminium, and nitrone. The non-ET routes involving radicals and OS apparently pertain to haloalkanes and ethers. Beneficial effects of antioxidants, evidently countering OS, are reported. Knowled...

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

    OpenAIRE

    Musthafa Mohamed Essa; Selvaraju Subash; Nady Braidy; Samir Al-Adawi; Lim, Chai K.; Tamilarasan Manivasagam; Guillemin, Gilles J.

    2013-01-01

    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...

  14. 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. PMID:28178319

  15. Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update.

    Science.gov (United States)

    Wu, Qing-Hua; Wang, Xu; Yang, Wei; Nüssler, Andreas K; Xiong, Ling-Yun; Kuča, Kamil; Dohnal, Vlastimil; Zhang, Xiu-Juan; Yuan, Zong-Hui

    2014-07-01

    Trichothecenes are a large family of structurally related toxins mainly produced by Fusarium genus. Among the trichothecenes, T-2 toxin and deoxynivalenol (DON) cause the most concern due to their wide distribution and highly toxic nature. Trichothecenes are known for their inhibitory effect on eukaryotic protein synthesis, and oxidative stress is one of their most important underlying toxic mechanisms. They are able to generate free radicals, including reactive oxygen species, which induce lipid peroxidation leading to changes in membrane integrity, cellular redox signaling, and in the antioxidant status of the cells. The mitogen-activated protein kinases signaling pathway is induced by oxidative stress, which also induces caspase-mediated cellular apoptosis pathways. Several new metabolites and novel metabolic pathways of T-2 toxin have been discovered very recently. In human cell lines, HT-2 and neosolaniol (NEO) are the major metabolites of T-2 toxin. Hydroxylation on C-7 and C-9 are two novel metabolic pathways of T-2 toxin in rats. The metabolizing enzymes CYP3A22, CYP3A29, and CYP3A46 in pigs, as well as the enzymes CYP1A5 and CYP3A37 in chickens, are able to catalyze T-2 toxin and HT-2 toxin to form the C-3'-OH metabolites. Similarly to carboxylesterase, CYP3A29 possesses the hydrolytic ability in pigs to convert T-2 toxin to NEO. T-2 toxin is able to down- or upregulate cytochrome P-450 enzymes in different species. The metabolism of DON in humans is region-dependent. Free DON and DON-glucuronide are considered to be the biomarkers for humans. The masked mycotoxin DON-3-β-D-glucoside can be hydrolyzed to free DON in the body. This review will provide useful information on the progress of oxidative stress as well as on the metabolism and the metabolizing enzymes of T-2 toxin and DON. Moreover, the literature will throw light on the blind spots of metabolism and toxicological studies in trichothecenes that have to be explored in the future.

  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. Effects of olive leave extract on metabolic disorders and oxidative stress induced by 2.45 GHz WIFI signals.

    Science.gov (United States)

    Salah, Myriam Ben; Abdelmelek, Hafedh; Abderraba, Manef

    2013-11-01

    We investigated the effect of olive leaves extract administration on glucose metabolism and oxidative response in liver and kidneys of rats exposed to radio frequency (RF). The exposure of rats to RF (2.45 GHz, 1h/day during 21 consecutive days) induced a diabetes-like status. Moreover, RF decreased the activities of glutathione peroxidase (GPx, -33.33% and -49.40%) catalase (CAT, -43.39% and -39.62%) and the superoxide dismutase (SOD, -59.29% and -68.53%) and groups thiol amount (-62.68% and -34.85%), respectively in liver and kidneys. Indeed, exposure to RF increased the malondialdehyde (MDA, 29.69% and 51.35%) concentration respectively in liver and kidneys. Olive leaves extract administration (100 mg/kg, ip) in RF-exposed rats prevented glucose metabolism disruption and restored the activities of GPx, CAT and SOD and thiol group amount in liver and kidneys. Moreover, olive leave extract administration was able to bring down the elevated levels of MDA in liver but not in kidneys. Our investigations suggested that RF exposure induced a diabetes-like status through alteration of oxidative response. Olive leaves extract was able to correct glucose metabolism disorder by minimizing oxidative stress induced by RF in rat tissues.

  18. Metabolic Signatures of Oxidative Stress and Their Relationship with Erythrocyte Membrane Surface Roughness Among Workers of Manual Materials Handling (MMH).

    Science.gov (United States)

    Ghosh, Subrata; Acharyya, Muktish; Majumder, Titlee; Bagchi, Anandi

    2015-12-01

    Brickfield workers in India perform manual materials handling (MMH) and as a result, are at a high risk of developing oxidative stress. This results in an alteration of the various markers of metabolic oxidative stress at the cellular level. Since red blood cell (RBC) is the central point where oxygen, glucose-6-phosphate dehydrogenase (G-6-PD), and glutathione (GSH) are involved, the surface roughness and its alteration and modeling with respect to workers exposed to MMH may be considered as helpful determinants in predicting early damage to the cell and restoring better health to the exposed population, that is, the worker exposed to stress. Hence, nanometric analysis of the surface roughness of the RBC may serve as an early indicator of the stress-related damage in these individuals. The purpose of the study was to identify early red blood corpuscular surface damage profile in terms of linear modeling correlating various biochemical parameters. Linear modeling has been aimed to be developed in order to demonstrate how individual oxidative stress markers such as malondialdehyde (MDA), G-6-PD, and reduced GSH are related to the RBC surface roughness [root mean square (RMS)]. Conventional analysis of these biochemical responses were evaluated in MMH laborers (age varying between 18 years and 21 years) and a comparable control group of the same age group (with sedentary lifestyles). Peak expiratory flow rate (PEFR) and RBC surface analysis by atomic-force microscopy (AFM) and correlated scanning probe microscopy (SPM-analytical software) with corresponding image analysis were performed immediately after completion of standardized exercise (MMH) at the brickfield. A number of correlated significances and regressive linear models were developed among MDA, G-6-PD, GSH, and RBC surface roughness. It appears that these linear models might be instrumental in predicting early oxidative damages related to specific occupational hazards.

  19. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome.

    Science.gov (United States)

    Marchesi, Chiara; Ebrahimian, Talin; Angulo, Orlando; Paradis, Pierre; Schiffrin, Ernesto L

    2009-12-01

    The metabolic syndrome represents a constellation of cardiovascular risk factors that promote the development of cardiovascular disease. Oxidative stress is a mediator of endothelial dysfunction and vascular remodeling. We investigated vascular dysfunction in the metabolic syndrome and the oxidant mechanisms involved. New Zealand obese (NZO) mice with metabolic syndrome and New Zealand black control mice were studied. NZO mice showed insulin resistance and increased visceral fat and blood pressure compared with New Zealand black mice. Mesenteric resistance arteries from NZO mice exhibited increased media:lumen ratio and media cross-sectional area, demonstrating hypertrophic vascular remodeling. Endothelium-dependent relaxation to acetylcholine, assessed by pressurized myography, was impaired in NZO mice, not affected by N(G)-nitro-l-arginine methyl ester, inhibitor of endothelial NO synthase, and improved by the antioxidant Tempol, suggesting reduced NO bioavailability and increased oxidative stress. Dimer:monomer ratio of endothelial NO synthase was decreased in NZO mice compared with New Zealand black mice, suggesting endothelial NO synthase uncoupling. Furthermore, vascular superoxide and peroxynitrite production was increased, as well as adhesion molecule expression. Perivascular adipose tissue of NZO mice showed increased superoxide production and NADPH oxidase activity, as well as adipocyte hypertrophy, associated with inflammatory Mac-3-positive cell infiltration. Vasoconstriction to norepinephrine decreased in the presence of perivascular adipose tissue in New Zealand black mice but was unaffected by perivascular adipose tissue in NZO mice, suggesting loss of perivascular adipose tissue anticontractile properties. Our data suggest that this rodent model of metabolic syndrome is associated with perivascular adipose inflammation and oxidative stress, hypertrophic resistance artery remodeling, and endothelial dysfunction, the latter a result of decreased NO

  20. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress.

    Science.gov (United States)

    Koskenkorva-Frank, Taija S; Weiss, Günter; Koppenol, Willem H; Burckhardt, Susanna

    2013-12-01

    Production of minute concentrations of superoxide (O2(*-)) and nitrogen monoxide (nitric oxide, NO*) plays important roles in several aspects of cellular signaling and metabolic regulation. However, in an inflammatory environment, the concentrations of these radicals can drastically increase and the antioxidant defenses may become overwhelmed. Thus, biological damage may occur owing to redox imbalance-a condition called oxidative and/or nitrosative stress. A complex interplay exists between iron metabolism, O2(*-), hydrogen peroxide (H2O2), and NO*. Iron is involved in both the formation and the scavenging of these species. Iron deficiency (anemia) (ID(A)) is associated with oxidative stress, but its role in the induction of nitrosative stress is largely unclear. Moreover, oral as well as intravenous (iv) iron preparations used for the treatment of ID(A) may also induce oxidative and/or nitrosative stress. Oral administration of ferrous salts may lead to high transferrin saturation levels and, thus, formation of non-transferrin-bound iron, a potentially toxic form of iron with a propensity to induce oxidative stress. One of the factors that determine the likelihood of oxidative and nitrosative stress induced upon administration of an iv iron complex is the amount of labile (or weakly-bound) iron present in the complex. Stable dextran-based iron complexes used for iv therapy, although they contain only negligible amounts of labile iron, can induce oxidative and/or nitrosative stress through so far unknown mechanisms. In this review, after summarizing the main features of iron metabolism and its complex interplay with O2(*-), H2O2, NO*, and other more reactive compounds derived from these species, the potential of various iron therapies to induce oxidative and nitrosative stress is discussed and possible underlying mechanisms are proposed. Understanding the mechanisms, by which various iron formulations may induce oxidative and nitrosative stress, will help us

  1. High-fat diet induces metabolic changes and reduces oxidative stress in female mouse hearts.

    Science.gov (United States)

    Barba, Ignasi; Miró-Casas, Elisabet; Torrecilla, José L; Pladevall, Eulàlia; Tejedor, Sergi; Sebastián-Pérez, Rubén; Ruiz-Meana, Marisol; Berrendero, José R; Cuevas, Antonio; García-Dorado, David

    2017-02-01

    After an acute myocardial infarction, obese patients generally have a better prognosis than their leaner counterparts, known as the "obesity paradox". In addition, female sex is associated with a lower risk of cardiac ischemic events and smaller infarct size compared to males. The objective of the present work was to study the metabolic phenotype and mitochondrial function associated to female sex and short-term high-fat diet. (1)H NMR spectra of mice heart extracts were analysed by mRMR variable selection and linear discriminant analysis was used to evaluate metabolic changes. In separate experiments, O2 consumption and H2O2 production were measured from isolated mitochondria as well as serum oxidation susceptibility. Fingerprinting showed that male hearts contained more myo-inositol, taurine and glutamate than female hearts. HFD reduced the levels of creatine, taurine citrate and acetate. Profiling showed increased alanine and fumarate in HFD suggesting altered glycolitic and Krebs cycle pathways. Female mice contained less glucose than males. Female sex nor HFD altered mitochondria oxygen consumption but both conditions reduced the amount of H2O2 produced in an additive manner. Serum of females had lower oxidation susceptibility than serum from males but there were no differences associated with HFD. In conclusion, female sex and short-term HFD have an effect on the myocardial metabolic pattern and reduce the amount of H2O2 produced by mitochondria in an additive manner suggesting different mechanisms of action. This could explain, at least in part, the protection afforded by female sex and the "obesity paradox".

  2. Metabolic syndrome increases oxidative stress but does not influence disability and short-time outcome in acute ischemic stroke patients.

    Science.gov (United States)

    Simão, Andrea Name Colado; Lehmann, Marcio Francisco; Alfieri, Daniela Frizon; Meloni, Milena Zardetto; Flauzino, Tamires; Scavuzzi, Bruna Miglioranza; de Oliveira, Sayonara Rangel; Lozovoy, Marcell Alysson Batisti; Dichi, Isaias; Reiche, Edna Maria Vissoci

    2015-12-01

    Oxidative stress has been implicated in the pathophysiology of cardiovascular disease and MetS and it may be one of molecular mechanisms involved in stroke. The aims of the present study were to verify differences in oxidative stress markers in acute ischemic stroke patients with and without MetS and to verify whether MetS influences disability and short time outcome of the patients. 148 patients with acute ischemic stroke were divided in two groups: with MetS (n = 92) and without MetS (n = 56). The modified Rankin Scale (mRS) was used for measuring the functional disability after 3-month follow-up. The study assessed the metabolic profile and oxidative stress markers. Stroke patients with MetS had higher levels of lipid hydroperoxides (p acute ischemic stroke patients with MetS and this elevation seems to be involved mainly with changes in lipid profile, but the presence of MetS did not influence short-time disability and survival of the acute ischemic stroke patients.

  3. Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats.

    Science.gov (United States)

    Yao, Hsien-Tsung; Hsu, Ya-Ru; Lii, Chong-Kuei; Lin, Ai-Hsuan; Chang, Keng-Hao; Yang, Hui-Ting

    2014-08-01

    The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. Male Wistar rats were fed a laboratory chow diet and GT or BT drink for 5 weeks. Control rats received de-ionized water instead of the tea drinks. Rats received the GT and BT drinks treatment for 5 weeks showed a significant increase in hepatic microsomal cytochrome P450 (CYP) 1A1 and CYP1A2, and a significant decrease in CYP2C, CYP2E1 and CYP3A enzyme activities. Results of immunoblot analyses of enzyme protein contents showed the same trend with enzyme activity. Significant increase in UDP-glucuronosyltransferase activity and reduced glutathione content in liver and lungs were observed in rats treated with both tea drinks. A lower lipid peroxide level in lungs was observed in rats treated with GT drink. Electrophoretic mobility shift assay revealed that both tea drinks decreased pregnane X receptor binding to DNA and increased nuclear factor-erythroid 2 p45-related factor 2 binding to DNA. These results suggest that feeding of both tea drinks to rats modulated DME activities and reduced oxidative stress in liver and lungs. GT drink is more effective on reducing oxidative stress than BT drink.

  4. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

    Science.gov (United States)

    Cahova, Monika; Chrastina, Petr; Hansikova, Hana; Drahota, Zdenek; Trnovska, Jaroslava; Skop, Vojtech; Spacilova, Jana; Malinska, Hana; Oliyarnyk, Olena; Papackova, Zuzana; Palenickova, Eliska; Kazdova, Ludmila

    2015-03-01

    The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

  5. 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.

  6. A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

    Science.gov (United States)

    Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

    2015-09-01

    A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders.

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

    Science.gov (United States)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio; Sharma, Animesh; Demirovic, Aida; Rao, Shalini; Young, Clifford; Aas, Per Arne; Ericsson, Ida; Sundan, Anders; Jensen, Ole Nørregaard; Slupphaug, Geir

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70-80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes 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 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 explored to elucidate their potential to overcome melphalan resistance.

  8. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.

    Science.gov (United States)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S; Calhoun, William J

    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 alcoholic lung disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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

  10. Oxidative stress and abnormal cholesterol metabolism in patients with post-cardiac arrest syndrome.

    Science.gov (United States)

    Nagase, Midori; Sakurai, Atsushi; Sugita, Atsunori; Matsumoto, Nozomi; Kubo, Airi; Miyazaki, Yusuke; Kinoshita, Kosaku; Yamamoto, Yorihiro

    2017-09-01

    Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients (n = 40) at the time of hospitalization by a significant increase in the percentage of the oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls (n = 55). Tissue oxidative damage in patients was suggested by the significant increase in plasma levels of free fatty acids (FFA) and the significant decrease in polyunsaturated fatty acid contents in total FFA. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Therefore, the FC/CE ratio significantly increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted from the liver. Time course changes of the above parameters were compared among 6 groups of patients divided according to outcome severity. Rapid declines of FC and CE were observed in patients who died within a day, while levels remained unchanged in patients discharged in a week. These data suggest that liver function is one of the key factors determining the survival of patients. Interestingly, therapeutic hypothermia treatment enhanced the increment of plasma ratio of coenzyme Q10 to total cholesterol at the end of rewarming.

  11. Regulation of oxidative phosphorylation complex activity: effects of tissue-specific metabolic stress within an allometric series and acute changes in workload.

    Science.gov (United States)

    Phillips, Darci; Covian, Raul; Aponte, Angel M; Glancy, Brian; Taylor, Joni F; Chess, David; Balaban, Robert S

    2012-05-01

    The concentration of mitochondrial oxidative phosphorylation complexes (MOPCs) is tuned to the maximum energy conversion requirements of a given tissue; however, whether the activity of MOPCs is altered in response to acute changes in energy conversion demand is unclear. We hypothesized that MOPCs activity is modulated by tissue metabolic stress to maintain the energy-metabolism homeostasis. Metabolic stress was defined as the observed energy conversion rate/maximum energy conversion rate. The maximum energy conversion rate was assumed to be proportional to the concentration of MOPCs, as determined with optical spectroscopy, gel electrophoresis, and mass spectrometry. The resting metabolic stress of the heart and liver across the range of resting metabolic rates within an allometric series (mouse, rabbit, and pig) was determined from MPOCs content and literature respiratory values. The metabolic stress of the liver was high and nearly constant across the allometric series due to the proportional increase in MOPCs content with resting metabolic rate. In contrast, the MOPCs content of the heart was essentially constant in the allometric series, resulting in an increasing metabolic stress with decreasing animal size. The MOPCs activity was determined in native gels, with an emphasis on Complex V. Extracted MOPCs enzyme activity was proportional to resting metabolic stress across tissues and species. Complex V activity was also shown to be acutely modulated by changes in metabolic stress in the heart, in vivo and in vitro. The modulation of extracted MOPCs activity suggests that persistent posttranslational modifications (PTMs) alter MOPCs activity both chronically and acutely, specifically in the heart. Protein phosphorylation of Complex V was correlated with activity inhibition under several conditions, suggesting that protein phosphorylation may contribute to activity modulation with energy metabolic stress. These data are consistent with the notion that metabolic

  12. Change in metallothionein phosphorylation state in Mya arenaria clams: implication in metal metabolism and oxidative stress

    Directory of Open Access Journals (Sweden)

    F Gagné

    2010-01-01

    Full Text Available The contamination of the benthic environment poses a threat to long-lived sessile organisms such as clams. The purpose of this study was to investigate metal contamination in tissues and changes in metallothioneins (MT in respect to its redox status in Mya arenaria clams collected at three polluted sites. The phosphorylation state of MT was also investigated to determine whether this state is changed in clams collected at heavy-metal contaminated site and its involvement in cytoprotective signaling during stress contamination. The results show that clams collected at least one of the three polluted sites presented significantly higher concentrations of silver (Ag, arsenic (As, cobalt (Co, copper (Cu, mercury (Hg, nickel (Ni, tin (Sn and lead (Pb in tissues. In the visceral tissue, total MT levels and the reduced, metal-binding form of the protein were significantly induced at the sites. The phosphorylation of MT and mitochondrial activity, as determined by electron transport and cytochrome c oxidase activities, were also significantly reduced at the contaminated sites. Reduced phosphate levels in MT were negatively correlated with total MT levels, suggesting that decreased phosphorylation was involved in kinase-mediated signaling during cellular stress and could possibly alter the protein’s affinity to confer cytoprotection against heavy metal contamination. These preliminary investigations revealed that the phosphorylation state could change in polluted environment and provide some clues on the modulation of binding affinities during heavy-metal and oxidative stress in clams.

  13. Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress.

    Science.gov (United States)

    Yu, Meiling; Xue, Jiangdong; Li, Yijing; Zhang, Weiqian; Ma, Dexing; Liu, Lian; Zhang, Zhigang

    2013-06-01

    Arsenic trioxide (As(2)O(3)) is an environmental toxicant and a potent antineoplastic agent. Exposure to arsenic causes renal cancer. Resveratrol is a well-known polyphenolic compound that is reported to reduce As(2)O(3)-induced cardiotoxicity. The present study aimed to investigate the effect of resveratrol on As(2)O(3)-induced nephrotoxicity and arsenic metabolism. Chinese Dragon-Li cats were injected with 1 mg/kg As(2)O(3) on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As(2)O(3) treatment. On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney. Urine samples were taken for arsenic speciation. In the resveratrol + As(2)O(3)-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased. The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As(2)O(3)-treated group. These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As(2)O(3)-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As(2)O(3) metabolism. These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity.

  14. Oxidative Stress and Antioxidant Defense

    OpenAIRE

    2012-01-01

    Abstract Reactive oxygen species (ROS) are produced by living organisms as a result of normal cellular metabolism and environmental factors, such as air pollutants or cigarette smoke. ROS are highly reactive molecules and can damage cell structures such as carbohydrates, nucleic acids, lipids, and proteins and alter their functions. The shift in the balance between oxidants and antioxidants in favor of oxidants is termed “oxidative stress.” Regulation of reducing and oxidizing (redox) state i...

  15. Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome.

    Science.gov (United States)

    Angelico, Francesco; Loffredo, Lorenzo; Pignatelli, Pasquale; Augelletti, Teresa; Carnevale, Roberto; Pacella, Antonio; Albanese, Fabiana; Mancini, Ilaria; Di Santo, Serena; Del Ben, Maria; Violi, Francesco

    2012-06-01

    The aim of this study was to assess whether adherence to a restricted-calorie, Mediterranean-type diet improves endothelial dysfunction and markers of oxidative stress in patients with metabolic syndrome. A moderately low-calorie (600 calories/day negative energy balance), low-fat, high-carbohydrate diet (syndrome. Participants were divided into two groups according to body weight loss > or syndrome. The coexistent decrease of NOX2 activation suggests a role for oxidative stress in eliciting artery dysfunction.

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

    Science.gov (United States)

    Parente-Rocha, Juliana Alves; Parente, Ana Flávia Alves; Baeza, Lilian Cristiane; Bonfim, Sheyla Maria Rondon Caixeta; Hernandez, Orville; McEwen, Juan G.; Bailão, Alexandre Melo; Taborda, Carlos Pelleschi; Borges, Clayton Luiz; Soares, Célia Maria de Almeida

    2015-01-01

    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. PMID:26360774

  17. Involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of Reaumuria soongorica to salt stress

    Institute of Scientific and Technical Information of China (English)

    YuBing Liu; Bo Cao; MeiLing Liu

    2013-01-01

    Reaumuria soongorica is a short woody shrub widely found in semi-arid areas of China. It can survive severe environ-mental stress including high salinity in its natural habitat. Thus, we investigated the involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of R. soongorica to saline environments. R. soon-gorica was treated with 0, 100, 200 and 400 mM NaCl solutions for 14 days. Soil salt content increased significantly by watering with high content of NaCl solution, and no variation between 8 and 14 days during treatment. The levels of pe-roxidation of lipid membranes (measured by malondialdehyde content) and the activities of three antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX)) increased under salt stress. Chlorophyll and carotenoid content decreased with increasing salt content. The ratio of Chl a/Chl b and carotenoid/Chl exhibited sig-nificant increase under 400 mM NaCl. However, total flavonoid and anthocyanin contents and key enzyme activities in the flavonoid pathway including phenylalanine ammonialyase (PAL) and Chalcone isomerase (CHI) decreased under salt stress. These findings possibly suggest that R. soongorica has an adaptation protection mechanism against salt-induced oxidative damage by inducing the activity of antioxidant enzymes and maintaining a steady level of carotenoid/Chl.

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

    Directory of Open Access Journals (Sweden)

    Nady Braidy

    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.

  19. Effects of stress upon the oxidative metabolism and its correlation with gastric ulcer formation: the role of sex.

    Science.gov (United States)

    Menéndez-Patterson, A; Florez-Lozano, J A; Marin, B

    1976-01-01

    The metabolic-oxidative activity of different nervous and glandular structures (amygdala, hypothalamus, lateral-frontal cerebral cortex, adrenal glands) in male and female rats under acute stress caused by physical immobilization, was determined. The sexual cycle of the female rat was controlled by examination of their vaginal frotis. One experimental group during estrus and another one during diestrus were selected. At the same time ovariectomy was performed on an experimental group in order to eliminate the hormonal influences of the ovary. Results show there are no significant differerneces in the oxidative metabolism. Nor in the numbers of ulcers. Hypothalamus-hypophyseal-adrenocortical activation was made manifest on obtaining significant differences in the weight of the adrenal glands, a fact long ago reported in a number of studies. Necropsy showed severe gastric hemorrhages and ulcer in the stomach. Nevertheless, no significant differences between the distinc experimental groups were obtained. The likely participation of sexual hormones in female rats is discussed in the light of our results.

  20. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

    Science.gov (United States)

    Díaz-Flores, Margarita; Cruz, Miguel; Duran-Reyes, Genoveva; Munguia-Miranda, Catarina; Loza-Rodríguez, Hilda; Pulido-Casas, Evelyn; Torres-Ramírez, Nayeli; Gaja-Rodriguez, Olga; Kumate, Jesus; Baiza-Gutman, Luis Arturo; Hernández-Saavedra, Daniel

    2013-10-01

    Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

  1. 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.

  2. Structural and functional analysis of the yeast N-acetyltransferase Mpr1 involved in oxidative stress tolerance via proline metabolism.

    Science.gov (United States)

    Nasuno, Ryo; Hirano, Yoshinori; Itoh, Takafumi; Hakoshima, Toshio; Hibi, Takao; Takagi, Hiroshi

    2013-07-16

    Mpr1 (sigma1278b gene for proline-analog resistance 1), which was originally isolated as N-acetyltransferase detoxifying the proline analog L-azetidine-2-carboxylate, protects yeast cells from various oxidative stresses. Mpr1 mediates the L-proline and L-arginine metabolism by acetylating L-Δ(1)-pyrroline-5-carboxylate, leading to the L-arginine-dependent production of nitric oxide, which confers oxidative stress tolerance. Mpr1 belongs to the Gcn5-related N-acetyltransferase (GNAT) superfamily, but exhibits poor sequence homology with the GNAT enzymes and unique substrate specificity. Here, we present the X-ray crystal structure of Mpr1 and its complex with the substrate cis-4-hydroxy-L-proline at 1.9 and 2.3 Å resolution, respectively. Mpr1 is folded into α/β-structure with eight-stranded mixed β-sheets and six α-helices. The substrate binds to Asn135 and the backbone amide of Asn172 and Leu173, and the predicted acetyl-CoA-binding site is located near the backbone amide of Phe138 and the side chain of Asn178. Alanine substitution of Asn178, which can interact with the sulfur of acetyl-CoA, caused a large reduction in the apparent kcat value. The replacement of Asn135 led to a remarkable increase in the apparent Km value. These results indicate that Asn178 and Asn135 play an important role in catalysis and substrate recognition, respectively. Such a catalytic mechanism has not been reported in the GNAT proteins. Importantly, the amino acid substitutions in these residues increased the L-Δ(1)-pyrroline-5-carboxylate level in yeast cells exposed to heat stress, indicating that these residues are also crucial for its physiological functions. These studies provide some benefits of Mpr1 applications, such as the breeding of industrial yeasts and the development of antifungal drugs.

  3. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available We have previously reported that acetylsalicylic acid (aspirin, ASA induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO, prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC, cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  4. 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.

  5. The incidences of oxidativestress occurrence following two metabolic support measures in critically ill patients

    Directory of Open Access Journals (Sweden)

    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

  6. Caffeine impacts in the clam Ruditapes philippinarum: Alterations on energy reserves, metabolic activity and oxidative stress biomarkers.

    Science.gov (United States)

    Cruz, Diogo; Almeida, Ângela; Calisto, Vânia; Esteves, Valdemar I; Schneider, Rudolf J; Wrona, Frederick J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2016-10-01

    Caffeine is known to be one of the most consumed psychoactive drugs. For this reason, caffeine is continuously released into the environment with potential impacts on inhabiting organisms. The current study evaluated the biochemical alterations induced in the clam species Ruditapes philippinarum after exposure for 28 days to caffeine (0.5, 3.0 and 18.0 μg/L). The results obtained showed that, with the increasing caffeine concentrations, an increase in clams defense mechanisms (such as antioxidant and biotransformation enzymes activity) was induced which was accompanied by an increase in protein content. Nevertheless, although an increase on defense mechanisms was observed, clams were not able to prevent cells from lipid peroxidation that increased with the increase of caffeine concentration. Furthermore, with the increase of exposure concentrations, clams increased their metabolic activity (measured by electron transport activity), reducing their energy reserves (glycogen content), to fight against oxidative stress. Overall, the present study demonstrated that caffeine may impact bivalves, even at environmentally relevant concentrations, inducing oxidative stress in organisms. The present study is an important contribution to address knowledge gaps regarding the impacts of long-term exposures to pharmaceuticals since most of the studies assessed the effects after acute exposures, most of them up to 96 h.

  7. Effects of Sesame Butter (Ardeh) versus Sesame Oil on Metabolic and Oxidative Stress Markers in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Haidari, Fatemeh; Mohammadshahi, Majid; Zarei, Mehdi; Gorji, Zahra

    2016-03-01

    Diabetes is one of the most common metabolic disorders and is related to oxidative-stress-induced diseases. Given the role of dietary antioxidants in the control and prevention of diabetes, this study aimed to examine the effects of sesame butter versus sesame oil on the serum levels of glucose, lipid profile, and oxidative stress biomarkers in diabetic rats. Forty male albino rats of Wistar strain were randomly divided into 4 groups (i.e., nondiabetic control rats, diabetic rats, diabetic rats treated with sesame butter, and diabetic rats treated with sesame oil). Experimental diabetes was induced with an intraperitoneal injection of streptozotocin (55 mg/kg). Sesame butter (1.25 g/kg) and sesame oil (0.5 g/kg) were given by oral gavage to the diabetic rats for 6 weeks. Finally, serum glucose, lipid profile, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were measured and analyzed statistically. Our data showed that the diabetic groups treated with sesame butter and sesame oil had significantly lower levels of glucose and higher levels of high-density lipoprotein than did the diabetic control group at the end of the study (PSesame butter supplementation also increased TAC and decreased MDA concentrations significantly in the diabetic rats (Psesame butter make it an excellent candidate for future human studies on diabetes, although further research is needed to determine the exact dose and duration of supplementation.

  8. Exercise effect on oxidative stress is independent of change in estrogen metabolism.

    Science.gov (United States)

    Schmitz, Kathryn H; Warren, Meghan; Rundle, Andrew G; Williams, Nancy I; Gross, Myron D; Kurzer, Mindy S

    2008-01-01

    The effect of exercise training on lipid peroxidation and endogenous estrogens is not well understood in premenopausal women. Exercise effects on these variables could mediate observed associations of exercise with hormonally related cancers, including breast cancer. The purpose of the study is to determine the effect of 15 weeks of aerobic exercise on lipid peroxidation, endogenous estrogens, and body composition in young, healthy eumenorrheic women. Fifteen sedentary premenopausal women (18-25 years) participated. Pre- and post-exercise training urine collection (three 24-h samples) started 48 h after most recent exercise session for analysis of a marker of lipid peroxidation (F(2)-isoprostane) and endogenous estrogens, including 2-hydroxyestrogens, 4-hydroxyestrogens, 16-alpha-hydroxyestrone, and ratios of these metabolites (2:16, 2:4). Body composition was measured by dual-energy X-ray absorptiometry, and F(2)-isoprostanes and estrogens were measured by gas chromatography-mass spectrometry. Aerobic exercise resulted in a 34% decrease in F(2)-isoprostane (P = 0.02), a 10% increase in fitness (P = 0.004), a 1.2 kg decrease in body mass (P = 0.007), and a 1.8 kg decrease in fat mass (P = 0.04). No significant changes were noted in estrogens. The effect of exercise training on oxidative stress may be relevant to risk for hormonally related cancers.

  9. CYP2E1, oxidative stress, post-translational modifications and lipid metabolism.

    Science.gov (United States)

    Lakshman, M Raj; Garige, Mamatha; Gong, Maokai A; Leckey, Leslie; Varatharajalu, Ravi; Redman, Robert S; Seth, Devanshi; Haber, Paul S; Hirsch, Kenneth; Amdur, Richard; Shah, Ruchi

    2013-01-01

    Chronic alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective glycosylation of lipid-carrying apolipoproteins such as apo E and apo J, resulting in defective VLDL assembly and intracellular lipid and lipoprotein transport, which in turn is responsible for alcoholic hepatosteatosis and ALD. The mechanism of ethanol action involves thedepletion of a unique RNA binding protein that specifically interacts with its 3'-UTR region of ST6Gal1 mRNA resulting in its destabilization and consequent appearance of asialoconjugates as alcohol biomarkers. With respect to ETOH effects on Cardio-Vascular Diseases, we conclude that CYP2E1 and ETOH mediated oxidative stress significantly down regulates not only the hepatic PON1 gene expression, but also serum PON1 and HCTLase activities accompanied by depletion of hepatic GSH, the endogenous antioxidant. These results strongly implicate the susceptibility of PON1 to increased ROS production. In contrast, betaine seems to be both hepatoprotective and atheroprotective by reducing hepatosteatosis and restoring not only liver GSH that quenches free radicals, but also the antiatherogenic PON1 gene expression and activity.

  10. Oxidative Stress in BPH

    Directory of Open Access Journals (Sweden)

    Murat Savas

    2009-01-01

    The present study has shown that there were not relationship between potency of oxidative stress and BPH. Further well designed studies should be planned to find out whether the oxidative stress-related parameters play role in BPH as an interesting pathology in regard of the etiopathogenesis. Keywords: benign prostatic hyperplasia, oxidative stress, prostate

  11. Black Beans, Fiber, and Antioxidant Capacity Pilot Study: Examination of Whole Foods vs. Functional Components on Postprandial Metabolic, Oxidative Stress, and Inflammation in Adults with Metabolic Syndrome.

    Science.gov (United States)

    Reverri, Elizabeth J; Randolph, Jody M; Steinberg, Francene M; Kappagoda, C Tissa; Edirisinghe, Indika; Burton-Freeman, Britt M

    2015-07-27

    Beans (Phaseolus vulgaris) contain bioactive components with functional properties that may modify cardiovascular risk. The aims of this pilot study were to evaluate the ability of black beans to attenuate postprandial metabolic, oxidative stress, and inflammatory responses and determine relative contribution of dietary fiber and antioxidant capacity of beans to the overall effect. In this randomized, controlled, crossover trial, 12 adults with metabolic syndrome (MetS) consumed one of three meals (black bean (BB), fiber matched (FM), and antioxidant capacity matched (AM)) on three occasions that included blood collection before (fasting) and five hours postprandially. Insulin was lower after the BB meal, compared to the FM or AM meals (p differences over time: AM > BB > FM. Oxidized LDL (oxLDL) was not different by meal, although a trend for declining oxLDL was observed after the BB and AM meals at five hours compared to the FM meal. Triglycerides and interleukin-6 (IL-6) increased in response to meals (p < 0.0001). Inclusion of black beans with a typical Western-style meal attenuates postprandial insulin and moderately enhances postprandial antioxidant endpoints in adults with MetS, which could only be partly explained by fiber content and properties of antioxidant capacity.

  12. Black Beans, Fiber, and Antioxidant Capacity Pilot Study: Examination of Whole Foods vs. Functional Components on Postprandial Metabolic, Oxidative Stress, and Inflammation in Adults with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Elizabeth J. Reverri

    2015-07-01

    Full Text Available Beans (Phaseolus vulgaris contain bioactive components with functional properties that may modify cardiovascular risk. The aims of this pilot study were to evaluate the ability of black beans to attenuate postprandial metabolic, oxidative stress, and inflammatory responses and determine relative contribution of dietary fiber and antioxidant capacity of beans to the overall effect. In this randomized, controlled, crossover trial, 12 adults with metabolic syndrome (MetS consumed one of three meals (black bean (BB, fiber matched (FM, and antioxidant capacity matched (AM on three occasions that included blood collection before (fasting and five hours postprandially. Insulin was lower after the BB meal, compared to the FM or AM meals (p < 0.0001. A significant meal × time interaction was observed for plasma antioxidant capacity (p = 0.002 revealing differences over time: AM > BB > FM. Oxidized LDL (oxLDL was not different by meal, although a trend for declining oxLDL was observed after the BB and AM meals at five hours compared to the FM meal. Triglycerides and interleukin-6 (IL-6 increased in response to meals (p < 0.0001. Inclusion of black beans with a typical Western-style meal attenuates postprandial insulin and moderately enhances postprandial antioxidant endpoints in adults with MetS, which could only be partly explained by fiber content and properties of antioxidant capacity.

  13. Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2011-01-01

    Full Text Available It has been demonstrated that oxidative stress has a ubiquitous role in neurodegenerative diseases. Major source of oxidative stress due to reactive oxygen species (ROS is related to mitochondria as an endogenous source. Although there is ample evidence from tissues of patients with neurodegenerative disorders of morphological, biochemical, and molecular abnormalities in mitochondria, it is still not very clear whether the oxidative stress itself contributes to the onset of neurodegeneration or it is part of the neurodegenerative process as secondary manifestation. This paper begins with an overview of how oxidative stress occurs, discussing various oxidants and antioxidants, and role of oxidative stress in diseases in general. It highlights the role of oxidative stress in neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis. The last part of the paper describes the role of oxidative stress causing deregulation of cyclin-dependent kinase 5 (Cdk5 hyperactivity associated with neurodegeneration.

  14. Oxidative stress parameters in urine from patients with disorders of propionate metabolism: a beneficial effect of L:-carnitine supplementation.

    Science.gov (United States)

    Ribas, Graziela S; Biancini, Giovana B; Mescka, Caroline; Wayhs, Carlos Y; Sitta, Angela; Wajner, Moacir; Vargas, Carmen R

    2012-01-01

    Propionic (PA) and methylmalonic (MMA) acidurias are inherited disorders caused by deficiency of propionyl-CoA carboxylase and methylmalonyl-CoA mutase, respectively. Affected patients present acute metabolic crises in the neonatal period and long-term neurological deficits. Treatments of these diseases include a protein restricted diet and L: -carnitine supplementation. L: -Carnitine is widely used in the therapy of these diseases to prevent secondary L: -carnitine deficiency and promote detoxification, and several recent in vitro and in vivo studies have reported antioxidant and antiperoxidative effects of this compound. In this study, we evaluated the oxidative stress parameters, isoprostane and di-tyrosine levels, and the antioxidant capacity, in urine from patients with PA and MMA at the diagnosis, and during treatment with L: -carnitine and protein-restricted diet. We verified a significant increase of isoprostanes and di-tyrosine, as well as a significant reduction of the antioxidant capacity in urine from these patients at diagnosis, as compared to controls. Furthermore, treated patients presented a marked reduction of isoprostanes and di-tyrosine levels in relation to untreated patients. In addition, patients with higher levels of protein and lipid oxidative damage, determined by di-tyrosine and isoprostanes levels, also presented lower urinary concentrations of total and free L: -carnitine. In conclusion, the present results indicate that treatment with low protein diet and L: -carnitine significantly reduces urinary biomarkers of protein and lipid oxidative damage in patients with disorders of propionate metabolism and that L: -carnitine supplementation may be specially involved in this protection.

  15. 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

  16. Dietary (-)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats.

    Science.gov (United States)

    Prince, Paula D; Lanzi, Cecilia Rodríguez; Toblli, Jorge E; Elesgaray, Rosana; Oteiza, Patricia I; Fraga, César G; Galleano, Monica

    2016-01-01

    High fructose consumption has been associated to deleterious metabolic conditions. In the kidney, high fructose causes renal alterations that contribute to the development of chronic kidney disease. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate risk factors of chronic diseases. This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by high fructose consumption in rats. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without supplementation with (-)-epicatechin (20mg/kg body weight/d) in the rat chow diet. Results showed that, in the presence of mild proteinuria, the renal cortex from fructose-fed rats exhibited fibrosis and decreases in nephrin, synaptopodin, and WT1, all indicators of podocyte function in association with: (i) increased markers of oxidative stress; (ii) modifications in the determinants of NO bioavailability, i.e., NO synthase (NOS) activity and expression; and (iii) development of a pro-inflammatory condition, manifested as NF-κB activation, and associated with high expression of TNFα, iNOS, and IL-6. Dietary supplementation with (-)-epicatechin prevented or ameliorated the adverse effects of high fructose consumption. These results suggest that (-)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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.

  18. Oxidative stress and myocarditis.

    Science.gov (United States)

    Tada, Yuko; Suzuki, Jun-Ichi

    2016-01-01

    Reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are produced highly in myocarditis. ROS, which not only act as effectors for pathogen killing but also mediate signal transduction in the stress responsive pathways, are closely related with both innate and adaptive immunity. On the other hand, oxidative stress overwhelming the capacity of anti-oxidative system generated in severe inflammation has been suggested to damage tissues and exacerbate inflammation. Oxidative stress worsens the autoimmunological process of myocarditis, and suppression of the anti-oxidative system and long-lasting oxidative stress could be one of the pathological mechanisms of cardiac remodeling leading to inflammatory cardiomyopathy. Oxidative stress is considered to be one of the promising treatment targets of myocarditis. Evidences of anti-oxidative treatments in myocarditis have not been fully established. Basic strategies of anti-oxidative treatments include inhibition of ROS production, activation of anti-oxidative enzymes and elimination of generated free radicals. ROS are produced by mitochondrial respiratory chain reactions and enzymes including NADPH oxidases, cyclooxygenase, and xanthine oxidase. Other systems involved in inflammation and stress response, such as NF-κB, Nrf2/Keap1, and neurohumoral factors also influence oxidative stress in myocarditis. The efficacy of anti-oxidative treatments could also depend on the etiology and the phases of myocarditis. We review in this article the pathological significance of ROS and oxidative stress, and the potential anti-oxidative treatments in myocarditis.

  19. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

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    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  20. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    Science.gov (United States)

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  1. Serum paraoxonase activity and oxidative stress and their relationship with obesity-related metabolic syndrome and non-alcoholic fatty liver disease in obese children and adolescents.

    Science.gov (United States)

    Torun, Emel; Gökçe, Selim; Ozgen, İlker Tolga; Aydın, Sinem; Cesur, Yasar

    2014-07-01

    Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome. A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II-III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress. As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased. Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.

  2. Brain responses to chronic social defeat stress: effects on regional oxidative metabolism as a function of a hedonic trait, and gene expression in susceptible and resilient rats.

    Science.gov (United States)

    Kanarik, Margus; Alttoa, Aet; Matrov, Denis; Kõiv, Kadri; Sharp, Trevor; Panksepp, Jaak; Harro, Jaanus

    2011-01-01

    Chronic social defeat stress, a depression model in rats, reduced struggling in the forced swimming test dependent on a hedonic trait-stressed rats with high sucrose intake struggled less. Social defeat reduced brain regional energy metabolism, and this effect was also more pronounced in rats with high sucrose intake. A number of changes in gene expression were identified after social defeat stress, most notably the down-regulation of Gsk3b and Map1b. The majority of differences were between stress-susceptible and resilient rats. Conclusively, correlates of inter-individual differences in stress resilience can be identified both at gene expression and oxidative metabolism levels. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  3. Monitoring of oxidative and metabolic stress during cardiac surgery by means of breath biomarkers: an observational study

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    Kischkel Sabine

    2007-09-01

    Full Text Available Abstract Background Volatile breath biomarkers provide a non-invasive window to observe physiological and pathological processes in the body. This study was intended to assess the impact of heart surgery with extracorporeal circulation (ECC onto breath biomarker profiles. Special attention was attributed to oxidative or metabolic stress during surgery and extracorporeal circulation, which can cause organ damage and poor outcome. Methods 24 patients undergoing cardiac surgery with extracorporeal circulation were enrolled into this observational study. Alveolar breath samples (10 mL were taken after induction of anesthesia, after sternotomy, 5 min after end of ECC, and 30, 60, 90, 120 and 150 min after end of surgery. Alveolar gas samples were withdrawn from the circuit under visual control of expired CO2. Inspiratory samples were taken near the ventilator inlet. Volatile substances in breath were preconcentrated by means of solid phase micro extraction, separated by gas chromatography, detected and identified by mass spectrometry. Results Mean exhaled concentrations of acetone, pentane and isoprene determined in this study were in accordance with results from the literature. Exhaled substance concentrations showed considerable inter-individual variation, and inspired pentane concentrations sometimes had the same order of magnitude than expired values. This is the reason why, concentrations were normalized by the values measured 120 min after surgery. Exhaled acetone concentrations increased slightly after sternotomy and markedly after end of ECC. Exhaled acetone concentrations exhibited positive correlation to serum C-reactive protein concentrations and to serum troponine-T concentrations. Exhaled pentane concentrations increased markedly after sternotomy and dropped below initial values after ECC. Breath pentane concentrations showed correlations with serum creatinine (CK levels. Patients with an elevated CK-MB (myocardial&brain/CK ratio had

  4. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

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    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.

  5. 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

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

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    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.

  7. 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

    2013-01-01

    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.

  8. 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

    2013-01-01

    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. PMID:23535332

  9. Thiol switches in redox regulation of chloroplasts: balancing redox state, metabolism and oxidative stress.

    Science.gov (United States)

    Dietz, Karl-Josef; Hell, Rüdiger

    2015-05-01

    In photosynthesizing chloroplasts, rapidly changing energy input, intermediate generation of strong reductants as well as oxidants and multiple participating physicochemical processes and pathways, call for efficient regulation. Coupling redox information to protein function via thiol modifications offers a powerful mechanism to activate, down-regulate and coordinate interdependent processes. Efficient thiol switching of target proteins involves the thiol-disulfide redox regulatory network, which is highly elaborated in chloroplasts. This review addresses the features of this network. Its conditional function depends on specificity of reduction and oxidation reactions and pathways, thiol redox buffering, but also formation of heterogeneous milieus by microdomains, metabolite gradients and macromolecular assemblies. One major player is glutathione. Its synthesis and function is under feedback redox control. The number of thiol-controlled processes and involved thiol switched proteins is steadily increasing, e.g., in tetrapyrrole biosynthesis, plastid transcription and plastid translation. Thus chloroplasts utilize an intricate and versatile redox regulatory network for intraorganellar and retrograde communication.

  10. 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.

  11. Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells.

    Science.gov (United States)

    Liu, Xi; Ye, Jingping; Wang, Lu; Li, Zhen; Zhang, Yucheng; Sun, Jiantao; Du, Chuang; Wang, Chunhong; Xu, Siyuan

    2017-02-01

    The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1α lower-expression (PGC-1α(-)) TM4 cells and PGC-1α overexpression (PGC-1α(+)) TM4 cells were used to explore the protective roles of PGC-1α against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC-1α, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC-1α(+)TM4 cells versus TM4 cells and were significantly amplified in PGC-1α(-)TM4 cells versus TM4 cells. These results suggest that PGC-1α is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure.

  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. Effects of methylmercury exposure on glutathione metabolism, oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks

    Science.gov (United States)

    Kenow, K.P.; Hoffman, D.J.; Hines, R.K.; Meyer, M.W.; Bickham, J.W.; Matson, C.W.; Stebbins, K.R.; Montagna, P.; Elfessi, A.

    2008-01-01

    We quantified the level of dietary mercury (Hg), delivered as methylmercury chloride (CH3HgCl), 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 :g Hg/g and 0.4 :g Hg/g, an ecologically relevant dietary mercury level, but not at 0.08 :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 :g Hg as CH3HgCl per gram wet food intake.

  14. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.

    Directory of Open Access Journals (Sweden)

    Hassina Massudi

    Full Text Available Nicotinamide adenine dinucleotide (NAD(+ is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+ also represents the sole substrate for the nuclear repair enzyme, poly(ADP-ribose polymerase (PARP and the sirtuin family of NAD-dependent histone deacetylases. Age associated increases in oxidative nuclear damage have been associated with PARP-mediated NAD(+ depletion and loss of SIRT1 activity in rodents. In this study, we further investigated whether these same associations were present in aging human tissue. Human pelvic skin samples were obtained from consenting patients aged between 15-77 and newborn babies (0-1 year old (n = 49 previously scheduled for an unrelated surgical procedure. DNA damage correlated strongly with age in both males (p = 0.029; r = 0.490 and females (p = 0.003; r = 0.600 whereas lipid oxidation (MDA levels increased with age in males (p = 0.004; r = 0.623 but not females (p = 0.3734; r = 0.200. PARP activity significantly increased with age in males (p<0.0001; r = 0.768 and inversely correlated with tissue NAD(+ levels (p = 0.0003; r = -0.639. These associations were less evident in females. A strong negative correlation was observed between NAD(+ levels and age in both males (p = 0.001; r = -0.706 and females (p = 0.01; r = -0.537. SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612 but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p<0.0001; r = 0.4962, and PARP activity and NAD(+ levels (p = 0.0213; r = 0.5241 in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD(+ catabolism in human tissue. The resulting NAD

  15. Salmonella proteomics under oxidative stress reveals coordinated regulation of antioxidant defense with iron metabolism and bacterial virulence.

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    Fu, Jiaqi; Qi, Linlu; Hu, Mo; Liu, Yanhua; Yu, Kaiwen; Liu, Qian; Liu, Xiaoyun

    2017-02-11

    Salmonella Typhimurium is a bacterial pathogen that can cause widespread gastroenteritis. Salmonella encounters reactive oxygen species both under free-living conditions and within their mammalian host during infection. To study its response to oxidative stress, we performed the first large-scale proteomic profiling of Salmonella upon exposure to H2O2. Among 1600 detected proteins, 83 proteins showed significantly altered abundance. Interestingly, only a subset of known antioxidants was induced, likely due to distinct regulatory mechanisms. In addition, we found elevation of several Salmonella acquired phage products with potential contribution to DNA repair under oxidative stress. Furthermore, we observed robust induction of iron-uptake systems and disruption of these pathways led to bacterial survival defects under H2O2 challenge. Importantly, this work is the first to report that oxidative stress severely repressed the Salmonella type III secretion system (T3SS), reducing its virulence. Biological significance Salmonella, a Gram-negative bacterial pathogen, encounters reactive oxygen species (ROS) both endogenously and exogenously. To better understand its response to oxidative stress, we performed the first large-scale profiling of Salmonella protein expression upon H2O2 treatment. Among 1600 quantified proteins, the abundance of 116 proteins was altered significantly. Notably, iron acquisition systems were induced to promote bacterial survival under oxidative stress. Furthermore, we are the first to report that oxidative stress severely repressed Salmonella type III secretion system and hence reduced its virulence. We believe that these findings will not only help us better understand the molecular mechanisms that Salmonella has evolved to counteract ROS but also the global impact of oxidative stress on bacterial physiology.

  16. The Role of Propolis in Oxidative Stress and Lipid Metabolism: A Randomized Controlled Trial

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    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.

  17. 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.

  18. Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M

    2010-01-01

    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. PMID:21191543

  19. NKT cell modulates NAFLD potentiation of metabolic oxidative stress-induced mesangial cell activation and proximal tubular toxicity

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    Alhasson, Firas; Dattaroy, Diptadip; Das, Suvarthi; Chandrashekaran, Varun; Seth, Ratanesh Kumar; Schnellmann, Rick G.

    2015-01-01

    Obesity and nonalcoholic fatty liver disease (NAFLD) are associated with the development and progression of chronic kidney disease. We recently showed that NAFLD induces liver-specific cytochrome P-450 (CYP)2E1-mediated metabolic oxidative stress after administration of the CYP2E1 substrate bromodichloromethane (BDCM) (Seth RK, Das S, Kumar A, Chanda A, Kadiiska MB, Michelotti G, Manautou J, Diehl AM, Chatterjee S. Toxicol Appl Pharmacol 274: 42–54, 2014; Seth RK, Kumar A, Das S, Kadiiska MB, Michelotti G, Diehl AM, Chatterjee S. Toxicol Sci 134:291–303, 2013). The present study examined the effects of CYP2E1-mediated oxidative stress in NAFLD leading to kidney toxicity. Mice were fed a high-fat diet for 12 wk to induce NAFLD. NAFLD mice were exposed to BDCM, a CYP2E1 substrate, for 4 wk. NAFLD + BDCM increased CYP2E1-mediated lipid peroxidation in proximal tubular cells compared with mice with NAFLD alone or BDCM-treated lean mice, thus ruling out the exclusive role of BDCM. Lipid peroxidation increased IL-1β, TNF-α, and interferon-γ. In parallel, mesangial cell activation was observed by increased α-smooth muscle actin and transforming growth factor-β, which was blocked by the CYP2E1 inhibitor diallyl sulphide both in vivo and in vitro. Mice lacking natural killer T cells (CD1d knockout mice) showed elevated (>4-fold) proinflammatory mediator release, increased Toll-like receptor (TLR)4 and PDGF2 mRNA, and mesangial cell activation in the kidney. Finally, NAFLD CD1D knockout mice treated with BDCM exhibited increased high mobility group box 1 and Fas ligand levels and TUNEL-positive nuclei, indicating that higher cell death was attenuated in TLR4 knockout mice. Tubular cells showed increased cell death and cytokine release when incubated with activated mesangial cells. In summary, an underlying condition of progressive NAFLD causes renal immunotoxicity and aberrant glomerular function possibly through high mobility group box 1-dependent TLR4 signaling

  20. Protective effects of Cynara scolymus leaves extract on metabolic disorders and oxidative stress in alloxan-diabetic rats.

    Science.gov (United States)

    Ben Salem, Maryem; Ben Abdallah Kolsi, Rihab; Dhouibi, Raouia; Ksouda, Kamilia; Charfi, Slim; Yaich, Mahdi; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Jamoussi, Kamel; Affes, Hanen

    2017-06-19

    Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. We determinate the antioxidant activity by ABTS (.+) and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS (.+) (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p rats, respectively associated with significant reduction (p rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was

  1. Hepatic transcriptional analysis in rats treated with Cassia occidentalis seed: involvement of oxidative stress and impairment in xenobiotic metabolism as a putative mechanism of toxicity.

    Science.gov (United States)

    Panigrahi, Gati Krushna; Yadav, Ashish; Yadav, Anuradha; Ansari, Kausar M; Chaturvedi, Rajnish K; Vashistha, Vipin M; Raisuddin, S; Das, Mukul

    2014-08-17

    The present study was undertaken to investigate the effect of Cassia occidentalis (CO) seeds on the transcriptional expression patterns of mRNAs in rat liver by microarray analysis. The results indicated that exposure of CO (0.5%) seeds in diet to rats differentially regulated 60 transcripts belonging to various metabolic pathways including, oxidative stress, xenobiotic metabolism, carbohydrate metabolism, cell cycle, apoptosis etc. The expression of AKT1, CAT, SOD1, CYP1A1, CYP2B1, TGF-β, BAX, CREB1, JNK1 and IL-6 were validated by the qRT-PCR. In addition, involvement of oxidative stress was observed due to marked depletion of glutathione, increase in lipid peroxidation and modulation of antioxidant enzymes in hepatic tissue of rats treated with 0.5-2.0% CO in diet. Furthermore, significant decrease in the levels of Phase 1 (EROD, MROD and PROD) and Phase 2 (QR and GST) enzymes following 0.5-2.0% CO exposure indicates the impairment of xenobiotic metabolism and possible accumulation of toxic ingredients of the seeds in liver. Overall, the study predicts the involvement of multiple pathways and related biomolecules in CO induced hepatotoxicity and the data may be useful in formulating strategies for therapeutic interventions of suspected CO poisoning study cases.

  2. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

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    Maísa Silva

    2015-01-01

    Full Text Available The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S, which was fed the AIN-93M diet, and the standard plus iron group (SI, which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

  3. Staphylococcal response to oxidative stress

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    Rosmarie eGaupp

    2012-03-01

    Full Text Available Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria’s interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host.

  4. Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers

    Energy Technology Data Exchange (ETDEWEB)

    Kasperczyk, Sławomir, E-mail: kaslav@mp.pl [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Dobrakowski, Michał [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Kasperczyk, Janusz [Dept. of Environmental Medicine and Epidemiology, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Ostałowska, Alina; Zalejska-Fiolka, Jolanta; Birkner, Ewa [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland)

    2014-10-01

    The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead. The population consisted of two randomly divided groups of healthy male volunteers exposed to lead. Workers in the first group (reference group) were not administered any antioxidants, while workers in the second group (CAR group) were treated orally with 10 mg of beta-carotene once a day for 12 weeks. Biochemical analysis included measuring markers of lead-exposure and oxidative stress in addition to the levels and activities of selected antioxidants. After treatment, levels of malondialdehyde, lipid hydroperoxides and lipofuscin significantly decreased compared with the reference group. However, the level of glutathione significantly increased compared with the baseline. Treatment with beta-carotene also resulted in significantly decreased glutathione peroxidase activity compared with the reference group, while the activities of other glutathione-related enzymes and of superoxide dismutase were not significantly changed. However, the activities of glucose-6-phosphate dehydrogenase and catalase, as well as the level of alpha-tocopherol, were significantly higher after treatment compared with the baseline. Despite controversy over the antioxidant properties of beta-carotene in vivo, our findings showed reduced oxidative stress after beta-carotene supplementation in chronic lead poisoning. - Highlights: • Beta-carotene reduces oxidative stress in lead-exposed workers. • Beta-carotene elevates glutathione level in lead-exposed workers. • Beta-carotene administration could be beneficial in lead poisoning.

  5. Sociodemographic and Lifestyle Determinants of Plasma Oxidative Stress Markers 8-OHdG and F2-Isoprostanes and Associations with Metabolic Syndrome.

    Science.gov (United States)

    Black, Catherine N; Bot, Mariska; Scheffer, Peter G; Penninx, Brenda W J H

    2016-01-01

    Background. Oxidative stress is increasingly important in health research. Therefore, it is necessary to understand which factors determine basal oxidative stress. This study examines the associations of various determinants with markers of oxidative DNA and lipid damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes. Methods. Data are from the Netherlands Study of Depression and Anxiety; 1117 subjects (18-65 years) without a current psychiatric diagnosis. Multivariable regression analyses were conducted with plasma levels of 8-OHdG and F2-isoprostanes (measured by LC/MS-MS) including sociodemographic, lifestyle, and sampling variables. Associations with metabolic syndrome (MetS) and chronic disease were examined. Results. 8-OHdG and F2-isoprostanes were weakly correlated (r = 0.06, p = 0.045). Both were positively associated with age and cotinine (cigarette exposure); 8-OHdG was lower in females and after longer sample storage. F2-isoprostanes were higher in females, alcohol users, and in samples collected in spring and lower in supplement users and those with more education. Both markers were lower in fasting subjects. F2-isoprostanes, not 8-OHdG, were positively associated with MetS. Conclusion. The weak correlation between 8-OHdG and F2-isoprostanes suggests they reflect specific aspects of oxidative stress. Both markers are associated with a range of sociodemographic, lifestyle, and sampling determinants which should be considered in future research. F2-isoprostanes are associated with MetS.

  6. Erythropoietin and oxidative stress.

    Science.gov (United States)

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2008-05-01

    Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor kappaB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care.

  7. Oxidative Stress and Neurodegenerative Disorders

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    Jie Li

    2013-12-01

    Full Text Available Living cells continually generate reactive oxygen species (ROS through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.

  8. Melatonin exerts a more potent effect than S-adenosyl-l-methionine against iron metabolism disturbances, oxidative stress and tissue injury induced by obstructive jaundice in rats.

    Science.gov (United States)

    Muñoz-Castañeda, Juan R; Túnez, Isaac; Herencia, Carmen; Ranchal, Isidora; González, Raúl; Ramírez, Luz M; Arjona, Alvaro; Barcos, Montserrat; Espejo, Isabel; Cruz, Adolfo; Montilla, Pedro; Padillo, Francisco J; Muntané, Jordi

    2008-07-30

    Melatonin and S-adenosyl-l-methionine (SAMe) prevent oxidative stress and tissue dysfunction in obstructive jaundice (OJ). Lipid peroxidation is exacerbated in the presence of trace amounts of iron (Fe). The study investigated the regulation by melatonin and SAMe the induction of oxidative stress, iron metabolism disturbances and tissue injury in an experimental model of OJ. Different parameters of lipid peroxidation, antioxidant status, tissue injury and Fe metabolism were determined in liver and blood. OJ induced Fe accumulation in liver, and increased transferrin (Tf) saturation and loosely bound Fe content in blood. Melatonin, and SAMe at lesser extent, enhanced protein Tf content in liver and blood, that reduced loosely bound Fe content in blood. Melatonin and SAMe did not affect ferritin (FT) and Tf mRNA expression, but reduced Tf receptor (TfR) mRNA expression in liver. In conclusion, the effect of melatonin and SAMe on Fe metabolism may be included in the beneficial properties of these agents on lipid peroxidation and tissue injury induced by OJ.

  9. 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

    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. 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). 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 to increase their thermal tolerance windows.

  10. Ocean warming enhances malformations, premature hatching, metabolic suppression and oxidative stress in the early life stages of a keystone squid.

    Directory of Open Access Journals (Sweden)

    Rui Rosa

    Full Text Available 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

  11. Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Simona Bo; Roberto Gambino; Marilena Durazzo; Sabrina Guidi; Elisa Tiozzo; Federica Ghione; Luigi Gentile; Maurizio Cassader; Gian Franco Pagano

    2005-01-01

    AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

  12. Bystander signaling via oxidative metabolism

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    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

  13. In high-light-acclimated coffee plants the metabolic machinery is adjusted to avoid oxidative stress rather than to benefit from extra light enhancement in photosynthetic yield.

    Science.gov (United States)

    Martins, Samuel C V; Araújo, Wagner L; Tohge, Takayuki; Fernie, Alisdair R; DaMatta, Fábio M

    2014-01-01

    Coffee (Coffea arabica L.) has been traditionally considered as shade-demanding, although it performs well without shade and even out-yields shaded coffee. Here we investigated how coffee plants adjust their metabolic machinery to varying light supply and whether these adjustments are supported by a reprogramming of the primary and secondary metabolism. We demonstrate that coffee plants are able to adjust its metabolic machinery to high light conditions through marked increases in its antioxidant capacity associated with enhanced consumption of reducing equivalents. Photorespiration and alternative pathways are suggested to be key players in reductant-consumption under high light conditions. We also demonstrate that both primary and secondary metabolism undergo extensive reprogramming under high light supply, including depression of the levels of intermediates of the tricarboxylic acid cycle that were accompanied by an up-regulation of a range of amino acids, sugars and sugar alcohols, polyamines and flavonoids such as kaempferol and quercetin derivatives. When taken together, the entire dataset is consistent with these metabolic alterations being primarily associated with oxidative stress avoidance rather than representing adjustments in order to facilitate the plants from utilizing the additional light to improve their photosynthetic performance.

  14. In high-light-acclimated coffee plants the metabolic machinery is adjusted to avoid oxidative stress rather than to benefit from extra light enhancement in photosynthetic yield.

    Directory of Open Access Journals (Sweden)

    Samuel C V Martins

    Full Text Available Coffee (Coffea arabica L. has been traditionally considered as shade-demanding, although it performs well without shade and even out-yields shaded coffee. Here we investigated how coffee plants adjust their metabolic machinery to varying light supply and whether these adjustments are supported by a reprogramming of the primary and secondary metabolism. We demonstrate that coffee plants are able to adjust its metabolic machinery to high light conditions through marked increases in its antioxidant capacity associated with enhanced consumption of reducing equivalents. Photorespiration and alternative pathways are suggested to be key players in reductant-consumption under high light conditions. We also demonstrate that both primary and secondary metabolism undergo extensive reprogramming under high light supply, including depression of the levels of intermediates of the tricarboxylic acid cycle that were accompanied by an up-regulation of a range of amino acids, sugars and sugar alcohols, polyamines and flavonoids such as kaempferol and quercetin derivatives. When taken together, the entire dataset is consistent with these metabolic alterations being primarily associated with oxidative stress avoidance rather than representing adjustments in order to facilitate the plants from utilizing the additional light to improve their photosynthetic performance.

  15. Hypoxia, Oxidative Stress and Fat

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    Nikolaus Netzer

    2015-06-01

    Full Text Available Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.

  16. Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.

    Science.gov (United States)

    Gonçalves, Ana Cristina; Alves, Raquel; Baldeiras, Inês; Cortesão, Emília; Carda, José Pedro; Branco, Claudia C; Oliveiros, Bárbara; Loureiro, Luísa; Pereira, Amélia; Nascimento Costa, José Manuel; Sarmento-Ribeiro, Ana Bela; Mota-Vieira, Luisa

    2017-01-01

    Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

  17. Role of Oxidative Stress in Prostate Cancer

    OpenAIRE

    Khandrika, Lakshmipathi; Kumar, Binod; Koul, Sweaty; Maroni, Paul; Koul, Hari K.

    2009-01-01

    As prostate cancer and aberrant changes in reactive oxygen species (ROS) become more common with aging, ROS signaling may play an important role in the development and progression of this malignancy. Increased ROS, otherwise known as oxidative stress, is a result of either increased ROS generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. ROS are products of normal cellular metabolism ...

  18. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

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    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.

  19. 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.

  20. Oxidative stress and glycemic regulation.

    Science.gov (United States)

    Ceriello, A

    2000-02-01

    Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration.

  1. Effects of exogenous nitric oxide on growth, active oxygen species metabolism, and photosynthetic characteristics in cucumber seedlings under NaCl stress

    Institute of Scientific and Technical Information of China (English)

    FAN Huaifu; GUO Shirong; JIAO Yansheng; ZHANG Runhua; LI Juan

    2007-01-01

    The study was conducted by means of nutrient solution culture to investigate the effects of exogenous nitric oxide (NO) on growth of cucumbe rseedlings,active oxygen species metabolism and photosynthetic characteristics in cucumber leaves under 50 mmol/L NaCl stress.The results showed that 10-400 μmol/L exogenous sodium nitroprusside (SNP),especially 100 μmol/L SNP,significantly alleviated the injury to seedlings and increased seedling growth.The activity of superoxide dismutase (SOD),peroxidase (POD),catalase (CAT),and ascorbate peroxidase (APX),and the contents of photosynthetic pigments and proline also increased under 50 mmol/L NaCI stress.Similarly,net photosynthetic rate (Pn),stomatal conductance (Gs),and transpiration rate (Tr) also increased significantly.However,exogenous nitric oxide application markedly decreased membrane permeahyde (MDA) and H2O2,and intercellular CO2 concentration (Ci) under 50 mmol/L NaCl stress.

  2. Sociodemographic and Lifestyle Determinants of Plasma Oxidative Stress Markers 8-OHdG and F2-Isoprostanes and Associations with Metabolic Syndrome

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    Catherine N. Black

    2016-01-01

    Full Text Available Background. Oxidative stress is increasingly important in health research. Therefore, it is necessary to understand which factors determine basal oxidative stress. This study examines the associations of various determinants with markers of oxidative DNA and lipid damage: 8-hydroxy-2′-deoxyguanosine (8-OHdG and F2-isoprostanes. Methods. Data are from the Netherlands Study of Depression and Anxiety; 1117 subjects (18–65 years without a current psychiatric diagnosis. Multivariable regression analyses were conducted with plasma levels of 8-OHdG and F2-isoprostanes (measured by LC/MS-MS including sociodemographic, lifestyle, and sampling variables. Associations with metabolic syndrome (MetS and chronic disease were examined. Results. 8-OHdG and F2-isoprostanes were weakly correlated (r = 0.06, p = 0.045. Both were positively associated with age and cotinine (cigarette exposure; 8-OHdG was lower in females and after longer sample storage. F2-isoprostanes were higher in females, alcohol users, and in samples collected in spring and lower in supplement users and those with more education. Both markers were lower in fasting subjects. F2-isoprostanes, not 8-OHdG, were positively associated with MetS. Conclusion. The weak correlation between 8-OHdG and F2-isoprostanes suggests they reflect specific aspects of oxidative stress. Both markers are associated with a range of sociodemographic, lifestyle, and sampling determinants which should be considered in future research. F2-isoprostanes are associated with MetS.

  3. Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans

    OpenAIRE

    Zhong-Cheng Luo; Jean-François Bilodeau; Anne Monique Nuyt; Fraser, William D; Pierre Julien; Francois Audibert; Lin Xiao; Carole Garofalo; Emile Levy

    2015-01-01

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), p...

  4. Oxidative stress & male infertility.

    Science.gov (United States)

    Makker, Kartikeya; Agarwal, Ashok; Sharma, Rakesh

    2009-04-01

    The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.

  5. Age-related changes to vascular protease-activated receptor 2 in metabolic syndrome: a relationship between oxidative stress, receptor expression, and endothelium-dependent vasodilation.

    Science.gov (United States)

    Maruyama, Kana; Kagota, Satomi; McGuire, John J; Wakuda, Hirokazu; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2017-04-01

    Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO) - cyclic GMP-mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome. Here we investigated mechanisms linking PAR2's vascular effects to phenotypic characteristics of male SHRSP.ZF rats at 10, 20, and 30 weeks of age. We found vasodilation responses to either 2fLIGRLO or enzyme-mediated PAR2 activation by trypsin were sustained until 20 weeks and lessened at 30 weeks. PAR2 protein and mRNA levels were lower in aortas at 30 weeks than at 10 and 20 weeks. PAR2-mediated responses positively correlated with PAR2 protein and mRNA levels. Decreased cGMP accumulation in the presence of 2fLIGRLO paralleled the decreased relaxations elicited by nitroprusside and the cGMP analog 8-pCPT-cGMP, and the less soluble guanylyl cyclase protein at 30 weeks. 2fLIGRLO-induced relaxation was negatively correlated with serum thiobarbituric acid reactive substances, an index of oxidative stress, which increased with age. Forward stepwise data regression supported a model of age-related decreases in PAR2 function resulting from decreased PAR2 mRNA and increased oxidative stress. We conclude that decreased responsiveness of aortic smooth muscle to NO and downregulation of receptor expression impair PAR2 functions at later stages of metabolic syndrome in SHRSP.ZF rats.

  6. Dose- and time-related changes in aerobic metabolism, chorionic disruption, and oxidative stress in embryonic medaka (Oryzias latipes): Underlying mechanisms for silver nanoparticle developmental toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Wu Yuan, E-mail: uyuan@mail.ustc.edu.cn [Department of Public Health, Anhui Medical University, Hefei (China); State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing (China); Zhou Qunfang [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing (China)

    2012-11-15

    Silver nanoparticles (AgNPs) are widely employed in commercial products, and are thus inevitably released into the aquatic environment. Many studies have indicated that AgNPs could induce toxicological effects on embryonic fish. To understand the mechanism of AgNP developmental toxicity, we determined the effects of AgNPs on the egg membrane, aerobic metabolism, antioxidant system, lipid peroxidation, as well as reactive oxygen species (ROS) and singlet oxygen ({sup 1}O{sub 2}) generation in early-life medaka fish (Oryzias latipes). AgNP treatment at 62.5-1000 {mu}g/L caused significant increase in retarded development and abnormalities. Destruction of the surface ornamentation and egg envelope was observed at a higher AgNP concentration ({>=}125 {mu}g/L) using light microscopy and scanning electron microscopy. A dose-dependent increase in lactate dehydrogenase activity, an indicator of anaerobic metabolism, and superoxide dismutase activity was observed in the treated embryos. In contrast, the total reduced glutathione level decreased. A high thiobarbituric acid reactive substance concentration was generated upon AgNP exposure from day 1 to day 7 postfertilisation. The biochemical parameters suggested that oxidative stress was induced by the AgNPs. Unexpectedly, a dose-dependent reduction in ROS and {sup 1}O{sub 2} generation upon high AgNP exposure ({>=}250 {mu}g/L) was observed. Although the morphological damages induced by the AgNPs were irreversible, restorable antioxidant defenses were noted in the well-developed embryos. This finding supported the idea that the stage of morphogenesis and organogenesis is a critical window to chemical exposure or environmental stress. Overall, the results suggested that hypoxia, disturbed egg chorion, and oxidative stress are mechanistically associated with AgNP toxicity in embryonic fish.

  7. Oxidative Stress in Myopia

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    Bosch-Morell Francisco

    2015-01-01

    Full Text Available Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

  8. Oxidative stress in myopia.

    Science.gov (United States)

    Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

    2015-01-01

    Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

  9. A STUDY OF OXIDATIVE STRESS IN DIABETES

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    Babu Rao

    2015-06-01

    Full Text Available Non - enzymatic free radical mediated oxidation of biological molecules, membranes and tissues is associated with a variety of pathological events such as cancer, aging and diabetes mellitus . [1] Increased oxidative stress is seen in both types of diabetes me llitus namely type 1 and type 2, irrespective of duration, complications and treatment. In diabetes mellitus, oxidative stress seems primarily due to both an increased plasma free radical concentration and a sharp decline in antioxidant defences . [1] Among the causes of enhanced free radical production, hyperglycemia and hyper insulinemia seem to play a major role , [2,3] Hyperglycemia is the more easily modifiable factor among the two and good glycemic control can reduce the oxidative stress. Controversy pers ists regarding the other possible mechanisms of increased oxidative stress in diabetes and whether oxidative stress normalizes with adequate metabolic control alone. The role of oxidative stress and diabetic complications has been extensively investigated. Oxidative stress has been suggested to be involved in the genesis of both macro and micro angiopathy [4,5] Prospective trials are now underway addressing the controversial issues of possible role of pharmacological antioxidants in preventing or at least de laying the onset of diabetic complications.

  10. Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2015-03-01

    Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

  11. Oxidative stress and ageing.

    Science.gov (United States)

    Birch-Machin, M A; Bowman, A

    2016-10-01

    Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering

  12. Oxidative stress in neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Xueping Chen; Chunyan Guo; Jiming Kong

    2012-01-01

    Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2-) and hydroxyl radical (OH-), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.

  13. Oxidative Stress and Anesthesia in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Peivandi Yazdi A

    2014-04-01

    Full Text Available Free radical and peroxide production lead to intracellular damage. On the other hand, free radicals are used by the human immune system to defend against pathogens. The aging process could be limited by oxidative stress in the short term. Chronic diseases like diabetes mellitus (DM are full-stress conditions in which remarkable metabolic functional destructions might happen. There is strong evidence regarding antioxidant impairment in diabetes. Performing a particular method for anesthesia in diabetic patients might prevent or modify excessive free radical formation and oxidative stress. It seems that prescribing antioxidant drugs could promote wound healing in diabetics.  

  14. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    Lan-fang Li; Jian Li

    2007-01-01

    Many studies on oxidative stress, insulin resistance, and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states. Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress. And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance. However, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications. Furthermore, it appears that oxidative stress is only one of the factors contributing to diabetic complications. Thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

  15. Periodontitis and increase in circulating oxidative stress

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    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  16. Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress.

    Science.gov (United States)

    Teimouri, Fatemeh; Amirkabirian, Nasim; Esmaily, Hadi; Mohammadirad, Azadeh; Aliahmadi, Atousa; Abdollahi, Mohammad

    2006-12-01

    The aim of this study was to evaluate effects of acute exposure to various doses of diazinon, a widely used synthetic organophosphorus (OP) insecticide on plasma glucose, hepatic cells key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress in rats. Diazinon was administered by gavage at doses of 15, 30 and 60 mg/ kg. The liver was perfused and removed under anaesthesia. The activities of glycogen phosphorylase (GP), phosphoenolpyruvate carboxykinase (PEPCK), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were analysed in liver homogenate. Administration of diazinon (15, 30 and 60 mg/kg) increased plasma glucose concentrations by 101.43% (P = 0.001), 103.68% (P = 0.000) and 160.65% (P = 0.000) of control, respectively. Diazinon (15, 30 and 60 mg/kg) increased hepatic GP activity by 43.5% (P = 0.05), 70.3% (P = 0.00) and 117.2% (P = 0.02) of control, respectively. In addition, diazinon (30 and 60 mg/kg) increased hepatic PEPCK by 77.3% (P = 0.000) and 93.5% (P = 0.000) of control, respectively. Diazinon (30 and 60 mg/kg) decreased liver TAC by 38% (P = 0.046) and 48% (P = 0.000) of control, respectively. Also diazinon (30 and 60 mg/kg) increased hepatic cell liver lipid peroxidation by 77% (P = 0.05) and 280% (P = 0.000) of control. The correlations between plasma glucose and hepatic cells TBARS (r2 = 0.537, P = 0.02), between plasma glucose and ChE activity (r2 = 0.81, P = 0.049) and between plasma glucose and hepatic cells GP activity (r2 = 0.833, P = 0.04) were significant. It is concluded that the liver cells are a site of toxic action of diazinon. Diazinon increases glucose release from liver into blood through activation of glycogenolysis and gluconeogenesis as a detoxication non-cholinergic mechanism to overwhelm diazinon-induced toxic stress. The results are in accordance with the hypothesis that OPs are a predisposing factor of diabetes.

  17. Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer

    Directory of Open Access Journals (Sweden)

    Ling Li

    2015-04-01

    Full Text Available Inhibition of glycolysis using 2-deoxy-d-glucose (2DG, 20 mM, 24–48 h combined with inhibition of the pentose cycle using dehydroepiandrosterone (DHEA, 300 µM, 24–48 h increased clonogenic cell killing in both human prostate (PC-3 and DU145 and human breast (MDA-MB231 cancer cells via a mechanism involving thiol-mediated oxidative stress. Surprisingly, when 2DG+DHEA treatment was combined with an inhibitor of glutathione (GSH synthesis (l-buthionine sulfoximine; BSO, 1 mM that depleted GSH>90% of control, no further increase in cell killing was observed during 48 h exposures. In contrast, when an inhibitor of thioredoxin reductase (TrxR activity (Auranofin; Au, 1 µM, was combined with 2DG+DHEA or DHEA-alone for 24 h, clonogenic cell killing was significantly increased in all three human cancer cell lines. Furthermore, enhanced clonogenic cell killing seen with the combination of DHEA+Au was nearly completely inhibited using the thiol antioxidant, N-acetylcysteine (NAC, 20 mM. Redox Western blot analysis of PC-3 cells also supported the conclusion that thioredoxin-1 (Trx-1 oxidation was enhanced by treatment DHEA+Au and inhibited by NAC. Importantly, normal human mammary epithelial cells (HMEC were not as sensitive to 2DG, DHEA, and Au combinations as their cancer cell counterparts (MDA-MB-231. Overall, these results support the hypothesis that inhibition of glycolysis and pentose cycle activity, combined with inhibition of Trx metabolism, may provide a promising strategy for selectively sensitizing human cancer cells to oxidative stress-induced cell killing.

  18. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  19. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

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    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  20. Oxidative Stress and HPV Carcinogenesis

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    Federico De Marco

    2013-02-01

    Full Text Available Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV, represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a number of other events have to concur in order to induce the viral infection into the (very rare neoplastic transformation. From this perspective, a number of putative viral, host, and environmental co-factors have been proposed as potential candidates. Among them oxidative stress (OS is an interesting candidate, yet comparatively underexplored. OS is a constant threat to aerobic organisms being generated during mitochondrial oxidative phosphorylation, as well as during inflammation, infections, ionizing irradiation, UV exposure, mechanical and chemical stresses. Epithelial tissues, the elective target for HPV infection, are heavily exposed to all named sources of OS. Two different types of cooperative mechanisms are presumed to occur between OS and HPV: I The OS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of co-carcinogenesis; and II OS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection. This manuscript was designed to summarize available data on this latter hypothesis. Experimental data and indirect evidences on promoting the activity of OS in viral infection and viral integration will be reviewed. The anti-apoptotic and pro-angiogenetic role of NO (nitric oxide and iNOS (inducible nitric oxide synthase will be discussed together with the OS/HPV cooperation in inducing cancer metabolism adaptation. Unexplored/underexplored aspects of the OS interplay with the HPV-driven carcinogenesis

  1. 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.

  2. 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.

  3. Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress

    OpenAIRE

    Stranahan, Alexis M.; Cutler, Roy G.; Button, Catherine; Telljohann, Richard; Mattson, Mark P.

    2011-01-01

    The structure and function of the hippocampus, a brain region critical for learning and memory, is impaired by obesity and hyperlipidemia. Peripheral cholesterol and sphingolipids increase progressively with aging and are associated with a range of age-related diseases. However, the mechanisms linking peripheral cholesterol metabolism to hippocampal neuroplasticity remain poorly understood. To determine whether diets that elevate serum cholesterol influence lipid metabolism in the hippocampus...

  4. Inflammation, Oxidative Stress, and Obesity

    Directory of Open Access Journals (Sweden)

    José A. Morales-González

    2011-05-01

    Full Text Available Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6; other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS, generating a process known as oxidative stress (OS. Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO, and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

  5. Genetics of oxidative stress in obesity.

    Science.gov (United States)

    Rupérez, Azahara I; Gil, Angel; Aguilera, Concepción M

    2014-02-20

    Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

  6. Genetics of Oxidative Stress in Obesity

    Directory of Open Access Journals (Sweden)

    Azahara I. Rupérez

    2014-02-01

    Full Text Available Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

  7. Oxidative Stress in Cystinosis Patients

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    Maria Helena Vaisbich

    2011-09-01

    Full Text Available Background/Aims: Nephropathic cystinosis (NC is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters. Methods: The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels. Results: We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p Conclusion: An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients.

  8. Acute heat stress induces oxidative stress in broiler chickens.

    Science.gov (United States)

    Lin, Hai; Decuypere, Eddy; Buyse, Johan

    2006-05-01

    The stress responses and possible oxidative damage in plasma, liver and heart were investigated in broiler chickens acutely exposed to high temperature. Eighty 5-week old broiler chickens were exposed to 32 degrees C for 6h. The extent of lipid peroxidation, activities of superoxide dismutase and total antioxidant power in plasma, liver and heart tissues were investigated. Meanwhile, the blood metabolites such as glucose, urate, triiodothyronine, thyroxine, corticosterone, ceruloplasmin and creatine kinase were measured before and after 3 and 6h of heat exposure. The results showed that oxidative stress could be induced in 5-week old broiler chickens by acute heat exposure (32 degrees C, 6h). The results suggest that the elevated body temperature can induce the metabolic changes that are involved in the induction of oxidative stress. The liver is more susceptible to oxidative stress than heart during acute heat exposure in broiler chickens. The oxidative stress should be considered as part of the stress response of broiler chickens to heat exposure.

  9. Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy

    Directory of Open Access Journals (Sweden)

    María Muriach

    2014-01-01

    Full Text Available Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB, a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

  10. BRCA1 and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yong Weon Yi

    2014-04-01

    Full Text Available The breast cancer susceptibility gene 1 (BRCA1 has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1’s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers.

  11. Molecular mechanisms of ROS production and oxidative stress in diabetes.

    Science.gov (United States)

    Newsholme, Philip; Cruzat, Vinicius Fernandes; Keane, Kevin Noel; Carlessi, Rodrigo; de Bittencourt, Paulo Ivo Homem

    2016-12-15

    Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation.

  12. Peroxisomes,oxidative stress,and inflammation

    Institute of Scientific and Technical Information of China (English)

    Stanley; R; Terlecky; Laura; J; Terlecky; Courtney; R; Giordano

    2012-01-01

    Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.

  13. ER stress and hepatic lipid metabolism

    Directory of Open Access Journals (Sweden)

    Huiping eZhou

    2014-05-01

    Full Text Available The endoplasmic reticulum (ER is an important player in regulating protein synthesis and lipid metabolism. Perturbation of ER homeostasis, referred as ER stress, has been linked to numerous pathological conditions, such as inflammation, cardiovascular diseases and metabolic disorders. The liver plays a central role in regulating nutrient and lipid metabolism. Accumulating evidence implicates that ER stress disrupts lipid metabolism and induces hepatic lipotoxicity. Here, we review the major ER stress signaling pathways, how ER stress contributes to the dysregulation of hepatic lipid metabolism, and the potential causative mechanisms of ER stress in hepatic lipotoxicity. Understanding the role of ER stress in hepatic metabolism may lead to the identification of new therapeutic targets for metabolic diseases.

  14. Drug-Induced Oxidative Stress and Toxicity

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    Damian G. Deavall

    2012-01-01

    Full Text Available Reactive oxygen species (ROS are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.

  15. The Metabolic Response of Arabidopsis Roots to Oxidative Stress is Distinct from that of Heterotrophic Cells in Culture and Highlights a Complex Relationship between the Levels of Transcripts,Metabolites,and Flux

    Institute of Scientific and Technical Information of China (English)

    Martin Lehmann; Markus Schwarzl(a)inder; Toshihiro Obata; Supaart Sirikantaramas; Meike Burow; Carl Erik Olsen; Takayuki Tohge; Mark D.Fricker; Birger Lindberg Mφller; Alisdair R.Fernie; Lee J.Sweetloveb; Miriam Laxa

    2009-01-01

    Metabolic adjustments are a significant,but poorly understood,part of the response of plants to oxidative stress.In a previous study (Baxter et al.,2007),the metabolic response of Arabidopsis cells in culture to induction of ox-idative stress by menadione was characterized.An emergency survival strategy was uncovered in which anabolic primary metabolism was largely down-regulated in favour of catabolic and antioxidant metabolism.The response in whole plant tissues may be different and we have therefore investigated the response of Arabidopsis roots to menadione treatment,analyzing the transcriptome,metabolome and key metabolic fluxes with focus on primary as well as secondary metab-olism.Using a redox-sensitive GFP,it was also shown that menadione causes redox perturbation,not just in the mitochon-drion,but also in the cytosol and plastids of roots.In the first 30 min of treatment,the response was similar to the cell culture:there was a decrease in metabolites of the TCA cycle and amino acid biosynthesis and the transcriptomic response was dominated by up-regulation of DNA regulatory proteins.After 2 and 6 h of treatment,the response of the roots was different to the cell culture.Metabolite levels did not remain depressed,but instead recovered and,in the case of pyruvate,some amino acids and aliphatic glucosinolates showed a steady increase above control levels.However,no major changes in fluxes of central carbon metabolism were observed and metabolic transcripts changed largely independently of the corresponding metabolites.Together,the results suggest that root tissues can recover metabolic activity after oxidative inhibition and highlight potentially important roles for glycolysis and the oxidative pentose phosphate pathway.

  16. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    Journal of Endocrinology, Metabolism and Diabetes of South Africa ... and oxidative stress in type 2 diabetes mellitus (T2DM) patients with that of healthy controls ... Conclusion: Early management through an antioxidant-rich diet and lifestyle ...

  17. A Molecular Web: Endoplasmic Reticulum Stress, Inflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Namrata eChaudhari

    2014-07-01

    Full Text Available Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded protein response (UPR through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS. Toxic accumulation of ROS within ER and mitochondria disturb fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways has been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease and others. In this review we have discussed the UPR signaling pathways, and networking between ER stress induced inflammatory pathways, oxidative stress and mitochondrial signaling events which further induce or exacerbate ER stress.

  18. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses

    Science.gov (United States)

    Nawrocka, Daria; Kornicka, Katarzyna; Śmieszek, Agnieszka

    2017-01-01

    Equine Metabolic Syndrome (EMS) is a steadily growing life-threatening endocrine disorder linked to insulin resistance, oxidative stress, and systemic inflammation. Inflammatory microenvironment of adipose tissue constitutes the direct tissue milieu for various cell populations, including adipose-derived mesenchymal stromal cells (ASCs), widely considered as a potential therapeutic cell source in the course of the treatment of metabolic disorders. Moreover, elevated oxidative stress induces inflammation in intestinal epithelial cells (IECs)—the first-line cells exposed to dietary compounds. In the conducted research, we showed that in vitro application of Spirulina platensis contributes to the restoration of ASCs’ and IECs’ morphology and function through the reduction of cellular oxidative stress and inflammation. Enhanced viability, suppressed senescence, and improved proliferation of ASCs and IECs isolated from metabolic syndrome-affected individuals were evident following exposition to Spirulina. A protective effect of the investigated extract against mitochondrial dysfunction and degeneration was also observed. Moreover, our data demonstrate that Spirulina extract effectively suppressed LPS-induced inflammatory responses in macrophages. In vivo studies showed that horses fed with a diet based on Spirulina platensis supplementation lost weight and their insulin sensitivity improved. Thus, our results indicate the engagement of Spirulina platensis nourishing as an interesting alternative approach for supporting the conventional treatment of equine metabolic syndrome. PMID:28771165

  19. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  20. Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

    Science.gov (United States)

    Igarashi, Kazuhiko; Watanabe-Matsui, Miki

    2014-04-01

    The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

  1. Anticonvulsant drugs, oxidative stress and nitric oxide.

    Science.gov (United States)

    Vega Rasgado, L A; Ceballos Reyes, G M; Vega-Diaz, M F

    2011-01-01

    Nitric Oxide (NO) is thought to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although its function is unclear and controversial. As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Here we investigated the role of NO in seizure mechanisms through oxidative stress generation by studying the effect of anticonvulsant drugs such as amino oxyacetic acid (AAOA), valproate (VALP), diazepam (DIAZ) and gabapentin (GBPTNA) on oxidative stress in the brain, estimated as free carbonyls by the method of Dalle and Rossi, and by measuring NO by the indirect method based on the Griess reaction. Results show that, except for AAOA and VALP, anticonvulsants did not significantly affect or decreased free carbonyls, but reversed the oxidative stress produced by pentylenetetrazole (PTZ) induced convulsions. Anticonvulsants except AAOA diminished NO levels and with the exception of VALP, counteracted the increase in NO generated by PTZ. Anticonvulsants decreased oxidative stress and NO especially in hippocampus (HI) and cortex (CX), and reversed PTZ effects on both parameters. PTZ diminished NO in HI, which could be explained since PTZ caused an increase on endothelial NO synthase but a decrease in neuronal NOS expression in this brain area. Since the drugs studied are modulating GABA levels, our results suggest that seizures generated by alterations in GABAergic transmission produce oxidative stress caused by NO, which can be reversed by anticonvulsants. The effects described differ among the brain regions studied and the NO synthase isoform affected.

  2. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Asieh Hosseini

    2013-01-01

    Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

  3. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yosuke Kayama

    2015-10-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

  4. Diabetic Cardiovascular Disease Induced by Oxidative Stress.

    Science.gov (United States)

    Kayama, Yosuke; Raaz, Uwe; Jagger, Ann; Adam, Matti; Schellinger, Isabel N; Sakamoto, Masaya; Suzuki, Hirofumi; Toyama, Kensuke; Spin, Joshua M; Tsao, Philip S

    2015-10-23

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

  5. Dietary total antioxidant capacity is inversely related to central adiposity as well as to metabolic and oxidative stress markers in healthy young adults

    Directory of Open Access Journals (Sweden)

    Zulet M Ángeles

    2011-08-01

    Full Text Available Abstract Background Dietary total antioxidant capacity (TAC has been assumed as a useful tool to assess the relationship between the cumulative antioxidant food capacity and several chronic disorders. The aim of this cross-sectional study was to investigate the potential relationships of dietary TAC with adiposity, metabolic and oxidative stress markers in healthy young adults. Methods This study enrolled 266 healthy subjects (105 men/ 161 women; 22 ± 3 years-old; 22.0 ± 2.7 kg/m2. Dietary intake, anthropometry, blood pressure, lifestyle features, and biochemical data were assessed with validated procedures. Results In linear regression analyses, dietary TAC values were inversely associated with glycemia, total cholesterol:HDL-c ratio, triglycerides and oxidized-LDL concentrations, and positively associated with HDL-c concentrations, independently of gender, age, smoking status, physical activity, vitamin use supplement, waist circumference, energy intake, fatty acid intake. In addition, plasma TAC was negatively correlated with ox-LDL concentrations (r= -0.20, P = 0.003, independently of the assessed confounding variables. Finally, dietary TAC values were inversely related to waist circumference values (r= -0.17, P = 0.005 as well as to lower mild central obesity occurrence (waist circumference ≥ 80/ 94 cm for women/ men, respectively. Conclusion Dietary TAC values are inversely associated with glucose and lipid biomarkers as well as with central adiposity measurements in healthy young adults, indicating dietary TAC as a useful tool to assess the health benefits of cumulative antioxidant capacity from food intake. In addition, the independent and inverse relationships of ox-LDL concentrations with dietary and plasma TAC respectively suggest a putative role of antioxidant rich-diet in the link between redox state and atherogenesis at early stage.

  6. The impact of oxidative stress on hair.

    Science.gov (United States)

    Trüeb, R M

    2015-12-01

    Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to detoxify the reactive intermediates or to repair the resulting damage. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage lipids, proteins, and DNA. They are generated by a multitude of endogenous and environmental challenges, while the body possesses endogenous defense mechanisms. With age, production of free radicals increases, while the endogenous defense mechanisms decrease. This imbalance leads to progressive damage of cellular structures, presumably resulting in the aging phenotype. While the role of oxidative stress has been widely discussed in skin aging, little focus has been placed on its impact on hair condition. Moreover, most literature on age-related hair changes focuses on alopecia, but it is equally important that the hair fibers that emerge from the scalp exhibit significant age-related changes that have equal impact on the overall cosmetic properties of hair. Sources of oxidative stress with impact on the pre-emerging fiber include: oxidative metabolism, smoking, UVR, and inflammation from microbial, pollutant, or irritant origins. Sources of oxidative stress with impact on the post-emerging fiber include: UVR (enhanced by copper), chemical insults, and oxidized scalp lipids. The role of the dermatologist is recognition and treatment of pre- and post-emerging factors for lifetime scalp and hair health.

  7. Research progress of oxidative stress of coronary heart disease patients with different glucose metabolism status%不同糖代谢状态冠心病患者氧化应激的研究进展

    Institute of Scientific and Technical Information of China (English)

    姚志灵; 陈亮; 王欣丽

    2015-01-01

    氧化应激水平可以通过抗氧化酶系水平、非酶系抗氧化水平及氧化产物水平检测。在糖尿病前期患者体内存在高氧化应激状态,随着糖代谢紊乱加重,体内自由基生成增加,抗氧化能力下降,氧化应激水平升高,氧化与抗氧化失衡。在2型糖尿病患者中,随着糖尿病的病程延长,氧化应激水平随之升高,且胰岛β细胞功能下降,胰岛素抵抗增加。动脉粥样硬化的发生发展与氧化应激有密切关系,冠心病患者体内已存在氧化应激,且机体抗氧化能力减弱。在冠心病合并糖尿病患者中,随着病情进展,氧化损伤程度呈逐渐加重趋势。本文就不同糖代谢状态冠心病患者氧化应激的相关性研究进展进行综述。%The level of oxidative stress can be tested by antioxidant enzyme system level, antioxidant non-enzyme dsystem level and oxidation products. High oxidative stress state exists in people who have pre-diabetes, and with the sugar metabolic disorder exacerbating, free radicals generation increased, the ability of anti-oxidation dropped, the lev-el of oxidative stress raised, oxidation and antioxidant imbalanced. In patients with type 2 diabetes, with the course of diabetes being longer, the level of oxidative stress will increase, and else the function of the islet beta cell dropped, in-sulin resistance increased. The development of atherosclerosis has deeply related with oxidative stress. There is oxida-tive stress in coronary heart disease patients, and the body's antioxidant capacity reduced. In patients with coronary heart disease and diabetes mellitus, as the disease progresses, the degree of oxidative damage also shows a trend of in-crease gradually. In this paper, the research progress of the correlation of oxidative stress of different glucose metabolism status in patients with coronary heart disease will be reviewed.

  8. Oxidative stress in Parkinson's disease.

    Science.gov (United States)

    Nikam, Shashikant; Nikam, Padmaja; Ahaley, S K; Sontakke, Ajit V

    2009-01-01

    Oxidative stress contributes to the cascade, leading to dopamine cell degeneration in Parkinson's disease. However, oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation. It is therefore difficult to determine whether oxidative stress leads to or is a consequence of, these events. Oxidative stress was assessed by estimating lipid peroxidation product in the form of thiobarbituric acid reactive substances, nitric oxide in the form of nitrite & nitrate. Enzymatic antioxidants in the form of superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin and non enzymatic antioxidant vitamins e.g. vitamin E and C in either serum or plasma or erythrocyte in 40 patients of Parkinson's disease in the age group 40-80 years. Trace elements e.g. copper, zinc and selenium were also estimated. Plasma thiobarbituric acid reactive substances and nitric oxide levels were Significantly high but superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin, vitamin-E, vitamin-C, copper, zinc and selenium levels were significantly low in Parkinson's disease when compared with control subjects. Present study showed that elevated oxidative stress may be playing a role in dopaminergic neuronal loss in substentia nigra pars compacta and involved in pathogenesis of the Parkinson's disease.

  9. Oxidative stress and hypertension.

    Science.gov (United States)

    Harrison, David G; Gongora, Maria Carolina

    2009-05-01

    This review has summarized some of the data supporting a role of ROS and oxidant stress in the genesis of hypertension. There is evidence that hypertensive stimuli, such as high salt and angiotensin II, promote the production of ROS in the brain, the kidney, and the vasculature and that each of these sites contributes either to hypertension or to the untoward sequelae of this disease. Although the NADPH oxidase in these various organs is a predominant source, other enzymes likely contribute to ROS production and signaling in these tissues. A major clinical challenge is that the routinely used antioxidants are ineffective in preventing or treating cardiovascular disease and hypertension. This is likely because these drugs are either ineffective or act in a non-targeted fashion, such that they remove not only injurious ROS Fig. 5. Proposed role of T cells in the genesis of hypertension and the role of the NADPH oxidase in multiple cells/organs in modulating this effect. In this scenario, angiotensin II stimulates an NADPH oxidase in the CVOs of the brain, increasing sympathetic outflow. Sympathetic nerve terminals in lymph nodes activate T cells, and angiotensin II also directly activates T cells. These stimuli also activate expression of homing signals in the vessel and likely the kidney, which attract T cells to these organs. T cells release cytokines that stimulate the vessel and kidney NADPH oxidases, promoting vasoconstriction and sodium retention. SFO, subfornical organ. 630 Harrison & Gongora but also those involved in normal cell signaling. A potentially important and relatively new direction is the concept that inflammatory cells such as T cells contribute to hypertension. Future studies are needed to understand the interaction of T cells with the CNS, the kidney, and the vasculature and how this might be interrupted to provide therapeutic benefit.

  10. Maternal rumen-protected methionine supplementation and its effect on blood and liver biomarkers of energy metabolism, inflammation, and oxidative stress in neonatal Holstein calves.

    Science.gov (United States)

    Jacometo, C B; Zhou, Z; Luchini, D; Trevisi, E; Corrêa, M N; Loor, J J

    2016-08-01

    In nonruminants, nutrition during pregnancy can program offspring development, metabolism, and health in later life. Rumen-protected Met (RPM) supplementation during the prepartum period improves liver function and immune response in dairy cows. Our aim was to investigate the effects of RPM during late pregnancy on blood biomarkers (23 targets) and the liver transcriptome (24 genes) in neonatal calves from cows fed RPM at 0.08% of diet dry matter/d (MET) for the last 21 d before calving or controls (CON). Blood (n=12 calves per diet) was collected at birth before receiving colostrum (baseline), 24 h after receiving colostrum, 14, 28, and 50 d (post-weaning) of age. Liver was sampled (n=8 calves per diet) via biopsy on d 4, 14, 28, and 50 of age. Growth and health were not affected by maternal diet. The MET calves had greater overall plasma insulin concentration and lower glucose and ratios of glucose-to-insulin and fatty acids-to-insulin, indicating greater systemic insulin sensitivity. Lower concentration of reactive oxygen metabolites at 14 d of age along with a tendency for lower overall concentration of ceruloplasmin in MET calves indicated a lesser degree of stress. Greater expression on d 4 of fructose-bisphosphatase 1 (FBP1), phosphoenolpyruvate carboxykinase 1 (PCK1), and the facilitated bidirectional glucose transporter SLC2A2 in MET calves indicated alterations in gluconeogenesis and glucose uptake and release. The data agree with the greater expression of the glucocorticoid receptor (GR). Greater expression on d 4 of the insulin receptor (INSR) and insulin-responsive serine/threonine-protein kinase (AKT2) in MET calves indicated alterations in insulin signaling. In that context, the similar expression of sterol regulatory element-binding transcription factor 1 (SREBF1) in CON and MET during the preweaning period followed by the marked upregulation regardless of diet after weaning (d 50) support the idea of changes in hepatic insulin sensitivity during

  11. Oxidative stress-induced metabolic changes in mouse C2C12 myotubes studied with high-resolution 13C, 1H, and 31P NMR spectroscopy

    DEFF Research Database (Denmark)

    Straadt, Ida K; Young, Jette F; Petersen, Bent O;

    2010-01-01

    In this study, stress in relation to slaughter was investigated in a model system by the use of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy for elucidating changes in the metabolites in C2C12 myotubes exposed to H(2)O(2)-induced stress. Oxidative stress resulted in lower...... to lower levels of the unlabeled ((12)C) lactate were identified in the (1)H spectra after stress exposure. These data indicate an increase in de novo synthesis of alanine, concomitant with a release of lactate from the myotubes to the medium at oxidative stress conditions. The changes in the metabolite...... levels of several metabolites, mainly amino acids; however, higher levels of alanine were apparent in the (13)C spectra after incubation with [(13)C(1)]glucose. In the (13)C spectra [(13)C(3)]lactate tended to increase after exposure to increasing concentrations of H(2)O(2); conversely, a tendency...

  12. Short-Term Effects of Chlorpromazine on Oxidative Stress in Erythrocyte Functionality: Activation of Metabolism and Membrane Perturbation

    Directory of Open Access Journals (Sweden)

    Silvana Ficarra

    2016-01-01

    Full Text Available The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism.

  13. Effect of dietary copper amount and source on copper metabolism and oxidative stress of weanling pigs in short-term feeding.

    Science.gov (United States)

    Huang, Y L; Ashwell, M S; Fry, R S; Lloyd, K E; Flowers, W L; Spears, J W

    2015-06-01

    Forty-eight weanling barrows were used to determine the effects of amount and source of dietary Cu on Cu metabolism, oxidative stress in the duodenum, and VFA ratios in the cecum of weanling pigs in short-term feeding. At 21 d of age, newly weaned pigs were stratified by BW (7.03 ± 1.20 kg) and equally assigned to 1 of the following dietary treatments: 1) control (5 mg supplemental Cu/kg diet from CuSO4), 2) 225 mg supplemental Cu/kg diet from CuSO4, or 3) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a complex diet until harvest on d 11 and 12. During harvest, bile and liver were obtained for mineral analysis, and liver samples were obtained for analysis of mRNA expression of Cu regulatory proteins. Digesta of duodenum, proximal jejunum, and ileum were collected for soluble Cu analysis. Mucosal scrapings of duodenum, proximal jejunum, and ileum were obtained for analysis of mucosal Cu concentration and mRNA expression of Cu regulatory proteins. Duodenal mucosal scrapings were also collected for analysis of malondialdehyde (MDA). Pigs fed high Cu had markedly greater (P pigs. Duodenal MDA concentrations were greater (P = 0.003) in CuSO4 vs. control pigs and tended (P = 0.06) to be greater than in TBCC pigs. Duodenal antioxidant 1 (Atox1) mRNA was downregulated (P pigs fed high Cu compared to controls and was not affected by Cu source. Compared with control pigs, those fed CuSO4 and TBCC had greater (P pigs. Hepatic Cu transporting β-polypeptide ATPase (Atp7b) was upregulated (P = 0.02) in the Cu-supplemented pigs compared with controls and did not differ among Cu sources. The acetate:propionate ratio in cecal contents was much greater in pigs supplemented with 225 mg Cu/kg diet than in controls. When fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO4. Feeding weanling pigs increased Cu resulted in modulation of duodenal and liver at the transcription level.

  14. Involvement of oxidative stress in Alzheimer disease.

    Science.gov (United States)

    Nunomura, Akihiko; Castellani, Rudy J; Zhu, Xiongwei; Moreira, Paula I; Perry, George; Smith, Mark A

    2006-07-01

    Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD, namely, metabolic, mitochondrial, metal, and cell-cycle abnormalities. Contrary to the commonly held notion that pathologic hallmarks of AD signify etiology, several lines of evidence now indicate that aggregation of amyloid-beta and tau is a compensatory response to underlying oxidative stress. Therefore, removal of proteinaceous accumulations may treat the epiphenomenon rather than the disease and may actually enhance oxidative damage. Although some antioxidants have been shown to reduce the incidence of AD, the magnitude of the effect may be modified by individual factors such as genetic predisposition (e.g. apolipoprotein E genotype) and habitual behaviors. Because caloric restriction, exercise, and intellectual activity have been experimentally shown to promote neuronal survival through enhancement of endogenous antioxidant defenses, a combination of dietary regimen of low total calorie and rich antioxidant nutrients and maintaining physical and intellectual activities may ultimately prove to be one of the most efficacious strategies for AD prevention.

  15. Potential Modulation of Sirtuins by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Leonardo Santos

    2016-01-01

    Full Text Available Sirtuins are a conserved family of NAD-dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1–7, all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein-protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD-consuming enzymes results in activation of SIRT1 and protection against obesity-related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions.

  16. Potential Modulation of Sirtuins by Oxidative Stress.

    Science.gov (United States)

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

    Sirtuins are a conserved family of NAD-dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1-7), all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein-protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD-consuming enzymes results in activation of SIRT1 and protection against obesity-related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions.

  17. Potential Modulation of Sirtuins by Oxidative Stress

    Science.gov (United States)

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

    Sirtuins are a conserved family of NAD-dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1–7), all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein-protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD-consuming enzymes results in activation of SIRT1 and protection against obesity-related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions. PMID:26788256

  18. Oxidative Stress and Periodontal Disease in Obesity.

    Science.gov (United States)

    Dursun, Erhan; Akalin, Ferda Alev; Genc, Tolga; Cinar, Nese; Erel, Ozcan; Yildiz, Bulent Okan

    2016-03-01

    Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women.Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated.Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status markers.Our results suggest that young obese, otherwise healthy, women show findings of early periodontal disease (gingival inflammation) compared with age-matched healthy lean women, and that local/periodontal oxidative stress generated by obesity seems to be associated with periodontal disease.

  19. Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

    Directory of Open Access Journals (Sweden)

    Maria Pantelidou

    2017-02-01

    Full Text Available Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism.

  20. Oxidative stress and leaf senescence

    Directory of Open Access Journals (Sweden)

    Sedigheh Hatami

    2011-11-01

    Full Text Available Abstract Background Senescence is an important developmental process that leads to the cell death through highly regulated genetically controlled processes in plants. Biotic and abiotic Oxidative stresses can also artificially induce senescence and increase the production of reactive oxygen species (ROS specifically in chloroplast. One of the important oxidative stresses is paraquat that induces deviation of electron from photosynthesis electron chain and lead to the production of more ROS in chloroplast. Plants have evolved special adoptive mechanism to reallocate nutrient to reproductive and juvenile organs in senescence and different oxidative stresses. Rubisco seems to be the most abundant protein in plants and is involved in many changes during senescence. Results In the present study, the effects of ROS on Rubisco during senescence and oxidative stresses were evaluated by measuring photosynthesis factors such as net photosynthesis rate (Pn, stomatal conductance (G, evaporation rate (E, intra cellular CO2 concentration (Ci, fluorescence and total protein during three stages of development. Our results showed that in paraquat treated plants, CO2 assimilation is the most effective factor that refers to Rubisco damages. The highest correlation and regression coefficient belonged to Ci, while correlation coefficient between photosynthesis rate and total protein was much smaller. Conclusion It appears in the early stage of oxidative stresses such as exposing to paraquat, ROS has the most effect on Rubisco activity that induces more susceptibility to Rubisco specific protease. Moreover, Rubisco deactivation acts as an initiative signal for Rubisco degradation.

  1. Pirin-like proteins are regulated by oxidative stress and iron in bacteroides fragilis and involved in the modulation of central energy metabolism and metronidazole susceptibility

    Science.gov (United States)

    Bacteroides fragilis is the most frequent anaerobe isolated from human infections. Clinical isolates of B. fragilis are among the highest aerotolerant anaerobic bacteria. The oxidative stress response (OSR) in B. fragilis induces an array of genes enabling them to survive prolonged oxygen exposure i...

  2. Plasma membrane calcium pump regulation by metabolic stress

    Institute of Scientific and Technical Information of China (English)

    Jason; IE; Bruce

    2010-01-01

    The plasma membrane Ca2+-ATPase(PMCA)is an ATPdriven pump that is critical for the maintenance of low resting[Ca2+]i in all eukaryotic cells.Metabolic stress, either due to inhibition of mitochondrial or glycolytic metabolism,has the capacity to cause ATP depletion and thus inhibit PMCA activity.This has potentially fatal consequences,particularly for non-excitable cells in which the PMCA is the major Ca2+efflux pathway.This is because inhibition of the PMCA inevitably leads to cytosolic Ca2+ overload and the consequent cell death.However,the relationship between metabolic stress,ATP depletion and inhibition of the PMCA is not as simple as one would have originally predicted.There is increasing evidence that metabolic stress can lead to the inhibition of PMCA activity independent of ATP or prior to substantial ATP depletion.In particular,there is evidence that the PMCA has its own glycolytic ATP supply that can fuel the PMCA in the face of impaired mitochondrial function.Moreover, membrane phospholipids,mitochondrial membrane potential,caspase/calpain cleavage and oxidative stress have all been implicated in metabolic stress-induced inhibition of the PMCA.The major focus of this review is to challenge the conventional view of ATP-dependent regulation of the PMCA and bring together some of the alternative or additional mechanisms by which metabolic stress impairs PMCA activity resulting in cytosolic Ca2+ overload and cytotoxicity.

  3. Oxidative Stress Correlates (OSC) in Diabetes Mellitus Patients.

    Science.gov (United States)

    Gillani, Syed Wasif; Azeem, Eman; Siddiqui, Ammar; Mian, Rashid Iqbal; Poh, Vinci; Sulaiman, Syed Azhar Syed; Baig, Mirza Rafiullah

    2016-01-01

    Diabetes mellitus (DM) is a considerable systemic metabolic disorder to exhibit various metabolic and cardiovascular disorders, mainly hyperglycemia. Our study aims to evaluate oxidative stress markers in DM patients and to determine the clinical correlates affecting the investigational parameters. To evaluate oxidative stress, the following parameters were included: tri-glycerides(TG), total cholesterol, low density lipoprotein cholesterol(LDL), oxidized LDL cholesterol(Ox LDL), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and plasminogen activator inhibitor(PAI) which were measured at single observation point. Patient clinical and demographic data were taken from registered medication profiles from the Outpatient Department. The diabetic subjects have significantly high measured values of endocrine(pdiabetic subjects. Elevated Ox-LDL, SOD and GSH-Px are associated with the diabetic patients. However, oxidative stress threshold values also showed high oxidative activity markers among controls. Clinical variables showed predictive information on oxidative activity among diabetes patients.

  4. Cardiopulmonary Bypass and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mustafa Zakkar

    2015-01-01

    Full Text Available The development of the cardiopulmonary bypass (CPB revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress.

  5. Hemoglobin oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Croci, S.; Ortalli, I.; Pedrazzi, G. [University of Parma, Istituto di Scienze Fisiche, INFM-Udr Parma (Italy); Passeri, G. [University of Parma, Dipartimento di Medicina Interna e Scienze Biomediche (Italy); Piccolo, P. [University of Parma, Istituto di Clinica chirurgica Generale, Toracica e Vascolare (Italy)

    2000-07-15

    Venous blood obtained from healthy donors and from patients suffering from breast cancer have been treated with acetylphenylhydrazine (APH) for different time. Moessbauer spectra of the packed red cells have been recorded and compared. The largest difference occurs after 50 min of treatment with APH where the patient samples show a broad spectral pattern indicating an advanced hemoglobin oxidation. These results may have some relevance in early cancer diagnosis.

  6. Hydrogen Sulfide Regulates Salt Tolerance in Rice by Maintaining Na+/K+ Balance, Mineral Homeostasis and Oxidative Metabolism Under Excessive Salt Stress

    Science.gov (United States)

    Mostofa, Mohammad G.; Saegusa, Daisuke; Fujita, Masayuki; Tran, Lam-Son Phan

    2015-01-01

    Being a salt sensitive crop, rice growth and development are frequently affected by soil salinity. Hydrogen sulfide (H2S) has been recently explored as an important priming agent regulating diverse physiological processes of plant growth and development. Despite its enormous prospects in plant systems, the role of H2S in plant stress tolerance is still elusive. Here, a combined pharmacological, physiological and biochemical approach was executed aiming to examine the possible mechanism of H2S in enhancement of rice salt stress tolerance. We showed that pretreating rice plants with H2S donor sodium bisulfide (NaHS) clearly improved, but application of H2S scavenger hypotaurine with NaHS decreased growth and biomass-related parameters under salt stress. NaHS-pretreated salt-stressed plants exhibited increased chlorophyll, carotenoid and soluble protein contents, as well as suppressed accumulation of reactive oxygen species (ROS), contributing to oxidative damage protection. The protective mechanism of H2S against oxidative stress was correlated with the elevated levels of ascorbic acid, glutathione, redox states, and the enhanced activities of ROS- and methylglyoxal-detoxifying enzymes. Notably, the ability to decrease the uptake of Na+ and the Na+/K+ ratio, as well as to balance mineral contents indicated a role of H2S in ion homeostasis under salt stress. Altogether, our results highlight that modulation of the level of endogenous H2S genetically or exogenously could be employed to attain better growth and development of rice, and perhaps other crops, under salt stress. Furthermore, our study reveals the importance of the implication of gasotransmitters like H2S for the management of salt stress, thus assisting rice plants to adapt to adverse environmental changes. PMID:26734015

  7. Hydrogen sulfide regulates salt tolerance in rice by maintaining Na+/K+ balance, mineral homeostasis and oxidative metabolism under excessive salt stress

    Directory of Open Access Journals (Sweden)

    Mohammad Golam Mostofa

    2015-12-01

    Full Text Available Being a salt sensitive crop, rice growth and development are frequently affected by soil salinity. Hydrogen sulfide (H2S has been recently explored as an important priming agent regulating diverse physiological processes of plant growth and development. Despite its enormous prospects in plant systems, the role of H2S in plant stress tolerance is still elusive. Here, a combined pharmacological, physiological and biochemical approach was executed aiming to examine the possible mechanism of H2S in enhancement of salt stress tolerance in rice. We show that pretreating rice plants with H2S donor sodium bisulfide (NaHS clearly improved, but application of H2S scavenger hypotaurine with NaHS decreased growth and biomass-related parameters under salt stress. NaHS-pretreated salt-stressed plants exhibited increased chlorophyll, carotenoid and soluble protein contents, as well as suppressed accumulation of reactive oxygen species (ROS, contributing to oxidative damage protection. The protective mechanism of H2S against oxidative stress was correlated with the elevated levels of ascorbic acid, glutathione, redox states, and the enhanced activities of ROS- and methylglyoxal-detoxifying enzymes. Notably, decreased uptake of Na+, decreased Na+/K+ ratio and balanced mineral contents indicated a role of H2S in ion homeostasis under salt stress. Altogether, our results highlight that modulation of the level of endogenous H2S genetically or exogenously could be employed to attain better growth and development of rice, and perhaps other crops, under salt stress. Furthermore, our study reveals the importance of the implication of gasotransmitter like H2S for the management of salt stress, thus assisting rice plants to adapt to adverse environmental changes.

  8. Oxidative stress-induced metabolic changes in mouse C2C12 myotubes studied with high-resolution 13C, 1H, and 31P NMR spectroscopy.

    Science.gov (United States)

    Straadt, Ida K; Young, Jette F; Petersen, Bent O; Duus, Jens Ø; Gregersen, Niels; Bross, Peter; Oksbjerg, Niels; Theil, Peter K; Bertram, Hanne C

    2010-02-10

    In this study, stress in relation to slaughter was investigated in a model system by the use of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy for elucidating changes in the metabolites in C2C12 myotubes exposed to H(2)O(2)-induced stress. Oxidative stress resulted in lower levels of several metabolites, mainly amino acids; however, higher levels of alanine were apparent in the (13)C spectra after incubation with [(13)C(1)]glucose. In the (13)C spectra [(13)C(3)]lactate tended to increase after exposure to increasing concentrations of H(2)O(2); conversely, a tendency to lower levels of the unlabeled ((12)C) lactate were identified in the (1)H spectra after stress exposure. These data indicate an increase in de novo synthesis of alanine, concomitant with a release of lactate from the myotubes to the medium at oxidative stress conditions. The changes in the metabolite levels could possibly be useful as markers for meat quality traits.

  9. Oxidative stress response in Paracoccidioides brasiliensis.

    Science.gov (United States)

    Campos, Elida G; Jesuino, Rosália Santos Amorim; Dantas, Alessandra da Silva; Brígido, Marcelo de Macedo; Felipe, Maria Sueli S

    2005-06-30

    Survival of pathogenic fungi inside human hosts depends on evasion from the host immune system and adaptation to the host environment. Among different insults that Paracoccidioides brasiliensis has to handle are reactive oxygen and nitrogen species produced by the human host cells, and by its own metabolism. Knowing how the parasite deals with reactive species is important to understand how it establishes infection and survives within humans. The initiative to describe the P. brasiliensis transcriptome fostered new approaches to study oxidative stress response in this organism. By examining genes related to oxidative stress response, one can evaluate the parasite's ability to face this condition and infer about possible ways to overcome this ability. We report the results of a search of the P. brasiliensis assembled expressed sequence tag database for homologous sequences involved in oxidative stress response. We described several genes coding proteins involved in antioxidant defense, for example, catalase and superoxide dismutase isoenzymes, peroxiredoxin, cytochrome c peroxidase, glutathione synthesis enzymes, thioredoxin, and the transcription factors Yap1 and Skn7. The transcriptome analysis of P. brasiliensis reveals a pathogen that has many resources to combat reactive species. Besides characterizing the antioxidant defense system in P. brasiliensis, we also compared the ways in which different fungi respond to oxidative damage, and we identified the basic features of this response.

  10. Does an extract of carob (Ceratonia siliqua L.) have chemopreventive potential related to oxidative stress and drug metabolism in human colon cells?

    Science.gov (United States)

    Klenow, Stefanie; Jahns, Franziska; Pool-Zobel, Beatrice L; Glei, Michael

    2009-04-08

    Phenolic ingredients of an aqueous carob extract are well characterized and consist of mainly gallic acid (GA). In order to assess possible chemopreventive mechanisms of carob, which can be used as a cacao substitute, effects on expression of genes related to stress response and drug metabolism were studied using human colon cell lines of different transformation state (LT97 and HT29). Stress-related genes, namely catalase (CAT) and superoxide dismutase (SOD2), were induced by carob extract and GA in LT97 adenoma, but not in HT29 carcinoma cells. Although corresponding protein products and enzyme activities were not elevated, pretreatment with carob extract and GA for 24 h reduced DNA damage in cells challenged with hydrogen peroxide (H(2)O(2)). In conclusion, carob extract and its major phenolic ingredient GA modulate gene expression and protect colon adenoma cells from genotoxic impact of H(2)O(2). Upregulation of stress-response genes could not be related to functional consequences.

  11. Space flight and oxidative stress

    Science.gov (United States)

    Stein, T. P.

    2002-01-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  12. Exercise and diet induced weight loss improves measures of oxidative stress and insulin sensitivity in adults with characteristics of the metabolic syndrome

    OpenAIRE

    Rector, R. Scott; Warner, Shana O.; Ying LIU; Hinton, Pamela S.; Sun, Grace Y.; Cox, Richard H.; Stump, Craig S.; Laughlin, M. Harold; Dellsperger, Kevin C.; Thomas, Tom R.

    2007-01-01

    Obesity and insulin resistance (IR) increase the risk for coronary heart disease; however, much of this risk is not attributable to traditional risk factors. We sought to determine whether weight loss associated with supervised aerobic exercise beneficially alters biomarkers of oxidative stress and whether these alterations are associated with improvements in measures of insulin resistance. Twenty-five sedentary and overweight to obese [body mass index (BMI) = 33.0 ± 0.8 kg/m2] individuals, w...

  13. Hemoglobin oxidative stress in cancer.

    Science.gov (United States)

    Della Rovere, F; Granata, A; Broccio, M; Zirilli, A; Broccio, G

    1995-01-01

    The role played by free radicals in carcinogenesis and their relationships with antioxidant pool and cancer have already been shown. Free radicals induce increased membrane permeability through membrane lipid peroxidation, protein oxidation and histamine release from mast cells. Free radicals also cause oxyhemoglobin oxidative stress which increases methemoglobin and hemichromes. For this reason, we studied the in vitro formation of methemoglobin at 0' and 90', dosed following the HPLC method, after oxidative stress of blood by means of acetylphenylhydrazine in 40 subjects with cancer and 40 healthy donors. The results showed that methemoglobin formation was highly significant in tumors as compared to controls (P < 0.0001). The statistical analyses we carried out showed that metHb formation is not affected by age, sex, smoking habit, red blood cell number, Hb, Ht or tumor staging. This makes us believe that free radicals alter erythrocyte membrane permeability and predenaturate oxyhemoglobin so that erythrocyte membrane becomes more susceptible to new oxidative stress. This caused the abnormal response we found. Our results clearly underline the role played by free radicals in tumorous disease and provide a successful and easy method to detect early, even in a pre-clinical stage, the presence of tumorous alterations in the human body.

  14. Methane oxidation needs less stressed plants.

    Science.gov (United States)

    Zhou, Xiaoqi; Smaill, Simeon J; Clinton, Peter W

    2013-12-01

    Methane oxidation rates in soil are liable to be reduced by plant stress responses to climate change. Stressed plants exude ethylene into soil, which inhibits methane oxidation when present in the soil atmosphere. Here we discuss opportunities to use 1-aminocyclopropane-1-carboxylate deaminase to manage methane oxidation by regulating plant stress responses.

  15. Skin aging and oxidative stress

    OpenAIRE

    Sayeeda Ahsanuddin; Minh Lam; Baron, Elma D.

    2016-01-01

    Skin aging occurs through two main pathways, intrinsic and extrinsic. These pathways have significant interaction in contributing to the aging phenotype, which includes skin laxity, wrinkling, pigmentation irregularities, and the appearance of neoplastic skin lesions. Here, we review the critical role that oxidative stress plays in skin aging, including its effects on signaling pathways involved in skin matrix formation and degradation, proteasome activity, as well as DNA structure. Furthermo...

  16. Therapeutic effect of aqueous extracts of three dietary spices and their mixture on lipid metabolism and oxidative stress in a rat model of chronic alcohol consumption.

    Science.gov (United States)

    Otunola, Gloria Aderonke; Afolayan, Anthony Jide

    2016-07-01

    The protective effect of aqueous extracts of three dietary spices, garlic, (Allium sativum), ginger (Zingiber officinale) and pepper (Capsicum frutescens) singly and combined was investigated using a rat model of chronic alcohol intake. Rats were given 30% ethanol, with or without aqueous extracts of garlic, ginger, pepper or mixture of the three administered at 200mg/kg body weight by oral gavage for 28 days. Lipid profile, lipid peroxidation, oxidative and antioxidative profiles of serum, faecal, liver, kidney, heart and brain tissues of the rats were analyzed. Alcohol treatment significantly elevated liver enzymes, lipid peroxidation, depleted antioxidant system and induced histopathological changes in the liver. These alterations were markedly ameliorated by treatment with aqueous extracts of the three spices singly or mixed at 200mg/kg body weight. These results suggest that aqueous extracts of garlic, ginger, pepper or a blend of the three protects against alcohol- induced hypercholesterolemia, lipid peroxidation, oxidative stress and liver damage.

  17. [Selenium and oxidative stress in cancer patients].

    Science.gov (United States)

    Gorozhanskaia, É G; Sviridova, S P; Dobrovol'skaia, M M; Zybrikhina, G N; Kashnia, Sh R

    2013-01-01

    In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen--NOx, the level of superoxide dismutase--Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug "Selenaze" (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0 +/- 2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1 +/- 1.1 microM, with normal range 28.4 +/- 0.9 microM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.

  18. The point about oxidative stress in molluscs

    Directory of Open Access Journals (Sweden)

    H Manduzio

    2005-07-01

    Full Text Available In the normal metabolism of the aerobic cell, oxygen is used for various biochemical reactions.Because of its two lone electrons of parallel spins, the molecular oxygen is stable. However, oxygengenerates Reactive Oxygenated Species or ROS by successive transfer of electrons. The ROS have astrong reactivity and can potentially interact with all other cellular components (lipids, proteins, DNA.They are at the origin of oxidations in chain by creating radicals. The cell has antioxidant systemswhich limit the effects of the ROS. These systems are composed of enzymes such as glutathionereductase, glutathione peroxidase, etc., and molecules of nonenzymatic nature like the reducedglutathione or vitamins. The production and the destruction of the radicals of oxygen coexist in a weakbalance. If this balance is broken in favour of the ROS, an oxidative stress is generated. Xenobioticscould influence this balance by catalysing production of ROS.

  19. Magnesium Oxide Induced Metabolic Alkalosis in Cattle

    OpenAIRE

    Ogilvie, T H; Butler, D G; Gartley, C J; Dohoo, I. R.

    1983-01-01

    A study was designed to compare the metabolic alkalosis produced in cattle from the use of an antacid (magnesium oxide) and a saline cathartic (magnesium sulphate). Six, mature, normal cattle were treated orally with a magnesium oxide (MgO) product and one week later given a comparable cathartic dose of magnesium sulphate (MgSO4).

  20. 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.

  1. 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.

  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...

  3. Oxidative and nitrosative stress in ammonia neurotoxicity.

    Science.gov (United States)

    Skowrońska, Marta; Albrecht, Jan

    2013-04-01

    Increased ammonia accumulation in the brain due to liver dysfunction is a major contributor to the pathogenesis of hepatic encephalopathy (HE). Fatal outcome of rapidly progressing (acute) HE is mainly related to cytotoxic brain edema associated with astrocytic swelling. An increase of brain ammonia in experimental animals or treatment of cultured astrocytes with ammonia generates reactive oxygen and nitrogen species in the target tissues, leading to oxidative/nitrosative stress (ONS). In cultured astrocytes, ammonia-induced ONS is invariably associated with the increase of the astrocytic cell volume. Interrelated mechanisms underlying this response include increased nitric oxide (NO) synthesis which is partly coupled to the activation of NMDA receptors and increased generation of reactive oxygen species by NADPH oxidase. ONS and astrocytic swelling are further augmented by excessive synthesis of glutamine (Gln) which impairs mitochondrial function following its accumulation in there and degradation back to ammonia ("the Trojan horse" hypothesis). Ammonia also induces ONS in other cell types of the CNS: neurons, microglia and the brain capillary endothelial cells (BCEC). ONS in microglia contributes to the central inflammatory response, while its metabolic and pathophysiological consequences in the BCEC evolve to the vasogenic brain edema associated with HE. Ammonia-induced ONS results in the oxidation of mRNA and nitration/nitrosylation of proteins which impact intracellular metabolism and potentiate the neurotoxic effects. Simultaneously, ammonia facilitates the antioxidant response of the brain, by activating astrocytic transport and export of glutathione, in this way increasing the availability of precursors of neuronal glutathione synthesis.

  4. Stress and Polyamine Metabolism in Fungi

    Science.gov (United States)

    Valdés-Santiago, Laura; Ruiz-Herrera, José

    2013-12-01

    Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  5. STRESS AND POLYAMINE METABOLISM IN FUNGI

    Directory of Open Access Journals (Sweden)

    Laura eValdés-Santiago

    2014-01-01

    Full Text Available Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  6. Stress and polyamine metabolism in fungi.

    Science.gov (United States)

    Valdés-Santiago, Laura; Ruiz-Herrera, José

    2013-01-01

    Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  7. Stress, visceral obesity, and metabolic complications.

    Science.gov (United States)

    Kyrou, Ioannis; Chrousos, George P; Tsigos, Constantine

    2006-11-01

    Stress is a state of threatened homeostasis or disharmony caused by intrinsic or extrinsic adverse forces and is counteracted by an intricate repertoire of physiologic and behavioral responses that aim to reestablish the challenged body equilibrium. The adaptive stress response depends upon an elaborate neuroendocrine, cellular, and molecular infrastructure, the stress system. Crucial functions of the stress system response are mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the central and peripheral components of the autonomic nervous system (ANS). The integrity of the HPA axis and the ANS and their precise interactions with other CNS components are essential for a successful response to the various stressors. Chronic stress represents a prolonged threat to homeostasis by persistent or frequently repeated stressors and may lead to manifestations that characterize a wide range of diseases and syndromes. Such states progressively lead to a deleterious overload with complications caused by both the persistent stressor and the detrimental prolongation of the adaptive response. The metabolic syndrome can be described as a state of deranged metabolic homeostasis characterized by the combination of central obesity, insulin resistance, dyslipidemia, and hypertension. The incidence of both obesity and the metabolic syndrome in modern Western societies has taken epidemic proportions over the past decades and often correlates with indices of stress in the affected populations. Stress, primarily through hyperactivation of the HPA axis, appears to contribute to the accumulation of fat tissue, and vice versa, obesity itself seems to constitute a chronic stressful state and may cause HPA axis dysfunction. In addition, the description of obesity as a systemic low grade inflammatory condition that contributes to the derangement of the metabolic equilibrium implies that the proinflammatory cytokines which are secreted by the adipocytes hold a potentially important

  8. Oxidative stress and hepatitis C virus

    OpenAIRE

    2013-01-01

    The disproportionate imbalance between the systemic manifestation of reactive oxygen species and body’s ability to detoxify the reactive intermediates is referred to as oxidative stress. Several biological processes as well as infectious agents, physiological or environmental stress, and perturbed antioxidant response can promote oxidative stress. Oxidative stress usually happens when cells are exposed to more electrically charged reactive oxygen species (ROS) such as H2O2 or O2-. The cells’ ...

  9. Periodontal treatment decreases plasma oxidized LDL level and oxidative stress.

    Science.gov (United States)

    Tamaki, Naofumi; Tomofuji, Takaaki; Ekuni, Daisuke; Yamanaka, Reiko; Morita, Manabu

    2011-12-01

    Periodontitis induces excessive production of reactive oxygen species in periodontal lesions. This may impair circulating pro-oxidant/anti-oxidant balance and induce the oxidation of low-density lipoprotein (LDL) in blood. The purpose of this study was to monitor circulating oxidized LDL and oxidative stress in subjects with chronic periodontitis following non-surgical periodontal treatment. Plasma levels of oxidized LDL and oxidative stress in 22 otherwise healthy non-smokers with chronic periodontitis (mean age 44.0 years) were measured at baseline and at 1 and 2 months after non-surgical periodontal treatment. At baseline, chronic periodontitis patients had higher plasma levels of oxidized LDL and oxidative stress than healthy subjects (p surgical periodontal treatment were effective in decreasing oxLDL, which was positively associated with a reduction in circulating oxidative stress.

  10. 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

  11. Oxidative stress and maternal obesity: feto-placental unit interaction.

    Science.gov (United States)

    Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

    2014-06-01

    To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Maternal and cord blood LC-HRMS metabolomics reveal alterations in energy and polyamine metabolism, and oxidative stress in very-low birth weight infants.

    Science.gov (United States)

    Alexandre-Gouabau, Marie-Cécile; Courant, Frédérique; Moyon, Thomas; Küster, Alice; Le Gall, Gwénaëlle; Tea, Illa; Antignac, Jean-Philippe; Darmaun, Dominique

    2013-06-07

    To assess the global effect of preterm birth on fetal metabolism and maternal-fetal nutrient transfer, we used a mass spectrometric-based chemical phenotyping approach on cord blood obtained at the time of birth. We sampled umbilical venous, umbilical arterial, and maternal blood from mothers delivering very-low birth weight (VLBW, with a median gestational age and weight of 29 weeks, and 1210 g, respectively) premature or full-term (FT) neonates. In VLBW group, we observed a significant elevation in the levels and maternal-fetal gradients of butyryl-, isovaleryl-, hexanoyl- and octanoyl-carnitines, suggesting enhanced short- and medium chain fatty acid β-oxidation in human preterm feto-placental unit. The significant decrease in glutamine-glutamate in preterm arterial cord blood beside lower levels of amino acid precursors of Krebs cycle suggest increased glutamine utilization in the fast growing tissues of preterm fetus with a deregulation in placental glutamate-glutamine shuttling. Enhanced glutathione utilization is likely to account for the decrease in precursor amino acids (serine, betaine, glutamate and methionine) in arterial cord blood. An increase in both the circulating levels and maternal-fetal gradients of several polyamines in their acetylated form (diacetylspermine and acetylputrescine) suggests an enhanced polyamine metabolic cycling in extreme prematurity. Our metabolomics study allowed the identification of alterations in fetal energy, antioxidant defense, and polyamines and purines flux as a signature of premature birth.

  13. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Science.gov (United States)

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. PMID:27293514

  14. Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic β cells.

    Science.gov (United States)

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

    Pancreatic β cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic β cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redox state thereby disrupting correct disulfide bond formation and proper protein folding. mTOR signaling regulates many metabolic processes including protein synthesis, cell growth, survival and proliferation. Oxidative stress inhibits mTORC1, which is considered an important suppressor of mitochondrial oxidative stress in β cells, and ultimately, controls cell survival. The interplay between ER stress and mTORC1 is complicated, since the unfolded protein response (UPR) activation can occur upstream or downstream of mTORC1. Persistent activation of mTORC1 initiates protein synthesis and UPR activation, while in the later phase induces ER stress. Chronic activation of ER stress inhibits Akt/mTORC1 pathway, while under particular settings, acute activation of UPR activates Akt-mTOR signaling. Thus, modulating mitochondrial oxidative stress and ER stress via mTOR signaling may be an approach that will effectively suppress obesity- or glucolipotoxicity-induced metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). In this review, we focus on the regulations between mTOR signaling and mitochondrial oxidative or ER stress in pancreatic β cells.

  15. Management of oxidative stress by microalgae.

    Science.gov (United States)

    Cirulis, Judith T; Scott, J Ashley; Ross, Gregory M

    2013-01-01

    The aim of this review is to provide an overview of the current research on oxidative stress in eukaryotic microalgae and the antioxidant compounds microalgae utilize to control oxidative stress. With the potential to exploit microalgae for the large-scale production of antioxidants, interest in how microalgae manage oxidative stress is growing. Microalgae can experience increased levels of oxidative stress and toxicity as a result of environmental conditions, metals, and chemicals. The defence mechanisms for microalgae include antioxidant enzymes such as superoxide dismutase, catalase, peroxidases, and glutathione reductase, as well as non-enzymatic antioxidant molecules such as phytochelatins, pigments, polysaccharides, and polyphenols. Discussed herein are the 3 areas the literature has focused on, including how conditions stress microalgae and how microalgae respond to oxidative stress by managing reactive oxygen species. The third area is how beneficial microalgae antioxidants are when administered to cancerous mammalian cells or to rodents experiencing oxidative stress.

  16. Oxidatively generated DNA/RNA damage in psychological stress states

    DEFF Research Database (Denmark)

    Jørgensen, Anders

    2013-01-01

    -oxodG and 8-oxoGuo, respectively). The main hypothesis was that psychological stress states are associated with increased DNA/RNA damage from oxidation. In a study of 40 schizophrenia patients and 40 healthy controls matched for age and gender, we found that 8-oxodG/8-oxoGuo excretion was increased...... correlations between 8-oxodG/8-ocoGuo excretion and 9AM plasma cortisol, but no associations to perceived stress. In an animal study of experimentally induced chronic stress performed in metabolism cages, we found no increase in urinary 8-oxodG/8-oxoGuo or cerebral (hippocampal and frontal cortex) levels...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased...

  17. Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gábor Csányi

    2014-04-01

    Full Text Available In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine.

  18. Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells.

    Science.gov (United States)

    Shrotriya, Sangeeta; Deep, Gagan; Lopert, Pamela; Patel, Manisha; Agarwal, Rajesh; Agarwal, Chapla

    2015-12-01

    Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells. © 2014 Wiley Periodicals, Inc.

  19. Carbonylation and Loss-of-Function Analyses of SBPase Reveal Its Metabolic Interface Role in Oxidative Stress, Carbon Assimilation, and Multiple Aspects of Growth and Development in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Xun-Liang Liu; Hai-Dong Yu; Yuan Guan; Ji-Kai Li; Fang-Qing Guo

    2012-01-01

    Sedoheptulose-1,7-bisphosphatase (SBPase) is a Calvin cycle enzyme and functions in photosynthetic carbon fixation.We found that SBPase was rapidly carbonylated in response to methyl viologen (MV) treatments in detached leaves of Arabidopsis plants.In vitro activity analysis of the purified recombinant SBPase showed that SBPase was carbonylated by hydroxyl radicals,which led to enzyme inactivation in an H2O2 dose-dependent manner.To determine the conformity with carbonylation-caused loss in enzymatic activity in response to stresses,we isolated a loss-of-function mutant sbp,which is deficient in SBPase-dependent carbon assimilation and starch biosynthesis,sbp mutant exhibited a severe growth retardation phenotype,especially for the developmental defects in leaves and flowers where SBPASE is highly expressed.The mutation of SBPASE caused growth retardation mainly through inhibition of cell division and expansion,which can be partially rescued by exogenous application of sucrose.Our findings demonstrate that ROS-induced oxidative damage to SBPase affects growth,development,and chloroplast biogenesis in Arabidopsis through inhibiting carbon assimilation efficiency.The data presented here provide a case study that such inactivation of SBPase caused by carbonyl modification may be a kind of adaptation for plants to restrict the operation of the reductive pentose phosphate pathway under stress conditions.

  20. Etiologies of sperm oxidative stress

    Directory of Open Access Journals (Sweden)

    Parvin Sabeti

    2016-04-01

    Full Text Available Sperm is particularly susceptible to reactive oxygen species (ROS during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions

  1. Crosstalk between oxidative and nitrosative stress and arterial stiffness.

    Science.gov (United States)

    Mozos, Ioana; Luca, Constantin Tudor

    2017-02-01

    Arterial stiffness, the expression of reduced arterial elasticity, is an effective predictor of cardiovascular disorders. Oxidative stress is an imbalance between exposure to toxic reactive oxygen species (ROS) and antioxidant systems. The increase in reactive nitrogen species (RNS) is termed nitrosative stress. We review the main mechanisms and products linking arterial stiffness with oxidative and nitrosative stress in several disorders, focusing on recent experimental and clinical data, and the mechanisms explaining benefits of antioxidant therapy. Oxidative and nitrosative stress play important roles in arterial stiffness elevation in several disorders, including diabetes mellitus, hypertension, metabolic syndrome, obesity, peripheral arterial disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, thalassemia, Kawasaki disease and malignant disorders. Oxidative and nitrosative stress are responsible for endothelial dysfunction due to uncoupling of the nitric oxide synthase, oxidative damage to lipids, proteins and DNA in vascular endothelial cells, associated with inflammation, arteriosclerosis and atherosclerosis. Regular physical exercise, caloric restriction, red wine, statins, sartans, metformin, oestradiol, curcumin and combinations of antioxidant vitamins are therapeutic strategies that may decrease arterial stiffness and oxidative stress thus reducing the risk of cardiovascular events. ROS and RNS represent potential therapeutic targets for preventing progression of arterial stiffness.

  2. Oxidative stress in neonatology: a review.

    Science.gov (United States)

    Mutinati, M; Pantaleo, M; Roncetti, M; Piccinno, M; Rizzo, A; Sciorsci, R L

    2014-02-01

    Free radicals are highly reactive oxidizing agents containing one or more unpaired electrons. Both in human and veterinary neonathology, it is generally accepted that oxidative stress functions as an important catalysator of neonatal disease. Soon after birth, many sudden physiological and environmental conditions make the newborn vulnerable for the negative effects of oxidative stress, which potentially can impair neonatal vitality. As a clinician, it is important to have in depth knowledge about factors affecting maternal/neonatal oxidative status and the cascades of events that enrol when the neonate is subjected to oxidative stress. This report aims at providing clinicians with an up-to-date review about oxidative stress in neonates across animal species. It will be emphasized which handlings and treatments that are applied during neonatal care or resuscitation can actually impose oxidative stress upon the neonate. Views and opinions about maternal and/or neonatal antioxydative therapy will be shared.

  3. Biomarkers of inflammation, metabolism, and oxidative stress in blood, liver, and milk reveal a better immunometabolic status in peripartal cows supplemented with Smartamine M or MetaSmart.

    Science.gov (United States)

    Osorio, J S; Trevisi, E; Ji, P; Drackley, J K; Luchini, D; Bertoni, G; Loor, J J

    2014-12-01

    The peripartal dairy cow experiences a state of reduced liver function coupled with increased inflammation and oxidative stress. This study evaluated the effect of supplementing basal diets with rumen-protected Met in the form of MetaSmart (MS) or Smartamine M (SM) (both from Adisseo Inc., Antony, France) during the peripartal period on blood and hepatic biomarkers of liver function, inflammation, and oxidative stress. Thirty-seven multiparous Holstein cows were fed the same basal diet from -50 to -21 d relative to expected calving [1.24 Mcal/kg of dry matter (DM); no Met supplementation]. From -21 d to calving, the cows received diets (1.54 Mcal/kg of DM) with no added Met (control, CON; n=13), CON plus MS (n=11), or CON plus SM (n=13). From calving through 30 d in milk (DIM), the cows received the same postpartal diet (1.75 Mcal/kg of DM; CON), or CON plus MS or CON plus SM. Liver and blood samples were harvested at various time points from -21 to 21 d relative to calving. Preplanned contrasts of CON versus SM + MS during prepartum (-21 and -10 d before calving) and postpartum (7, 14, and 21 d after calving) responses were evaluated. Cows fed MS or SM compared with CON had lower overall concentrations of plasma ceruloplasmin and serum amyloid A (SAA). Compared with CON, Met-supplemented cows had greater overall plasma oxygen radical absorbance capacity. Liver concentrations of glutathione and carnitine also were greater overall with Met supplementation. Milk choline and liver phosphatidylcholine were lower overall in cows fed Met compared with controls. Liver tissue choline concentrations did not differ. Data indicate that supplemental Met enhanced de novo glutathione and carnitine synthesis in liver and, thus, increased antioxidant and β-oxidation capacity. The greater decrease of IL-6 after calving coupled with lower ceruloplasmin and SAA in Met-supplemented cows indicated a reduction in proinflammatory signaling within liver. The lower hepatic

  4. Radical-free biology of oxidative stress

    OpenAIRE

    2008-01-01

    Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the “redox hypothesis,” is that oxidative stress occurs as a consequence of disruption of thi...

  5. Oxidative Stress in Patients With Nongenital Warts

    OpenAIRE

    Sezai Sasmaz; Ozer Arican; Ergul Belge Kurutas

    2005-01-01

    Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male) and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT), glucose-6-phosphat...

  6. Impact of Oxidative Stress in Fetal Programming

    Directory of Open Access Journals (Sweden)

    Loren P. Thompson

    2012-01-01

    Full Text Available Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

  7. Oxidative stress: Biomarkers and novel therapeutic pathways.

    Science.gov (United States)

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2010-03-01

    Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

  8. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    Science.gov (United States)

    Papatheodorou, Louisa; Weiss, Norbert

    2007-11-01

    Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

  9. Epigenetics and Oxidative Stress in Aging

    Directory of Open Access Journals (Sweden)

    Amy Guillaumet-Adkins

    2017-01-01

    Full Text Available Aging is a multifactorial process characterized by the progressive loss of physiological functions, leading to an increased vulnerability to age-associated diseases and finally to death. Several theories have been proposed to explain the nature of aging. One of the most known identifies the free radicals produced by the mitochondrial metabolism as the cause of cellular and DNA damage. However, there are also several evidences supporting that epigenetic modifications, such as DNA methylation, noncoding RNAs, and histone modifications, play a critical role in the molecular mechanism of aging. In this review, we explore the significance of these findings and argue how the interlinked effects of oxidative stress and epigenetics can explain the cause of age-related declines.

  10. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats.

    Science.gov (United States)

    Sani, Nur Fathiah Abdul; Belani, Levin Kesu; Sin, Chong Pui; Rahman, Siti Nor Amilah Abdul; Das, Srijit; Chi, Thent Zar; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P diabetic rats compared to diabetic control rats.

  11. Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Nur Fathiah Abdul Sani

    2014-01-01

    Full Text Available Diabetic complications occur as a result of increased reactive oxygen species (ROS due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight. Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight, ginger (60 mg/kg body weight, and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, reduced glutathione (GSH: oxidized glutathione (GSSG, and malondialdehyde (MDA. The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P<0.05 SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P<0.05 in STZ-induced diabetic rats compared to diabetic control rats.

  12. p-Hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock.

    Directory of Open Access Journals (Sweden)

    Antonella Cotoia

    Full Text Available The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001 than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent.

  13. p-Hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock.

    Science.gov (United States)

    Cotoia, Antonella; Scrima, Rosella; Gefter, Julia V; Piccoli, Claudia; Cinnella, Gilda; Dambrosio, Michele; Fink, Mitchell P; Capitanio, Nazzareno

    2014-01-01

    The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent.

  14. Markers of Oxidative Stress and Neuroprogression in Depression Disorder.

    Science.gov (United States)

    Vaváková, Magdaléna; Ďuračková, Zdeňka; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.

  15. Markers of Oxidative Stress and Neuroprogression in Depression Disorder

    Directory of Open Access Journals (Sweden)

    Magdaléna Vaváková

    2015-01-01

    Full Text Available Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.

  16. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

  17. Correlation between blood glucose fluctuations and activation of oxidative stress in type 1 diabetic children during the acute metabolic disturbance period

    Institute of Scientific and Technical Information of China (English)

    WU Di; GONG Chun-xiu; MENG Xi; YANG Qiu-lan

    2013-01-01

    Background Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS).Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM).However,there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations.Methods We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011.They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS).Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2α (8-isoPGF2α).Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment.Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE),largest amplitude of glycemic excursions (LAGE),standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE).The correlations between glucose parameters and the index of oxidative stress were analyzed.Results Urine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs.(675.23±354.59) ng,P=0.019).There was a correlation between urine 8-isoPGF2α level and MAGE (r=0.321,P=-0.039),a significant correlation between low-density lipoprotein and urine 8-isoPGF2α level (r=0.419,P=0.03).There was no significant correlation between urine 8-isoPGF2α level and blood pressure,glycosylated hemoglobin (HbA1c),fasting C-peptide or other lipid indices.Conclusion A correlation between urine 8-isoPGF2α levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM.

  18. Less Stress : Oxidative stress and glutathione kinetics in preterm infants

    NARCIS (Netherlands)

    D. Rook (Denise)

    2013-01-01

    textabstractDue to immature antioxidant defenses, preterm infants are at susceptible to oxidative stress, which is associated with bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. The general aim of this thesis was to study oxidative stress in preterm infants

  19. Less Stress : Oxidative stress and glutathione kinetics in preterm infants

    NARCIS (Netherlands)

    D. Rook (Denise)

    2013-01-01

    textabstractDue to immature antioxidant defenses, preterm infants are at susceptible to oxidative stress, which is associated with bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. The general aim of this thesis was to study oxidative stress in preterm infants

  20. Molecular and biochemical responses of Volvox carteri to oxidative stress

    Science.gov (United States)

    Lingappa, U.; Rankin-Gee, E. K.; Lera, M.; Bebour, B.; Marcu, O.

    2014-03-01

    Understanding the intracellular response to environmental stresses is a key aspect to understanding the limits of habitability for life as we know it. A wide range of relevant stressors, from heat shock to radiation, result in the intracellular production of reactive oxygen species (ROS). ROS are used physiologically as signaling molecules to cause changes in gene expression and metabolism. However, ROS, including superoxide (O2-) and peroxides, are also highly reactive molecules that cause oxidative damage to proteins, lipids and DNA. Here we studied stress response in the multicellular, eukaryotic green alga Volvox carteri, after exposure to heat shock conditions. We show that the ROS response to heat stress is paralleled by changes in photosynthetic metabolism, antioxidant enzyme activity and gene expression, and fluctuations in the elemental composition of cells. Metabolism, as measured by pulse amplitude modulated (PAM) fluorometry over two hours of heat stress, showed a linear decrease in the photosynthetic efficiency of Volvox. ROS quantification uncovered an increase in ROS in the culture medium, paralleled by a decrease in ROS within the Volvox colonies, suggesting an export mechanism is utilized to mitigate stress. Enzyme kinetics indicated an increase in superoxide dismutase (SOD) activity over the heat stress timecourse. Using X-ray fluorescence (XRF) at the Stanford Synchrotron Radiation Lightsource, we show that these changes coincide with cell-specific import/export and intracellular redistribution of transition elements and halides, suggesting that the cellular metallome is also engaged in mediating oxidative stress in Volvox.

  1. Oxidative Stress and Epilepsy: Literature Review

    Science.gov (United States)

    Aguiar, Carlos Clayton Torres; Almeida, Anália Barbosa; Araújo, Paulo Victor Pontes; de Abreu, Rita Neuma Dantas Cavalcante; Chaves, Edna Maria Camelo; do Vale, Otoni Cardoso; Macêdo, Danielle Silveira; Woods, David John; Fonteles, Marta Maria de França; Vasconcelos, Silvania Maria Mendes

    2012-01-01

    Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy. Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed. Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age. PMID:22848783

  2. Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria.

    Science.gov (United States)

    Santos, N A G; Bezerra, C S Catão; Martins, N M; Curti, C; Bianchi, M L P; Santos, A C

    2008-01-01

    Nephrotoxicity is the major dose-limiting factor of cisplatin chemotherapy. Reactive oxygen species generated in mitochondria are thought to be the main cause of cellular damage in such injury. The present study examined, in vivo, the protective potential of the hydroxyl radical scavenger dimethylthiourea (DMTU) against cisplatin-induced effects on renal mitochondrial bioenergetics, redox state and oxidative stress. Adult male Wistar rats (200 to 220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by 125 mg/Kg, i.p., twice a day until they were killed). The third group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The fourth group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until they were killed. Animals were killed 72 h after the treatment. Besides not presenting any direct effect on mitochondria, DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, suppressing the occurrence of acute renal failure. All the following cisplatin-induced effects were prevented by DMTU: (1) increased plasmatic levels of creatinine and blood urea nitrogen (BUN); (2) decreased ATP content, calcium uptake and electrochemical potential; (3) oxidation of lipids, including cardiolipin; and oxidation of proteins, including sulfhydryl, and aconitase enzyme, as well as accumulation of carbonyl proteins; (4) depletion of the antioxidant defense (NADPH and GSH) and (5) increased activity of the apoptosis executioner caspase-3. Our findings show the important role played by mitochondria and hydroxyl radicals in cisplatin-induced nephrotoxicity, as well as the effectiveness of DMTU in

  3. Oxidative stress, circulating antioxidants, and dietary preferences in songbirds.

    Science.gov (United States)

    Alan, Rebecca R; McWilliams, Scott R

    2013-03-01

    Oxidative stress is an unavoidable consequence of metabolism and increases during intensive exercise. This is especially problematic for migratory birds that metabolize fat to fuel long-distance flight. Birds can mitigate damage by increasing endogenous antioxidants (e.g. uric acid) or by consuming dietary antioxidants (e.g. tocopherol). During flight, birds may increase protein catabolism of lean tissue which may increase circulating uric acid and many birds also consume an antioxidant-rich frugivorous diet during autumn migration. We evaluated three related hypotheses in a migratory passerine: (1) protein consumption is positively related to circulating antioxidants, (2) a dietary oxidative stressor [i.e. polyunsaturated fatty acid (PUFA)] influences antioxidant capacity and oxidative damage, and (3) oxidative stress influences dietary antioxidant preferences. White-throated Sparrows (Zonotrichia albicollis) consuming a high protein diet increased circulating uric acid; however, uric acid, antioxidant capacity, and oxidative stress did not differ between birds consuming a high PUFA versus a low PUFA diet, despite increased oxidative damage in high PUFA birds. Birds did not prefer antioxidant-rich diets even when fed high PUFA, low protein. We conclude that White-throated Sparrows successfully mitigated oxidative damage associated with a high PUFA diet and mounted an endogenous antioxidant response independent of uric acid, other circulating antioxidants, and dietary antioxidants.

  4. [STUDY OF GLUTATHIONE AND ENZYMES OF ITS METABOLISM UNDER THE INFLUENCE OF ENRICHED DAIRY PRODUCTS FOR PROPHYLACTIC USE IN CONDITIONS OF OXIDATIVE STRESS CAUSED BY EXCESSIVE EXERCISE].

    Science.gov (United States)

    Boyarskaya, L A; Turchaninov, D V; Efremenko, E S; Bogdashin, I V; Vilms, E A; Yunatskaya, T A

    2015-01-01

    There was performed the study of the activity of the antioxidant system of glutathione under regular taking of enriched with micronutrients dairy products "Bifidin " and "Prolacta" in conditions ofsimulation of xcessive exercise loads. Target of research: white outbred male rats weighing 180-200 g (n = 68). Research methods and equipment: information retrieval, biochemical, and statistical. In the subacute experiment there was established that in conditions of excessive exercise loads (CEEL) the body of the rat meets with significant oxidative stress, causing the suppression of the activity of glutathione system: the number of reduced glutathione and the activity of selenium-dependent glutathione-peroxidase decline. Regular taking of dairy products "Bifidin" and "Prolacta" in conditions of CEEL (active training process) allows effectively to neutralize lipid peroxidation processes and normalize indices of the system of glutathione. There is established an increase in the activity ofglutathione-S-transferase in the homogenates of liver tissue in the simulation CEEL in combination with the use ofproduct "Bifidin".

  5. Effect on morphology, oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination.

    Science.gov (United States)

    Lv, Yingjun; Liu, Zhijun; Tian, Yujie; Chen, Hongbo

    2013-03-01

    Cases of pet poisoning and infant renal calculus have attracted much attention to the toxicity of melamine and its derivatives, such as cyanuric acid. Although individually melamine and cyanuric acid have low toxicity, their simultaneous presence can cause severe damage. Little is known about their adverse effects on the reproductive system. In this study, mice were orally administrated 1, 5 or 25 mg/kg/d of both melamine and cyanuric acid for 13 weeks. Lethargy, rough hair, and reduction of food and water intake and of body and testis weight were found after exposure to the combination, and pathological changes were found in the morphology of the testes, such as disruption of the seminiferous tubule structure, decrease of the spermatogenic cell series and coagulation necrosis. Total antioxidant capacity and superoxide dismutase activities and glutathione concentration was lower and malondialdehyde concentration was higher than in control mice. The activities of malate dehydrogenase, lactate dehydrogenase and Na(+)/K(+)-ATPase were also lower in combination treated mice than in control mice. These results indicate that the combined exposure to both melamine and cyanuric acid damaged testes in mice by either a direct or indirect effect, which may be related to renal failure and secondary anorexia. Oxidative stress and lower energy production levels both contributed to the testicular damage.

  6. Oxidants and antioxidants relevance in rats' pulmonary induced oxidative stress

    Science.gov (United States)

    Zamfir, C; Eloaie Zugun, F; Cojocaru, E; Tocan, L

    2011-01-01

    Introduction: Even if the reactive oxygen species were discovered, described and detailed a long time ago, there is still little data about the mechanisms of oxidative stress, their tissular effects and about an efficient antioxidant strategy, involving animal experimental models. It has been shown that the lung is one of the most exposed organs to the oxidative stress. The particular effects of different types of oxidative stress on lungs were investigated in this experimental study, in order to quantify the intensity and the extent of the pulmonary damage, featuring the antioxidant enzymatic protective role. Methods: The study of lung injury was performed on four distinct groups of Wistar rats: a control group versus a group exposed to continuous light deprivation versus a group exposed to nitrofurantoin versus a group exposed to continuous light deprivation, to nitrofurantoin and vitamin C. Pulmonary samples were taken and treated for microscopic analysis. A qualitative immunohistochemical estimation of pulmonary superoxide dismutase 1(SOD 1) was performed. Blood tests were used in order to reveal the presence and intensity of oxidative stress. Results: Continuous light deprivation and the chronic administration of nitrofurantoin acted as oxidants with a certain involvement in lung damage– vascular and alveolar wall disturbances. Adding an antioxidant, such as vitamin C, considerably improved lung reactivity to oxidative stress. Conclusion: The chronic exposure to oxidants in the induced oxidative stress sustains the development of specific lung alterations. SOD 1 positive reaction underlines the complex enzymatic defense in oxidative stress. PMID:22567046

  7. Oxidative stress in primary glomerular diseases

    DEFF Research Database (Denmark)

    Markan, Suchita; Kohli, Harbir Singh; Sud, Kamal;

    2008-01-01

    To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure.......To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure....

  8. Association of mercury and selenium with altered glutathione metabolism and oxidative stress in diving ducks from the San Francisco Bay region

    Science.gov (United States)

    Hoffman, D.J.; Ohlendorf, H.M.; Marn, C.M.; Pendleton, G.W.

    1998-01-01

    Adult male greater scaup (Aythya marila) (GS), surf scoters (Melanitta perspicillata)(SS), and ruddy ducks (Oxyura jamaicensis) (RD) were collected from Suisun Bay and coastal Tomales Bay in the greater San Francisco Bay area to assess exposure to inorganic contaminants. Hepatic selenium (Se) concentrations were highest in GS (geometric mean = 67 ppm, dw) and SS (119 ppm) in Suisun Bay, whereas hepatic mercury (Hg) was highest (19 ppm) in GS and SS from Tomales Bay. Hepatic Se and Hg were lower in RD and did not differ between locations. Hepatic supernatants were assayed for enzymes related to glutathione metabolism and antioxidant activity including: glucose-6-phosphate dehydrogenase (G-6-PDH), glutathione peroxidase (GSH-peroxidase), glutathione reductase (GSSG-reductase), and glutathione-S-transferase (GSH-transferase). GSH-peroxidase activity was higher in SS and RD, and G-6-PDH higher in GS and SS from Suisun Bay than Tomales Bay. GSSG-reductase was higher in SS from Suisun Bay. The ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) was greater in all species from Tomales Bay. The following significant relationships were found in one or more species with increasing hepatic Hg concentration: lower body, liver and heart weights; decreased hepatic GSH concentration, G-6-PDH and GSH-peroxidase activities; increased ratio of GSSG to GSH, and increased GSSG-reductase activity. With increasing hepatic Se concentration, GSH-peroxidase increased but GSH decreased. It is concluded that measurement of associated enzymes in conjunction with thiol status may be a useful bioindicator to discriminate between Hg and Se effects. Concentrations of mercury and selenium and variable affected have been associated with adverse effects on reproduction and neurological function in experimental studies with mallards.

  9. Oxidative stress response in sugarcane

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Soares Netto

    2001-12-01

    Full Text Available Oxidative stress response in plants is still poorly understood in comparison with the correspondent phenomenon in bacteria, yeast and mammals. For instance, nitric oxide is assumed to play various roles in plants although no nitric oxide synthase gene has yet been isolated. This research reports the results of a search of the sugarcane expressed sequence tag (SUCEST database for homologous sequences involved in the oxidative stress response. I have not found any gene similar to nitric oxide synthase in the SUCEST database although an alternative pathway for nitric oxide synthesis was proposed. I have also found several genes involved in antioxidant defense, e.g. metal chelators, low molecular weight compounds, antioxidant enzymes and repair systems. Ascorbate (vitamin C is a key antioxidant in plants because it reaches high concentrations in cells and is a substrate for ascorbate peroxidase, an enzyme that I found in different isoforms in the SUCEST database. I also found many enzymes involved in the biosynthesis of low molecular weight antioxidants, which may be potential targets for genetic manipulation. The engineering of plants for increased vitamin C and E production may lead to improvements in the nutritional value and stress tolerance of sugarcane. The components of the antioxidant defense system interact and their synthesis is probably closely regulated. Transcription factors involved in regulation of the oxidative stress response in bacteria, yeast and mammals differ considerably among themselves and when I used them to search the SUCEST database only genes with weak similarities were found, suggesting that these transcription regulators are not very conserved. The involvement of reactive oxygen species and antioxidants in plant defense against pathogens is also discussed.A resposta ao estresse oxidativo não é bem conhecida em plantas como em bactérias, leveduras e humanos. Por exemplo, assume-se que óxido nítrico tem várias fun

  10. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism

    National Research Council Canada - National Science Library

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-01-01

    .... We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells...

  11. The Effect of Oxidative Stress and Antioxidants on Men Fertility

    Directory of Open Access Journals (Sweden)

    Abolfazl Akbari

    2013-07-01

    Full Text Available Background: Various factors affects men fertility and oxidative stress as an important factor which affects fertility has recently got great concern. Oxidative stress refers to conditions of imbalance between productions of reactive oxygen species (ROS and antioxidant defense mechanism. Reactive species of oxygen, free radicals and peroxide are produced in the cell when metabolism of oxygen is incomplete in the mitochondrial respiratory chain.Materials and Methods: In this review we will consider effect of oxidative stress on male fertility and the principal antioxidant defences.Results: Factors such as hypoxia, cytokines, growth factors, chemotherapy, radio frequency waves and UV radiation can increase ROS production. Oxidative stress as one of the strongest physiological factors can lead to damage of sperm and reduction of seminal plasma quality and thereby cause infertility in men. Enzymatic and non-enzymatic defences inhibit oxidant attack. The enzymatic defense include: superoxide dismutases, glutathione peroxidases, and catalase. The non-enzymatic defences include ascorbate (vitamin C and a-tocopherol (vitamin E, beta carotene, and albumin, which neutralize free radicals. Conclusion: Oxidative stress affects male fertility through induction of lipid peroxidation, inactivation of proteins, impair of sperm motility and DNA damage.

  12. Metal-related oxidative stress in birds

    Energy Technology Data Exchange (ETDEWEB)

    Koivula, Miia J., E-mail: miikoi@utu.f [Department of Biology, Section of Ecology, University of Turku, FI-20014 Turku (Finland); Eeva, Tapio, E-mail: teeva@utu.f [Department of Biology, Section of Ecology, University of Turku, FI-20014 Turku (Finland)

    2010-07-15

    Metals can cause oxidative stress by increasing the formation of reactive oxygen species (ROS), which render antioxidants incapable of defence against growing amounts of free radicals. Metal toxicity is related to their oxidative state and reactivity with other compounds. Our aim is to review the mechanisms on how metals cause oxidative stress and what is known about metal-induced oxidative stress in wildlife. Taking birds as model organisms, we summarize the mechanisms responsible for antioxidant depletion and give a view of how to detect metal-induced oxidative stress in birds by using different biomarkers. The mechanisms producing the harmful effects of oxidative stress are complex with different biomolecular mechanisms associated with ecotoxicological and ecological aspects. The majority of the studies concerning metals and ROS related to oxidative stress have focused on the biomolecular level, but little is known about the effects at the cellular level or at the level of individuals or populations. - Free-living birds can be used as effective indicators of metal-induced oxidative stress.

  13. PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

    Science.gov (United States)

    Pacak, Karel

    2012-01-01

    The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto

  14. Is the Oxidative Stress Really a Disease?

    Directory of Open Access Journals (Sweden)

    Fogarasi Erzsébet

    2016-03-01

    Full Text Available Oxidative stress is an imbalance between free radicals or other reactive species and the antioxidant activity of the organism. Oxidative stress can induce several illnesses such as cardiovascular disease, neurodegenerative disorders, diabetes, cancer, Alzheimer and Parkinson. The biomarkers of oxidative stress are used to test oxidative injury of biomolecules. The indicators of lipid peroxidation (malondialdehyde, 4-hydroxy- 2-nonenal, 2-propenal, isoprostanes, of protein oxidation (carbonylated proteins, tyrosine derivatives, of oxidative damage of DNA, and other biomarkers (glutathione level, metallothioneins, myeloperoxidase activity are the most used oxidative stress markers. Diseases caused by oxidative stress can be prevented with antioxidants. In human body are several enzymes with antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and spin traps. Antioxidants are synthetized in the organism (glutathione or arrive in the body by nutrition (ascorbic acid, vitamin E, carotenoids, flavonoids, resveratrol, xanthones. Different therapeutic strategies to reduce oxidative stress with the use of synthetic molecules such as nitrone-based antioxidants (phenyl-α-tert-butyl-nitrone (PBN, 2,4-disulphophenyl- N-tert-butylnitrone (NXY-059, stilbazulenyl nitrone (STAZN, which scavenge a wide variety of free radical species, increase endogenous antioxidant levels and inhibits free radical generation are also tested in animal models.

  15. Oxidative stress in the neonate.

    Science.gov (United States)

    Robles, R; Palomino, N; Robles, A

    2001-11-01

    The aim of this study is to determine the oxidative state of term and preterm neonates at the moment of birth and during the first days of life, and the influence of exposure to oxygen on the premature neonates.A total of 20 neonates were selected. Group A: 10 healthy full-term neonates, and Group B: 10 preterm neonates with no other pathology associated, requiring oxygen therapy. Venous samples were taken in cord at 3 and 72 h in Group A, and in cord at 3, 24 and 72 h and 7 days in Group B.Hydroperoxides, Q10 coenzyme (Co Q10) and alpha-tocopherol were measured within the erythrocyte membrane. Levels of hydroperoxides present in erythrocyte membrane were higher than normal both in Group A and in Group B at birth. This increase was greater in the group of premature neonates. Levels of alpha-tocopherol at birth increase significantly at 72 h in term neonates. Among the premature newborns, alpha-tocopherol levels are two to three times lower at birth and do not rise to higher levels as in the term neonate group. Fall in levels of Co Q10 in erythrocyte membranes is observed, and perhaps is due to the role of Co Q10 in maintaining the pool of reduced tocopherol. At birth, the neonate presents an increase of markers of oxidative stress and a decrease of their antioxidant defenses. This difference is greater as gestational age decreases. The application of oxygen therapy resulted in these levels which remain low throughout the study period.

  16. Reactive species and diabetes: counteracting oxidative stress to improve health.

    Science.gov (United States)

    Pérez-Matute, Patricia; Zulet, M Angeles; Martínez, J Alfredo

    2009-12-01

    Oxidative stress is at the very core of metabolism. Reactive species behave as true second messengers that control important cellular functions. However, under pathological conditions, abnormally large concentrations of these species may lead to permanent changes in signal transduction and gene expression. Attenuation of oxidative stress as a way to improve several diseases such as diabetes has flourished as one of the main challenges of research. The lack of evidence to prove the benefits from antioxidant compounds has led to boost these strategies. Inhibition of reactive oxygen species (ROS) production through the development of inhibitors against NADPH oxidase and mitochondria offers an alternative approach to conventional antioxidant therapies. There is a need to understand oxidative stress process to implement health-disorder approaches.

  17. Oxidative stress in atherosclerosis and diabetes.

    Science.gov (United States)

    Lankin, V Z; Lisina, M O; Arzamastseva, N E; Konovalova, G G; Nedosugova, L V; Kaminnyi, A I; Tikhaze, A K; Ageev, F T; Kukharchuk, V V; Belenkov, Yu N

    2005-07-01

    We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus.

  18. Geraniol, alone and in combination with pioglitazone, ameliorates fructose-induced metabolic syndrome in rats via the modulation of both inflammatory and oxidative stress status.

    Directory of Open Access Journals (Sweden)

    Sherehan M Ibrahim

    Full Text Available Geraniol (GO potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg in ameliorating metabolic syndrome (MetS induced by fructose in drinking water was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR-γ transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE. These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1β, and tumor necrosis factor-α, as well as hepatic lipid peroxides and nitric oxide (NO was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-γ reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical

  19. Role of Nrf2 in Oxidative Stress and Toxicity

    Science.gov (United States)

    Ma, Qiang

    2015-01-01

    Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body’s needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol–based redox signaling. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense. PMID:23294312

  20. Evaluation of oxidative stress using exhaled breath 8‑isoprostane ...

    African Journals Online (AJOL)

    2013-08-05

    Aug 5, 2013 ... oxidative stress in exhaled breath condensate (EBC). Those two studies have ... species (ROS) produced during aerobic metabolism and antioxidant .... GFR, presence of OS in CKD depends upon the increases in the level of ...

  1. PARTICULATE MATTER, OXIDATIVE STRESS AND ...

    Science.gov (United States)

    Particulate matter (PM), a component of air pollution has been epidemiologically associated with sudden deaths, cardiovascular and respiratory illnesses. The effects are more pronounced in patients with pre-existing conditions such as asthma, diabetes or obstructive pulmonary disorders. Clinical and experimental studies have historically focused on the cardiopulmonary effects of PM. However, since PM particles carry numerous biocontaminants that are capable of triggering free radical production and cytokine release, the possibility that PM may affect organs systems sensitive to oxidative stress must be considered. Four independent studies that summarize the neurochemical and neuropathological changes found in the brains of PM exposed animals are described here. These were recently presented at two 2007 symposia sponsored by the Society of Toxicology (Charlotte, NC) and the International Neurotoxicology Association (Monterey, CA). Particulates are covered with biocontaminants (e.g., endotoxins, mold, pollen) which convey free radical activity that can damage the lipids, nucleic acids, and proteins of target cells on contact and stimulate inflammatory cytokine release. Although, the historical focus of PM toxicity has been cardiopulmonary targets, it is now appreciated that inhaled nano-size (liver, kidneys, testes, lymph nodes) (Takenaka et aI

  2. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

    Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven;

    2015-01-01

    SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino...... acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous....... It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured...

  3. Oxidative Stress Related Diseases in Newborns

    Directory of Open Access Journals (Sweden)

    Yasemin Ozsurekci

    2016-01-01

    Full Text Available We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases.

  4. Today’s oxidative stress markers

    Directory of Open Access Journals (Sweden)

    Marta Czerska

    2015-07-01

    Full Text Available Oxidative stress represents a situation where there is an imbalance between the reactive oxygen species (ROS and the availability and the activity of antioxidants. This balance is disturbed by increased generation of free radicals or decreased antioxidant activity. It is very important to develop methods and find appropriate biomarkers that may be used to assess oxidative stress in vivo. It is significant because appropriate measurement of such stress is necessary in identifying its role in lifestyle-related diseases. Previously used markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS or malondialdehyde (MDA, are progressively being supplemented by new ones, such as isoprostanes (IsoPs and their metabolites or allantoin. This paper is focusing on the presentation of new ones, promising markers of oxidative stress (IsoPs, their metabolites and allantoin, taking into account the advantage of those markers over markers used previously. Med Pr 2015;66(3:393–405

  5. Oxidative stress and chronic kidney disease.

    Science.gov (United States)

    Brown, Scott A

    2008-01-01

    Slowing the rate of progression of chronic kidney disease (CKD) is a critical part of the management of affected dogs and cats. Renal oxidant stress is a previously unrecognized factor in the progression of canine CKD and is likely to be similarly important in feline CKD. Renin-angiotensin antagonism, calcium channel antagonism, n-3 polyunsaturated fatty acid, and antihypertensive and antiproteinuric therapy are commonly recommended for dogs and cats with CKD. These therapies would be expected to reduce renal oxidant stress by decreasing reactive oxygen species generation. Newer data indicate that dietary supplementation with specific antioxidants is an important consideration for limiting renal oxidant stress and progression of CKD.

  6. 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.

  7. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.;

    2002-01-01

    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  8. Chaperones, but not oxidized proteins, are ubiquitinated after oxidative stress

    DEFF Research Database (Denmark)

    Kästle, Marc; Reeg, Sandra; Rogowska-Wrzesinska, Adelina;

    2012-01-01

    After oxidative stress proteins which are oxidatively modified are degraded by the 20S proteasome. However, several studies documented an enhanced ubiquitination of yet unknown proteins. Since ubiqutination is a prerequisite for degradation by the 26S proteasome in an ATP-dependent manner......, we were able to confirm an increase of ubiquitinated proteins 16h upon oxidative stress. Therefore, we isolated ubiquitinated proteins from hydrogen peroxide treated cells, as well as from control and lactacystin, an irreversible proteasome inhibitor, treated cells, and identified some......, ubiquitinated proteins confirm the thesis that ubiquitination upon oxidative stress is no random process to degrade the mass of oxidized proteins, but concerns a special group of functional proteins....

  9. Oxidative stress in patients with nongenital warts.

    Science.gov (United States)

    Sasmaz, Sezai; Arican, Ozer; Kurutas, Ergul Belge

    2005-08-31

    Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male) and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (Pstress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  10. Oxidative stress and bivalves: a proteomic approach

    Directory of Open Access Journals (Sweden)

    B McDonagh

    2008-09-01

    Full Text Available Bivalves are of major importance in aquatic ecology, aquaculture, are widely used as sentinel species in environmental toxicology and show remarkable plasticity to molecular oxygen. Excess reactive oxygen species (ROS arising from molecular oxygen can cause oxidative stress and this is also a consequence of exposure to many common environmental pollutants. Indices of oxidative stress have therefore found favor as biomarkers of exposure and effect in environmental toxicology. However, there is a growing body of literature on the use of discovery-led proteomics methods to detect oxidative stress in bivalves. This is because proteins absorb up to 70 % of ROS leading to complication of the proteome. This article explores the background to these developments and assesses the practice and future potential of proteomics in the study of oxidative stress in bivalves.

  11. Biomarkers of stress-mediated metabolic deregulation in diabetes mellitus.

    Science.gov (United States)

    Johar, Dina R; Bernstein, Larry H

    2017-04-01

    This review illustrates the relationship of oxidative and nitrative stress to diabetes mellitus and its complications. This is of considerable interest because diabetes mellitus is a lifetime systemic metabolic disease that may have childhood or adult onset and affects not only a triad of pancreatic islet cell insulin, pituitary insulin-like growth hormone, and liver steatosis, it has a long-term association with adiposity, atherosclerosis, coronary vascular disease, kidney disease of the nature afferent arteriolar sclerosis and nodular glomerulosclerosis, cerebrovascular disease, and amyloid deposition in the pancreas and kidney. Only at the end of the 20th century do we gain insight into oxidative and nitrative stress and their consequences. Of special interest here is the fact that reactive oxygen and nitrogen radicals are with us generated throughout the life cycle, and the roles for glutathione and Fe(3+) are key elements in the metabolic picture, which brings into the picture dietary factors. More research is required to demonstrate the clinical relivance of naturally-occuring whole-food antioxidants in ameliorating human diabetic complications in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Region-specific changes in activities of cell death-related proteases and nitric oxide metabolism in rat brain in a chronic unpredictable stress model.

    Science.gov (United States)

    Tishkina, Anna; Rukhlenko, Alexey; Stepanichev, Mikhail; Levshina, Irina; Pasikova, Natalia; Onufriev, Mikhail; Moiseeva, Yulia; Piskunov, Alexey; Gulyaeva, Natalia

    2012-12-01

    Effects of a chronic combined unpredictable stress on activities of two cell death-related proteases, calpain and cathepsin B, were studied along with indices of nitrergic system in rat brain structures. Male Wistar rats were subjected to a 2-week-long combined stress (combination of unpaired flash light and moderate footshock associated with a white noise session). Stress resulted in a significant loss in the body and thymus weight and increased defecation in the open field test, though neither motor and exploratory activity, nor plasma corticosterone differed from the respective control levels. Decreased calpain activity and increased cathepsin B activity were demonstrated in the hippocampus of stressed rats (previously we have shown that caspase-3 activity was significantly suppressed in the brain of rats subjected to same type of stress). A significant reduction in the number of NOS-containing neurons was accompanied by a chronic stressinduced decline in NOS activity in the neocortex. Similar changes were observed in the hippocampus. However, levels of NO metabolites were elevated in both structures. Thus, stress-induced structural modifications in the brain may be mediated by disturbances in the nitrergic system and increased lysosomal proteolysis.

  13. Oxidative stress and bivalves: a proteomic approach

    OpenAIRE

    2008-01-01

    Bivalves are of major importance in aquatic ecology, aquaculture, are widely used as sentinel species in environmental toxicology and show remarkable plasticity to molecular oxygen. Excess reactive oxygen species (ROS) arising from molecular oxygen can cause oxidative stress and this is also a consequence of exposure to many common environmental pollutants. Indices of oxidative stress have therefore found favor as biomarkers of exposure and effect in environmental toxicology. However, there i...

  14. Oxidative stress effects of thinner inhalation

    OpenAIRE

    2011-01-01

    Thinners are chemical mixtures used as industrial solvents. Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Thinner sniffing causes damage to the brain, kidney, liver, lung, and reproductive system. We discuss some proposed mechanism by which thinner induces damage. Recently, the induction of oxidative stress has been suggested as a possible mechanism of damage. This paper reviews the current evidence for oxidative stress effects induced ...

  15. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  16. Oxidative stress: Lipid peroxidation products as predictors in disease progression

    Directory of Open Access Journals (Sweden)

    Suranjana Ray Halder

    2014-09-01

    Full Text Available Oxidative stress is implicated in the pathogenesis of numerous disease processes, including diabetes mellitus, atherosclerosis, ischemia reperfusion injury, rheumatoid arthritis, neurodegenerative diseases as well as in the aging process. Chemical modification of amino acids in protein during lipid peroxidation (LPO results in the formation of lipoxidation products, which may serve as indicators of oxidative stress in vivo. The various types of aldehydes such as 4-hydroxynonenal, malondialdehyde, acrolein and others produced during LPO may serve as potent oxidative stress biomarkers. Their activation in different signaling cascades lead to apoptosis, differentiation, proliferation, etc., Increased amount of these aldehydes in aging or with metabolic complications or in other diseases indicate their pathophysiological significance. Thus, LPO products or other oxidative stress biomarkers may open the way for the development of early detection, prevention, and therapeutic strategies for stress associated human diseases. Now-a-days, antioxidant supplementation has become an increasingly popular practice to restore the redox homeostatic condition of the cell. Disease specific, target directed, bioavailable antioxidants may be beneficial for sustenance of the quality-of-life in future days. [J Exp Integr Med 2014; 4(3.000: 151-164

  17. Oxidative stress, insulin resistance, dyslipidemia and type 2diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Surapon Tangvarasittichai

    2015-01-01

    Oxidative stress is increased in metabolic syndromeand type 2 diabetes mellitus (T2DM) and this appearsto underlie the development of cardiovascular disease,T2DM and diabetic complications. Increased oxidativestress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM.

  18. The effects of anesthetic agents on oxidative stress

    Science.gov (United States)

    Yakan, Selvinaz; Düzgüner, Vesile

    2016-04-01

    Oxidative stress can be defined as the instability between antioxidant defense of the body and the production of free radical that causes peroxydation on the lipid layer. Free radicals are reactive oxygen species that are produced in the course of normal metabolisms of aerobe organisms and they may cause disorders in cell structure and organelles by interacting macromolecules, like lipid, protein, nucleic acids. Therefore, they may cause cardiovascular, immune system, liver, kidney illnesses and many other illnesses like cancer, aging, cataract, diabetes. It is known that many drugs used for the purpose of anesthetizing may cause lipid peroxidation in organism. For these reasons, determining the Oxidative stress index of anaesthetic stress chosen in the ones that are exposed to long term anaesthetic agents and anaesthesia appliccations, is so substantial.

  19. Aldose reductase, oxidative stress and diabetic mellitus

    Directory of Open Access Journals (Sweden)

    Waiho eTang

    2012-05-01

    Full Text Available Diabetes mellitus (DM is a complex metabolic disorder arising from lack of insulin production or insulin resistance 1. DM is a leading cause of morbidity and mortality in the developed world, particularly from vascular complications such as atherothrombosis in the coronary vessels. Aldose reductase (AR [ALR2; EC 1.1.1.21], a key enzyme in the polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol, leading to excessive accumulation of intracellular reactive oxygen species (ROS in various tissues of DM including the heart, vasculature, neurons, eyes and kidneys. As an example, hyperglycemia through such polyol pathway induced oxidative stress, may have dual heart actions, on coronary blood vessel (atherothrombosis and myocardium (heart failure leading to severe morbidity and mortality (reviewed in 2. In cells cultured under high glucose conditions, many studies have demonstrated similar AR-dependent increases in ROS production, confirming AR as an important factor for the pathogenesis of many diabetic complications. Moreover, recent studies have shown that AR inhibitors may be able to prevent or delay the onset of cardiovascular complications such as ischemia/reperfusion injury, atherosclerosis and atherothrombosis. In this review, we will focus on describing pivotal roles of AR in the pathogenesis of cardiovascular diseases as well as other diabetic complications, and the potential use of AR inhibitors as an emerging therapeutic strategy in preventing DM complications.

  20. One-year follow-up of clinical, metabolic and oxidative stress profile of morbid obese patients after laparoscopic sleeve gastrectomy. 8-oxo-dG as a clinical marker

    Directory of Open Access Journals (Sweden)

    Lidia Monzo-Beltran

    2017-08-01

    Full Text Available Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40 kg/m2 at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG technique. As compared with normal weight subjects matched in age, peripheral blood mononuclear cells (PBMc of obese patients present a significant reduction of the antioxidant enzyme activities superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx as well as a significant increase of the oxidized/reduced glutathione ratio (GSSG/GSH in these cells. Lipid peroxidation is significantly increased in the patient group as shown by the increased levels of malondialdehyde (MDA in PBMc and the amount of F2-Isoprostanes (F2-IsoPs released in urine. In addition, the DNA damage product 8-oxo-7,8-2′-deoxyguanosine (8-oxo-dG was also observed to be increased in serum and urine of morbid obese patients as compared with the control group. After LSG, an improvement of their ponderal and metabolic profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in PBMc and biological fluids. The observed changes of urinary 8-oxo-dG levels correlate positively with its serum concentration, the lipid peroxidation products MDA and F2-IsoPs, triglycerides, glucose, insulin, HOMA index and body weight and negatively with the percentage of weight and BMI loss and antioxidant activities. We conclude that the analysis of urinary 8-oxo-dG could be validated as a useful marker for the

  1. [Biological consequences of oxidative stress induced by pesticides].

    Science.gov (United States)

    Grosicka-Maciąg, Emilia

    2011-06-17

    Pesticides are used to protect plants and numerous plant products. They are also utilized in several industrial branches. These compounds are highly toxic to living organisms. In spite of close supervision in the use of pesticides there is a serious risk that these agents are able to spread into the environment and contaminate water, soil, food, and feedstuffs. Recently, more and more studies have been focused on understanding the toxic mechanisms of pesticide actions. The data indicate that the toxic action of pesticides may include the induction of oxidative stress and accumulation of free radicals in the cell. Long-lasting or acute oxidative stress disturbs cell metabolism and is able to produce permanent changes in the structure of proteins, lipids, and DNA. The proteins that are oxidized may lose or enhance their activity. Moreover, the proteins oxidized are able to form aggregates that inhibit the systems responsible for protein degradation and lead to alterations of proteins in the cell. Once oxidized, lipids have the capacity to damage and depolarize cytoplasmic membranes. Free oxygen radicals are harmful to DNA including damage to single nitric bases, DNA strand breaks and adduct production. Many studies indicate that oxidative stress may accelerate development of numerous diseases including cancer and neurodegenerative ones such as Alzheimer’s and Parkinson’s disease and may also be responsible for infertility.

  2. mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases.

    Science.gov (United States)

    Yang, Z; Ming, X-F

    2012-12-01

    The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic diseases accelerate aging process. Studies in experimental animal models demonstrate similarity of metabolic and cardiovascular phenotypes in metabolic diseases and old age, e.g. insulin resistance, oxidative stress, chronic low grade inflammation, cardiac hypertrophy, cardiac fibrosis, and heart failure, as well as vascular dysfunctions. Despite intensive research, the molecular mechanisms linking metabolic stress, aging, and ultimately cardiovascular diseases are still elusive. Although the mammalian target of rapamycin (mTOR) signalling is a well known regulator of metabolism and lifespan in model organisms, its central role in linking metabolic stress, aging and cardiovascular diseases is recently emerging. In this article, we review the evidence supporting the role of mTOR signalling as a molecular interface connecting metabolic stress, aging and cardiovascular diseases. The therapeutic potentials of targeting mTOR signalling to protect against metabolic and age-associated cardiovascular diseases are discussed. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  3. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    Full Text Available

    Inflammation is a common response in the human liver. It is involved in chronic hepatitis, cirrhosis, steatosis, ischemiareperfusion damage, hepatocarcinomas and in the development of metastasis. Reactive oxygen species (ROS production is part of the inflammatory processes. It is implicated in many physiological and pathological situations and can induce mutations in key cancer genes. Normally, this process is prevented by DNA repair enzymatic systems that maintain sequence fidelity during DNA replication. However, overproduction of free radicals in chronic inflammatory diseases is thought to saturate the ability of the cell to repair DNA damage prior to replications. Inflammation-induced genetic damage is not unique to the liver, and it might contribute to the development of mutations in several organs. An example is the chronic inflammatory response in ulcerative colitis that ultimately could lead to neoplasia.

    There is compelling evidence to suggest that most known environmental risk factors for HCC development lead to generation of reactive oxygen species (ROS. Indeed, hepatitis C virus (HCV, alcohol and hepatitis B virus (HBV have all been associated with oxidative stress. Direct production of oxidative stress by HCV core protein has been shown. A link between oxidative stress and liver pathogenesis is also supported by the successful use of antioxidant therapy to treat liver injury caused by chronic HCV infection, although it is not currently used for effective therapy. Ethanol metabolism via the alcohol dehydrogenase pathway and microsomal ethanol oxidizing system contribute substantially to the production of acetaldehyde and generation of ROS. HBx via its association with mitochondria has been shown to induce oxidative stress which in turn leads to activation of a

  4. Uptake and metabolism of iron oxide nanoparticles in brain cells.

    Science.gov (United States)

    Petters, Charlotte; Irrsack, Ellen; Koch, Michael; Dringen, Ralf

    2014-09-01

    Magnetic iron oxide nanoparticles (IONPs) are used for various applications in biomedicine, for example as contrast agents in magnetic resonance imaging, for cell tracking and for anti-tumor treatment. However, IONPs are also known for their toxic effects on cells and tissues which are at least in part caused by iron-mediated radical formation and oxidative stress. The potential toxicity of IONPs is especially important concerning the use of IONPs for neurobiological applications as alterations in brain iron homeostasis are strongly connected with human neurodegenerative diseases. Since IONPs are able to enter the brain, potential adverse consequences of an exposure of brain cells to IONPs have to be considered. This article describes the pathways that allow IONPs to enter the brain and summarizes the current knowledge on the uptake, the metabolism and the toxicity of IONPs for the different types of brain cells in vitro and in vivo.

  5. Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses

    KAUST Repository

    Zhang, Weipeng

    2013-11-11

    Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses.

  6. Adult neurogenesis transiently generates oxidative stress.

    Directory of Open Access Journals (Sweden)

    Noah M Walton

    Full Text Available An increasing body of evidence suggests that alterations in neurogenesis and oxidative stress are associated with a wide variety of CNS diseases, including Alzheimer's disease, schizophrenia and Parkinson's disease, as well as routine loss of function accompanying aging. Interestingly, the association between neurogenesis and the production of reactive oxidative species (ROS remains largely unexamined. The adult CNS harbors two regions of persistent lifelong neurogenesis: the subventricular zone and the dentate gyrus (DG. These regions contain populations of quiescent neural stem cells (NSCs that generate mature progeny via rapidly-dividing progenitor cells. We hypothesized that the energetic demands of highly proliferative progenitors generates localized oxidative stress that contributes to ROS-mediated damage within the neuropoietic microenvironment. In vivo examination of germinal niches in adult rodents revealed increases in oxidized DNA and lipid markers, particularly in the subgranular zone (SGZ of the dentate gyrus. To further pinpoint the cell types responsible for oxidative stress, we employed an in vitro cell culture model allowing for the synchronous terminal differentiation of primary hippocampal NSCs. Inducing differentiation in primary NSCs resulted in an immediate increase in total mitochondria number and overall ROS production, suggesting oxidative stress is generated during a transient window of elevated neurogenesis accompanying normal neurogenesis. To confirm these findings in vivo, we identified a set of oxidation-responsive genes, which respond to antioxidant administration and are significantly elevated in genetic- and exercise-induced model of hyperactive hippocampal neurogenesis. While no direct evidence exists coupling neurogenesis-associated stress to CNS disease, our data suggest that oxidative stress is produced as a result of routine adult neurogenesis.

  7. Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Luisina I Onofrio

    2015-02-01

    Full Text Available The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH, and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood.We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat as control group, or a medium fat diet, MFD (14% fat in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD or MFD (I+MFD for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model.We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection

  8. Oxidative Stress in Patients With Nongenital Warts

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2005-01-01

    Full Text Available Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT, glucose-6-phosphate dehydrogenase (G6PD, superoxide dismutase (SOD, and malondialdehyde (MDA in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (P<.05. However, we could not define a statistically significant correlation between these increased enzyme activities and MDA levels and the type, the duration, the number, and the location of lesions. We determined possible suppression of T cells during oxidative stress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  9. Oxidative stress inhibits calpain activity in situ.

    Science.gov (United States)

    Guttmann, R P; Johnson, G V

    1998-05-22

    In this study, the effects of oxidative stress on calpain-mediated proteolysis and calpain I autolysis in situ were examined. Calpain activity was stimulated in SH-SY5Y human neuroblastoma cells with the calcium ionophore, ionomycin. Calpain-mediated proteolysis of the membrane-permeable fluorescent substrate N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4-methylcouma rin, as well as the endogenous protein substrates microtubule-associated protein 2, tau and spectrin, was measured. Oxidative stress, induced by addition of either doxorubicin or 2-mercaptopyridine N-oxide, resulted in a significant decrease in the extent of ionophore-stimulated calpain activity of both the fluorescent compound and the endogenous substrates compared with control, normoxic conditions. Addition of glutathione ethyl ester, as well as other antioxidants, resulted in the retention/recovery of calpain activity, indicating that oxidation-induced calpain inactivation was preventable/reversible. The rate of autolytic conversion of the large subunit of calpain I from 80 to 78 to 76 kDa was decreased during oxidative stress; however, the extent of calpain autolysis was not altered. These data indicate that oxidative stress may reversibly inactivate calpain I in vivo.

  10. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Marina Galicia-Moreno

    2016-01-01

    Full Text Available Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC. This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

  11. Stressful life events and incident metabolic syndrome : The Hoorn study

    NARCIS (Netherlands)

    Rutters, F.; Pilz, S.; Koopman, A.D.; Rauh, S.P.; Pouwer, F.; Stehouwer, C.D.; Elders, P.J.; Nijpels, G.; Dekker, J.M.

    2015-01-01

    Stressful life events are associated with the metabolic syndrome in cross-sectional studies, but prospective studies addressing this issue are rare and limited. We therefore evaluated whether the number of stressful life events is associated with incident metabolic syndrome. We assessed the

  12. Stressful life events and incident metabolic syndrome : the Hoorn study

    NARCIS (Netherlands)

    Rutters, Femke; Pilz, Stefan; Koopman, Anitra D M; Rauh, Simone P; Pouwer, Frans; Stehouwer, Coen D A; Elders, Petra J; Nijpels, Giel; Dekker, Jacqueline M

    2015-01-01

    Stressful life events are associated with the metabolic syndrome in cross-sectional studies, but prospective studies addressing this issue are rare and limited. We therefore evaluated whether the number of stressful life events is associated with incident metabolic syndrome. We assessed the associat

  13. Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus)

    Science.gov (United States)

    Ventura, Luciana L.A.; Fortes, Nathália C.L.; Santiago, Helton C.; Caliari, Marcelo V.; Gomes, Maria A.

    2017-01-01

    Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7) or a standard diet with 4.15 kcal/g (CT; n = 7) for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in adipose

  14. Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Luciana L.A. Ventura

    2017-03-01

    Full Text Available Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7 or a standard diet with 4.15 kcal/g (CT; n = 7 for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL, triglycerides (TGL and glycemia (GLI in the plasma; cytokines (IL-6, IL-10 and TNF-α and hormones (adiponectin and leptin in adipose tissue; activity of superoxide dismutase (SOD and catalase (CAT, extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in

  15. Exogenous ATP administration prevents ischemia/reperfusion-induced oxidative stress and tissue injury by modulation of hypoxanthine metabolic pathway in rat ovary

    Directory of Open Access Journals (Sweden)

    Serkan Kumbasar

    2014-07-01

    Full Text Available In this study, xanthine oxidase (XO, malondialdehyde (MDA, myeloperoxidase (MPO and glutathione (GSH levels in the ovarian tissues of rats during the development of ischemia and postischemia-induced reperfusion were investigated, and the effect of ATP on ischemia-reperfusion (I/R damage was biochemically and histopathologically examined. The results of the biochemical analyses demonstrated that ATP significantly reduced the level of XO and MDA and increased the amount of GSH in both ischemia and I/R-applied ovarian tissue at the doses administered. Furthermore, ATP significantly suppressed the increase in MPO activity that occurred following the application of post ischemia reperfusion in the ovarian tissue. The biochemical results obtained in the present study coincide with the histological findings. The severity of the pathological findings, such as dilatation, congestion, haemorrhage, oedema and polymorphonuclear nuclear leukocytes (PMNLs, increased in parallel with the increase observed in the products of XO metabolism. In conclusion, exogenously applied ATP prevented I/R damage by reducing the formation of XO in ischemic ovarian tissue.

  16. Oxidative stress, mitochondrial damage and neurodegenerative diseases****

    Institute of Scientific and Technical Information of China (English)

    Chunyan Guo; Li Sun; Xueping Chen; Danshen Zhang

    2013-01-01

    Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. Al these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive thera-peutic interventions for the treatment of various neurodegenerative diseases.

  17. Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone.

    Science.gov (United States)

    Capogrosso, Roberta Francesca; Cozzoli, Anna; Mantuano, Paola; Camerino, Giulia Maria; Massari, Ada Maria; Sblendorio, Valeriana Teresa; De Bellis, Michela; Tamma, Roberto; Giustino, Arcangela; Nico, Beatrice; Montagnani, Monica; De Luca, Annamaria

    2016-04-01

    Antioxidants have a great potential as adjuvant therapeutics in patients with Duchenne muscular dystrophy, although systematic comparisons at pre-clinical level are limited. The present study is a head-to-head assessment, in the exercised mdx mouse model of DMD, of natural compounds, resveratrol and apocynin, and of the amino acid taurine, in comparison with the gold standard α-methyl prednisolone (PDN). The rationale was to target the overproduction of reactive oxygen species (ROS) via disease-related pathways that are worsened by mechanical-metabolic impairment such as inflammation and over-activity of NADPH oxidase (NOX) (taurine and apocynin, respectively) or the failing ROS detoxification mechanisms via sirtuin-1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (resveratrol). Resveratrol (100mg/kg i.p. 5days/week), apocynin (38mg/kg/day per os), taurine (1g/kg/day per os), and PDN (1mg/kg i.p., 5days/week) were administered for 4-5 weeks to mdx mice in parallel with a standard protocol of treadmill exercise and the outcome was evaluated with a multidisciplinary approach in vivo and ex vivo on pathology-related end-points and biomarkers of oxidative stress. Resveratrol≥taurine>apocynin enhanced in vivo mouse force similarly to PDN. All the compounds reduced the production of superoxide anion, assessed by dihydroethidium staining, with apocynin being as effective as PDN, and ameliorated electrophysiological biomarkers of oxidative stress. Resveratrol also significantly reduced plasma levels of creatine kinase and lactate dehydrogenase. Force of isolated muscles was little ameliorated. However, the three compounds improved histopathology of gastrocnemius muscle more than PDN. Taurine>apocynin>PDN significantly decreased activated NF-kB positive myofibers. Thus, compounds targeting NOX-ROS or SIRT1/PGC-1α pathways differently modulate clinically relevant DMD-related endpoints according to their mechanism of action. With the

  18. Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress.

    Science.gov (United States)

    Codoñer-Franch, Pilar; Valls-Bellés, Victoria; Arilla-Codoñer, Angela; Alonso-Iglesias, Eulalia

    2011-12-01

    Evidence of obesity-induced oxidative stress in adults has emerged in the past several years, and similar evidence has been demonstrated in children more recently. The reactive species of oxygen or nitrogen can chemically alter all major classes of biomolecules by modifying their structure and function. Organisms have developed mechanisms to protect biomolecules from the deleterious effects of free radicals. These include the enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as water and lipid-soluble antioxidants, such as glutathione, ascorbate (vitamin C), α-tocopherol (vitamin E), and β-carotene. Obesity creates oxidant conditions that favor the development of comorbid diseases. Energy imbalances lead to the storage of excess energy in adipocytes, resulting in both hypertrophy and hyperplasia. These processes are associated with abnormalities of adipocyte function, particularly mitochondrial stress and disrupted endoplasmic reticulum function. In this sense, oxidative stress can also be induced by adipocyte associated inflammatory macrophages. There is a close link among obesity, a state of chronic low-level inflammation, and oxidative stress. In addition, the dysregulation of adipocytokines, which are secreted by adipose tissue and promoted by oxidative stress, act synergistically in obesity-related metabolic abnormalities. Adipocytokines link the local and systemic inflammation responses in the context of obesity. It is thought that the evaluation of oxidative status may allow for the identification of patients at an increased risk of complications. Decreasing the levels of chronic inflammation and oxidative stress in childhood may decrease cardiovascular morbidity and mortality in adulthood. Copyright © 2011 Mosby, Inc. All rights reserved.

  19. Biomarkers of oxidative stress in antioxidant therapy

    Directory of Open Access Journals (Sweden)

    Wilfredo Mañon Rossi

    2016-04-01

    Full Text Available Biomarkers are used regularly in medical practice to provide objective markers of health status of a person, as well as the physiological response of the body to a pharmacological therapeutic intervention. In the specific case of the use of antioxidant products (antioxidant therapy, it is necessary to measure both biomarkers of oxidative stress level of the person as those that are specific to a physiological or pathological progression of a disease disorder. This paper describes the main biomarkers of oxidative general and specific stress as well as laboratory techniques, which should be taken into account when measuring the effectiveness of antioxidant therapies.

  20. Oxidative stress in development: nature or nurture?

    Science.gov (United States)

    Dennery, Phyllis A

    2010-10-15

    An unavoidable consequence of aerobic respiration is the generation of reactive oxygen species (ROS). These may negatively impact development. Nevertheless, a certain amount of oxidative stress is required to allow for the normal progression of embryonic and fetal growth. Alterations in placental oxidative stress results in altered placental function and ultimately altered fetal growth and/or developmental programming leading to long-term consequences into adulthood. This article reviews the role of redox in fetal development and will focus on how developmental programming is influenced by the fetal and placental redox state as well as discuss potential therapeutic interventions.

  1. Oxidative Stress in Schizophrenia: An Integrated Approach

    Science.gov (United States)

    Bitanihirwe, Byron K.Y.; Woo, Tsung-Ung W.

    2010-01-01

    Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia. In particular, oxidative damage to lipids, proteins, and DNA as observed in schizophrenia is known to impair cell viability and function, which may subsequently account for the deteriorating course of the illness. Currently available evidence points towards an alteration in the activities of enzymatic and nonenzymatic antioxidant systems in schizophrenia. In fact, experimental models have demonstrated that oxidative stress induces behavioural and molecular anomalies strikingly similar to those observed in schizophrenia. These findings suggest that oxidative stress is intimately linked to a variety of pathophysiological processes, such as inflammation, oligodendrocyte abnormalities, mitochondrial dysfunction, hypoactive N-methyl-D-aspartate receptors and the impairment of fast-spiking gamma-aminobutyric acid interneurons.[bkyb1] Such self-sustaining mechanisms may progressively worsen producing the functional and structural consequences associated with schizophrenia. Recent clinical studies have shown antioxidant treatment to be effective in ameliorating schizophrenic symptoms. Hence, identifying viable therapeutic strategies to tackle oxidative stress and the resulting physiological disturbances provide an exciting opportunity for the treatment and ultimately prevention of schizophrenia. PMID:20974172

  2. Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease.

    Science.gov (United States)

    Arana, Carlos; Moreno-Fernández, Ana María; Gómez-Moreno, Gerardo; Morales-Portillo, Cristóbal; Serrano-Olmedo, Isabel; de la Cuesta Mayor, M Carmen; Martín Hernández, Tomás

    2017-05-01

    The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (Pperiodontal health. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Improved Growth and Stress Tolerance in the Arabidopsis oxt1 Mutant Triggered by Altered Adenine Metabolism

    Institute of Scientific and Technical Information of China (English)

    Suchada Sukrong; Kil-Young Yun; Patrizia Stadler; Charan Kumar; Tony Facciuolo; Barbara A.Moffatt; Deane L.Falcone

    2012-01-01

    Plants perceive and respond to environmental stresses with complex mechanisms that are often associated with the activation of antioxidant defenses.A genetic screen aimed at isolating oxidative stress-tolerant lines of Arabidopsis thaliana has identified oxt1,a line that exhibits improved tolerance to oxidative stress and elevated temperature but displays no apparent deleterious growth effects under non-stress conditions.Oxt1 harbors a mutation that arises from the altered expression of a gene encoding adenine phosphoribosyltransferase (APT1),an enzyme that converts adenine to adenosine monophosphate (AMP),indicating a link between purine metabolism,whole-plant growth responses,and stress acclimation.The oxt1 mutation results in decreased APT1 expression that leads to reduced enzymatic activity.Correspondingly,oxt1 plants possess elevated levels of adenine.Decreased APT enzyme activity directly correlates with stress resistance in transgenic lines that ectopically express APT1.The metabolic alteration in oxt1 plants also alters the expression of several antioxidant defense genes and the response of these genes to oxidative challenge.Finally,it is shown that manipulation of adenine levels can induce stress tolerance to wild-type plants.Collectively,these results show that alterations in cellular adenine levels can trigger stress tolerance and improve growth,leading to increases in plant biomass.The results also suggest that adenine might play a part in the signals that modulate responses to abiotic stress and plant growth.

  4. Toxicological and pharmacological concerns on oxidative stress and related diseases

    Energy Technology Data Exchange (ETDEWEB)

    Saeidnia, Soodabeh [Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411 (Iran, Islamic Republic of); College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon (Canada); Abdollahi, Mohammad, E-mail: Mohammad@TUMS.Ac.Ir [Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411 (Iran, Islamic Republic of)

    2013-12-15

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

  5. Different Impacts of Cardiovascular Risk Factors on Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Sebastian Blesa

    2011-09-01

    Full Text Available The objective of the study was to evaluate oxidative stress (OS status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT with and without metabolic syndrome, familial hypercholesterolemia (FH and familial combined hyperlipidemia (FCH with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase and activation of both pro-oxidant enzyme (NAPDH oxidase components and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN were measured in mononuclear cells of controls (n = 20 and patients (n = 90 by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to

  6. Differences in metabolism between the biofilm and planktonic response to metal stress.

    Science.gov (United States)

    Booth, Sean C; Workentine, Matthew L; Wen, Jing; Shaykhutdinov, Rustem; Vogel, Hans J; Ceri, Howard; Turner, Raymond J; Weljie, Aalim M

    2011-07-01

    Bacterial biofilms are known to withstand the effects of toxic metals better than planktonic cultures of the same species. This phenomenon has been attributed to many features of the sessile lifestyle not present in free-swimming populations, but the contribution of intracellular metabolism has not been previously examined. Here, we use a combined GC-MS and (1)H NMR metabolomic approach to quantify whole-cell metabolism in biofilm and planktonic cultures of the multimetal resistant bacterium Pseudomonas fluorescens exposed to copper ions. Metabolic changes in response to metal exposure were found to be significantly different in biofilms compared to planktonic cultures. Planktonic metabolism indicated an oxidative stress response that was characterized by changes to the TCA cycle, glycolysis, pyruvate and nicotinate and niacotinamide metabolism. Similar metabolic changes were not observed in biofilms, which were instead dominated by shifts in exopolysaccharide related metabolism suggesting that metal stress in biofilms induces a protective response rather than the reactive changes observed for the planktonic cells. From these results, we conclude that differential metabolic shifts play a role in biofilm-specific multimetal resistance and tolerance. An altered metabolic response to metal toxicity represents a novel addition to a growing list of biofilm-specific mechanisms to resist environmental stress.

  7. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  8. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

    OpenAIRE

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K.; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F.; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E.; Sonveaux, Pierre

    2015-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning th...

  9. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Science.gov (United States)

    Melov, Simon; Adlard, Paul A; Morten, Karl; Johnson, Felicity; Golden, Tamara R; Hinerfeld, Doug; Schilling, Birgit; Mavros, Christine; Masters, Colin L; Volitakis, Irene; Li, Qiao-Xin; Laughton, Katrina; Hubbard, Alan; Cherny, Robert A; Gibson, Brad; Bush, Ashley I

    2007-06-20

    Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

  10. Methylglyoxal promotes oxidative stress and endothelial dysfunction.

    Science.gov (United States)

    Sena, Cristina M; Matafome, Paulo; Crisóstomo, Joana; Rodrigues, Lisa; Fernandes, Rosa; Pereira, Paulo; Seiça, Raquel M

    2012-05-01

    Modern diets can cause modern diseases. Research has linked a metabolite of sugar, methylglyoxal (MG), to the development of diabetic complications, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether MG could directly influence endothelial function, oxidative stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 months were compared with the respective control rats. The effects of MG were investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from the different groups. Insulin resistance, NO bioavailability, glycation, a pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats significantly reduced the efficacy of NO-dependent vasorelaxation (pMethylglyoxal treated GK rats significantly aggravated endothelial dysfunction, oxidative stress, AGEs accumulation and diminished NO bioavailability when compared with control GK rats. These results indicate that methylglyoxal induced endothelial dysfunction in normal Wistar rats and aggravated the endothelial dysfunction present in GK rats. The mechanism is at least in part by increasing oxidative stress and/or AGEs formation with a concomitant increment of inflammation and a decrement in NO bioavailability. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of atherosclerosis and development of macrovascular diabetic complication.

  11. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Directory of Open Access Journals (Sweden)

    Simon Melov

    Full Text Available Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD: tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2 die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576 with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

  12. Mechanism of Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Sonia Gandhi

    2012-01-01

    Full Text Available Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.

  13. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  14. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Quaroni, Andrea [Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Cornell University, Ithaca, NY 14853–6401 (United States); Autore, Giuseppina [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Severino, Lorella [Department of Pathology and Animal Health, Division of Toxicology, School of Veterinary Medicine, University of Naples “Federico II”, Via Delpino 1, 80137 Naples (Italy); Marzocco, Stefania, E-mail: smarzocco@unisa.it [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy)

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

  15. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.

    Science.gov (United States)

    Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M; Dhabhar, Firdaus S; Su, Yali; Epel, Elissa

    2013-09-01

    Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (pcortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed

  16. Simvastatin and oxidative stress in humans

    DEFF Research Database (Denmark)

    Rasmussen, Sanne Tofte; Andersen, Jon Thor Trærup; Nielsen, Torben Kjær

    2016-01-01

    Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes......-blinded, placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine.......1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced...

  17. Oxidative stress in benign prostate hyperplasia.

    Science.gov (United States)

    Zabaiou, N; Mabed, D; Lobaccaro, J M; Lahouel, M

    2016-02-01

    To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.

  18. Anticholinesterase Toxicity and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Dejan Milatovic

    2006-01-01

    Full Text Available Anticholinesterase compounds, organophosphates (OPs and carbamates (CMs are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS, and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents.

  19. Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells.

    Science.gov (United States)

    Borrego, Stacey L; Fahrmann, Johannes; Datta, Rupsa; Stringari, Chiara; Grapov, Dmitry; Zeller, Michael; Chen, Yumay; Wang, Ping; Baldi, Pierre; Gratton, Enrico; Fiehn, Oliver; Kaiser, Peter

    2016-01-01

    The majority of cancer cells have a unique metabolic requirement for methionine that is not observed in normal, non-tumorigenic cells. This phenotype is described as "methionine dependence" or "methionine stress sensitivity" in which cancer cells are unable to proliferate when methionine has been replaced with its metabolic precursor, homocysteine, in cell culture growth media. We focus on the metabolic response to methionine stress in the triple negative breast cancer cell line MDA-MB-468 and its methionine insensitive derivative cell line MDA-MB-468res-R8. Using a variety of techniques including fluorescence lifetime imaging microscopy (FLIM) and extracellular flux assays, we identified a metabolic down-regulation of oxidative phosphorylation in both MDA-MB-468 and MDA-MB-468res-R8 cell types when cultured in homocysteine media. Untargeted metabolomics was performed by way of gas chromatography/time-of-flight mass spectrometry on both cell types cultured in homocysteine media over a period of 2 to 24 h. We determined unique metabolic responses between the two cell lines in specific pathways including methionine salvage, purine/pyrimidine synthesis, and the tricarboxylic acid cycle. Stable isotope tracer studies using deuterium-labeled homocysteine indicated a redirection of homocysteine metabolism toward the transsulfuration pathway and glutathione synthesis. This data corroborates with increased glutathione levels concomitant with increased levels of oxidized glutathione. Redirection of homocysteine flux resulted in reduced generation of methionine from homocysteine particularly in MDA-MB-468 cells. Consequently, synthesis of the important one-carbon donor S-adenosylmethionine (SAM) was decreased, perturbing the SAM to S-adenosylhomocysteine ratio in MDA-MB-468 cells, which is an indicator of the cellular methylation potential. This study indicates a differential metabolic response between the methionine sensitive MDA-MB-468 cells and the methionine insensitive

  20. Piracetam improves mitochondrial dysfunction following oxidative stress.

    Science.gov (United States)

    Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

    2006-01-01

    1.--Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. 2.--Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. 3.--Piracetam treatment at concentrations between 100 and 1000 microM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 microM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. 4.--Piracetam treatment (100-500 mg kg(-1) daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. 5.--In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients.

  1. Spirulina maxima and its effect on antioxidant activity in fructose induced oxidative stress with histopathological observations

    OpenAIRE

    Jarouliya Urmila; Zacharia Anish; Keservani Raj K.; Prasad Godavarthi B.K.S

    2015-01-01

    Diabetes mellitus is a metabolic disorder characterised by hyperglycemia and oxidative stress. The aim of the present study is to explore the antioxidant effect of Spirulina maxima in rat model along with the histopathological observations. Diabetes was induced by feeding 10% fructose solution orally to Wistar rats (n = 6) for 30 days, analysed for plasma blood glucose and the markers of the oxidative stress [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and thiobarbit...

  2. Metabolic consequences of stress during childhood and adolescence.

    Science.gov (United States)

    Pervanidou, Panagiota; Chrousos, George P

    2012-05-01

    Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity

  3. The role of iron as a mediator of oxidative stress in Alzheimer disease.

    Science.gov (United States)

    Castellani, Rudy J; Moreira, Paula I; Perry, George; Zhu, Xiongwei

    2012-01-01

    Iron is both essential for maintaining a spectrum of metabolic processes in the central nervous system and elsewhere, and potent source of reactive oxygen species. Redox balance with respect to iron, therefore, may be critical to human neurodegenerative disease but is also in need of better understanding. Alzheimer disease (AD) in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

  4. Biochemical and biomolecular aspects of oxidative stress due to acute and severe hypoxia in human muscle tissue.

    Science.gov (United States)

    Corbucci, G G; Sessego, R; Velluti, C; Salvi, M

    1995-01-01

    Mitochondrial oxidative stress was investigated in severe and acute hypoxia and in reperfusion applied to human muscle tissues. The biochemical and biomolecular relationship between the response of the respiratory-chain enzymic complexes and the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive mechanism which antagonizes the oxidative damage due to acute and severe tissue hypoxia.

  5. Oxidative stress and Alzheimer disease.

    Science.gov (United States)

    Christen, Y

    2000-02-01

    Research in the field of molecular biology has helped to provide a better understanding of both the cascade of biochemical events that occurs with Alzheimer disease (AD) and the heterogeneous nature of the disease. One hypothesis that accounts for both the heterogeneous nature of AD and the fact that aging is the most obvious risk factor is that free radicals are involved. The probability of this involvement is supported by the fact that neurons are extremely sensitive to attacks by destructive free radicals. Furthermore, lesions are present in the brains of AD patients that are typically associated with attacks by free radicals (eg, damage to DNA, protein oxidation, lipid peroxidation, and advanced glycosylation end products), and metals (eg, iron, copper, zinc, and aluminum) are present that have catalytic activity that produce free radicals. beta-Amyloid is aggregated and produces more free radicals in the presence of free radicals; beta-amyloid toxicity is eliminated by free radical scavengers. Apolipoprotein E is subject to attacks by free radicals, and apolipoprotein E peroxidation has been correlated with AD. In contrast, apolipoprotein E can act as a free radical scavenger and this behavior is isoform dependent. AD has been linked to mitochondrial anomalies affecting cytochrome-c oxidase, and these anomalies may contribute to the abnormal production of free radicals. Finally, many free radical scavengers (eg, vitamin E, selegeline, and Ginkgo biloba extract EGb 761) have produced promising results in relation to AD, as has desferrioxamine-an iron-chelating agent-and antiinflammatory drugs and estrogens, which also have an antioxidant effect.

  6. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

    2016-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.

  7. GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells.

    Science.gov (United States)

    Abrego, Jaime; Gunda, Venugopal; Vernucci, Enza; Shukla, Surendra K; King, Ryan J; Dasgupta, Aneesha; Goode, Gennifer; Murthy, Divya; Yu, Fang; Singh, Pankaj K

    2017-08-01

    The increased rate of glycolysis and reduced oxidative metabolism are the principal biochemical phenotypes observed in pancreatic ductal adenocarcinoma (PDAC) that lead to the development of an acidic tumor microenvironment. The pH of most epithelial cell-derived tumors is reported to be lower than that of plasma. However, little is known regarding the physiology and metabolism of cancer cells enduring chronic acidosis. Here, we cultured PDAC cells in chronic acidosis (pH 6.9-7.0) and observed that cells cultured in low pH had reduced clonogenic capacity. However, our physiological and metabolomics analysis showed that cells in low pH deviate from glycolytic metabolism and rely more on oxidative metabolism. The increased expression of the transaminase enzyme GOT1 fuels oxidative metabolism of cells cultured in low pH by enhancing the non-canonical glutamine metabolic pathway. Survival in low pH is reduced upon depletion of GOT1 due to increased intracellular ROS levels. Thus, GOT1 plays an important role in energy metabolism and ROS balance in chronic acidosis stress. Our studies suggest that targeting anaplerotic glutamine metabolism may serve as an important therapeutic target in PDAC. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Claudia Consales

    2012-01-01

    Full Text Available Electromagnetic fields (EMFs originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.

  9. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells.

    Science.gov (United States)

    Reisz, Julie A; Wither, Matthew J; Dzieciatkowska, Monika; Nemkov, Travis; Issaian, Aaron; Yoshida, Tatsuro; Dunham, Andrew J; Hill, Ryan C; Hansen, Kirk C; D'Alessandro, Angelo

    2016-09-22

    Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH. Progressive increases in PPP/glycolysis ratios were determined via metabolic flux analysis after spiking (13)C1,2,3-glucose in erythrocyte concentrates stored in Additive Solution-3 under blood bank conditions for up to 42 days. Proteomics analyses revealed a storage-dependent oxidation of GAPDH at functional Cys152, 156, 247, and His179. Activity loss by oxidation occurred with increasing storage duration and was progressively irreversible. Irreversibly oxidized GAPDH accumulated in stored erythrocyte membranes and supernatants through storage day 42. By combining state-of-the-art ultra-high-pressure liquid chromatography-mass spectrometry metabolic flux analysis with redox and switch-tag proteomics, we identify for the first time ex vivo functionally relevant reversible and irreversible (sulfinic acid; Cys to dehydroalanine) oxidations of GAPDH without exogenous supplementation of excess pro-oxidant compounds in clinically relevant blood products. Oxidative and metabolic lesions, exacerbated by storage under hyperoxic conditions, were ameliorated by hypoxic storage. Storage-dependent reversible oxidation of GAPDH represents a mechanistic adaptation in stored erythrocytes to promote PPP activation and generate reducing equivalents. Removal of irreversibly oxidized, functionally compromised GAPDH identifies enhanced vesiculation as a self-protective mechanism in ex vivo aging erythrocytes.

  10. Modulation of thiamine metabolism in Zea mays seedlings under conditions of abiotic stress.

    Science.gov (United States)

    Rapala-Kozik, Maria; Kowalska, Ewa; Ostrowska, Katarzyna

    2008-01-01

    The responses of plants to abiotic stress involve the up-regulation of numerous metabolic pathways, including several major routes that engage thiamine diphosphate (TDP)-dependent enzymes. This suggests that the metabolism of thiamine (vitamin B1) and its phosphate esters in plants may be modulated under various stress conditions. In the present study, Zea mays seedlings were used as a model system to analyse for any relation between the plant response to abiotic stress and the properties of thiamine biosynthesis and activation. Conditions of drought, high salt, and oxidative stress were induced by polyethylene glycol, sodium chloride, and hydrogen peroxide, respectively. The expected increases in the abscisic acid levels and in the activities of antioxidant enzymes including catalase, ascorbate peroxidase, and glutathione reductase were found under each stress condition. The total thiamine compound content in the maize seedling leaves increased under each stress condition applied, with the strongest effects on these levels observed under the oxidative stress treatment. This increase was also found to be associated with changes in the relative distribution of free thiamine, thiamine monophosphate (TMP), and TDP. Surprisingly, the activity of the thiamine synthesizing enzyme, TMP synthase, responded poorly to abiotic stress, in contrast to the significant enhancement found for the activities of the TDP synthesizing enzyme, thiamine pyrophosphokinase, and a number of the TDP/TMP phosphatases. Finally, a moderate increase in the activity of transketolase, one of the major TDP-dependent enzymes, was detectable under conditions of salt and oxidative stress. These findings suggest a role of thiamine metabolism in the plant response to environmental stress.

  11. Oxidative stress and anti-oxidative mobilization in burn injury.

    Science.gov (United States)

    Parihar, Arti; Parihar, Mordhwaj S; Milner, Stephen; Bhat, Satyanarayan

    2008-02-01

    A severe burn is associated with release of inflammatory mediators which ultimately cause local and distant pathophysiological effects. Mediators including Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are increased in affected tissue, which are implicated in pathophysiological events observed in burn patients. The purpose of this article is to understand the role of oxidative stress in burns, in order to develop therapeutic strategies. All peer-reviewed, original and review articles published in the English language literature relevant to the topic of oxidative stress in burns in animals and human subjects were selected for this review and the possible roles of ROS and RNS in the pathophysiology of burns are discussed. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources in burns. Free radicals have been found to have beneficial effects on antimicrobial action and wound healing. However following a burn, there is an enormous production of ROS which is harmful and implicated in inflammation, systemic inflammatory response syndrome, immunosuppression, infection and sepsis, tissue damage and multiple organ failure. Thus clinical response to burn is dependent on the balance between production of free radicals and its detoxification. Supplementation of antioxidants in human and animal models has proven benefit in decreasing distant organ failure suggesting a cause and effect relationship. We conclude that oxidative damage is one of the mechanisms responsible for the local and distant pathophysiological events observed after burn, and therefore anti-oxidant therapy might be beneficial in minimizing injury in burned patients.

  12. Oxidative stress and the high altitude environment

    Directory of Open Access Journals (Sweden)

    Jakub Krzeszowiak

    2013-03-01

    Full Text Available In the recent years there has been considerable interest in mountain sports, including mountaineering, owing to the general availability of climbing clothing and equipment as well trainings and professional literature. This raised a new question for the environmental and mountain medicine: Is mountaineering harmful to health? Potential hazards include the conditions existing in the alpine environment, i.e. lower atmospheric pressure leading to the development of hypobaric hypoxia, extreme physical effort, increased UV radiation, lack of access to fresh food, and mental stress. A reasonable measure of harmfulness of these factors is to determine the increase in the level of oxidative stress. Alpine environment can stimulate the antioxidant enzyme system but under specific circumstances it may exceed its capabilities with simultaneous consumption of low-molecular antioxidants resulting in increased generation of reactive oxygen species (ROS. This situation is referred to as oxidative stress. Rapid and uncontrolled proliferation of reactive oxygen species leads to a number of adverse changes, resulting in the above-average damage to the lipid structures of cell membranes (peroxidation, proteins (denaturation, and nucleic acids. Such situation within the human body cannot take place without resultant systemic consequences. This explains the malaise of people returning from high altitude and a marked decrease in their physical fitness. In addition, a theory is put forward that the increase in the level of oxidative stress is one of the factors responsible for the onset of acute mountain sickness (AMS. However, such statement requires further investigation because the currently available literature is inconclusive. This article presents the causes and effects of development of oxidative stress in the high mountains.

  13. Lysosomal stress: a new player in perturbed lipid metabolism

    NARCIS (Netherlands)

    Gabriel, T.L.

    2017-01-01

    Lysosomes are involved in many different essential cellular processes, among others organelle and molecule degradation, exocytosis, cell energy metabolism, cholesterol and sphingolipid level regulation. Lysosomal stress has a strong impact on the immune system, affecting specially macrophages as the

  14. Lysosomal stress: a new player in perturbed lipid metabolism

    NARCIS (Netherlands)

    Gabriel, T.L.

    2017-01-01

    Lysosomes are involved in many different essential cellular processes, among others organelle and molecule degradation, exocytosis, cell energy metabolism, cholesterol and sphingolipid level regulation. Lysosomal stress has a strong impact on the immune system, affecting specially macrophages as the

  15. Acute vagal stimulation attenuates cardiac metabolic response to β-adrenergic stress.

    Science.gov (United States)

    Vimercati, Claudio; Qanud, Khaled; Ilsar, Itamar; Mitacchione, Gianfranco; Sarnari, Roberto; Mania, Daniella; Faulk, Ryan; Stanley, William C; Sabbah, Hani N; Recchia, Fabio A

    2012-12-01

    The effects of vagal stimulation (VS) on cardiac energy substrate metabolism are unknown. We tested the hypothesis that acute VS alters the balance between free fatty acid (FFA) and carbohydrate oxidation and opposes the metabolic effects of β-adrenergic stimulation. A clinical-type selective stimulator of the vagal efferent fibres was connected to the intact right vagus in chronically instrumented dogs. VS was set to reduce heart rate by 30 beats min(-1), and the confounding effects of bradycardia were then eliminated by pacing the heart at 165 beats min(-1). [(3)H]Oleate and [(14)C]glucose were infused to measure FFA and glucose oxidation. The heart was subjected to β-adrenergic stress by infusing dobutamine at 5, 10 and 15 μg kg(-1) min(-1) before and during VS. VS did not significantly affect baseline cardiac performance, haemodynamics or myocardial metabolism. However, at peak dobutamine stress, VS attenuated the increase in left ventricular pressure-diameter area from 235.9 ± 72.8 to 167.3 ± 55.8%, and in cardiac oxygen consumption from 173.9 ± 23.3 to 127.89 ± 6.2% (both P < 0.05), and thus mechanical efficiency was not enhanced. The increase in glucose oxidation fell from 289.3 ± 55.5 to 131.1 ± 20.9% (P < 0.05), while FFA oxidation was not increased by β-adrenergic stress and fell below baseline during VS only at the lowest dose of dobutamine. The functional and in part the metabolic changes were reversed by 0.1 mg kg(-1) atropine i.v. Our data show that acute right VS does not affect baseline cardiac metabolism, but attenuates myocardial oxygen consumption and glucose oxidation in response to adrenergic stress, thus functioning as a cardio-selective antagonist to β-adrenergic activation.

  16. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  17. Does iodine biofortification affect oxidative metabolism in lettuce plants?

    Science.gov (United States)

    Blasco, Begoña; Ríos, Juan Jose; Leyva, Rocío; Cervilla, Luis Miguel; Sánchez-Rodríguez, Eva; Rubio-Wilhelmi, María Mar; Rosales, Miguel Angel; Ruiz, Juan Manuel; Romero, Luis

    2011-09-01

    Plants produce low levels of reactive oxygen species (ROS), which form part of basic cell chemical communication; however, different types of stress can lead to an overexpression of ROS that can damage macromolecules essential for plant growth and development. Iodine is vital to human health, and iodine biofortification programs help improve the human intake through plant consumption. This biofortification process has been shown to influence the antioxidant capacity of lettuce plants, suggesting that the oxidative metabolism of the plant may be affected. The results of this study demonstrate that the response to oxidative stress is variable and depends on the form of iodine applied. Application of iodide (I(-)) to lettuce plants produces a reduction in superoxide dismutase (SOD) activity and an increase in catalase (CAT) and L-galactono dehydrogenase enzyme activities and in the activity of antioxidant compounds such as ascorbate (AA) and glutathione. This did not prove a very effective approach since a dose of 80 μM produced a reduction in the biomass of the plants. For its part, application of iodate (IO (3) (-) ) produced an increase in the activities of SOD, ascorbate peroxidase, and CAT, the main enzymes involved in ROS detoxification; it also increased the concentration of AA and the regenerative activities of the Halliwell-Asada cycle. These data confirm the non-phytotoxicity of IO (3) (-) since there is no lipid peroxidation or biomass reduction. According to our results, the ability of IO (3) (-) to induce the antioxidant system indicates that application of this form of iodine may be an effective strategy to improve the response of plants to different types of stress.

  18. Oxidative stress and stress signaling: menace of diabetic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Loren E WOLD; Asli F CEYLAN-ISIK; Jun REN

    2005-01-01

    Cardiovascular disease is the most common cause of death in the diabetic population and is currently one of the leading causes of death in the United States and other industrialized countries. The health care expenses associated with cardiovascular disease are staggering, reaching more than US$350 billion in 2003. The risk factors for cardiovascular disease include high fat/cholesterol levels,alcoholism, smoking, genetics, environmental factors and hypertension, which are commonly used to gauge an individual's risk of cardiovascular disease and to track their progress during therapy. Most recently, these factors have become important in the early prevention of cardiovascular diseases. Oxidative stress, the imbalance between reactive oxygen species production and breakdown by endogenous antioxidants, has been implicated in the onset and progression of cardiovascular diseases such as congestive heart failure and diabetes-associated heart dysfunction (diabetic cardiomyopathy). Antioxidant therapy has shown promise in preventing the development of diabetic heart complications. This review focuses on recent advances in oxidative stress theory and antioxidant therapy in diabetic cardiomyopathy, with an emphasis on the stress signaling pathways hypothesized to be involved. Many of these stress signaling pathways lead to activation of reactive oxygen species, major players in the development and progression of diabetic cardiomyopathy.

  19. Oxidative stress and CCN1 protein in human skin connective tissue aging

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    2016-06-01

    Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

  20. Oxidative stress and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Javier eBlesa

    2015-07-01

    Full Text Available Parkinson disease is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in Parkinson’s Disease. Environmental factors, such as neurotoxins, insecticides like rotenone, pesticides like Paraquat, dopamine itself and genetic mutations in Parkinson’s Disease related proteins contribute to mitochondrial dysfunction which precedes reactive oxygen species formation. In this mini review, we give an update of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the neurodegenerative process.

  1. Oxidative stress and Parkinson’s disease

    Science.gov (United States)

    Blesa, Javier; Trigo-Damas, Ines; Quiroga-Varela, Anna; Jackson-Lewis, Vernice R.

    2015-01-01

    Parkinson disease (PD) is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in PD. Environmental factors, such as neurotoxins, pesticides, insecticides, dopamine (DA) itself, and genetic mutations in PD-associated proteins contribute to mitochondrial dysfunction which precedes reactive oxygen species formation. In this mini review, we give an update of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the neurodegenerative process. PMID:26217195

  2. Roles of the tyrosine isomers meta-tyrosine and ortho-tyrosine in oxidative stress.

    Science.gov (United States)

    Ipson, Brett R; Fisher, Alfred L

    2016-05-01

    The damage to cellular components by reactive oxygen species, termed oxidative stress, both increases with age and likely contributes to age-related diseases including Alzheimer's disease, atherosclerosis, diabetes, and cataract formation. In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring of the amino acid phenylalanine, which then produces the abnormal tyrosine isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o-tyrosine concentrations have been used as a biological marker of oxidative stress, there is emerging evidence from bacterial, plant, and mammalian studies demonstrating that these isomers, particularly m-tyrosine, directly produce adverse effects to cells and tissues. These new findings suggest that the abnormal tyrosine isomers could in fact represent mediators of the effects of oxidative stress. Consequently the accumulation of m- and o-tyrosine may disrupt cellular homeostasis and contribute to disease pathogenesis, and as result, effective defenses against oxidative stress can encompass not only the elimination of reactive oxygen species but also the metabolism and ultimately the removal of the abnormal tyrosine isomers from the cellular amino acid pool. Future research in this area is needed to clarify the biologic mechanisms by which the tyrosine isomers damage cells and disrupt the function of tissues and organs and to identify the metabolic pathways involved in removing the accumulated isomers after exposure to oxidative stress.

  3. Oxidant Stress in Renal Inflammation: Mechanisms and Remedies

    NARCIS (Netherlands)

    Ishola, D.A.

    2006-01-01

    Our overall hypothesis was that oxidant stress is a central player in renal inflammation; pharmacological reduction of oxidant stress should therefore relieve renal inflammation. We explored pro- and anti-oxidant mechanisms in three experimental renal injury models. OXIDANT-DEPENDENT RENAL

  4. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging.Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction fol...

  5. Study of Oxidative Stress in Vitiligo

    OpenAIRE

    2010-01-01

    Vitiligo is an idiopathic, acquired, circumscribed, hypomelanotic skin disorder, characterized by milky white patches of different sizes and shapes. It is due to the destruction of melanocytes resulting in the absence of pigment production of the skin and mucosal surfaces. Oxidative stress has been implicated in pathophysiology of vitiligo. To study the activity of blood Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) in vitiligo patients. A case–control study was conducted in whi...

  6. Oxidative stress in prostate hyperplasia and carcinogenesis

    OpenAIRE

    Udensi K. Udensi; Tchounwou, Paul B.

    2016-01-01

    Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the a...

  7. Nuclear lamins and oxidative stress in cell proliferation and longevity.

    Science.gov (United States)

    Shimi, Takeshi; Goldman, Robert D

    2014-01-01

    In mammalian cells, the nuclear lamina is composed of a complex fibrillar network associated with the inner membrane of the nuclear envelope. The lamina provides mechanical support for the nucleus and functions as the major determinant of its size and shape. At its innermost aspect it associates with peripheral components of chromatin and thereby contributes to the organization of interphase chromosomes. The A- and B-type lamins are the major structural components of the lamina, and numerous mutations in the A-type lamin gene have been shown to cause many types of human diseases collectively known as the laminopathies. These mutations have also been shown to cause a disruption in the normal interactions between the A and B lamin networks. The impact of these mutations on nuclear functions is related to the roles of lamins in regulating various essential processes including DNA synthesis and damage repair, transcription and the regulation of genes involved in the response to oxidative stress. The major cause of oxidative stress is the production of reactive oxygen species (ROS), which is critically important for cell proliferation and longevity. Moderate increases in ROS act to initiate signaling pathways involved in cell proliferation and differentiation, whereas excessive increases in ROS cause oxidative stress, which in turn induces cell death and/or senescence. In this review, we cover current findings about the role of lamins in regulating cell proliferation and longevity through oxidative stress responses and ROS signaling pathways. We also speculate on the involvement of lamins in tumor cell proliferation through the control of ROS metabolism.

  8. Oxidative stress and male reproductive health

    Directory of Open Access Journals (Sweden)

    Robert J Aitken

    2014-02-01

    Full Text Available One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high levels of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair (BER pathway, 8-oxoguanine glycosylase 1 (OGG1. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins (APE1, XRCC1 needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceivedin vitro and serves as a driver for current research into the origins of free radical generation in the germ line.

  9. Stressful life events and incident metabolic syndrome: the Hoorn study.

    Science.gov (United States)

    Rutters, Femke; Pilz, Stefan; Koopman, Anitra D M; Rauh, Simone P; Pouwer, Frans; Stehouwer, Coen D A; Elders, Petra J; Nijpels, Giel; Dekker, Jacqueline M

    2015-01-01

    Stressful life events are associated with the metabolic syndrome in cross-sectional studies, but prospective studies addressing this issue are rare and limited. We therefore evaluated whether the number of stressful life events is associated with incident metabolic syndrome. We assessed the association between the number of stressful life events experienced in the 5 years up until baseline and incident metabolic syndrome after 6.5 years at follow-up in the Hoorn study, a middle-aged and elderly population-based cohort. Participants with prevalent metabolic syndrome at baseline were excluded. Metabolic syndrome was defined according to the Adult Treatment Panel III, including fasting plasma glucose levels, HDL-C levels, triglyceride levels, waist circumference and hypertension. We included 1099 participants (47% male; age 60 ± 7 years). During 6.5 years of follow-up, 238 participants (22%) developed the metabolic syndrome. Logistic regression adjusted for age, sex, education level and follow-up duration showed a positive association between the number of stressful life events at baseline and incident metabolic syndrome [OR 1.13 (1.01-1.27) per event, p = 0.049]. In addition, a Poisson model showed a significant positive association between the number of stressful life events at baseline and the number of metabolic syndrome factors at follow-up [OR 1.05 (1.01-1.11) per event, p = 0.018]. Finally, we observed a significant association between the number of stressful life events at baseline and waist circumference at follow-up [adjusted for confounders β 0.86 (0.39-1.34) cm per event, p metabolic syndrome during 6.5 years of follow-up, in a middle-aged and elderly population-based cohort.

  10. Role of mitochondrial oxidative stress in hypertension

    Science.gov (United States)

    Ungvari, Zoltan

    2013-01-01

    Based on mosaic theory, hypertension is a multifactorial disorder that develops because of genetic, environmental, anatomical, adaptive neural, endocrine, humoral, and hemodynamic factors. It has been recently proposed that oxidative stress may contribute to all of these factors and production of reactive oxygen species (ROS) play an important role in the development of hypertension. Previous studies focusing on the role of vascular NADPH oxidases provided strong support of this concept. Although mitochondria represent one of the most significant sources of cellular ROS generation, the regulation of mitochondrial ROS generation in the cardiovascular system and its pathophysiological role in hypertension are much less understood. In this review, the role of mitochondrial oxidative stress in the pathophysiology of hypertension and cross talk between angiotensin II signaling, pathways involved in mechanotransduction, NADPH oxidases, and mitochondria-derived ROS are considered. The possible benefits of therapeutic strategies that have the potential to attenuate mitochondrial oxidative stress for the prevention/treatment of hypertension are also discussed. PMID:24043248

  11. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress.

    Science.gov (United States)

    Liu, Shaobin; Zeng, Tingying Helen; Hofmann, Mario; Burcombe, Ehdi; Wei, Jun; Jiang, Rongrong; Kong, Jing; Chen, Yuan

    2011-09-27

    Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar concentration and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest average size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O(2)(•-)) induced reactive oxygen species (ROS) production is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidation capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidation stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We envision that physicochemical properties of graphene-based materials, such as density of functional groups, size, and conductivity, can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials.

  12. Iron, Oxidative Stress and Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Taifeng Zhuang

    2014-09-01

    Full Text Available Both iron deficiency and hyperglycemia are highly prevalent globally for pregnant women. Iron supplementation is recommended during pregnancy to control iron deficiency. The purposes of the review are to assess the oxidative effects of iron supplementation and the potential relationship between iron nutrition and gestational diabetes. High doses of iron (~relative to 60 mg or more daily for adult humans can induce lipid peroxidation in vitro and in animal studies. Pharmaceutical doses of iron supplements (e.g., 10× RDA or more for oral supplements or direct iron supplementation via injection or addition to the cell culture medium for a short or long duration will induce DNA damage. Higher heme-iron intake or iron status measured by various biomarkers, especially serum ferritin, might contribute to greater risk of gestational diabetes, which may be mediated by iron oxidative stress though lipid oxidation and/or DNA damage. However, information is lacking about the effect of low dose iron supplementation (≤60 mg daily on lipid peroxidation, DNA damage and gestational diabetes. Randomized trials of low-dose iron supplementation (≤60 mg daily for pregnant women are warranted to test the relationship between iron oxidative stress and insulin resistance/gestational diabetes, especially for iron-replete women.

  13. 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...

  14. Work stress and metabolic syndrome in radiologists: first evidence.

    Science.gov (United States)

    Magnavita, Nicola; Fileni, Adriano

    2014-02-01

    Scientific data have amply demonstrated that work stress increases the risk of cardiovascular disease. However, less attention has been given to the association between stress and metabolic syndrome. In this study, our aim was to investigate the relationship between work stress and metabolic syndrome in a population of radiologists. Radiologists and radiotherapists taking part in scientific conferences were invited to compile a questionnaire to evaluate work stress and the main parameters for diagnosing metabolic syndrome (obesity, hypertension, elevated cholesterol level, elevated triglycerides, and hyperglycemia). Most of the doctors taking part in the survey (n = 383, 58.6 %) were found to have at least one pathological component; 47 subjects (7.1 %) had metabolic syndrome. All the variables indicating work stress, whether derived from Karasek's demand/control model or from the effort/reward model devised by Siegrist, were significant predictors of metabolic syndrome components. Radiologists with elevated levels of stress had a significantly higher risk of being affected by metabolic syndrome than colleagues with lower stress levels, whether stress was defined as "job strain", i.e., elevated work load and reduced discretionary power (OR 4.89, 95 % CI 2.51-9.55), or as "effort reward imbalance", i.e., mismatch between effort and reward for the work performed (OR 4.66, 95 % CI 2.17-10.02). Should the results of this cross-sectional study be confirmed by a subsequent longitudinal survey, they would indicate the need for prompt organizational intervention to reduce occupational stress in radiologists.

  15. Shear stress induced stimulation of mammalian cell metabolism

    Science.gov (United States)

    Mcintire, L. V.; Frangos, J. A.; Eskin, S. G.

    1988-01-01

    A flow apparatus was developed for the study of the metabolic response of anchorage dependent cells to a wide range of steady and pulsatile shear stresses under well controlled conditions. Human umbilical vein endothelial cell monolayers were subjected to steady shear stresses of up to 24 dynes/sq cm, and the production of prostacyclin was determined. The onset of flow led to a burst in prostacyclin production which decayed to a long term steady state rate (SSR). The SSR of cells exposed to flow was greater than the basal release level, and increased linearly with increasing shear stress. It is demonstrated that shear stresses in certain ranges may not be detrimental to mammalian cell metabolism. In fact, throughout the range of shear stresses studied, metabolite production is maximized by maximizing shear stress.

  16. Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging?

    Science.gov (United States)

    Salmon, Adam B; Richardson, Arlan; Pérez, Viviana I

    2010-03-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an "antiaging" action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging.

  17. Oxidative Stress and Anxiety: Relationship and Cellular Pathways

    Directory of Open Access Journals (Sweden)

    Jaouad Bouayed

    2009-01-01

    Full Text Available High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal anxiety and also on a possible causal relationship between cellular oxidative stress and emotional stress. This review examines the recent discoveries made on the link between oxidative status and normal anxiety levels and the putative role of oxidative stress in genesis of anxiety. We discuss the different opinions and questions that exist in the field and review the methodological approaches that are being used to determine a causal relationship between oxidative and emotional stress.

  18. The impact of respiration and oxidative stress response on recombinant α-amylase production by Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Martinez Ruiz, José Luis; Meza, Eugenio; Petranovic, Dina

    2016-01-01

    to purify a secreted product. However, recombinant production at high rates represents a significant metabolic burden for the yeast cells, which results in oxidative stress and ultimately affects the protein production capacity. Here we describe a method to reduce the overall oxidative stress...... by overexpressing the endogenous HAP1 gene in a S. cerevisiae strain overproducing recombinant α-amylase. We demonstrate how Hap1p can activate a set of oxidative stress response genes and meanwhile contribute to increase the metabolic rate of the yeast strains, therefore mitigating the negative effect of the ROS...

  19. Arecoline aggravates hypothyroidism in metabolic stress in mice.

    Science.gov (United States)

    Dasgupta, Romi; Chatterjee, Aniruddha; Sarkar, Supriti; Maiti, B R

    2017-05-01

    Millions of people consume betel nut for increased capacity of work. It contains arecoline which is highly toxic and has several untoward side effects on endocrine functions. In this article, the role of arecoline on thyroid function under metabolic stress was investigated in mice. Water or food-deprivation, each for 5 days, caused ultrastructural degeneration of thyro-follicular cells, evident from pycnotic nuclei, scanty rough endoplasmic reticulum and mitochondria followed by depletion of blood serum T3 and T4 levels with alteration of TSH level as compared with control. Thyroid activity was also suppressed ultrastructurally as well as at hormonal level after arecoline administration. Further, arecoline treatment in water deprivation or food deprivation stress also caused thyroid dysfunction beyond that of metabolic stress, as evident from further ultrastructural degeneration of thyrocytes and depletion of thyroid hormones in mice. The findings suggest that arecoline aggravates hypothyroid condition in metabolic stress in mice.

  20. Role of oxidative stress in female reproduction.

    Science.gov (United States)

    Agarwal, Ashok; Gupta, Sajal; Sharma, Rakesh K

    2005-07-14

    In a healthy body, ROS (reactive oxygen species) and antioxidants remain in balance. When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS) occurs. OS influences the entire reproductive lifespan of a woman and even thereafter (i.e. menopause). OS results from an imbalance between prooxidants (free radical species) and the body's scavenging ability (antioxidants). ROS are a double-edged sword - they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract. ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy. It has been suggested that OS modulates the age-related decline in fertility. It plays a role during pregnancy and normal parturition and in initiation of preterm labor. Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor. Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants. There is growing literature on the effects of OS in female reproduction with involvement in the pathophysiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions. Numerous studies have shown that OS plays a role in the pathophysiology of infertility and assisted fertility. There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility. This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes. It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques. The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal embryopathies, preterm

  1. Role of oxidative stress in female reproduction

    Directory of Open Access Journals (Sweden)

    Sharma Rakesh K

    2005-07-01

    Full Text Available Abstract In a healthy body, ROS (reactive oxygen species and antioxidants remain in balance. When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS occurs. OS influences the entire reproductive lifespan of a woman and even thereafter (i.e. menopause. OS results from an imbalance between prooxidants (free radical species and the body's scavenging ability (antioxidants. ROS are a double-edged sword – they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract. ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy. It has been suggested that OS modulates the age-related decline in fertility. It plays a role during pregnancy and normal parturition and in initiation of preterm labor. Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor. Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants. There is growing literature on the effects of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions. Numerous studies have shown that OS plays a role in the pathoysiology of infertility and assisted fertility. There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility. This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes. It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques. The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal

  2. Pathway and mechanism of oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.

  3. Oxidative stress mediates physiological costs of begging in magpie (Pica pica nestlings.

    Directory of Open Access Journals (Sweden)

    Gregorio Moreno-Rueda

    Full Text Available BACKGROUND: Theoretical models predict that a cost is necessary to guarantee honesty in begging displays given by offspring to solicit food from their parents. There is evidence for begging costs in the form of a reduced growth rate and immunocompetence. Moreover, begging implies vigorous physical activity and attentiveness, which should increase metabolism and thus the releasing of pro-oxidant substances. Consequently, we predict that soliciting offspring incur a cost in terms of oxidative stress, and growth rate and immune response (processes that generate pro-oxidants substances are reduced in order to maintain oxidative balance. METHODOLOGY/PRINCIPAL FINDINGS: We test whether magpie (Pica pica nestlings incur a cost in terms of oxidative stress when experimentally forced to beg intensively, and whether oxidative balance is maintained by reducing growth rate and immune response. Our results show that begging provokes oxidative stress, and that nestlings begging for longer bouts reduce growth and immune response, thereby maintaining their oxidative status. CONCLUSIONS/SIGNIFICANCE: These findings help explaining the physiological link between begging and its associated growth and immunocompetence costs, which seems to be mediated by oxidative stress. Our study is a unique example of the complex relationships between the intensity of a communicative display (begging, oxidative stress, and life-history traits directly linked to viability.

  4. Lidocaine Oxidation by Electrogenerated Reactive Oxygen Species in the Light of Oxidative Drug Metabolism

    NARCIS (Netherlands)

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

    2010-01-01

    The study of oxidative drug metabolism by Cytochrome P450s (P450) is important in the earlier stages of drug development. For this purpose, automated analytical techniques are needed for fast and accurate estimation of oxidative drug metabolism. Previous studies have shown that electrochemistry in c

  5. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    Science.gov (United States)

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  6. Role of serum levels of irisin and oxidative stress markers in pregnant women with and without gestational diabetes.

    Science.gov (United States)

    Usluoğullari, Betül; Usluogullari, Celil Alper; Balkan, Fevzi; Orkmez, Mustafa

    2017-05-01

    Irisin regulates glucose levels, lipid levels, insulin sensitivity, and low-grade inflammation. Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy, and is associated with increased rates of perinatal problems. Oxidative stress biomarkers have a role in the pathogenesis of patients with GDM. In total, 94 patients were included in our study including 46 control patients and 48 patients with GDM. Fasting blood glucose, HOMA-IR, total oxidative stress (TOS), irisin, and oxidative stress index (OSI) levels of the patients were measured. Serum OGTT, OSI, irisin HOMA, TOS, and insulin levels were statistically significantly higher in the patient group than in the control group. This was the first study to investigate the relation between serum irisin levels and oxidative stress markers in patients with GDM. The results revealed that irisin is an oxidative stress marker and a metabolic protective hormone.

  7. Renal Dopamine Receptors, Oxidative Stress, and Hypertension

    Directory of Open Access Journals (Sweden)

    Ines Armando

    2013-08-01

    Full Text Available Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1, paraoxonase 2 (PON2, and heme oxygenase 2 (HO-2, all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice.

  8. Renal dopamine receptors, oxidative stress, and hypertension.

    Science.gov (United States)

    Cuevas, Santiago; Villar, Van Anthony; Jose, Pedro A; Armando, Ines

    2013-08-27

    Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1), paraoxonase 2 (PON2), and heme oxygenase 2 (HO-2), all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice.

  9. Oxidative Stress in Obesity: A Critical Component in Human Diseases

    Directory of Open Access Journals (Sweden)

    Lucia Marseglia

    2014-12-01

    Full Text Available Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS. Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.

  10. Apoptosis and oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    Radi, Elena; Formichi, Patrizia; Battisti, Carla; Federico, Antonio

    2014-01-01

    Neurodegenerative disorders affect almost 30 million individuals leading to disability and death. These disorders are characterized by pathological changes in disease-specific areas of the brain and degeneration of distinct neuron subsets. Despite the differences in clinical manifestations and neuronal vulnerability, the pathological processes appear similar, suggesting common neurodegenerative pathways. Apoptosis seems to play a key role in the progression of several neurologic disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis as demonstrated by studies on animal models and cell lines. On the other hand, research on human brains reported contradictory results. However, many dying neurons have been detected in brains of patients with neurodegenerative diseases, and these conditions are often associated with significant cell loss accompanied by typical morphological features of apoptosis such as chromatin condensation, DNA fragmentation, and activation of cysteine-proteases, caspases. Cell death and neurodegenerative conditions have been linked to oxidative stress and imbalance between generation of free radicals and antioxidant defenses. Multiple sclerosis, stroke, and neurodegenerative diseases have been associated with reactive oxygen species and nitric oxide. Here we present an overview of the involvement of neuronal apoptosis and oxidative stress in the most important neurodegenerative diseases, mainly focusing the attention on several genetic disorders, discussing the interaction between primary genetic abnormalities and the apoptotic pathways.

  11. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress.

    Science.gov (United States)

    Naudi, Alba; Jove, Mariona; Ayala, Victoria; Cassanye, Anna; Serrano, Jose; Gonzalo, Hugo; Boada, Jordi; Prat, Joan; Portero-Otin, Manuel; Pamplona, Reinald

    2012-01-01

    Oxidative stress has been implicated in diabetes long-term complications. In this paper, we summarize the growing evidence suggesting that hyperglycemia-induced overproduction of superoxide by mitochondrial electron transport chain triggers a maladaptive response by affecting several metabolic and signaling pathways involved in the pathophysiology of cellular dysfunction and diabetic complications. In particular, it is our goal to describe physiological mechanisms underlying the mitochondrial free radical production and regulation to explain the oxidative stress derived from a high intracellular glucose concentration and the resulting maladaptive response that leads to a cellular dysfunction and pathological state. Finally, we outline potential therapies for diabetes focused to the prevention of mitochondrial oxidative damage.

  12. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

    Science.gov (United States)

    López-López, Ana Laura; Jaime, Herlinda Bonilla; Escobar Villanueva, María Del Carmen; Padilla, Malinalli Brianza; Palacios, Gonzalo Vázquez; Aguilar, Francisco Javier Alarcón

    2016-07-01

    Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic

  13. Oxidative stress associated with exercise, psychological stress and life-style factors

    DEFF Research Database (Denmark)

    Møller, P; Wallin, H; Knudsen, Lisbeth E.

    1996-01-01

    generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress. Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress....... Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property....

  14. Effects of Exogenous Nitric Oxide on Reactive Oxygen Metabolism of Walnut Seedlings under Low Temperature Stress%外源NO对低温胁迫下核桃幼苗活性氧代谢的影响

    Institute of Scientific and Technical Information of China (English)

    相昆; 徐颖; 李国田; 王晓芳; 张美勇

    2016-01-01

    [目的]研究外源 NO处理对低温胁迫下核桃幼苗活性氧代谢系统的影响,探讨其影响核桃抗寒性的可能作用机制,寻找通过施加外源 NO提高果树抗逆性的新方法,为外源 NO在未来核桃抗逆生产中的广泛应用提供理论基础.[方法]以抗寒性不同的'香玲'、'鲁果12 号'核桃品种为材料,采用人工气候室模拟低温处理与叶片喷施 SNP相结合的方法,研究 SNP(200 μmol·L -1)对低温胁迫下核桃幼苗活性氧代谢的影响.[结果]1) 正常生长条件下,喷施 SNP对核桃幼苗叶片质膜透性、叶绿素含量、超氧阴离子( O·-2 )产生速率、过氧化氢( H2 O2 )含量、膜脂过氧化产物丙二醛( MDA)含量、脯氨酸( Pro)含量和超氧化物歧化酶( SOD)活性、过氧化氢酶( CAT)活性影响不大,显著提高了过氧化物酶(POD)、脱氢抗坏血酸还原酶(DHAR)、抗坏血酸过氧化物酶(APX)、谷胱甘肽还原酶( GR)活性和抗坏血酸( AsA)、谷胱甘肽( GSH)含量以及 AsA/DHA 和 GSH/GSSG 比值,降低了氧化型抗坏血酸(DHA)和还原型谷胱甘肽(GSH)含量,但2 个品种的各项指标变化程度不同.2) 低温胁迫下,SNP 处理可显著提高核桃幼苗叶片 POD,SOD,CAT,APX 和GR 等抗氧化物酶活性,同时,提高叶绿素和Pro,AsA,DHA,GSH,GSSG含量,减少 H2 O2和 MDA的积累,降低 O·-2 产生速率和细胞质膜相对透性,2 个品种的变化幅度不同.[结论]低温胁迫下,外源 NO 处理可增强核桃幼苗叶片抗氧化物酶活性,提高抗氧化剂含量,维持抗坏血酸 -谷胱甘肽( AsA-GSH)循环系统的稳定性,降低 H2 O2、MDA的积累及 O·-2 的产生速率,从而减轻活性氧对核桃叶片的伤害,保护细胞膜结构的稳定性,增强抗寒性.%[Objective]Effects of exogenous nitric oxide ( NO ) on the active oxygen metabolism system of walnut seedlings under low temperature stress were studied,in order to investigate the possible mechanism of exogenous NO on the

  15. Anti-oxidative effects of Rooibos tea (Aspalathus linearis on immobilization-induced oxidative stress in rat brain.

    Directory of Open Access Journals (Sweden)

    In-Sun Hong

    Full Text Available Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea's ability to (i reverse the increase in stress-related metabolites (5-HIAA and FFA, (ii prevent lipid peroxidation (LPO, (iii restore stress-induced protein degradation (PD, (iv regulate glutathione metabolism (GSH and GSH/GSSG ratio, and (v modulate changes in the activities of antioxidant enzymes (SOD and CAT.

  16. Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Bhaskar Ponugoti

    2012-01-01

    Full Text Available Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

  17. Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Aparna Areti

    2014-01-01

    Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

  18. Recent Advances in Polyamine Metabolism and Abiotic Stress Tolerance

    Directory of Open Access Journals (Sweden)

    Parimalan Rangan

    2014-01-01

    Full Text Available Global warming is an alarming problem in agriculture and its effect on yield loss has been estimated to be five per cent for every degree centigrade rise in temperature. Plants exhibit multiple mechanisms like optimizing signaling pathway, involvement of secondary messengers, production of biomolecules specifically in response to stress, modulation of various metabolic networks in accordance with stress, and so forth, in order to overcome abiotic stress factors. Many structural genes and networks of pathway were identified and reported in plant systems for abiotic stress tolerance. One such crucial metabolic pathway that is involved in normal physiological function and also gets modulated during stress to impart tolerance is polyamine metabolic pathway. Besides the role of structural genes, it is also important to know the mechanism by which these structural genes are regulated during stress. Present review highlights polyamine biosynthesis, catabolism, and its role in abiotic stress tolerance with special reference to plant systems. Additionally, a system based approach is discussed as a potential strategy to dissect the existing variation in crop species in unraveling the interacting regulatory components/genetic determinants related to PAs mediated abiotic stress tolerance.

  19. Oxidative stress inhibition and oxidant activity by fibrous clays.

    Science.gov (United States)

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Gómez-Vidales, Virginia

    2015-09-01

    Fibrous clays (sepiolite, palygorskite) are produced at 1.2m tonnes per year and have a wide range of industrial applications needing to replace long-fibre length asbestos. However, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the effect of sepiolite (Vallecas, Spain) and palygorskite (Torrejón El Rubio, Spain) on cell damage via oxidative stress (determined as the progress of lipid peroxidation, LP). The extent of LP was assessed using the Thiobarbituric Acid Reactive Substances assay. The oxidant activity by fibrous clays was quantified using Electron-Paramagnetic Resonance. Sepiolite and palygorskite inhibited LP, whereby corresponding IC50 values were 6557±1024 and 4250±289μgmL(-1). As evidenced by dose-response experiments LP inhibition by palygorskite was surface-controlled. Fibrous clay surfaces did not stabilize HO species, except for suspensions containing 5000μgmL(-1). A strong oxidant (or weak anti-oxidant) activity favours the inhibition of LP by fibrous clays.

  20. Stressful life events and incident metabolic syndrome

    DEFF Research Database (Denmark)

    Rutters, Femke; Pilz, Stefan; Koopman, Anitra D M

    2015-01-01

    . Metabolic syndrome was defined according to the Adult Treatment Panel III, including fasting plasma glucose levels, HDL-C levels, triglyceride levels, waist circumference and hypertension. We included 1099 participants (47% male; age 60 ± 7 years). During 6.5 years of follow-up, 238 participants (22...

  1. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Katherine M. Aird

    2015-05-01

    Full Text Available Replication stress induced by nucleotide deficiency plays an important role in cancer initiation. Replication stress in primary cells typically activates the cellular senescence tumor-suppression mechanism. Senescence bypass correlates with development of cancer, a disease characterized by metabolic reprogramming. However, the role of metabolic reprogramming in the cellular response to replication stress has been little explored. Here, we report that ataxia telangiectasia mutated (ATM plays a central role in regulating the cellular response to replication stress by shifting cellular metabolism. ATM inactivation bypasses senescence induced by replication stress triggered by nucleotide deficiency. This was due to restoration of deoxyribonucleotide triphosphate (dNTP levels through both upregulation of the pentose phosphate pathway via increased glucose-6-phosphate dehydrogenase (G6PD activity and enhanced glucose and glutamine consumption. These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation. Our data indicate that ATM status couples replication stress and metabolic reprogramming during senescence.