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Sample records for activity oxidative stress

  1. 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.

  2. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    JTEkanem

    effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ... SOD is an important enzyme family in living cells for maintaining ..... one unit of activity with oxidation rate of organic substrate in.

  3. 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.

  4. Oxidative stress

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    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.

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

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    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.

  6. Oxidative stress level and tyrosinase activity in vitiligo patients

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    Eskandani M

    2010-01-01

    Full Text Available Background: Vitiligo is an acquired pigmentary disorder of the skin. Genetic factors, oxidative stress, autoimmunity, and neurochemical agents might be contributing factors for the development of the disease. Aims: To evaluate the oxidative stress level and tyrosinase activity in vitiligo patients and to compare them with healthy volunteers. Materials and Methods: We used Comet assay to evaluate DNA strand breaks in peripheral blood cells of active vitiligo patients. We then extracted total protein from lesional and nonlesional skin of ten selected patients. Tyrosinase activity was found to play a crucial role in melanogenesis. Results: The basal level of systemic oxidative DNA strand breaks in leukocytes increased in vitiligo patients compared to healthy participants. We observed that tyrosinase activity in lesional skin was lower than in nonlesional skin. Conclusion: Our finding suggests that increased levels of oxidative stress might impact tyrosinase activity and eumelanin synthesis via anabolism pathway of melanin synthesis. In sum, we observed a negative correlation between levels of systemic oxidative stress and of tyrosinase activity.

  7. Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa

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    Gurunathan S

    2012-11-01

    cell viability, induced oxidative stress, and DNA fragmentation.Conclusion: The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P. aeruginosa viability increased in a dose- and time-dependent manner. Exposure to GO and rGO induced significant production of superoxide radical anion compared to control. GO and rGO showed dose-dependent antibacterial activity against P. aeruginosa cells through the generation of reactive oxygen species, leading to cell death, which was further confirmed through resulting nuclear fragmentation. The data presented here are novel in that they prove that GO and rGO are effective bactericidal agents against P. aeruginosa, which would be used as a future antibacterial agent.Keywords: graphene oxide, reduced graphene oxide, beta-mercaptoethanol, oxidative stress, antimicrobial activity

  8. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

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    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  9. Oxidative Stress and Maxi Calcium-Activated Potassium (BK Channels

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    Anton Hermann

    2015-08-01

    Full Text Available All cells contain ion channels in their outer (plasma and inner (organelle membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells, alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences.

  10. Oxidative stress

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    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

  11. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity.

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    Fukuda, Sanae; Nojima, Junzo; Motoki, Yukari; Yamaguti, Kouzi; Nakatomi, Yasuhito; Okawa, Naoko; Fujiwara, Kazumi; Watanabe, Yasuyoshi; Kuratsune, Hirohiko

    2016-07-01

    We sought to determine whether oxidative stress and anti-oxidative activity could act as biomarkers that discriminate patients with chronic fatigue syndrome (CFS) from healthy volunteers at acute and sub-acute fatigue and resting conditions. We calculated the oxidative stress index (OSI) from reactive oxygen metabolites-derived compounds (d-ROMs) and the biological antioxidant potential (BAP). We determined changes in d-ROMs, BAP, and OSI in acute and sub-acute fatigue in two healthy groups, and compared their values at rest between patients with CFS (diagnosed by Fukuda 1994 criteria) and another group of healthy controls. Following acute fatigue in healthy controls, d-ROMs and OSI increased, and BAP decreased. Although d-ROMs and OSI were significantly higher after sub-acute fatigue, BAP did not decrease. Resting condition yielded higher d-ROMs, higher OSI, and lower BAP in patients with CFS than in healthy volunteers, but lower d-ROMs and OSI when compared with sub-acute controls. BAP values did not significantly differ between patients with CFS and controls in the sub-acute condition. However, values were significantly higher than in the resting condition for controls. Thus, measured of oxidative stress (d-ROMS) and anti-oxidative activity (BAP) might be useful for discriminating acute, sub-acute, and resting fatigue in healthy people from patients with CFS, or for evaluating fatigue levels in healthy people.

  12. Oxidative stress and myocarditis.

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    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.

  13. Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.

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    Shah, Amit Aakash; Dey-Rao, Rama; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2016-06-01

    Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.

  14. Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies.

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    Pathak, S K; Sharma, R A; Steward, W P; Mellon, J K; Griffiths, T R L; Gescher, A J

    2005-01-01

    Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. Oxidative stress may be linked to the effects of androgens, anti-oxidant systems and the pre-malignant condition, high-grade prostatic intraepithelial neoplasia. Cyclooxygenase-2 activity has been linked with prostate carcinogenesis. Evidence suggests that oxidative stress and cyclo-oxygenase-2 activity may be mechanistically linked. Agents such as anti-oxidants and cyclo-oxgenase-2 inhibitors may be of value in the chemoprevention of prostate cancer. The feasibility of intervention with such agents will depend on the development and validation of biomarkers for clinical trials, particularly markers of oxidative damage caused by reactive oxygen species (ROS). A greater understanding of the molecular events associated with oxidative stress will enhance the development of such biomarkers and should result in better strategies for the chemoprevention of prostate cancer.

  15. Oxidant stress promotes disease by activating CaMKII.

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    Anderson, Mark E

    2015-12-01

    CaMKII is activated by oxidation of methionine residues residing in the regulatory domain. Oxidized CaMKII (ox-CaMKII) is now thought to participate in cardiovascular and pulmonary diseases and cancer. This invited review summarizes current evidence for the role of ox-CaMKII in disease, considers critical knowledge gaps and suggests new areas for inquiry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway.

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    Zhu, Yao; Zhang, Ya-Jie; Liu, Wei-Wei; Shi, Ai-Wu; Gu, Ning

    2016-08-09

    Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2)-regulated genes such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone1) (NQO1). However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and improved the activities of superoxide dismutase (SOD) and catalase (CAT), resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

  17. Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

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    Yao Zhu

    2016-08-01

    Full Text Available Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL, one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2-regulated genes such as heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase (quinone1 (NQO1. However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS and malondialdehyde (MDA, and improved the activities of superoxide dismutase (SOD and catalase (CAT, resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

  18. Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo.

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    Dong, Yunzhou; Zhang, Miao; Wang, Shuangxi; Liang, Bin; Zhao, Zhengxing; Liu, Chao; Wu, Mingyuan; Choi, Hyoung Chul; Lyons, Timothy J; Zou, Ming-Hui

    2010-06-01

    The oxidation of LDLs is considered a key step in the development of atherosclerosis. How LDL oxidation contributes to atherosclerosis remains poorly defined. Here we report that oxidized and glycated LDL (HOG-LDL) causes aberrant endoplasmic reticulum (ER) stress and that the AMP-activated protein kinase (AMPK) suppressed HOG-LDL-triggered ER stress in vivo. ER stress markers, sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) activity and oxidation, and AMPK activity were monitored in cultured bovine aortic endothelial cells (BAECs) exposed to HOG-LDL or in isolated aortae from mice fed an atherogenic diet. Exposure of BAECs to clinically relevant concentrations of HOG-LDL induced prolonged ER stress and reduced SERCA activity but increased SERCA oxidation. Chronic administration of Tempol (a potent antioxidant) attenuated both SERCA oxidation and aberrant ER stress in mice fed a high-fat diet in vivo. Likewise, AMPK activation by pharmacological (5'-aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside, metformin, and statin) or genetic means (adenoviral overexpression of constitutively active AMPK mutants) significantly mitigated ER stress and SERCA oxidation and improved the endothelium-dependent relaxation in isolated mouse aortae. Finally, Tempol administration markedly attenuated impaired endothelium-dependent vasorelaxation, SERCA oxidation, ER stress, and atherosclerosis in ApoE(-/-) and ApoE(-/-)/AMPKalpha2(-/-) fed a high-fat diet. We conclude that HOG-LDL, via enhanced SERCA oxidation, causes aberrant ER stress, endothelial dysfunction, and atherosclerosis in vivo, all of which are inhibited by AMPK activation.

  19. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

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    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

    2014-11-01

    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. SIRT1 Activating Compounds Reduce Oxidative Stress and Prevent Cell Death in Neuronal Cells

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    Reas S Khan

    2012-12-01

    Full Text Available Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol and SRTAW04 reduced ROS levels, and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase, a mitochondrial enzyme, and promoted deacetylation of PGC-1α, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.

  1. Oxidative Stress and Anti-Oxidant Enzyme Activities in the Trophocytes and Fat Cells of Queen Honeybees (Apis mellifera)

    OpenAIRE

    Hsieh, Yu-Shan; Hsu, Chin-Yuan

    2013-01-01

    Trophocytes and fat cells of queen honeybees have been used for delayed cellular senescence studies, but their oxidative stress and anti-oxidant enzyme activities with advancing age are unknown. In this study, we assayed reactive oxygen species (ROS) and anti-oxidant enzymes in the trophocytes and fat cells of young and old queens. Young queens had lower ROS levels, lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and higher thioredoxin reductase ...

  2. Silica nanoparticles induce endoplasmic reticulum stress response, oxidative stress and activate the mitogen-activated protein kinase (MAPK signaling pathway

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    Verena Christen

    2014-01-01

    Full Text Available Application of silica nanoparticles (SiO2-NPs may result in human exposure. Here we investigate unexplored modes of action by which SiO2-NPs with average size of 225 nm act on human hepatoma cells (Huh7. We focused on the endoplasmic (ER stress response and on mitogen-activated protein kinase (MAPK signaling pathways. Both pathways were induced. ER stress and the associated three unfolded protein response (UPR pathways were activated as demonstrated by significant inductions of BiP and XBP-1s and a moderate but significant induction of ATF-4 at 0.05 and 0.5 mg/ml. In addition to activation of NFкB interferon stimulated genes IP-10, IRF-9, and ISG-15 were up-regulated. As a consequence of ER stress, the pro-inflammatory cytokine TNFα and PP2Ac were induced following exposure to 0.05 mg/ml SiO2-NPs. Additionally, this occurred at 0.005 mg/ml SiO2-NPs for TNFα at 24 h. This in turn led to a strong transcriptional induction of MAP-kinases and its target genes cJun, cMyc and CREB. A strong transcriptional down-regulation of the proapoptotic gene p53 occurred at 0.05 and 0.5 mg/ml SiO2-NP. Exposure of Huh7 cells to the anti-oxidant N-acetyl cysteine reduced transcriptional induction of ER stress markers demonstrating a link between the induction of oxidative stress and ER stress. Our study demonstrates that SiO2-NPs lead to strong ER stress and UPR induction, oxidative stress, activation of MAPK signaling and down-regulation of p53. All of these activated pathways, which are analyzed here for the first time in detail, inhibit apoptosis and induce cell proliferation, which may contribute to a hepatotoxic, inflammatory and tumorigenic action of SiO2-NPs.

  3. Circulating biologically active oxidized phospholipids show on-going and increased oxidative stress in older male mice

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    Jinbo Liu

    2013-01-01

    Significance: Oxidatively modified phospholipids are increased in the circulation during common, mild oxidant stresses of aging, or in male compared to female animals. Turnover of these biologically active phospholipids by rapid transport into liver and kidney is unchanged, so circulating levels reflect continuously increased production.

  4. Lung cancer: what are the links with oxidative stress, physical activity and nutrition.

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    Filaire, Edith; Dupuis, Carmen; Galvaing, Géraud; Aubreton, Sylvie; Laurent, Hélène; Richard, Ruddy; Filaire, Marc

    2013-12-01

    Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition.

  5. Systemic Prolidase Activity and Oxidative Stress in Keratoconus.

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    Kılıç, Raşit; Cumurcu, Tongabay; Sancaktar, Enver; Evliyaoğlu, Osman; Sezer, Hafize

    2016-01-01

    Our aim was to evaluate the serum prolidase activity, total antioxidant capacity (TAC) and total oxidant status (TOS) in patients with keratoconus. A total 69 keratoconus patients and 72 control subjects with similar age and gender were evaluated within the scope of this study. The keratoconus group was divided into four stages with the modified Krumeich classification. Serum prolidase activity, TAC and TOS were measured and compared between the patient and control groups. The median serum prolidase enzyme activity value was 528.3 (684.1-416.7) U/L in the keratoconus group and 606.2 (812.9-482.3) U/L in the control group. The difference between the groups was statistically significant (p = 0.027). The median TAC value was 1.24 (1.37-1.05) mmol/L in the keratoconus group and 1.29 (1.38-1.18) mmol/L in the control group. The median TOS value was 2 (4-1) μmol/L in the keratoconus group and 3 (4-2) μmol/L in the control group. There was no statistically significant difference between the two groups in terms of TAC or TOS (p = 0.113 and p = 0.366, respectively). There was a positive correlation between TAC and TOS in keratoconus group but not in the control group (r = 0.670, p = 0.001 and r = 0.141, p = 0.241, respectively). No significant relationship was seen between the keratoconus group stages and serum prolidase activity, TAS or TOS (p = 0.894, p = 0.155 and p = 0.381, respectively). In conclusion, a significant relationship was found between decreased serum prolidase activity and keratoconus but there was no significant relationship between keratoconus and serum TAC or TOS.

  6. Influence of Oxidative Stress on Biocontrol Activity of Cryptococcus laurentii against Blue Mold on Peach Fruit

    Science.gov (United States)

    Zhang, Zhanquan; Chen, Jian; Li, Boqiang; He, Chang; Chen, Yong; Tian, Shiping

    2017-01-01

    The limitations of chemical fungicides for the control of postharvest diseases have recently become more apparent. The utilization of antagonistic microorganisms is a promising alternative to that of fungicides to control postharvest decay. In previous studies, the antagonistic yeast Cryptococcus laurentii has shown excellent effects of biocontrol and great potential for practical application. Adverse conditions, such as oxidative stress, limit the practical application of antagonistic yeast. In this study, we investigated the oxidative stress tolerance of C. laurentii and the associated mechanisms. The results indicated that exogenous oxidative stress has a significant effect on the viability and biocontrol efficiency of C. laurentii. H2O2-induced oxidative stress led to the accumulation of reactive oxygen species. The results of flow cytometric analysis suggested that apoptosis is responsible for the reduced survival rate of C. laurentii under oxidative stress. Using tests of antioxidant activity, we found that C. laurentii could employ enzymatic systems to resist exogenous oxidative stress. The addition of exogenous glutathione, a non-enzymatic antioxidant, to the media can significantly enhance oxidative tolerance and biocontrol efficiency of C. laurentii. PMID:28210254

  7. Tear Film and Serum Prolidase Activity and Oxidative Stress in Patients With Keratoconus.

    Science.gov (United States)

    Göncü, Tuğba; Akal, Ali; Adıbelli, Fatih Mehmet; Çakmak, Sevim; Sezen, Hatice; Yılmaz, Ömer Faruk

    2015-09-01

    To determine and compare the serum and tear film prolidase activity (PA) between patients with keratoconus and healthy subjects. Also, we aimed to evaluate the serum oxidative stress level and the correlation with serum PA in patients with keratoconus. This prospective, comparative clinical study included 31 patients with keratoconus and 33 age-matched and sex-matched control subjects. All participants underwent a detailed ophthalmologic examination. Serum and tear samples were obtained from all participants. Tears and serum PA and serum oxidative stress markers were measured. No significant differences in demographic characteristics were detected between groups (P > 0.05). The serum PA was significantly lower in the keratoconus group than in the control group (895.6 ± 198.7 vs. 1145.9 ± 285.4 U/L, P keratoconus group than in the control group; however, this difference was not significant (3075.4 ± 672.2 vs. 3225.8 ± 903.2 U·L⁻¹·g⁻¹ protein, P = 0.45). Oxidative stress markers, such as total oxidant status and oxidative stress index, were found to be significantly higher in the keratoconus group (P keratoconus than in the controls. Additionally, serum oxidative stress markers were found to be higher than those of the controls. Thus, prolidase and systemic oxidative stress may have a role in the pathogenesis of keratoconus.

  8. Influence of Oxidative Stress on Biocontrol Activity of Cryptococcus laurentii against Blue Mold on Peach Fruit.

    Science.gov (United States)

    Zhang, Zhanquan; Chen, Jian; Li, Boqiang; He, Chang; Chen, Yong; Tian, Shiping

    2017-01-01

    The limitations of chemical fungicides for the control of postharvest diseases have recently become more apparent. The utilization of antagonistic microorganisms is a promising alternative to that of fungicides to control postharvest decay. In previous studies, the antagonistic yeast Cryptococcus laurentii has shown excellent effects of biocontrol and great potential for practical application. Adverse conditions, such as oxidative stress, limit the practical application of antagonistic yeast. In this study, we investigated the oxidative stress tolerance of C. laurentii and the associated mechanisms. The results indicated that exogenous oxidative stress has a significant effect on the viability and biocontrol efficiency of C. laurentii. H2O2-induced oxidative stress led to the accumulation of reactive oxygen species. The results of flow cytometric analysis suggested that apoptosis is responsible for the reduced survival rate of C. laurentii under oxidative stress. Using tests of antioxidant activity, we found that C. laurentii could employ enzymatic systems to resist exogenous oxidative stress. The addition of exogenous glutathione, a non-enzymatic antioxidant, to the media can significantly enhance oxidative tolerance and biocontrol efficiency of C. laurentii.

  9. The association between physical activity and sex-specific oxidative stress in older adults.

    Science.gov (United States)

    Takahashi, Masaki; Miyashita, Masashi; Park, Jong-Hwan; Kim, Hyun-Shik; Nakamura, Yoshio; Sakamoto, Shizuo; Suzuki, Katsuhiko

    2013-01-01

    Oxidative stress increases with advancing age and is a mediator of several diseases including cancer, cardiovascular disease, and diabetes. Moreover, postmenopausal women have a lower estrogen concentration, which is associated with elevated oxidative stress. However, there is no definitive evidence regarding the relationship between daily physical activity and oxidative stress status in older adults, including postmenopausal women. Twenty-nine adults (age, 70.1 ± 1.0 years, mean ± SE; 12 women and 17 men) were examined in this cross-sectional study. Prior to blood collection, the participants were asked to wear a uniaxial accelerometer for 4 consecutive weeks to determine their level of physical activity. After a 48-h period of physical activity avoidance and a 10-h overnight fast, venous blood samples were obtained from each participant. Fasting plasma derivatives of reactive oxygen metabolites (d-ROMs) and malondialdehyde (MDA) concentrations of oxidative stress markers were negatively correlated with the amount of physical activity in women (d-ROMs; r = -0.708, p = 0.002) (MDA; r = -0.549, p = 0. 028), but not in men. Fasting plasma biological antioxidant potential of antioxidant capacity marker was positively correlated with the amount of physical activity in women (BAP; r = 0.657, p = 0.006) (GSH; r = 0.549, p = 0.028), but not in men. Moreover, superoxide dismutase activity of antioxidant capacity marker was positively correlated with the amount of physical activity in men (r = 0.627, p = 0.039), but not in women. There were no associations between physical activity and other oxidative stress markers (reduced and oxidized glutathione, glutathione peroxidise, thioredoxin). These findings suggest that regular physical activity may have a protective effect against oxidative stress by increasing total antioxidant capacity, especially in postmenopausal women. Key PointsIt is important to consider daily physical activity status when evaluating antioxidant

  10. Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers.

    Science.gov (United States)

    Aslan, Mehmet; Duzenli, Ufuk; Esen, Ramazan; Soyoral, Yasemin Usul

    2017-10-01

    The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; p<0.001). Moreover, obese subjects have lower levels of TAC than in those in healthy subjects (p<0.001). In the Pearson's correlation analysis, enzyme activity of prolidase was positively related with TOS (p<0.001, r=0.529) and OSI (p<0.001, r=0.519) as well as BMI (p<0.001, r=0.692) and inversely related with TAC (p<0.05, r=-0.405) in obese subjects. Increased serum prolidase activity and decreased antioxidant levels are likely to be a results of increased of oxidative stress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

    Science.gov (United States)

    Pujol-Lereis, Luciana M; Schäfer, Nicole; Kuhn, Laura B; Rohrer, Bärbel; Pauly, Diana

    2016-01-01

    Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye.

  12. Markers of oxidative stress and erythrocyte antioxidant enzyme activity in older men and women with differing physical activity.

    Science.gov (United States)

    Rowiński, Rafał; Kozakiewicz, Mariusz; Kędziora-Kornatowska, Kornelia; Hübner-Woźniak, Elżbieta; Kędziora, Józef

    2013-11-01

    The aim of the present study was to examine the relationship between markers of oxidative stress and erythrocyte antioxidant enzyme activity and physical activity in older men and women. The present study included 481 participants (233 men and 248 women) in the age group 65-69 years (127 men and 125 women) and in the age group 90 years and over (106 men and 123 women). The classification of respondents by physical activity was based on answers to the question if, in the past 12 months, they engaged in any pastimes which require physical activity. The systemic oxidative stress status was assessed by measuring plasma iso-PGF2α and protein carbonyl concentration as well as erythrocyte antioxidant enzymes activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The concentration of plasma iso-PGF2α and protein carbonyls (CP) was lower in groups of younger men and women compared to the respective older groups. In all examined groups, physical activity resulted in decrease of these oxidative stress markers and simultaneously caused adaptive increase in the erythrocyte SOD activity. Additionally, in active younger men CAT, GPx, and GR activities were higher than in sedentary ones. In conclusion, oxidative stress increase is age-related, but physical activity can reduce oxidative stress markers and induce adaptive increase in the erythrocyte antioxidant enzyme activity, especially SOD, even in old and very old men and women. © 2013.

  13. Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

    Science.gov (United States)

    Kunchithapautham, Kannan; Atkinson, Carl; Rohrer, Bärbel

    2014-01-01

    Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. PMID:24711457

  14. Palm kernel cake extract exerts hepatoprotective activity in heat-induced oxidative stress in chicken hepatocytes.

    Science.gov (United States)

    Oskoueian, Ehsan; Abdullah, Norhani; Idrus, Zulkifli; Ebrahimi, Mahdi; Goh, Yong Meng; Shakeri, Majid; Oskoueian, Armin

    2014-10-02

    Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens. This study was performed to evaluate the hepatoprotective potential of PKC extract in heat-induced oxidative stress in chicken hepatocytes. The nature of the active metabolites and elucidation of the possible mechanism involved were also investigated. The PKC extract possessed free radical scavenging activity with values significantly (p Heat-induced oxidative stress in chicken hepatocyte impaired the total protein, lipid peroxidation and antioxidant enzymes activity significantly (p heat-induced hepatocytes with PKC extract (125 μg/ml) and silymarin as positive control increased these values significantly (p stress biomarkers including TNF-like, IFN-γ and IL-1β genes; NF-κB, COX-2, iNOS and Hsp70 proteins expression upon heat stress in chicken hepatocytes. The PKC extract and silymarin were able to alleviate the expression of all of these biomarkers in heat-induced chicken hepatocytes. The gas chromatography-mass spectrometry analysis of PKC extract showed the presence of fatty acids, phenolic compounds, sugar derivatives and other organic compounds such as furfural which could be responsible for the observed hepatoprotective activity. Palm kernel cake extract could be a potential agent to protect hepatocytes function under heat induced oxidative stress.

  15. 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.

  16. Blood superoxiddismutase and catalase: enzymes activity under oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Каріна Леонідівна Шамелашвілі

    2015-05-01

    Full Text Available The activity of catalase and superoxide dismutase depends not only on the used compounds of rhenium, and also on their dimensional structure and form of applying. It is established that the cis- and trans-isomers of complex compounds of rhenium did countervailing effect on superoxide dismutase and catalase activities. Cis-isomers of Rhenium dycarboxylats agreed increased activity of superoxide dismutase and catalase. While under the action of trans-isomers, where increased activity of superoxide dismutase, catalase activity decreased

  17. Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice.

    Directory of Open Access Journals (Sweden)

    Yu-Kun Jennifer Zhang

    Full Text Available Acute fasting causes elevated oxidative stress. The current study investigated the effects of the nuclear factor erythoid 2-related factor 2 (Nrf2, the sensor of oxidative stress in cells, on energy homeostasis and liver pathophysiology during fasting. Feed was removed from mice possessing none (Nrf2-null, normal (wild-type, WT, enhanced (Keap1-knockdown, K1-KD, and maximum (hepatocyte-specific Keap1-knockout, K1-HKO Nrf2 activity in liver for 24 h. Body weight, blood glucose, and blood lipid profiles were similar among mice with graded Nrf2 activity under either fed or fasted conditions. Fasting reduced liver size in mice expressing Nrf2, but not in Nrf2-null mice. Nrf2-null mice accumulated more non-esterified free fatty acids and triglycerides in liver after fasting than the other genotypes of mice. Fatty acids are mainly catabolized in mitochondria, and Nrf2-null mice had lower mitochondrial content in liver under control feeding conditions, which was further reduced by fasting. In contrast, mitochondrial contents in mice with enhanced Nrf2 activity were not affected by fasting. Oxidative stress, determined by staining of free radicals and quantification of malondialdehyde equivalents, was highest in Nrf2-null and lowest in K1-HKO mice after fasting. The exacerbated oxidative stress in livers of Nrf2-null mice is predicted to lead to damages to mitochondria, and therefore diminished oxidation and increased accumulation of lipids in livers of Nrf2-null mice. In summary, the Nrf2-regulated signaling pathway is critical in protecting mitochondria from oxidative stress during feed deprivation, which ensures efficient utilization of fatty acids in livers of mice.

  18. Oxidative Stress in BPH

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    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

  19. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Akhilesh Kumar Verma

    2015-01-01

    Full Text Available Prolidase deficiency has been related to mental retardation and oxidative stress. The study aimed to observe plasma prolidase activity (PPA, total oxidant status (TOS, total antioxidant status (TAS, and oxidative stress index (OSI in patients with Parkinson’s disease (PD. 240 subjects with PD and 150 healthy volunteers were considered as cases and controls, respectively. PPA, TOS, TAS, and OSI were measured spectrophotometrically. PPA and TAS in cases were more significantly decreased than controls (P<0.01, while TOS and OSI were significantly increased (P<0.001. In cases, nonsignificant, positive correlation was observed between PPA and TOS and OSI while significant, negative correlation was observed between PPA and TAS (P=0.047. PPA in cases was nonsignificantly decreased with increased duration of PD (P=0.747 while TAS was significantly decreased (P<0.001 and TOS and OSI were significantly increased (P<0.001. It was observed that higher age groups had decreased PPA, and TAS and increased TOS and OSI compared to lower age groups in cases. In summary, patients with PD have decreased PPA and increased oxidative stress compared to healthy volunteers. PPA was associated with oxidative stress markers in patients with PD. Decreased PPA and TAS and increased TOS and OSI were associated with progression of disease and higher age.

  20. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson's Disease

    Science.gov (United States)

    Verma, Akhilesh Kumar; Raj, Janak; Sharma, Vivek; Singh, Tej Bali; Srivastava, Shalabh; Srivastava, Ragini

    2015-01-01

    Prolidase deficiency has been related to mental retardation and oxidative stress. The study aimed to observe plasma prolidase activity (PPA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) in patients with Parkinson's disease (PD). 240 subjects with PD and 150 healthy volunteers were considered as cases and controls, respectively. PPA, TOS, TAS, and OSI were measured spectrophotometrically. PPA and TAS in cases were more significantly decreased than controls (P < 0.01), while TOS and OSI were significantly increased (P < 0.001). In cases, nonsignificant, positive correlation was observed between PPA and TOS and OSI while significant, negative correlation was observed between PPA and TAS (P = 0.047). PPA in cases was nonsignificantly decreased with increased duration of PD (P = 0.747) while TAS was significantly decreased (P < 0.001) and TOS and OSI were significantly increased (P < 0.001). It was observed that higher age groups had decreased PPA, and TAS and increased TOS and OSI compared to lower age groups in cases. In summary, patients with PD have decreased PPA and increased oxidative stress compared to healthy volunteers. PPA was associated with oxidative stress markers in patients with PD. Decreased PPA and TAS and increased TOS and OSI were associated with progression of disease and higher age. PMID:26347150

  1. Inhibition of rat brain microsomal cytochrome P450-dependent dealkylation activities by an oxidative stress.

    Science.gov (United States)

    Lagrange, P; El-Bachá, R D; Netter, P; Minn, A

    2001-08-01

    There is increasing evidence that an oxidative stress not only alters cellular lipids and nucleic acids, but also numerous proteins. This oxidation results in alterations of some cellular functions, either by reversible modifications allowing a post-transcriptional regulation of enzyme activities or receptor affinities, or by irreversible modifications of the protein, triggering its inactivation and destruction. In the present work, we examined the effects of an experimental oxidative stress on rat brain microsomal cytochrome P450-dependent dealkylation activities. For that purpose, superoxide anions were produced either by the NADPH-dependent redox cycling of a quinine, menadione, or by the addition of apomorphine, which produces by autoxidation both superoxide anions and apomorphine-derived quinones. The inhibition of brain cytochrome P450-dependent alkoxyresorufin O-dealkylase activities was dependent on both menadione or apomorphine concentrations. Simultaneously, an increase of microsomal carbonyl groups was recorded. Immunoblotting characterization of brain microsomal oxidized protein was carried out, using antibodies raised against 2,4-dinitrophenylhydrazine as a reagent of protein carbonyl groups, and a revelation by a chemiluminescence method. We observed an increase in cerebral CYP1A protein oxidation, related to menadione concentration, suggesting that oxidation of cytochrome P450 protein may result in its catalytic inactivation.

  2. Oxidative Stress in Neurodegeneration

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    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.

  3. Induction of Mitochondrial Dysfunction and Oxidative Stress in Leishmania donovani by Orally Active Clerodane Diterpene

    Science.gov (United States)

    Kathuria, Manoj; Bhattacharjee, Arindam; Sashidhara, Koneni V.; Singh, Suriya Pratap

    2014-01-01

    This study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (K-09) in Leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in L. donovani promastigotes. Mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the cytosol, impairing ATP production. Oxidative stress caused the depletion of reduced glutathione, while pretreatment with antioxidant N-acetyl cysteine (NAC) was able to abrogate oxidative stress. However, NAC failed to restore the mitochondrial membrane potential or intracellular calcium homeostasis after K-09 treatment, suggesting that the generation of oxidative stress is a downstream event relative to the other events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were observed. Electron microscopy studies revealed gross morphological alterations typical of apoptosis, including severe mitochondrial damage, pyknosis of the nucleus, structural disruption of the mitochondrion-kinetoplast complex, flagellar pocket alterations, and the displacement of organelles. Moreover, an increased number of lipid droplets was detected after K-09 treatment, which is suggestive of altered lipid metabolism. Our results indicate that K-09 induces mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death in L. donovani promastigotes, sharing many features with metazoan apoptosis. These mechanistic insights provide a basis for further investigation toward the development of K-09 as a potential drug candidate for VL. PMID:25070112

  4. Bovine embryo survival under oxidative-stress conditions is associated with activity of the NRF2-mediated oxidative-stress-response pathway.

    Science.gov (United States)

    Amin, Ahmed; Gad, Ahmed; Salilew-Wondim, Dessie; Prastowo, Sigit; Held, Eva; Hoelker, Michael; Rings, Franca; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

    2014-06-01

    In present study, we sought to examine the ability of preimplantation bovine embryos to activate the NF-E2-related factor 2 (NRF2)-mediated oxidative-stress response under an oxidative stress environment. In vitro 2-, 4-, 8-, 16-cell-, and blastocyst-stage embryos were cultured under low (5%) or high (20%) oxygen levels. The expression of NRF2, KEAP1 (NRF2 inhibitor), antioxidants downstream of NRF2, and genes associated with embryo metabolism were analyzed between the embryo groups using real-time quantitative PCR. NRF2 and KEAP1 protein abundance, mitochondrial activity, and accumulation of reactive oxygen species (ROS) were also investigated in blastocysts of varying competence that were derived from high- or low-oxygen levels. The expression levels of NRF2 and its downstream antioxidant genes were higher in 8-cell, 16-cell, and blastocyst stages under high oxygen tension, whereas KEAP1 expression was down-regulated under the same conditions. Higher expression of NRF2 and lower ROS levels were detected in early (competent) blastocysts compared to their late (noncompetent) counterparts in both oxygen-tension groups. Similarly, higher levels of active nuclear NRF2 protein were detected in competent blastocysts compared to their noncompetent counterparts. Thus, the survival and developmental competence of embryos cultured under oxidative stress are associated with activity of the NRF2-mediated oxidative stress response pathway during bovine pre-implantation embryo development.

  5. Physical activity and soybean products : interests in management of oxidant stress associated to type 1 diabetes

    OpenAIRE

    Malardé, Ludivine

    2012-01-01

    Oxidant stress (OS) is well known to contribute to the onset and the development of diabetic complications. OS mainly result from marked rises in blood glucose level. Insulin treatment is required to keep patients alive, but fails to prevent long term complications progression, which result from hyperglycemic induced OS.In healthy people, diet and/or physical activity succeed to significantly reduce OS. Physical activity exhibit moreover glucoregulatory properties.Consequently, the aim of thi...

  6. Redox regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress.

    Science.gov (United States)

    Stankovic-Valentin, Nicolas; Drzewicka, Katarzyna; König, Cornelia; Schiebel, Elmar; Melchior, Frauke

    2016-06-15

    To sense and defend against oxidative stress, cells depend on signal transduction cascades involving redox-sensitive proteins. We previously identified SUMO (small ubiquitin-related modifier) enzymes as downstream effectors of reactive oxygen species (ROS). Hydrogen peroxide transiently inactivates SUMO E1 and E2 enzymes by inducing a disulfide bond between their catalytic cysteines. How important their oxidation is in light of many other redox-regulated proteins has however been unclear. To selectively disrupt this redox switch, we identified a catalytically fully active SUMO E2 enzyme variant (Ubc9 D100A) with strongly reduced propensity to maintain a disulfide with the E1 enzyme in vitro and in cells. Replacement of Ubc9 by this variant impairs cell survival both under acute and mild chronic oxidative stresses. Intriguingly, Ubc9 D100A cells fail to maintain activity of the ATM-Chk2 DNA damage response pathway that is induced by hydrogen peroxide. In line with this, these cells are also more sensitive to the ROS-producing chemotherapeutic drugs etoposide/Vp16 and Ara-C. These findings reveal that SUMO E1~E2 oxidation is an essential redox switch in oxidative stress.

  7. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction

    Directory of Open Access Journals (Sweden)

    Smita I. Negi

    2015-01-01

    Full Text Available Animal models have suggested a role of renin-angiotensin system (RAS activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF. Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs, F2-isoprostanes (IsoPs, and ratios of oxidized to reduced glutathione (Eh GSH and cysteine (Eh CyS were measured. Angiotensin converting enzyme (ACE levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p=0.04, higher body mass index (BMI (p=0.003, less oxidized Eh CyS (p=0.001, lower DROMs (p=0.02, and lower IsoP (p=0.03. Higher BMI (OR: 1.3; 95% CI: 1.1–1.6 and less oxidized Eh CyS (OR: 1.2; 95% CI: 1.1–1.4 maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01–1.05, ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF.

  8. Reactive Oxygene Species and Thioredoxin Activity in Plants at Development of Hypergravity and Oxidative Stresses

    Science.gov (United States)

    Jadko, Sergiy

    Early increasing of reactive oxygen species (ROS) content, including H2O2, occurs in plant cells under various impacts and than these ROS can function as signaling molecules in starting of cell stress responses. At the same time thioredoxins (TR) are significant ROS and H2O2 sensors and transmitters to activation of various redox sensitive proteins, transcription factors and MAP kinases. This study was aimed to investigate early increasing of ROS and H2O2 contents and TR activity in the pea roots and in tissue culture under hypergravity and oxidative stresses. Pea roots of 3-5 days old seedlings and 12-14 days old tissue culture of Arabidopsis thaliana were studied. The pea seedlings were grown on wet filter paper and the tissue culture was grown on MS medium in dark conditions under 24oC. Hypergravity stress was induced by centrifugation at 10 and 15 g. Chemiluminescence (ChL) intensity for ROS concentration, H2O2 content and TR activity were determined. All experiments were repeated by 3-5 times. Early and reliable increasing of ChL intensity and H2O2 contents in the pea roots and in the tissue culture took place under hypergravity and oxidative stresses to 30, 60 and 90 min. At the same time TR activity increased on 11 and 19 percents only to 60 and 90 min. Thus under hypergravity and oxidative stresses in both investigated plants take place early increasing of ROS and H2O2 contents which as second messengers lead to increasing of TR activity with creating of ROS-TR stress signaling pathway.

  9. Plasma Homocysteine Is Associated with Increased Oxidative Stress and Antioxidant Enzyme Activity in Welders

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    Hung-Hsin Liu

    2013-01-01

    Full Text Available The purpose of this study was to examine the association of vitamin B6 status and plasma homocysteine with oxidative stress and antioxidant capacities in welders. Workers were divided into either the welding exposure group (n=57 or the nonexposure controls (n=42 based on whether they were employed as welders. There were no significant differences in vitamin B6 status and plasma homocysteine concentration between the welding exposure group and the nonexposure controls. The welding exposure group had significantly higher levels of oxidized low-density lipoprotein cholesterol and lower erythrocyte glutathione concentration and superoxide dismutase (SOD activities when compared to nonexposure controls. Plasma pyridoxal 5′-phosphate concentration did not correlate with oxidative stress indicators or antioxidant capacities in either group. However, plasma homocysteine significantly correlated with total antioxidant capacity (TAC (partial rs=-0.34, P<0.05 and erythrocyte SOD activities (partial rs=0.29, P<0.05 after adjusting for potential confounders in the welding exposure group. In the welding exposure group, adequate vitamin B6 status was not associated with oxidative stress or antioxidant capacities. However, elevated plasma homocysteine seemed to be a major contributing factor to antioxidant capacities (TAC and erythrocyte SOD activities in welders.

  10. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

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    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  11. Investigating Endothelial Activation and Oxidative Stress in relation to Glycaemic Control in a Multiethnic Population

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    E. M. Brady

    2012-01-01

    Full Text Available Aim. An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA and White Europeans (WE residing in the UK. Methods. 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1α and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively. Results. 2,3-Dinor-8-iso-prostaglandin-F1α levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79 versus 8.46 (7.71, 9.29, P=0.021 after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (β=1.08, 95% CI:1.02, 1.14, P=0.009, fasting (β=1.06, 95% CI: 1.02, 1.10, P=0.002, and 2 hr glucose (β=1.02, 95% CI: 1.00, 1.04, P=0.052. In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P<0.001. No ethnic differences in ICAM-1 were observed. Conclusion. These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.

  12. Investigating Endothelial Activation and Oxidative Stress in relation to Glycaemic Control in a Multiethnic Population

    Science.gov (United States)

    Brady, E. M.; Webb, D. R.; Morris, D. H.; Khunti, K.; Talbot, D. S. C.; Sattar, N.; Davies, M. J.

    2012-01-01

    Aim. An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK. Methods. 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1α and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively. Results. 2,3-Dinor-8-iso-prostaglandin-F1α levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (β = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (β = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (β = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed. Conclusion. These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted. PMID:23304116

  13. Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.

    Science.gov (United States)

    Eduviere, Anthony T; Umukoro, S; Aderibigbe, Adegbuyi O; Ajayi, Abayomi M; Adewole, Folashade A

    2015-07-01

    Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

    Science.gov (United States)

    de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

    2016-12-01

    Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with

  15. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

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    Klingelhoeffer Christoph

    2012-05-01

    Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

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

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    Jarouliya Urmila

    2015-12-01

    Full Text Available 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 thiobarbituric acid reactive substances (TBARS]. These biochemical studies were associated with histopathological examination of liver and kidney sections. The microalga Spirulina maxima being rich in proteins and other essential nutrients is widely used as a food supplement. S. maxima at a dose of 5 and 10% per kg and the metformin (500 mg/kg as reference drug were given orally for 30 days to the diabetic rats. Diabetic rats showed significant (p < 0.001 elevations in plasma blood glucose, thiobarbituric acid-reactive substances and significant reduction in catalase, superoxide dismutase and reduced glutathione activity. Oral administration of 5 and 10% aqueous extract of S. maxima for 30 days restored not only of blood glucose levels but also markers of oxidative stress. Histopathological observations of tissues manifested that the S. maxima administration had the protective and therapeutic effects against fructose-induced abnormalities in diabetic rats. It is concluded that S. maxima is effective in reinstating the antioxidant activity in addition to its antidiabetic effect in type 2 diabetic rats.

  17. Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Laishram Pradeepkumar Singh; Amartya Mishra; Debjit Saha; Snehasikta Swarnakar

    2011-01-01

    AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis. RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro . In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro . Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

  18. 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

  19. Iron: the Redox-active center of oxidative stress in Alzheimer disease.

    Science.gov (United States)

    Castellani, Rudy J; Moreira, Paula I; Liu, Gang; Dobson, Jon; Perry, George; Smith, Mark A; Zhu, Xiongwei

    2007-10-01

    Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. 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.

  20. In vivo antioxidant activity of bark extract of Bixa orellana L. against acetaminophen- induced oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Smilin Bell Aseervatham G; Shamna R; Sangeetha B; Sasikumar JM

    2012-01-01

    Objective: To evaluate the in vivo activity of bark extract of Bixa orellana L. (B. orellana) against acetaminophen induced oxidative stress. Methods: In the present study, antioxidant activity ofB. orellana was evaluated by using normal and acetaminophen induced oxidative stressed rats at the dose of 100 mg/kg and 200 mg/kg p.o. oraly daily for 20 days. The animal's body weight was checked before and after treatment. Different biochemical parameters such as serum glutamate pyruvate transaminases, serum glutamate oxalo transaminases, alkaline phosphatase, total bilirubin, cholesterol, protein, lactate dehydrogenase, superoxide dismutase, catalase, ascorbic acid, lipid peroxide was performed. Histopathological analysis of the control and the hepatotoxicity induced rats were performed. Results: It was observed that the B. orellana bark extract showed significant protective activity against acetaminophen induced damage at 200 mg/kg dose level, while the 100 mg/kg dose showed moderate activity. Conclusions: From the result obtained in the present study suggest that B. orellana bark extract elicit protective activity through antioxidant activity on acetaminophen induced hepatic damage in rats.

  1. Antioxidative and neuroprotective activities of peanut sprout extracts against oxidative stress in SK-N-SH cells

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    Pranee Lertkaeo

    2017-01-01

    Conclusions: PSE has neuroprotective activities against oxidative stress in SK-N-SH cells induced by PQ, suggesting that PSE is a highly promising agent in the prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

  2. Relationship between physical activity and markers of oxidative stress in independent community-living elderly individuals.

    Science.gov (United States)

    Fraile-Bermúdez, A B; Kortajarena, M; Zarrazquin, I; Maquibar, A; Yanguas, J J; Sánchez-Fernández, C E; Gil, J; Irazusta, A; Ruiz-Litago, F

    2015-10-01

    The aim of the present study was to examine the relationship between objective data of physical activity and markers of oxidative stress in older men and women. Participants were old adults, aged≥60years (61 women and 34 men) who were all capable of performing basic daily activities by themselves and lived on their own. To describe physical activity we used objective data measured by accelerometers which record active and sedentary periods during everyday life for five days. Determination of oxidative stress was conducted from three perspectives: determination plasma total antioxidant status (TAS), plasma antioxidant enzyme activities, i.e., glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), and membrane lipid peroxidation (TBARS). In the group of women, those who met physical activity recommendations (WR) had lower level of TAS. In addition, the moderate to vigorous physical activity (MVPA) was negatively correlated with TAS. Simultaneously, MVPA was correlated with increase in the GPx antioxidant enzyme activity, and the counts per minute were positively correlated with CAT activity. In the group of men, the cpm and the MVPA were negatively correlated with lipid peroxidation while lifestyle physical activity was positively correlated with CAT activity. These findings suggest that MVPA in the elderly although it is related to a decrease in the TAS in women, induces adaptive increase in antioxidant enzyme activity and decreases lipid peroxidation in both women and men. These results suggest that at this time of life, it is not only the amount of physical activity performed that is important but also its intensity. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho, E-mail: kihos@catholic.ac.kr

    2013-09-20

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.

  4. Oxidative stress generation of silver nanoparticles in three bacterial genera and its relationship with the antimicrobial activity.

    Science.gov (United States)

    Quinteros, M A; Cano Aristizábal, V; Dalmasso, P R; Paraje, M G; Páez, P L

    2016-10-01

    Oxidative stress is a condition caused by the high intracellular concentrations of reactive oxygen species (ROS) that includes superoxide anion radicals, hydroxyl radicals and hydrogen peroxide. Nanoparticles could cause rapid generation of free radicals by redox reactions. ROS can react directly with membrane lipids, proteins and DNA and are normally scavenged by antioxidants that are capable of neutralizing; however, elevated concentrations of ROS in bacterial cells can result in oxidative stress. The aim of this work was contribute to the knowledge of action mechanism of silver nanoparticles (Ag-NPs) and their relation to the generation of oxidative stress in bacteria. We demonstrated that Ag-NPs generated oxidative stress in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa mediated by the increment of ROS and this increase correlated with a better antimicrobial activity. On the other hand, we showed that the oxidative stress caused by the Ag-NPs biosynthesized was associated to a variation in the level of reactive nitrogen intermediates (RNI). Oxidative stress in bacteria can result from disruption of the electronic transport chain due to the high affinity of Ag-NPs for the cell membrane. This imbalance in the oxidative stress was evidentiated by a macromolecular oxidation at level of DNA, lipids and proteins in E. coli exposed to Ag-NPs. The formation of ROS and RNI by Ag-NPs may also be considered to explain the bacterial death.

  5. Oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes exposed to clomazone (in vitro).

    Science.gov (United States)

    Santi, Adriana; Menezes, Charlene; Duarte, Marta Maria F; Leitemperger, Jossiele; Lópes, Thais; Loro, Vania L

    2011-09-01

    The aim of this study was to investigate the effect of clomazone herbicide on oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes in in vitro conditions. The activity of catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE), as well as the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were measured in human erythrocytes exposed (in vitro) to clomazone at varying concentrations in the range of 0, 100, 250 and 500 µg/L for 1 h at 37 °C.TBARS levels were significantly higher in erythrocytes incubated with clomazone at 100, 250 and 500 µg/L. However, erythrocyte CAT and AChE activities were decreased at all concentrations tested. SOD activity was increased only at 100 µg/L of clomazone. GSH levels did not change with clomazone exposure. These results clearly showed clomazone to induce oxidative stress and AChE inhibition in human erythrocytes (in vitro). We, thus, suggest a possible role of ROS on toxicity mechanism induced by clomazone in humans.

  6. Binding to WGR domain by salidroside activates PARP1 and protects hematopoietic stem cells from oxidative stress.

    Science.gov (United States)

    Li, Xue; Erden, Ozlem; Li, Liang; Ye, Qidong; Wilson, Andrew; Du, Wei

    2014-04-20

    A component of the base excision repair pathway, poly(ADP-ribose) polymerase-1 (PARP1) functions in multiple cellular processes, including DNA repair and programmed cell death. We previously showed that Salidroside, a phenylpropanoid glycoside isolated from medicinal plants, prevented the loss of hematopoietic stem cells (HSCs) in native mice and rescued HSCs repopulating in transplanted recipients under oxidative stress. The aim of this study was to investigate the mechanism by which PARP1 activation by Salidroside maintains HSCs under oxidative stress. We found that although there were no spontaneous defects in hematopoiesis in Parp1(-/-) mice, oxidative stress compromised the repopulating capacity of Parp1(-/-) HSCs in transplanted recipient mice. A biochemical study using truncated proteins lacking the defined functional domains of PARP1 showed that the tryptophan-glycine-arginine-rich (WGR) domain of PARP1 was critical for Salidroside binding and subsequent PARP1 activation under oxidative stress. Functionally, complementation of Parp1(-/-) HSCs with full-length PARP1WT, but not the PARP1R591K mutant in WGR domain restored Salidroside-stimulated PARP1 activation in vitro. Mechanistically, activated PARP1 by Salidroside enhanced the repopulating capacity of the stressed HSCs by accelerating oxidative DNA damage repair. INNOVATIONS AND CONCLUSION: Our findings reveal the action of mechanism for Salidroside in PARP1 stimulation and a novel role of PARP1 activation in maintaining HSC function under oxidative stress.

  7. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation.

    Science.gov (United States)

    Hybertson, Brooks M; Gao, Bifeng; Bose, Swapan K; McCord, Joe M

    2011-08-01

    For the past 40 years or so, oxidative stress has been increasingly recognized as a contributing factor in aging and in various forms of pathophysiology generally associated with aging. Our view of oxidative stress has been largely "superoxide-centric", as we focused on the pathological sources of this oxygen-derived free radical and the types of molecular havoc it can wreak, as well as on the protection provided by the antioxidant enzymes, especially the superoxide dismutases, catalases, and glutathione peroxidases. In the last decade our view of oxidative stress has broadened considerably, and it is now often seen as an imbalance that has its origins in our genes, and the ways in which gene expression is regulated. At the center of this new focus is the transcription factor called nuclear factor (erythroid-derived 2)-like 2, or Nrf2. Nrf2 is referred to as the "master regulator" of the antioxidant response, modulating the expression of hundreds of genes, including not only the familiar antioxidant enzymes, but large numbers of genes that control seemingly disparate processes such as immune and inflammatory responses, tissue remodeling and fibrosis, carcinogenesis and metastasis, and even cognitive dysfunction and addictive behavior. Thus, the dysregulation of Nrf2-regulated genes provides a logical explanation for the connections, both direct and indirect, between observable oxidative stress and perhaps 200 human diseases involving these various physiological processes, each reflecting a network involving many gene products. The evolutionary self-association of these many genes under the common control of Nrf2 suggests that the immune and inflammatory systems may present the largest demand for increased antioxidant protection, apart from constitutive oxidative stress resulting from mitochondrial oxygen consumption for metabolic purposes. Gene expression microarray data on human primary vascular endothelial cells and on the SK-N-MC human neuroblastoma-derived cell

  8. Endoplasmic reticulum stress-sensing mechanism is activated in Entamoeba histolytica upon treatment with nitric oxide.

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    Julien Santi-Rocca

    Full Text Available The Endoplasmic Reticulum stores calcium and is a site of protein synthesis and modification. Changes in ER homeostasis lead to stress responses with an activation of the unfolded protein response (UPR. The Entamoeba histolytica endomembrane system is simple compared to those of higher eukaryotes, as a canonical ER is not observed. During amoebiasis, an infection of the human intestine and liver by E. histolytica, nitric oxide (NO triggers an apoptotic-like event preceded by an impairment of energy production and a loss of important parasite pathogenic features. We address the question of how this ancient eukaryote responds to stress induced by immune components (i.e. NO and whether stress leads to ER changes and subsequently to an UPR. Gene expression analysis suggested that NO triggers stress responses marked by (i dramatic up-regulation of hsp genes although a bona fide UPR is absent; (ii induction of DNA repair and redox gene expression and iii up-regulation of glycolysis-related gene expression. Enzymology approaches demonstrate that NO directly inhibits glycolysis and enhance cysteine synthase activity. Using live imaging and confocal microscopy we found that NO dramatically provokes extensive ER fragmentation. ER fission in E. histolytica appears as a protective response against stress, as it has been recently proposed for neuron self-defense during neurologic disorders. Chronic ER stress is also involved in metabolic diseases including diabetes, where NO production reduces ER calcium levels and activates cell death. Our data highlighted unique cellular responses of interest to understand the mechanisms of parasite death during amoebiasis.

  9. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-02-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.

  10. Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.

    Science.gov (United States)

    Rodríguez-Fuentes, Gabriela; Rubio-Escalante, Fernando J; Noreña-Barroso, Elsa; Escalante-Herrera, Karla S; Schlenk, Daniel

    2015-01-01

    Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression.

  11. Stem cell factor (SCF) protects osteoblasts from oxidative stress through activating c-Kit-Akt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lei [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China); Wu, Zhong [Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Yin, Gang; Liu, Haifeng; Guan, Xiaojun; Zhao, Xiaoqiang [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China); Wang, Jianguang, E-mail: jianguangwang@163.com [Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Jianguo, E-mail: gehujianguo68@163.com [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China)

    2014-12-12

    Highlights: • SCF receptor c-Kit is functionally expressed in primary and transformed osteoblasts. • SCF protects primary and transformed osteoblasts from H{sub 2}O{sub 2}. • SCF activation of c-Kit in osteoblasts, required for its cyto-protective effects. • c-Kit mediates SCF-induced Akt activation in cultured osteoblasts. • Akt activation is required for SCF-regulated cyto-protective effects in osteoblasts. - Abstract: Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H{sub 2}O{sub 2}). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H{sub 2}O{sub 2}. Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H{sub 2}O{sub 2} was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H{sub 2}O{sub 2} activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H{sub 2}O{sub 2}-induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress.

  12. Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride.

    Science.gov (United States)

    Bhadauria, Monika; Nirala, Satendra Kumar; Shukla, Sangeeta

    2007-08-01

    Induction of CYP 2E1 by carbon tetrachloride (CCl(4)) is one of the central pathways by which CCl(4) generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl(4) to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl(4) (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and gamma-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl(4) exposure. Toxic effect of CCl(4) was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl(4). Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl(4). These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and

  13. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kaijun [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Jiang, Yiqian [The First People Hospital of Xiaoshan, Hangzhou (China); Wang, Wei; Ma, Jian [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Chen, Min, E-mail: eyedrchenminzj@163.com [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China)

    2015-12-25

    Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H{sub 2}O{sub 2}) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H{sub 2}O{sub 2}-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H{sub 2}O{sub 2} were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H{sub 2}O{sub 2}. Reversely, escin was more potent against H{sub 2}O{sub 2} damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H{sub 2}O{sub 2} was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling.

  14. Sir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregation.

    Science.gov (United States)

    Sorolla, M Alba; Nierga, Clara; Rodríguez-Colman, M José; Reverter-Branchat, Gemma; Arenas, Alicia; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

    2011-06-01

    Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG trinucleotide repeats, leading to an elongated polyglutamine sequence (polyQ) in the huntingtin protein. Misfolding of mutant polyQ proteins with expanded tracts results in aggregation, causing cytotoxicity. Oxidative stress in HD has been documented in humans as important to disease progression. Using yeast cells as a model of HD, we report that when grown at high glucose concentration, cells expressing mutant polyQ do not show apparent oxidative stress. At higher cell densities, when glucose becomes limiting and cells are metabolically shifting from fermentation to respiration, protein oxidation and catalase activity increases in relation to the length of the polyQ tract. Oxidative stress, either endogenous as a result of mutant polyQ expression or exogenously generated, increases Sir2 levels. Δ sir2 cells expressing expanded polyQ lengths show signs of oxidative stress even at the early exponential phase. In a wild-type background, isonicotinamide, a Sir2 activator, decreases mutant polyQ aggregation and the stress generated by expanded polyQ. Taken together, these results describe mutant polyQ proteins as being more toxic in respiring cells, causing oxidative stress and an increase in Sir2 levels. Activation of Sir2 would play a protective role against this toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Serum prolidase activity, oxidative stress, and antioxidant enzyme levels in patients with renal cell carcinoma.

    Science.gov (United States)

    Pirinççi, Necip; Kaba, Mehmet; Geçit, İlhan; Güneş, Mustafa; Yüksel, Mehmet Bilgehan; Tanık, Serhat; Arslan, Ayşe; Demir, Halit

    2016-02-01

    Prolidase is a member of the matrix metalloproteinase family. It plays a vital role in collagen turnover, matrix remodeling, and cell growth. Reactive oxygen species (ROS) have been implicated in the pathogenesis of various diseases, including cancers. Oxidative stress can cause tumor angiogenesis and may be carcinogenic. However, the relationship between antioxidant capacity and various cancers has been researched in several clinical trials. In our study, we aimed to identify serum prolidase activity, oxidative stress, and antioxidant enzyme levels in patients with renal tumors and to evaluate their relationships with each other. A total of 37 male patients with renal cell cancer and with a mean age of 56.28 ± 3.1 were included in the study. The control group comprising 36 male patients (mean age 56.31 ± 2.9) was randomly selected among the volunteers. Serum samples for measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels were kept at -20°C until they were used. Serum prolidase activity and MDA levels were significantly higher in renal cancer patients than in controls (all, p levels were significantly lower (p antioxidant levels in renal cancer. © The Author(s) 2013.

  16. Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G

    Directory of Open Access Journals (Sweden)

    Jason L.J. Lin

    2016-07-01

    Full Text Available Endonuclease G (EndoG is a mitochondrial protein that is released from mitochondria and relocated into the nucleus to promote chromosomal DNA fragmentation during apoptosis. Here, we show that oxidative stress causes cell-death defects in C. elegans through an EndoG-mediated cell-death pathway. In response to high reactive oxygen species (ROS levels, homodimeric CPS-6—the C. elegans homolog of EndoG—is dissociated into monomers with diminished nuclease activity. Conversely, the nuclease activity of CPS-6 is enhanced, and its dimeric structure is stabilized by its interaction with the worm AIF homolog, WAH-1, which shifts to disulfide cross-linked dimers under high ROS levels. CPS-6 thus acts as a ROS sensor to regulate the life and death of cells. Modulation of the EndoG dimer conformation could present an avenue for prevention and treatment of diseases resulting from oxidative stress.

  17. Analgesic activity of piracetam: effect on cytokine production and oxidative stress.

    Science.gov (United States)

    Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A

    2013-04-01

    Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Oxidative stress and inflammation modulate peroxisome proliferator-activated receptors with regional discrepancy in diabetic heart.

    Science.gov (United States)

    Lee, Ting-I; Kao, Yu-Hsun; Chen, Yao-Chang; Pan, Nan-Hung; Chen, Yi-Jen

    2010-08-01

    Peroxisome proliferator-activated receptors (PPARs) play a pivotal role in myocardial lipid and glucose homeostasis. We investigated the effects of diabetes on PPAR isoforms in different cardiac regions and explored whether proinflammatory cytokines or oxidative stress modulate PPARs in diabetic hearts. Male Wistar rats were separated into control, diabetes and ascorbate-treated diabetes groups. Real-time PCR and Western blot analysis were performed on PPAR isoforms, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, from left and right atria and ventricles. Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity was quantified through photometric measurements. In control hearts, PPAR-alpha was most expressed, and PPAR-gamma least expressed in mRNA and protein levels. Diabetes decreased the protein and mRNA levels of PPAR-alpha and PPAR-delta. Ascorbate attenuated the diabetes-induced down-regulations of PPAR-alpha and PPAR-delta proteins in all cardiac regions and down-regulation of PPAR-alpha mRNA in the left atrium. In PPAR-gamma, the protein and mRNA levels were increased in diabetic atria and ventricles, which were decreased by ascorbate. Moreover, diabetes increased the TNF-alpha and IL-6 protein levels, and NAD(P)H oxidase activities in atria and ventricles. Ascorbate attenuated the increase of TNF-alpha, IL-6 protein levels and NAD(P)H oxidase activity in the atria, but only attenuated the increase of NAD(P)H oxidase activities in the ventricles. Peroxisome proliferator-activated receptor isoforms are differentially expressed in the atria and ventricles. Diabetes can modulate PPARs through increased inflammatory cytokines and oxidative stress, which are attenuated by ascorbate treatment.

  19. Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Akinori, E-mail: morita@tokushima-u.ac.jp [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Department of Radiological Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509 (Japan); Tanimoto, Keiji; Murakami, Tomoki; Morinaga, Takeshi [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Hosoi, Yoshio, E-mail: hosoi@med.tohoku.ac.jp [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Department of Radiation Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)

    2014-01-24

    Highlights: • Oxidative ATM activation can occur in the absence of nuclear DNA damage response. • The oxidized Hep G2 cells were subjected to subcellular fractionation. • The obtained results suggest that the ATM activation occurs in mitochondria. • ATM failed to respond to oxidative stress in mitochondria-depleted Hep G2 cells. • Mitochondria are required for the oxidative activation of ATM. - Abstract: Ataxia–telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in DNA damage response (DDR). A recent study reported that oxidized ATM can be active in the absence of DDR. However, the issue of where ATM is activated by oxidative stress remains unclear. Regarding the localization of ATM, two possible locations, namely, mitochondria and peroxisomes are possible. We report herein that ATM can be activated when exposed to hydrogen peroxide without inducing nuclear DDR in Hep G2 cells, and the oxidized cells could be subjected to subcellular fractionation. The first detergent-based fractionation experiment revealed that active, phosphorylated ATM was located in the second fraction, which also contained both mitochondria and peroxisomes. An alternative fractionation method involving homogenization and differential centrifugation, which permits the light membrane fraction containing peroxisomes to be produced, but not mitochondria, revealed that the light membrane fraction contained only traces of ATM. In contrast, the heavy membrane fraction, which mainly contained mitochondrial components, was enriched in ATM and active ATM, suggesting that the oxidative activation of ATM occurs in mitochondria and not in peroxisomes. In Rho 0-Hep G2 cells, which lack mitochondrial DNA and functional mitochondria, ATM failed to respond to hydrogen peroxide, indicating that mitochondria are required for the oxidative activation of ATM. These findings strongly suggest that ATM can be activated in response to oxidative stress in mitochondria

  20. Temperature stress, anti-oxidative enzyme activity and virus acquisition in Bemisia tabaci (Hemiptera: Aleyrodidae)

    Science.gov (United States)

    In most eukaryotic systems, antioxidants provide protection when cells are exposed to stressful environmental conditions. Antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, function in a stepwise series with SOD initially preventing oxidative damage by conve...

  1. Physical activity attenuates intermittent hypoxia-induced spatial learning deficits and oxidative stress

    National Research Council Canada - National Science Library

    Gozal, David; Nair, Deepti; Goldbart, Aviv D

    2010-01-01

    Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying...

  2. Oxidative stress in the blood of patients with active localized vitiligo:

    OpenAIRE

    2008-01-01

    Objectives: Vitiligo is an acquired skin disease characterized by white areas on the skin. The pathogenesis of the disease is still unclear. Some findings show that oxidative stress could be an important phenomenon in the pathophysiology of vitiligo. Methods: We evaluated 16 consecutive localized vitiligo patients and 16 healthy controls of a similar age and sex distribution. We measured their indicators of oxidative stress such as catalase (CAT), superoxide dismutase (SOD), glucose 6-phospha...

  3. 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...

  4. Dietary whey protein stimulates mitochondrial activity and decreases oxidative stress in mouse female brain.

    Science.gov (United States)

    Shertzer, Howard G; Krishan, Mansi; Genter, Mary Beth

    2013-08-26

    In humans and experimental animals, protein-enriched diets are beneficial for weight management, muscle development, managing early stage insulin resistance and overall health. Previous studies have shown that in mice consuming a high fat diet, whey protein isolate (WPI) reduced hepatosteatosis and insulin resistance due in part to an increase in basal metabolic rate. In the current study, we examined the ability of WPI to increase energy metabolism in mouse brain. Female C57BL/6J mice were fed a normal AIN-93M diet for 12 weeks, with (WPI group) or without (Control group) 100g WPI/L drinking water. In WPI mice compared to controls, the oxidative stress biomarkers malondialdehyde and 4-hydroxyalkenals were 40% lower in brain homogenates, and the production of hydrogen peroxide and superoxide were 25-35% less in brain mitochondria. Brain mitochondria from WPI mice remained coupled, and exhibited higher rates of respiration with proportionately greater levels of cytochromes a+a3 and c+c1. These results suggested that WPI treatment increased the number or improved the function of brain mitochondria. qRT-PCR revealed that the gene encoding a master regulator of mitochondrial activity and biogenesis, Pgc-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) was elevated 2.2-fold, as were the PGC-1alpha downstream genes, Tfam (mitochondrial transcription factor A), Gabpa/Nrf-2a (GA-binding protein alpha/nuclear respiratory factor-2a), and Cox-6a1 (cytochrome oxidase-6a1). Each of these genes had twice the levels of transcript in brain tissue from WPI mice, relative to controls. There was no change in the expression of the housekeeping gene B2mg (beta-2 microglobulin). We conclude that dietary whey protein decreases oxidative stress and increases mitochondrial activity in mouse brain. Dietary supplementation with WPI may be a useful clinical intervention to treat conditions associated with oxidative stress or diminished mitochondrial activity in the

  5. Effect of ageing and oxidative stress on antioxidant enzyme activity in different regions of the rat kidney.

    Science.gov (United States)

    Thiab, Noor Riyadh; King, Nicola; Jones, Graham L

    2015-10-01

    Oxidative stress has been implicated in ageing and the pathogenesis of chronic kidney disease. We examined levels of antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and superoxide dismutase as modulated by age and oxidative stress in different regions of the kidney. Antioxidant enzymes were examined in different regions of the kidney in male Wistar rats. Kidneys from rats of different ages (5, 12, 36 and 60 weeks) were dissected into cortex, outer medulla and inner medulla. Tissues were incubated for 30 min with or without 0.2 mM H2O2 to induce oxidative stress. Antioxidant enzyme activities progressively decreased with age under both control and stress conditions (P Antioxidant enzyme activities were greater in the cortex (P < 0.05) by comparison with the outer and inner medulla, respectively.

  6. 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.

  7. Staphylococcal response to oxidative stress

    Directory of Open Access Journals (Sweden)

    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.

  8. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

  9. Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage.

    Science.gov (United States)

    Páramo, Blanca; Montiel, Teresa; Hernández-Espinosa, Diego R; Rivera-Martínez, Marlene; Morán, Julio; Massieu, Lourdes

    2013-11-01

    The mechanisms leading to neuronal death during glucose deprivation have not been fully elucidated, but a role of oxidative stress has been suggested. In the present study we have investigated whether the production of reactive oxygen species during glucose deprivation, contributes to the activation of calpain, a calcium-dependent protease involved in neuronal injury associated with brain ischemia and cerebral trauma. We have observed a rapid activation of calpain, as monitored by the cleavage of the cytoskeletal protein α-spectrin, after glucose withdrawal, which is reduced by inhibitors of xanthine oxidase, phospholipase A2 and NADPH oxidase. Results suggest that phospholipase A2 and NADPH oxidase contribute to the early activation of calpain after glucose deprivation. In particular NOX2, a member of the NADPH oxidase family is involved, since reduced stimulation of calpain activity is observed after glucose deprivation in hippocampal slices from transgenic mice lacking a functional NOX2. We observed an additive effect of the inhibitors of xanthine oxidase and phospholipase A2 on both ROS production and calpain activity, suggesting a synergistic action of these two enzymes. The present results provide new evidence showing that reactive oxygen species stimulate calpain activation during glucose deprivation and that this mechanism is involved in neuronal death.

  10. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

  11. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela, E-mail: daniela.parolaro@uninsubria.it [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  12. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  13. Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis.

    Science.gov (United States)

    Bingül, İlknur; Başaran-Küçükgergin, Canan; Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-07-01

    The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-β protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.

  14. Rapamycin Inhibits ALDH Activity, Resistance to Oxidative Stress, and Metastatic Potential in Murine Osteosarcoma Cells

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    Xiaodong Mu

    2013-01-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone. Mortality is determined by the presence of metastatic disease, but little is known regarding the biochemical events that drive metastases. Two murine OS cell lines, K7M2 and K12, are related but differ significantly in their metastatic potentials: K7M2 is highly metastatic whereas K12 displays much less metastatic potential. Using this experimental system, the mammalian target of rapamycin (mTOR pathway has been implicated in OS metastasis. We also discovered that aldehyde dehydrogenase (ALDH, a stem cell marker activity is higher in K7M2 cells than K12 cells. Rapamycin treatment reduces the expression and enzymatic activity of ALDH in K7M2 cells. ALDH inhibition renders these cells more susceptible to apoptotic death when exposed to oxidative stress. Furthermore, rapamycin treatment reduces bone morphogenetic protein-2 (BMP2 and vascular endothelial growth factor (VEGF gene expression and inhibits K7M2 proliferation, migration, and invasion in vitro. Inhibition of ALDH with disulfiram correlated with decreased mTOR expression and activity. In conclusion, we provide evidence for interaction between mTOR activity, ALDH activity, and metastatic potential in murine OS cells. Our work suggests that mTOR and ALDH are therapeutic targets for the treatment and prevention of OS metastasis.

  15. The Influence of Gasotransmitters on Membrane Permeability and Activity of Tonoplast H+-ATPase Under Oxidative Stress

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    E.V. Spiridonova

    2016-05-01

    Full Text Available The investigation of the influence of gasotransmitters – a new class of signaling molecules – on the root tissues of red beet (Beta vulgaris L. was conducted. It was found, that hydrogen sulfide (H2S had some stabilizing effect on cellular membranes, reducing their permeability detected with the aid of conductometric technique. The reliable influence of carbon monoxide (CO and nitrogen oxide (NO in our experiments was not observed. A significant increase in efflux of electrolytes from beet tissue under oxidative stress was observed. The addition of gasotransmitters failed to reduce it reliably. Under normal conditions, no appreciable effect of gasotransmitters on tonoplast H+-ATPase transport activity was found. Under oxidative stress, NO and H2S increased the H+-ATPase activity, reduced significantly by the impact of hydrogen peroxide, but did not recover it completely. CO enhanced the negative impact of oxidative stress, and reduced H+-ATPase transport activity. The results obtained suggest a possible conclusion that the gaseous signaling molecules take part in the regulation of transport processes in plant cell through the control of H+-ATPase activity under oxidative stress.

  16. Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress.

    Science.gov (United States)

    Liu, Ze-Qun; Shen, Ming; Wu, Wang-Jun; Li, Bo-Jiang; Weng, Qian-Nan; Li, Mei; Liu, Hong-Lin

    2015-06-01

    Many studies have demonstrated that oxidative stress-induced apoptosis is a main cause of follicular atresia. Reactive oxygen species (ROS)-induced granulosa cell (GC) apoptosis is regulated by a variety of signaling pathways involving numerous genes and transcription factors. In this study, we found expression of the p53-upregulated modulator of apoptosis (PUMA), a BH3-only Bcl-2 subfamily protein, in ovarian GCs during oxidative stress. By overexpression and knockdown of Forkhead box O1 (FoxO1), we found that FoxO1 regulates PUMA at the protein level. Moreover, as c-Jun N-terminal kinase (JNK) has been shown to activate FoxO1 by promoting its nuclear import, we used a JNK inhibitor to reduce FoxO1 activation and detected decreased PUMA messenger RNA expression and protein levels during oxidative stress. In addition, in vivo oxidative stress-induced upregulation of PUMA was found following injection of 3 nitropropionic acid in mice. In conclusion, oxidative stress increases PUMA expression regulated by FoxO1 in follicular GCs.

  17. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin-Bae [The Division of Cardiology, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-Gu, Seoul (Korea, Republic of); Kim, Changsoo [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Choi, Eunmi [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Park, Sanghoon; Park, Hyelim; Pak, Hui-Nam; Lee, Moon-Hyoung [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Shin, Dong Chun [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Hwang, Ki-Chul [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Joung, Boyoung, E-mail: cby6908@yuhs.ac [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-02-15

    Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague–Dawley rats, QT interval was increased from 115.0 ± 14.0 to 142.1 ± 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 μg/ml for 30 min, n = 5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p = 0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5 mmol/L, n = 3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5 μg/ml for 20 min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5 mmol/L, n = 5), nifedipine (10 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce

  18. Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.

    Science.gov (United States)

    Kuehne, Andreas; Emmert, Hila; Soehle, Joern; Winnefeld, Marc; Fischer, Frank; Wenck, Horst; Gallinat, Stefan; Terstegen, Lara; Lucius, Ralph; Hildebrand, Janosch; Zamboni, Nicola

    2015-08-01

    Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance.

  19. Functional activity of neutrophils in diabetes mellitus and coronary heart disease: role of myeloperoxidase in the development of oxidative stress.

    Science.gov (United States)

    Gorudko, I V; Kostevich, V A; Sokolov, A V; Shamova, E V; Buko, I V; Konstantinova, E E; Vasiliev, V B; Cherenkevich, S N; Panasenko, O M

    2012-11-01

    We performed a comparative analysis of functional activity of neutrophils in patients with type 2 diabetes mellitus with and without symptoms of CHD. Enhanced H2O2 production by neutrophils in response to N-formyl-Met-Leu-Phe (fMLP) was found in patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus associated with CHD, fMLP-induced release of myeloperoxidase from azurophilic granules of neutrophils was reduced and plasma myeloperoxidase level was elevated. Increased peroxidase activity of myeloperoxidase, reduced plasma catalase activity, and increased levels of TBA-reactive lipid peroxidation products and oxidized glutathione were detected in patients of both groups. Since myeloperoxidase is an important neutrophilic mediator of oxidative stress, its increased activity in the blood can be an additional marker of oxidative stress and cardiovascular risk in patients with diabetes mellitus.

  20. Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity.

    Science.gov (United States)

    Greenspan, H C; Aruoma, O I

    1994-05-01

    The cascade of events resulting from 'oxidative stress' is markedly similar to that which can initiate apoptosis, a possible mechanism of immune-cell loss in patients with HIV infection and AIDS. Since primary and secondary metabolites found in plants can act as synergistic antioxidants, and can prevent oxidation-induced cell death, Howard Greenspan and Okezie Aruoma ask whether or not these compounds can be useful in inhibiting viral activation and the death of immune cells in HIV/AIDS.

  1. Effect of Oxidative Stress on Lecithin Cholesterol Acyl Transferase Activity in Newly Detected Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Suman Doddaman

    2015-04-01

    Full Text Available Background: Oxidative Stress and Lecithin Cholesterol Acyl Transferase (LCAT activity is widely accepted participant in the development and progression of diabetes and its complications. Aim and Objectives: The present study has been undertaken to evaluate the effect of oxidative stress on LCAT activity in newly detected type 2 Diabetes Mellitus (DM, and its role in development and progression of diabetes and its complications. Materials and Methods: 200 participants were enrolled in the study, 100 with newly detected type 2 DM were taken as study group and 100 age and sex matched healthy participants were taken as control group. Biochemical parameters like serum Malondialdehyde (MDA, Superoxide Dismutase (SOD, LCAT activity, Total cholesterol, Triacylglycerol, HDL, LDL, VLDL and erythrocyte reduced glutathione levels were analyzed in all the participants. Results: The patients with type 2 DM showed increased oxidative stress (p<0.05 and decreased LCAT activity (p<0.001 and HDL levels (p<0.001. Conclusion: Study concludes that increased oxidative stress might be responsible for the reduced LCAT activity. This may be involved in pathogenesis of atherosclerosis and could be an alarming finding for the risk of atherosclerosis in newly detected type 2 DM.

  2. Palm kernel cake extract exerts hepatoprotective activity in heat-induced oxidative stress in chicken hepatocytes

    OpenAIRE

    Oskoueian, Ehsan; Abdullah, Norhani; Idrus, Zulkifli; Ebrahimi, Mahdi; Goh, Yong Meng; SHAKERI, Majid; Oskoueian, Armin

    2014-01-01

    Background Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens. Methods This study was performed to evaluate the hepatoprotective potential of PKC extract in heat-induced oxidative stress in chicken hepatocytes. The nature of the acti...

  3. 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.

  4. Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

    Science.gov (United States)

    Horiba, Minori; Kamiya, Tetsuro; Hara, Hirokazu; Adachi, Tetsuo

    2017-01-01

    Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues and has emerged as a novel technology for medical applications. NTAPP affects cells not only directly, but also indirectly with previously prepared plasma-activated medium (PAM). The objective of this study was to demonstrate the preconditioning effects of “mild PAM” which was prepared under relatively mild conditions, on fibroblasts against cellular injury generated by a high dose of hydrogen peroxide (H2O2). We observed the preconditioning effects of mild PAM containing approximately 50 μM H2O2. Hydrogen peroxide needs to be the main active species in mild PAM for it to exert preconditioning effects because the addition of catalase to mild PAM eliminated these effects. The nuclear translocation and recruitment of nuclear factor erythroid 2-related factor 2 (Nrf2) to antioxidant response elements (ARE) in heme oxygenase 1 (HO-1) promoters and the up-regulation of HO-1 were detected in fibroblasts treated with mild PAM. The addition of ZnPP, a HO-1-specific inhibitor, or the knockdown of Nrf2 completely abrogated the preconditioning effects. Our results demonstrate that mild PAM protects fibroblasts from oxidative stress by up-regulating HO-1, and the H2O2-induced activation of the Nrf2-ARE pathway needs to be involved in this reaction. PMID:28169359

  5. Serum antioxidant enzymes activities and oxidative stress levels in patients with acute ischemic stroke: influence on neurological status and outcome.

    Science.gov (United States)

    Milanlioglu, Aysel; Aslan, Mehmet; Ozkol, Halil; Çilingir, Vedat; Nuri Aydın, Mehmet; Karadas, Sevdegül

    2016-03-01

    Oxidative stress is well believed to play a role in the pathogenesis of acute ischemic stroke. Reports on antioxidant enzyme activities in patients with stroke are conflicting. Therefore, the aim of this study was to investigate serum antioxidant enzyme activities and oxidative stress levels in patients with acute ischemic stroke within 1st, 5th, and 21st day after stroke onset and also the relationship between these results and the clinical status of patients. The current study comprised 45 patients with acute ischemic stroke and 30 healthy controls. Serum malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activities were measured spectrophotometrically. Serum MDA levels were significantly higher in acute ischemic stroke patients within 24 h after stroke onset than controls (p levels did not change (p > 0.05). Serum SOD activity was significantly lower in 21st day compared to SOD activity of controls (p levels, GSH-Px, and CAT activities did not change significantly. Our study demonstrated that acute ischemic stroke patients have increased oxidative stress and decreased antioxidant enzymes activities. These findings indicated that an imbalance of oxidant and antioxidant status might play a role in the pathogenesis of acute ischemic stroke.

  6. Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide.

    Science.gov (United States)

    Zhang, Feng; Jin, Huanhuan; Wu, Li; Shao, Jiangjuan; Zhu, Xiaojing; Chen, Anping; Zheng, Shizhong

    2017-01-01

    Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS), the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs) were cultured and stimulated with hydrogen peroxide (H2O2) for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S) levels within HSCs, but iodoacetamide (IAM) reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis.

  7. Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-01-01

    Full Text Available Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS, the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs were cultured and stimulated with hydrogen peroxide (H2O2 for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S levels within HSCs, but iodoacetamide (IAM reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis.

  8. LRRK2 enhances oxidative stress-induced neurotoxicity via its kinase activity.

    Science.gov (United States)

    Heo, Hye Young; Park, Ji-Min; Kim, Cy-Hyun; Han, Baek Soo; Kim, Kwang-Soo; Seol, Wongi

    2010-02-15

    LRRK2 is an autosomal dominant gene whose mutations cause familial Parkinson's disease (PD). The LRRK2 protein contains a functional kinase and a GTPase domain. PD phenotypes caused by LRRK2 mutations are similar to those of idiopathic PD, implying that LRRK2 is an important participant in PD pathogenesis. Of LRRK2's PD-specific mutations, the G2019S is the most frequently observed one. Its over-expression is known to increase kinase activity and neurotoxicity compared to wild type (WT) LRRK2. Here, using a simple colorimetric cell viability assay, we analyzed LRRK2's neurotoxicity in dopaminergic SN4741 cells following treatment with hydrogen peroxide. When WT, G2019S, or empty vector was expressed in SN4741 cells, cell death was modestly and significantly increased in the order of G2019S>WT>vector. When these transfected cells were treated with hydrogen peroxide to mimic oxidative stress, cellular neurotoxicity was enhanced in the same order (i.e. G2019S>WT>vector). Moreover, incubation of SN4741 cells with conditioned medium from cells expressing G2019S and subjected to hydrogen peroxide treatment exhibited 10-15% more cell death than conditioned medium from cells transfected with vector or WT, suggesting that G2019S-expressing cells secrete a factor(s) affecting viability of neighboring cells. The kinase domain was mapped to be responsible for oxidative stress-induced neurotoxicity. In addition, over-expression of WT and G2019S LRRK2 lead to a weak, but significant, increase in intracellular reactive oxygen species (ROS) in the order of G2019S>WT as measured by DCFH-DA assay in both the presence and absence of H(2)O(2) treatment. Furthermore, in G2019S-expressing cells, co-expression of the anti-oxidant protein DJ-1 or ERK inhibitor treatment restored survival rate to a level similar to that of cells transfected with control vector under H(2)O(2) treatment. Taken together, our data suggest that the LRRK2 kinase domain increases the generation of ROS and causes

  9. Experimental Priapism is Associated with Increased Oxidative Stress and Activation of Protein Degradation Pathways in Corporal Tissue

    Science.gov (United States)

    Kanika, Nirmala D.; Melman, Arnold; Davies, Kelvin P.

    2010-01-01

    Priapism is a debilitating disease for which there is at present no clinically accepted pharmacologic intervention. It has been estimated that priapism lasting more than 24 hours in patients is associated with a 44–90% rate of erectile dysfunction (ED). In this investigation we determined in two animal models of priapism (opiorpin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity, and oxidatively damaged proteins in corporal tissue. Using Western blot analysis we demonstrated there is up regulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysososomal autophage protein, LC3. The anti-apoptotic protein, Bcl-2, was also up regulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. Since oxidative stress is known to mediate the development of ED resulting from several etiologies (for example ED resulting from diabetes and aging) we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress. PMID:21085184

  10. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Science.gov (United States)

    2010-01-01

    Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in vitro blood-placental barrier (BPB) model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC) activator in TR-TBT cells. Also, calcium ion (Ca2+) was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS) and diethyl maleate (DEM) significantly increased taurine uptake, but H2O2 and nitric oxide (NO) donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus. PMID:20804613

  11. Endothelial cell activation, oxidative stress and inflammation induced by a panel of metal-based nanomaterials

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Cao, Yi; Roursgaard, Martin

    2015-01-01

    The importance of composition, size, crystal structure, charge and coating of metal-based nanomaterials (NMs) were evaluated in human umbilical vein endothelial cells (HUVECs) and/or THP-1 monocytic cells. Biomarkers of oxidative stress and inflammation were assessed because they are important in...

  12. Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress.

    Science.gov (United States)

    Run-mei, Xiao; Jun-jun, Wang; Jing-ya, Chen; Li-juan, Sun; Yong, Chen

    2014-08-01

    Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma. The aim of the present work was to evaluate the impact of arecoline on human hepatic cytochrome P450 (CYP) enzymes in vitro and rat hepatic CYP enzymes, as well as the hepatic oxidative stress and liver injury of rats in vivo. The in vitro results indicated that arecoline hydrobromide (AH) has no significant effect on the activities of CYP2B, 2C9, 3A4, 1A2, 2E1 and 2D6 in human liver microsome (HLM). However, oral administration of AH at 4 and 20 mg/kg/d for seven consecutive days significantly increased the activities of rat hepatic CYP2B, 2E1, 2D, 3A, 2C and 1A2. In addition, AH at 100 mg/kg/d significantly increased the levels of ALT, AST and MDA, decreased the levels of SOD, CAT, GSH-Px and GSH, in rat liver. The in vivo induction of AH on rat hepatic CYP isoforms suggested that the high risk of metabolic interaction should be existed when the substrate drugs of the six kinds of CYP isoforms was administered in betel-quid use human. Furthermore, the in vivo results also suggested that AH-induced hepatoxicity should be associated with the induction of AH on rat hepatic CYP2E1 and 2B.

  13. Dual role of superoxide dismutase 2 induced in activated microglia: oxidative stress tolerance and convergence of inflammatory responses.

    Science.gov (United States)

    Ishihara, Yasuhiro; Takemoto, Takuya; Itoh, Kouichi; Ishida, Atsuhiko; Yamazaki, Takeshi

    2015-09-11

    Microglia are activated quickly in response to external pathogens or cell debris and clear these substances via the inflammatory response. However, excessive activation of microglia can be harmful to host cells due to the increased production of reactive oxygen species and proinflammatory cytokines. Superoxide dismutase 2 (SOD2) is reportedly induced under various inflammatory conditions in the central nervous system. We herein demonstrated that activated microglia strongly express SOD2 and examined the role of SOD2, focusing on regulation of the microglial activity and the susceptibility of microglia to oxidative stress. When rat primary microglia were treated with LPS, poly(I:C), peptidoglycan, or CpG oligodeoxynucleotide, respectively, the mRNA and protein levels of SOD2 largely increased. However, an increased expression of SOD2 was not detected in the primary neurons or astrocytes, indicating that SOD2 is specifically induced in microglia under inflammatory conditions. The activated microglia showed high tolerance to oxidative stress, whereas SOD2 knockdown conferred vulnerability to oxidative stress. Interestingly, the production of proinflammatory cytokines was increased in the activated microglia treated with SOD2 siRNA compared with that observed in the control siRNA-treated cells. Pretreatment with NADPH oxidase inhibitors, diphenylene iodonium and apocynin, decreased in not only reactive oxygen species generation but also the proinflammatory cytokine expression. Notably, SOD2 knockdown largely potentiated the nuclear factor κB activity in the activated microglia. Taken together, increased SOD2 conferred tolerance to oxidative stress in the microglia and decreased proinflammatory cytokine production by attenuating the nuclear factor κB activity. Therefore, SOD2 might regulate neuroinflammation by controlling the microglial activities.

  14. 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.

  15. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com; Jiang, Shengdan, E-mail: jiangsd@126.com; Jiang, Leisheng, E-mail: leisheng_jiang@126.com

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  16. A search for hepatoprotective activity of fruit extract of Mangifera indica L. against oxidative stress cytotoxicity.

    Science.gov (United States)

    Pourahmad, Jalal; Eskandari, Mohammad Reza; Shakibaei, Rashin; Kamalinejad, Mohammad

    2010-03-01

    Mango (Mangifera indica L.) and their components are commonly used in folk medicine for many curative effects. The protective effects of different concentrations of aqueous extract of Mangifera indica L. fruit (Mango Extract) (20, 50 and 100 microg/ml) and also gallic acid (100 microM) as a pure compound in the extract were examined against oxidative stress toxicity induced by cumene hydroperoxide (CHP) in isolated rat hepatocytes. The extracts and gallic acid (100 microM) protected the hepatocyte against all oxidative stress markers including cell lysis, ROS generation, lipid peroxidation, glutathione depletion, mitochondrial membrane potential decrease, lysosomal membrane oxidative damage and cellular proteolysis. Mango Extracts (20, 50 and 100 microg/ml) were more effective than gallic acid (100 microM) in protecting hepatocytes against CHP induced lipid peroxidation. On the other hand gallic acid (100 microM) acted more effective than Mango Extracts (20, 50 and 100 microg/ml) at preventing lysosomal membrane damage. In addition H(2)O(2) scavenging effect of all extracts were determined in hepatocytes and compared with gallic acid (100 microM). There were no significance differences (PMango Extract against liver injury associated with oxidative stress.

  17. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.

    Science.gov (United States)

    Qiang, Xiaoyan; Xu, Lulu; Zhang, Miao; Zhang, Pengcheng; Wang, Yinhang; Wang, Yongchen; Zhao, Zheng; Chen, Huan; Liu, Xie; Zhang, Yubin

    2016-04-15

    Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid β-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.

  18. Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis

    Science.gov (United States)

    Solcà, Manuela S.; Andrade, Bruno B.; Abbehusen, Melissa Moura Costa; Teixeira, Clarissa R.; Khouri, Ricardo; Valenzuela, Jesus G.; Kamhawi, Shaden; Bozza, Patrícia Torres; Fraga, Deborah Bittencourt Mothé; Borges, Valeria Matos; Veras, Patrícia Sampaio Tavares; Brodskyn, Claudia Ida

    2016-01-01

    Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti–sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines. PMID:27595802

  19. Assessing the Protective Activity of a Recently Discovered Phenolic Compound against Oxidative Stress Using Computational Chemistry.

    Science.gov (United States)

    Villuendas-Rey, Yenny; Alvarez-Idaboy, Juan Raul; Galano, Annia

    2015-12-28

    The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times and 4 orders of magnitude better than Trolox for that purpose in lipid and aqueous media, respectively. It was also found to react faster with HOO(•) than other known antioxidants such as resveratrol and ascorbic acid. DHMBA is also predicted to be able to sequester Cu(II) ions, consequently inhibiting the OS induced by Cu(II)-ascorbate mixtures and downgrading the (•)OH production via the Haber-Weiss reaction. However, it is proposed that DHMBA is more efficient as a primary antioxidant (free radical scavenger), than as a secondary antioxidant (metal ion chelator). In addition, it was found that DHMBA can be efficiently regenerated in aqueous solution, at physiological pH. Such regeneration is expected to contribute to increase the antioxidant protection exerted by DHMBA. These results suggest that probably synthetic routes for this compound should be pursued, because albeit its abundance in nature is rather low, its antioxidant activity is exceptional.

  20. 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.

  1. Nitric oxide-activated hydrogen sulfide is essential for cadmium stress response in bermudagrass (Cynodon dactylon (L). Pers.).

    Science.gov (United States)

    Shi, Haitao; Ye, Tiantian; Chan, Zhulong

    2014-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous molecules, serving as important secondary messengers in plant response to various biotic and abiotic stresses. However, the interaction between NO and H2S in plant stress response was largely unclear. In this study, endogenous NO and H2S were evidently induced by cadmium stress treatment in bermudagrass, and exogenous applications of NO donor (sodium nitroprusside, SNP) or H2S donor (sodium hydrosulfide, NaHS) conferred improved cadmium stress tolerance. Additionally, SNP and NaHS treatments alleviated cadmium stress-triggered plant growth inhibition, cell damage and reactive oxygen species (ROS) burst, partly via modulating enzymatic and non-enzymatic antioxidants. Moreover, SNP and NaHS treatments also induced the productions of both NO and H2S in the presence of Cd. Interestingly, combined treatments with inhibitors and scavengers of NO and H2S under cadmium stress condition showed that NO signal could be blocked by both NO and H2S inhibitors and scavengers, while H2S signal was specifically blocked by H2S inhibitors and scavengers, indicating that NO-activated H2S was essential for cadmium stress response. Taken together, we assigned the protective roles of endogenous and exogenous NO and H2S in bermudagrass response to cadmium stress, and speculated that NO-activated H2S might be essential for cadmium stress response in bermudagrass.

  2. Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity.

    Science.gov (United States)

    Vinciguerra, Manlio; Santini, Maria Paola; Claycomb, William C; Ladurner, Andreas G; Rosenthal, Nadia

    2009-12-10

    Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD(+)-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic.

  3. The biphasic redox sensing of SENP3 accounts for the HIF-1 transcriptional activity shift by oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Ying WANG; Jie YANG; Kai YANG; Hui CANG; Xin-zhi HUANG; Hui LI; Jing YI

    2012-01-01

    Aim:To investigate the mechanisms underlying the biphasic redox regulation of hypoxia-inducible factor-1 (HIF-1) transcriptional activity under different levels of oxidative stress caused by reactive oxidative species (ROS).Methods:HeLa cells were exposed to different concentrations of H2O2 as a simple model for mild and severe oxidative stress.Luciferase reporter assay and/or quantitative real-time PCR were used to investigate the transcriptional activity.Immunoblot was used to detect protein expression.Chromatin immunoprecipitation assay was used to detect HIF-1/DNA binding.The interaction of p300with HIF-1α or with SENP3,and the SUMO2/3 conjugation states of p300 were examined by coimmunoprecipitation.Results:HIF-1 transcriptional activity in HeLa cells was enhanced by low doses (0.05-0.5 mmol/L) of H202,but suppressed by high doses (0.75-8.0 mmol/L) of H2O2.The amount of co-activator p300 bound to HIF-1α in HeLa cells was increased under mild oxidative stress,but decreased under severe oxidative stress.The ROS levels differentially modified cysteines 243 and 532 in the cysteine protease SENP3,regulating the interaction of SENP3 with p300 to cause different SUMOylation of p300,thus shifting HIF-1 transcriptional activity.Conclusion:The shift of HIF-1 transactivation by ROS is correlated with and dependent on the biphasic redox sensing of SENP3 that leads to the differential SENP3/p300 interaction and the consequent fluctuation in the p300 SUMOylation status.

  4. Blood Pressure Reduction is Associated With the Changes in Oxidative Stress and Endothelial Activation in Hypertension, Regardless of Antihypertensive Therapy

    Directory of Open Access Journals (Sweden)

    Martina Mihalj

    2016-10-01

    Full Text Available Background/Aims: Hypertensive patients present with increased oxidative stress and frequently receive angiotensin II (ANGII receptor type I blockers (ARB for blood pressure (BP reduction. Recent studies revealed an important role of ANGII in maintaining vascular oxidative homeostasis, including sustaining normal sodium dismutase activity. This study aimed to investigate the effects of antihypertensive therapy and also vitamin C/E supplementation on BP, oxidative stress and endothelial activation in patients with essential hypertension. Methods: Newly discovered patients received ARB/olmesartan or the Ca2+-channel blocker (CCB/amlodipine, and additionally vitamin C/E or placebo throughout weeks 9-16. ELISA was used to determine 8-iso-prostaglendin F2-alpha (8iPGF2α and endothelial activation markers. Results: In both groups BP was normalized during first 8 weeks of therapy. Vitamins C/E had no additional BP-lowering effect. The vitamins C/E supplementation was not effective in reducing absolute values of 8iPGF2α; however; the magnitude of 8iPGF2α reduction was significantly greater in patients taking vitamins C/E in the CCB group. Although plasma 8iPGF2α positively correlated to BP, a significant decrease occurred during an additional 8 weeks of treatment. There were no changes in endothelial activation markers related to the specific action of ARB or CCB. Conclusions: Present study suggests that observed oxidative stress is a consequence of hypertension. BP reduction is associated with the observed decrease in oxidative stress and changes in endothelial activation regardless of antihypertensive therapy.

  5. 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.

  6. 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.

  7. The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress-activated Protein Kinase, Nitric Oxide and Cortisol

    Directory of Open Access Journals (Sweden)

    Alexander Panossian

    2007-01-01

    Full Text Available Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK, the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO, cortisol, testosterone, prostaglandin E2, leukotriene B4 and thromboxane B2 were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the fi nal treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200–300% cf basal levels following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their anti-depressant activity as well as their positive effects on mental performance under stress.

  8. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol.

    Science.gov (United States)

    Panossian, Alexander; Hambardzumyan, Marina; Hovhanissyan, Areg; Wikman, Georg

    2007-01-01

    Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E(2), leukotriene B(4) and thromboxane B(2) were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200-300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress.

  9. THE ROLE OF PROTEIN OXIDATIVE MODIFICATION IN REDOX-REGULATION OF CASPASE-3 ACTIVITY IN BLOOD LYMPHOCYTES DURING OXIDATIVE STRESS IN VITRO

    Directory of Open Access Journals (Sweden)

    O. L. Nosareva

    2015-01-01

    Full Text Available The formation of oxidative stress lies at the heart of many frequent and socially-important diseases. Blood lymphocytes are the cells which provide immunological control of our organism. As a result of their function implementation blood lymphocytes contact with different endogenic and exogenic factors, which can lead to active oxygen species production activation, macromolecules oxidative modification and to cell survival alteration. At the present time it is essential to expand and deepen the fundamental knowledge of blood lymphocytes apoptosis regulation peculiarities. The research objective was to establish the interaction among alterations of glutathione system condition, carbonylation level, protein glutathionylation and caspase-3 activity in blood lymphocytes during oxidative stress in vitro.Material and Methods. The material for research was blood lymphocytes cultivated with addition of hydrogen peroxide in final concentration of 0,5 mmol and/or protein SH-group inhibitor N-ethylmaleimide – 5 mmol, protector – 5 mmol – 1,4-dithioerythritol. Reduced, oxidized and protein-bound glutathione concentration was measured by method of spectropho-tometry, additionally, the ratio size of reduced to oxidized thiol fraction was estimated. With help of enzymoimmunoassay the level of protein carbonyl derivatives was evaluated; caspase-3 activity was registered by spectrofluorometric method.Results. Protein SH-group blocking in blood lymphocytes during oxidative stress in vitro was accompanied by protein-bound glutathione concentration rapid decrease in connection with increase of protein carbonyl derivatives content and caspase-3 activity. Protein SH-group protection in blood lymphocytes during oxidative stress in vitro was accompanied by concentration increase of protein-bound glutathione and protein carbonyl derivatives under comparable values of enzyme activity under study.Conclusion. The carried out research shows that caspase-3 and protein

  10. CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through upregulating L-type calcium channel activity.

    Science.gov (United States)

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-09-01

    A specialized culture medium termed ciliary neurotrophic factor-treated astrocyte-conditioned medium (CNTF-ACM) allows investigators to assess the peripheral effects of CNTF-induced activated astrocytes upon cultured neurons. CNTF-ACM has been shown to upregulate neuronal L-type calcium channel current activity, which has been previously linked to changes in mitochondrial respiration and oxidative stress. Therefore, the aim of this study was to evaluate CNTF-ACM's effects upon mitochondrial respiration and oxidative stress in rat cortical neurons. Cortical neurons, CNTF-ACM, and untreated control astrocyte-conditioned medium (UC-ACM) were prepared from neonatal Sprague-Dawley rat cortical tissue. Neurons were cultured in either CNTF-ACM or UC-ACM for a 48-h period. Changes in the following parameters before and after treatment with the L-type calcium channel blocker isradipine were assessed: (i) intracellular calcium levels, (ii) mitochondrial membrane potential (ΔΨm), (iii) oxygen consumption rate (OCR) and adenosine triphosphate (ATP) formation, (iv) intracellular nitric oxide (NO) levels, (v) mitochondrial reactive oxygen species (ROS) production, and (vi) susceptibility to the mitochondrial complex I toxin rotenone. CNTF-ACM neurons displayed the following significant changes relative to UC-ACM neurons: (i) increased intracellular calcium levels (p ACM (p ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through elevating L-type calcium channel activity.

  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. Zinco, estresse oxidativo e atividade física Zinc, oxidative stress and physical activity

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    Josely Correa Koury

    2003-12-01

    Full Text Available A atividade física intensa aumenta a formação de espécies reativas de oxigênio que podem causar lesões musculares e danos na membrana de eritrócitos, prejudicando o desempenho de atletas. Para prevenir os efeitos causados pelo estresse oxidativo, o organismo possui vários mecanismos antioxidantes, alguns dependentes de zinco. As propriedades antioxidantes desse mineral são explicadas pelo seu papel na regulação da síntese da metalotioneína, na estrutura da enzima superóxido dismutase e na proteção de agrupamentos sulfidrila de proteínas de membranas celulares por antagonismo com metais pró-oxidantes como ferro e cobre. Estudos têm demonstrado que a fragilidade osmótica de eritrócitos está relacionada à função do zinco na membrana celular. Atletas geralmente apresentam ingestão dietética desse mineral insuficiente para compensar as perdas aumentadas pelo suor e urina e para atender a demanda bioquímica. Este trabalho de revisão visa mostrar a importância biológica e nutricional do zinco na proteção antioxidante durante a atividade física intensa.During intense physical activity there is an increased production of reactive oxygen species that can cause muscle injury and damage to erythrocyte cell membranes, thus impairing athletic performance. In order to prevent the effects caused by oxidative stress, the organism has several antioxidant mechanisms, some of which depending on zinc. The antioxidant properties of this mineral are explained by its role in the regulation of metallothionein synthesis, in the structure of superoxide dismutase, and in the protection of sulfhydryl groups of cell membrane proteins through antagonism with pro-oxidant metals such as iron and copper. Recent studies have shown that the osmotic fragility of erythrocytes is related to the zinc function in cell membranes. Athletes generally have dietary zinc intakes inadequate to compensate for the increased sweat and urine losses to meet and

  13. ANTIOXIDANT ACTIVITY OF MAJORANA HORTENSIS LEAVES SUBJECTED TO OXIDATIVE STRESS IN AN IN VITRO SYSTEM

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    Palaniswamy Radha

    2011-06-01

    Full Text Available Oxidative stress can arise from an imbalance between the generation and elimination of reactive oxygen species leading to the excess levels, which in turn cause various diseases and cell death. Reactive oxygen species can be eliminated by a number of enzymic and non-enzymic antioxidant defense mechanisms. This was studied in Majorana hortensis using in vitro model simulating the in vivo system. Precision-cut goat liver slices were challenged with a standard oxidant (H2O2 both in the presence and in the absence of the different extracts of the leaves. The enzymic and non-enzymic antioxidants were analyzed in the homogenate of the liver slices after incubation. The oxidant treated liver slices showed a decrease in the levels of antioxidants compared to the untreated control. But in the presence of the leaf extracts, the antioxidant status was reverted back to a significant extent. Thus, the results showed that the leaf extracts of the candidate plant can improve the antioxidant status in the goat liver slices exposed in vitro to oxidative stress.

  14. AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

    Science.gov (United States)

    Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

    2016-10-01

    Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Altered expression and activities of enzymes involved in thiamine diphosphate biosynthesis in Saccharomyces cerevisiae under oxidative and osmotic stress.

    Science.gov (United States)

    Kowalska, Ewa; Kujda, Marta; Wolak, Natalia; Kozik, Andrzej

    2012-08-01

    Thiamine diphosphate (TDP) serves as a cofactor for enzymes engaged in pivotal carbohydrate metabolic pathways, which are known to be modulated under stress conditions to ensure the cell survival. Recent reports have proven a protective role of thiamine (vitamin B(1)) in the response of plants to abiotic stress. This work aimed at verifying a hypothesis that also baker's yeast, which can synthesize thiamine de novo similarly to plants and bacteria, adjust thiamine metabolism to adverse environmental conditions. Our analyses on the gene expression and enzymatic activity levels generally showed an increased production of thiamine biosynthesis enzymes (THI4 and THI6/THI6), a TDP synthesizing enzyme (THI80/THI80) and a TDP-requiring enzyme, transketolase (TKL1/TKL) by yeast subjected to oxidative (1 mM hydrogen peroxide) and osmotic (1 M sorbitol) stress. However, these effects differed in magnitude, depending on yeast growth phase and presence of thiamine in growth medium. A mutant thi4Δ with increased sensitivity to oxidative stress exhibited enhanced TDP biosynthesis as compared with the wild-type strain. Similar tendencies were observed in mutants yap1Δ and hog1Δ defective in the signaling pathways of the defense against oxidative and osmotic stress, respectively, suggesting that thiamine metabolism can partly compensate damages of yeast general defense systems.

  16. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  17. Exogenous l-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

    DEFF Research Database (Denmark)

    Garcia, Vinicius P; Rocha, Helena N M; Silva, Gustavo M;

    2016-01-01

    AIMS: Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l-arginine-NO pathway. Exogenous l-arginine improves endothelial function to prevent the onset of cardiovascular ...... between groups during the saline infusion (P>0.05). SIGNIFICANCE: Exogenous l-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension.......AIMS: Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l-arginine-NO pathway. Exogenous l-arginine improves endothelial function to prevent the onset of cardiovascular...

  18. High susceptibility of activated lymphocytes to oxidative stress-induced cell death

    Directory of Open Access Journals (Sweden)

    Giovanna R. Degasperi

    2008-03-01

    Full Text Available The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.O presente estudo demonstra que linfócitos ativados de baço de ratos portadores do tumor de Walker 256 são mais susceptíveis à morte celular necrótica induzida por tert-butil hidroperóxido (t-BOOH in vitro quando comparados aos controles. O quelante de ferro e antioxidante deferoxamina, o quelante intracelular de Ca2+ BAPTA, o antagonista de canal de Ca2+ nifedipina ou o inibidor da transição de permeabilidade mitocondrial ciclosporina-A, mas não o inibidor de calcineurina FK-506, inibiram de maneira similar a morte celular induzida por t-BOOH em linfócitos ativados e controles. Os linfócitos ativados apresentaram redução do potencial de membrana mitocondrial induzida por t-BOOH num mecanismo sensível a ciclosporina-A. Nossos resultados indicam que o aumento da concentração de Ca2+ citosólico em linfócitos ativados aumenta a susceptibilidade dos mesmos à morte celular induzida por estresse oxidativo, num mecanismo envolvendo a participação do poro de transição de permeabilidade mitocondrial.

  19. 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...

  20. Redox regulation of human OGG1 activity in response to cellular oxidative stress.

    Science.gov (United States)

    Bravard, Anne; Vacher, Monique; Gouget, Barbara; Coutant, Alexandre; de Boisferon, Florence Hillairet; Marsin, Stéphanie; Chevillard, Sylvie; Radicella, J Pablo

    2006-10-01

    8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity.

  1. Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression.

    Science.gov (United States)

    Kruzel, Marian L; Actor, Jeffrey K; Zimecki, Michał; Wise, Jasen; Płoszaj, Paulina; Mirza, Shaper; Kruzel, Mark; Hwang, Shen-An; Ba, Xueqing; Boldogh, Istvan

    2013-12-01

    Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. The aim of this study was to scale-up expression and purification of rhLF in a CHO expression system, verify its glycan primary structure, and assess its biological properties in cell culture models. A stable CHO cell line producing >200mg/L of rhLF was developed and established. rhLF was purified by a single-step cation-exchange chromatography procedure. The highly homogenous rhLF has a molecular weight of approximately 80 kDa. MALDI-TOF mass spectrometric analysis revealed N-linked, partially sialylated glycans at two glycosylation sites, typical for human milk LF. This novel rhLF showed a protective effect against oxidative stress in a similar manner to its natural counterpart. In addition, rhLF revealed a modulatory effect on cellular redox via upregulation of key antioxidant enzymes. These data imply that the CHO-derived rhLF is fully compatible with the native molecule, thus it has promise for human therapeutic applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. The Paraoxonase 1 Arylesterase Activity, Total Oxidative Stress, Nitric Oxide and Vitamin C Levels in Maternal Serum, and Their Relation to Birth Weight of Newborn.

    Science.gov (United States)

    Mogarekar, Mukund Ramchandra; Dhabe, Mahendra G; Gujrathi, Chanchal C

    2016-10-01

    Aim of this study is to find out clinical relevance of estimating PON1 arylesterase activity, total oxidative stress (TOS), nitric oxide (NO), and vitamin C levels in maternal serum for prediction of birth weight of newborn. We have investigated the PON1 arylesterase activity, TOS, NO, vitamin C, total protein, and albumin levels in 56 postnatal clinic patients having newborn weighing 2500 gm. Samples were collected immediately after delivery. PON1 arylesterase activity levels show significant decrease in cases as compared to controls (93.27 ± 13.76 kU/l vs. 112.77 ± 9.42 kU/l). Nitric oxide (nitrate + nitrite) levels are also found to be significantly decreased in cases with respect to controls (22.89 ± 2.65 umol/l vs. 24.73 ± 3.80 umol/l). Total oxidative stress is significantly increased in cases than in control subjects (23.34 ± 2.64 μmol H2O2 equiv./l vs. ± 21.43 ± 2.47 μmol H2O2 equiv/l). Vitamin C levels are also significantly decreased in cases as compared to controls (1.23 ± 0.25 mg/dl vs. 1.34 ± 0.28 mg/dl). Positive correlation between neonatal birth weight and maternal serum PON1 arylesterase activity (r = 0.682, p stress (r = -0.478, p levels with increased total oxidative stress in maternal serum may be considered as the additional risk factors for the development of low birth weight newborn.

  3. Protein Mediated Oxidative Stress in Patients with Diabetes and its Associated Neuropathy: Correlation with Protein Carbonylation and Disease Activity Markers

    Science.gov (United States)

    Almogbel, Ebtehal

    2017-01-01

    Introduction Free radicals have been implicated as Diabetes Mellitus (DM) contributors in type 2 DM and its associated Diabetes Mellitus Neuropathy (DMN). However, the potential for protein mediated oxidative stress to contribute disease pathogenesis remains largely unexplored. Aim To investigate the status and contribution of protein mediated oxidative stress in patients with DM or DMN and to explore whether oxidative protein modification has a role in DM progression to DM associated neuropathy. Materials and Methods Sera from 42 DM and 37 DMN patients with varying levels of disease activities biomarkers (HbA1C, patients’ age or disease duration) and 21 age- and sex-matched healthy controls were evaluated for serum levels of protein mediated oxidative stress. Results Serum analysis showed significantly higher levels of protein carbonyl contents in both DM and DMN patients compared with healthy controls. Importantly, not only was there an increased number of subjects positive for protein carbonylation, but also the levels of protein carbonyl contents were significantly higher among DM and DMN patients, whose HbA1C were ≥8.8 as compared with patients with lower HbA1C (HbA1Cdiabetes to diabetes neuropathy. Conclusion These findings support an association between protein oxidation and DM or DMN progression. The stronger response observed in patients with higher HbA1C or patients’ ages or disease durations suggests, that protein mediated oxidative stress may be useful in evaluating the progression of DM and its associated DMN and in elucidating the mechanisms of these disorders pathogenesis.

  4. Positive correlation between PSI response and oxidative pentose phosphate pathway activity during salt stress in an intertidal macroalga.

    Science.gov (United States)

    Huan, Li; Xie, Xiujun; Zheng, Zhenbing; Sun, Feifei; Wu, Songcui; Li, Moyang; Gao, Shan; Gu, Wenhui; Wang, Guangce

    2014-08-01

    Studies have demonstrated that photosynthetic limitations and starch degradation are responses to stress; however, the relationship between the two is seldom described in detail. In this article, the effects of salt stress on photosynthesis, the levels of NADPH and total RNA, the starch content and the activities of glucose-6-phosphate dehydrogenase (G6PDH) and ribulose-5-phosphate kinase (RPK) were evaluated. In thalli that underwent salt treatments, the cyclic electron flow through PSI showed greater stress tolerance than the flow through PSII. Even though the linear electron flow was suppressed by DCMU, the cyclic electron flow still operated. The electron transport rate I (ETRI) increased as the salinity increased when the thalli recovered in seawater containing DCMU. These results suggested that PSI receives electrons from a source other than PSII. Furthermore, the starch content and RPK activity decreased, while the content of NADPH and total RNA, and the activity of G6PDH increased under salt stress. Soluble sugar from starch degradation may enter the oxidative pentose phosphate pathway (OPPP) to produce NADPH and ribose 5-phosphate. Data analysis suggests that NADPH provides electrons for PSI in Ulva prolifera during salt stress, the OPPP participates in the stress response and total RNA is synthesized in excess to assist recovery.

  5. The leishmanicidal activity of oleuropein is selectively regulated through inflammation- and oxidative stress-related genes.

    Science.gov (United States)

    Kyriazis, Ioannis D; Koutsoni, Olga S; Aligiannis, Nektarios; Karampetsou, Kalliopi; Skaltsounis, Alexios-Leandros; Dotsika, Eleni

    2016-08-09

    Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities. Our previous findings showed that oleuropein exhibits leishmanicidal effects against three Leishmania spp. in vitro, and minimizes the parasite burden in L. donovani-infected BALB/c mice. The aim of the present study is to investigate the possible mechanism(s) that mediate this leishmanicidal activity. We determined the efficacy of oleuropein in elevating ROS and NO production in L. donovani-infected J774A.1 macrophages and in explanted splenocytes and hepatocytes obtained from L. donovani-infected BALB/c mice. We also assessed the expression of genes that are related to inflammation, T-cell polarization and antioxidant defense, in splenocytes. Finally, we determined the ratios of specific IgG2a/IgG1 antibodies and DTH reactions in L. donovani-infected BALB/c mice treated with oleuropein. Oleuropein was able to elevate ROS production in both in vitro and in vivo models of visceral leishmaniasis and raised NO production in ex vivo cultures of splenocytes and hepatocytes. The extensive oxidative stress found in oleuropein-treated mice was obviated by the upregulation of the host's antioxidant enzyme (mGCLC) and the simultaneous downregulation of the corresponding enzyme of the parasite (LdGCLC). Moreover, oleuropein was able to mount a significant Th1 polarization characterized by the expression of immune genes (IL-12β, IL-10, TGF-β1, IFN-γ) and transcription factors (Tbx21 and GATA3). Moreover, this immunomodulatory effect was also correlated with an inhibitory effect on IL-1β gene expression, rather than with the expression of IL-1α, IL-1rn and TNF-α. Furthermore, oleuropein-treated BALB/c mice mounted a delayed-type hypersensitivity (DTH) response and an

  6. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

  7. Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Oxidative Stress in Zebrafish Hair Cells.

    Science.gov (United States)

    Kasica, Natalia; Podlasz, Piotr; Sundvik, Maria; Tamas, Andrea; Reglodi, Dora; Kaleczyc, Jerzy

    2016-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide, with known antiapoptotic functions. Our previous in vitro study has demonstrated the ameliorative role of PACAP-38 in chicken hair cells under oxidative stress conditions, but its effects on living hair cells is now yet known. Therefore, the aim of the present study was to investigate in vivo the protective role of PACAP-38 in hair cells found in zebrafish (Danio rerio) sense organs-neuromasts. To induce oxidative stress the 5-day postfertilization (dpf) zebrafish larvae were exposed to 1.5 mM H2O2 for 15 min or 1 h. This resulted in an increase in caspase-3 and p-38 MAPK level in the hair cells as well as in an impairment of the larvae basic behavior. To investigate the ameliorative role of PACAP-38, the larvae were incubated with a mixture of 1.5 mM H2O2 and 100 nM PACAP-38 following 1 h preincubation with 100 nM PACAP-38 only. PACAP-38 abilities to prevent hair cells from apoptosis were investigated. Whole-mount immunohistochemistry and confocal microscopy analyses revealed that PACAP-38 treatment decreased the cleaved caspase-3 level in the hair cells, but had no influence on p-38 MAPK. The analyses of basic locomotor activity supported the protective role of PACAP-38 by demonstrating the improvement of the fish behavior after PACAP-38 treatment. In summary, our in vivo findings demonstrate that PACAP-38 protects zebrafish hair cells from oxidative stress by attenuating oxidative stress-induced apoptosis.

  8. Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Saquib, Quaiser [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Attia, Sabry M. [Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Siddiqui, Maqsood A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Aboul-Soud, Mourad A.M. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Biochemistry Department, Faculty of Agriculture, Cairo University, 12613 Giza (Egypt); Al-Khedhairy, Abdulaziz A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Giesy, John P. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Canada S7N 5B3 (Canada); Zoology Department and Center for Integrative Toxicology, Michigan State University, East Lansing 48824 (United States); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Microbiology, Faculty of Agricultural Sciences, AMU, Aligarh (India)

    2012-02-15

    Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G{sub 2}/M arrest and appearance of a distinctive SubG{sub 1} peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced

  9. Morin modulates the oxidative stress-induced NF-kappaB pathway through its anti-oxidant activity.

    Science.gov (United States)

    Kim, Ji Min; Lee, Eun Kyeong; Park, Gwangli; Kim, Mi Kyung; Yokozawa, Takako; Yu, Byung Pal; Chung, Hae Young

    2010-04-01

    Morin is a flavone that has anti-inflammatory effects through a mechanism that is not well understood. Based on the extreme sensitive nature of the transcription factor, NF-kB to redox change, it is postulated that morin's anti-NF-kappaB activation likely depends on its ability to scavenge excessive reactive species [RS]. The present study assessed the extent of morin's ability to modulate RS-induced NF-kappaB activation through its scavenging activity. Results indicate that morin neutralized RS in vitro and inhibited t-BHP-induced RS generation. It also examined morin for suppressed redox-sensitive transcription factor NF-kappaB activation via reduced DNA binding activity, I kappaB alpha phosphorylation and p65/p50 nuclear translocation. The more important finding was that suppression of the NF-kappaB cascade by morin was modulated through the ERK and p38 MAPKs signal transduction pathways in endothelial cells. As a consequence, morin's anti-oxidant effect extended expression level of NF-kappaB dependent pro-inflammatory genes, thereby reducing COX-2, iNOS and 5-LOX. The data indicate that morin has strong anti-oxidative power against RS-induced NF-kappaB modulation through the ERK and p38 MAPKs signalling pathways by its RS scavenging activity. The significance of the current study is the new revelation that morin may have potential as an effective anti-inflammatory therapeutic agent.

  10. Oxidative stress activates the TRPM2-Ca(2+)-CaMKII-ROS signaling loop to induce cell death in cancer cells.

    Science.gov (United States)

    Wang, Qian; Huang, Lihong; Yue, Jianbo

    2016-12-20

    High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca(2+)-permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca(2+) influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca(2+)-CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca(2+)-CaMKII-ROS signal loop to inhibit autophagy and induce cell death.

  11. 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.

  12. 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

  13. Increased activity of the antioxidants systems modulate the oxidative stress in saliva of toddlers with early childhood caries.

    Science.gov (United States)

    Silva, Priscila Vieira da; Troiano, Jéssica Antonini; Nakamune, Ana Cláudia M S; Pessan, Juliano Pelim; Antoniali, Cristina

    2016-10-01

    This study aimed to evaluate the oxidative stress levels and the enzymatic and non-enzymatic antioxidant systems in saliva of toddlers with severe early childhood caries (S-ECC). Unstimulated saliva samples were collected at the morning from 0 to 3 year-old S-ECC (n=30) or caries-free (CF) children (n=30/group) for evaluation of oxidative stress (OS) and total antioxidant capacity (TAC), which were measured by the ferric reducing antioxidant power (FRAP) assay, as well as to assess the activity of enzymatic (superoxide dismutase, SOD) and non-enzymatic (uric acid, UA) antioxidant systems, respectively. Data were analyzed by Student's t-test (psaliva of S-ECC children (0.083mg/mL) than in the CF group (0.070mg/mL). Oxidative damage was significantly lower in saliva of S-ECC children (0.0019μmol/L/mg protein) than in CF children (0.0039μmol/L/mg protein), while salivary TAC (61.5μmol/L), SOD activity (36.6 UE/mL) and uric acid (7.05mg/mL) were significantly higher in saliva of S-ECC when compared to the CF group (49.1μmol/L, 26.8 UE/mL and 5.02mg/mL, respectively for TAC, SOD and UA). Oxidative stress levels were significantly lower in saliva of S-ECC children, what might be associated with the increased activity of salivary enzymatic (SOD) and non-enzymatic (uric acid) antioxidant systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of temperature on oxidative stress parameters and enzyme activity in tissues of Cape river crab (Potamanautes perlatus) following exposure to silver nanoparticles (AgNPs)

    CSIR Research Space (South Africa)

    Walters, Chavon R

    2016-01-01

    Full Text Available of oxidative stress was studied in the gills and hepatopancreas of the Cape River crab Potamonautes perlatus. Responses were assessed through activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and the nonenzymatic...

  15. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    Science.gov (United States)

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-05

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  16. Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress.

    Science.gov (United States)

    Miramón, Pedro; Dunker, Christine; Windecker, Hanna; Bohovych, Iryna M; Brown, Alistair J P; Kurzai, Oliver; Hube, Bernhard

    2012-01-01

    Neutrophils are key players during Candida albicans infection. However, the relative contributions of neutrophil activities to fungal clearance and the relative importance of the fungal responses that counteract these activities remain unclear. We studied the contributions of the intra- and extracellular antifungal activities of human neutrophils using diagnostic Green Fluorescent Protein (GFP)-marked C. albicans strains. We found that a carbohydrate starvation response, as indicated by up-regulation of glyoxylate cycle genes, was only induced upon phagocytosis of the fungus. Similarly, the nitrosative stress response was only observed in internalised fungal cells. In contrast, the response to oxidative stress was observed in both phagocytosed and non-phagocytosed fungal cells, indicating that oxidative stress is imposed both intra- and extracellularly. We assessed the contributions of carbohydrate starvation, oxidative and nitrosative stress as antifungal activities by analysing the resistance to neutrophil killing of C. albicans mutants lacking key glyoxylate cycle, oxidative and nitrosative stress genes. We found that the glyoxylate cycle plays a crucial role in fungal resistance against neutrophils. The inability to respond to oxidative stress (in cells lacking superoxide dismutase 5 or glutathione reductase 2) renders C. albicans susceptible to neutrophil killing, due to the accumulation of reactive oxygen species (ROS). We also show that neutrophil-derived nitric oxide is crucial for the killing of C. albicans: a yhb1Δ/Δ mutant, unable to detoxify NO•, was more susceptible to neutrophils, and this phenotype was rescued by the nitric oxide scavenger carboxy-PTIO. The stress responses of C. albicans to neutrophils are partially regulated via the stress regulator Hog1 since a hog1Δ/Δ mutant was clearly less resistant to neutrophils and unable to respond properly to neutrophil-derived attack. Our data indicate that an appropriate fungal response to all

  17. Fumigant Activity of the Psidium guajava Var. Pomifera (Myrtaceae Essential Oil in Drosophila melanogaster by Means of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Antonio Ivanildo Pinho

    2014-01-01

    Full Text Available The guava fruit, Psidium guajava var. pomifera (Myrtaceae family, is a native plant from South America. Its leaves and fruits are widely used in popular medicine in tropical and subtropical countries. Drosophila melanogaster has been used as one of the main model organisms in genetic studies since the 1900s. The extensive knowledge about this species makes it one of the most suitable organisms to study many aspects of toxic compound effects. Due to the lack of studies on the effects of the bioactive compounds present in the P. guajava var. pomifera essential oil, we performed a phytochemical characterization by CG-MS and evaluated the toxicity induced by the essential oil in the D. melanogaster insect model. In order to understand the biochemical mechanisms of toxicity, changes on the Nrf2 signaling as well as hallmarks of oxidative stress response were followed in the exposed flies. Our results showed that exposure of insects to the P. guajava oil increased mortality and locomotor deficits in parallel with an oxidative stress response signaling. Therefore, it suggested a bioinsecticidal activity for P. guajava volatile compounds by means of oxidative stress. Further studies are ongoing to identify which oil compounds are responsible for such effect.

  18. Fumigant activity of the Psidium guajava var. pomifera (Myrtaceae) essential oil in Drosophila melanogaster by means of oxidative stress.

    Science.gov (United States)

    Pinho, Antonio Ivanildo; Wallau, Gabriel Luz; Nunes, Mauro Eugenio Medina; Leite, Nadghia Figueiredo; Tintino, Saulo Relison; da Cruz, Litiele Cezar; da Cunha, Francisco Assis Bezerra; da Costa, José Galberto Martins; Douglas Melo Coutinho, Henrique; Posser, Thais; Franco, Jeferson Luis

    2014-01-01

    The guava fruit, Psidium guajava var. pomifera (Myrtaceae family), is a native plant from South America. Its leaves and fruits are widely used in popular medicine in tropical and subtropical countries. Drosophila melanogaster has been used as one of the main model organisms in genetic studies since the 1900s. The extensive knowledge about this species makes it one of the most suitable organisms to study many aspects of toxic compound effects. Due to the lack of studies on the effects of the bioactive compounds present in the P. guajava var. pomifera essential oil, we performed a phytochemical characterization by CG-MS and evaluated the toxicity induced by the essential oil in the D. melanogaster insect model. In order to understand the biochemical mechanisms of toxicity, changes on the Nrf2 signaling as well as hallmarks of oxidative stress response were followed in the exposed flies. Our results showed that exposure of insects to the P. guajava oil increased mortality and locomotor deficits in parallel with an oxidative stress response signaling. Therefore, it suggested a bioinsecticidal activity for P. guajava volatile compounds by means of oxidative stress. Further studies are ongoing to identify which oil compounds are responsible for such effect.

  19. Mechanisms underlying the exquisite sensitivity of Candida albicans to combinatorial cationic and oxidative stress that enhances the potent fungicidal activity of phagocytes.

    Science.gov (United States)

    Kaloriti, Despoina; Jacobsen, Mette; Yin, Zhikang; Patterson, Miranda; Tillmann, Anna; Smith, Deborah A; Cook, Emily; You, Tao; Grimm, Melissa J; Bohovych, Iryna; Grebogi, Celso; Segal, Brahm H; Gow, Neil A R; Haynes, Ken; Quinn, Janet; Brown, Alistair J P

    2014-07-15

    Immune cells exploit reactive oxygen species (ROS) and cationic fluxes to kill microbial pathogens, such as the fungus Candida albicans. Yet, C. albicans is resistant to these stresses in vitro. Therefore, what accounts for the potent antifungal activity of neutrophils? We show that simultaneous exposure to oxidative and cationic stresses is much more potent than the individual stresses themselves and that this combinatorial stress kills C. albicans synergistically in vitro. We also show that the high fungicidal activity of human neutrophils is dependent on the combinatorial effects of the oxidative burst and cationic fluxes, as their pharmacological attenuation with apocynin or glibenclamide reduced phagocytic potency to a similar extent. The mechanistic basis for the extreme potency of combinatorial cationic plus oxidative stress--a phenomenon we term stress pathway interference--lies with the inhibition of hydrogen peroxide detoxification by the cations. In C. albicans this causes the intracellular accumulation of ROS, the inhibition of Cap1 (a transcriptional activator that normally drives the transcriptional response to oxidative stress), and altered readouts of the stress-activated protein kinase Hog1. This leads to a loss of oxidative and cationic stress transcriptional outputs, a precipitous collapse in stress adaptation, and cell death. This stress pathway interference can be suppressed by ectopic catalase (Cat1) expression, which inhibits the intracellular accumulation of ROS and the synergistic killing of C. albicans cells by combinatorial cationic plus oxidative stress. Stress pathway interference represents a powerful fungicidal mechanism employed by the host that suggests novel approaches to potentiate antifungal therapy. Importance: The immune system combats infection via phagocytic cells that recognize and kill pathogenic microbes. Human neutrophils combat Candida infections by killing this fungus with a potent mix of chemicals that includes

  20. Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier.

    Science.gov (United States)

    Zhang, Yue-Hong; Li, Juan; Yang, Wei-Zhong; Xian, Zhuan-Hua; Feng, Qi-Ting; Ruan, Xiang-Cai

    2017-01-01

    To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp) in mitochondria of D407 cells. D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123) alone and in the presence of P-gp inhibitor (Tariquidar) using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC) for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

  1. Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier

    Directory of Open Access Journals (Sweden)

    Yue-Hong Zhang

    2017-07-01

    Full Text Available AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123 alone and in the presence of P-gp inhibitor (Tariquidar using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

  2. D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering ATPase activities and oxidative stress in guinea pigs.

    Science.gov (United States)

    Cheng, Po-Wen; Liu, Shing-Hwa; Young, Yi-Ho; Lin-Shiau, Shoei-Yn

    2006-09-01

    Cisplatin has been used as a chemotherapeutic agent to treat many kinds of malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been reported. However, the underlying biochemical change in the inner ear or central vestibular nervous system is not fully understood. In this study, we attempted to examine whether cisplatin-induced vestibulotoxicity and D-methionine protection were correlated with the changes of ATPase activities and oxidative stress of ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory center of VOR system) of guinea pigs. By means of a caloric test coupled with electronystagmographic recordings, we found that cisplatin exposure caused a dose-dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of slow phase velocity (SPV). In addition, cisplatin significantly inhibited the Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the ampullary tissue with a good dose-response relationship but not those of cerebellar cortex. Regression analysis indicated that a decrease of SPV was well correlated with the reduction of Na(+), K(+)-ATPase and Ca(2+)-ATPase activities of the ampullary tissue. D-Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in a correlated manner. Moreover, cisplatin exposure led to a significant dose-dependent increase of lipid peroxidation and nitric oxide concentrations of the vestibules, which could be significantly suppressed by D-methionine. However, cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated cisplatin-induced vestibulotoxicity associated with ionic disturbance through its antioxidative property.

  3. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Go J., E-mail: medical21go@yahoo.co.jp; Saya, Hideyuki

    2014-01-10

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup high}/ c-Myc {sup low} and proliferative cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup low}/ c-Myc {sup high}.

  4. A multifunctional, light-activated prochelator inhibits UVA-induced oxidative stress.

    Science.gov (United States)

    Franks, Andrew T; Wang, Qin; Franz, Katherine J

    2015-11-01

    UVA radiation can damage cells and tissues by direct photodamage of biomolecules as well as by initiating metal-catalyzed oxidative stress. In order to alleviate both concerns simultaneously, we synthesized a multifunctional prochelator PC-HAPI (2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (trans)-3-(2,4-dihydroxyphenyl)acrylate) that contains a trans-(o-hydroxy)cinnamate ester photocleavable protecting group that is cleaved upon UVA exposure to release a coumarin, umbelliferone, and an aroylhydrazone metal chelator, HAPI (N'-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide). While the prochelator PC-HAPI exhibits negligible affinity for iron, it responds rapidly to UVA irradiation and converts to an iron-binding chelator that inhibits iron-catalyzed formation of reactive oxygen species and protects cells from UVA damage.

  5. Metal ions, not metal-catalyzed oxidative stress, cause clay leachate antibacterial activity.

    Directory of Open Access Journals (Sweden)

    Caitlin C Otto

    Full Text Available Aqueous leachates prepared from natural antibacterial clays, arbitrarily designated CB-L, release metal ions into suspension, have a low pH (3.4-5, generate reactive oxygen species (ROS and H2O2, and have a high oxidation-reduction potential. To isolate the role of pH in the antibacterial activity of CB clay mixtures, we exposed three different strains of Escherichia coli O157:H7 to 10% clay suspensions. The clay suspension completely killed acid-sensitive and acid-tolerant E. coli O157:H7 strains, whereas incubation in a low-pH buffer resulted in a minimal decrease in viability, demonstrating that low pH alone does not mediate antibacterial activity. The prevailing hypothesis is that metal ions participate in redox cycling and produce ROS, leading to oxidative damage to macromolecules and resulting in cellular death. However, E. coli cells showed no increase in DNA or protein oxidative lesions and a slight increase in lipid peroxidation following exposure to the antibacterial leachate. Further, supplementation with numerous ROS scavengers eliminated lipid peroxidation, but did not rescue the cells from CB-L-mediated killing. In contrast, supplementing CB-L with EDTA, a broad-spectrum metal chelator, reduced killing. Finally, CB-L was equally lethal to cells in an anoxic environment as compared to the aerobic environment. Thus, ROS were not required for lethal activity and did not contribute to toxicity of CB-L. We conclude that clay-mediated killing was not due to oxidative damage, but rather, was due to toxicity associated directly with released metal ions.

  6. Daily sesame oil supplementation attenuates local renin-angiotensin system via inhibiting MAPK activation and oxidative stress in cardiac hypertrophy.

    Science.gov (United States)

    Liu, Chuan-Teng; Liu, Ming-Yie

    2017-04-01

    The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was gavaged (0.5 or 1 ml/kg/day for 7 days) after 4 weeks of DOCA/salt treatment. Cardiac histopathology, RAS parameters, expression of MAPKs, reactive oxygen species and lipid peroxidation were assessed 24 h after the last dose of sesame oil. Sesame oil significantly decreased the size of cardiomyocytes and the levels of cardiac renin, angiotensin-converting enzyme and angiotensin II. In addition, sesame oil down-regulated the expression of angiotensin type 1 receptor, JNK and p38 MAPK and apoptosis signal regulating kinase 1, c-Fos and c-Jun in rats receiving DOCA/salt. Furthermore, the induction of nicotinamide adenine dinucleotide phosphate oxidase, superoxide anion and hydroxyl radical and lipid peroxidation by DOCA/salt were inhibited by sesame oil. Sesame oil modulates cardiac RAS to ameliorate LVH by inhibiting MAPK activation and lowering oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

    Science.gov (United States)

    Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

    2016-10-01

    Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  9. BDE-47 induces oxidative stress, activates MAPK signaling pathway, and elevates de novo lipogenesis in the copepod Paracyclopina nana.

    Science.gov (United States)

    Lee, Min-Chul; Puthumana, Jayesh; Lee, Seung-Hwi; Kang, Hye-Min; Park, Jun Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Seo, Jung Soo; Park, Heum Gi; Om, Ae-Son; Lee, Jae-Seong

    2016-12-01

    Brominated flame retardant, 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), has received grave concerns as a persistent organic pollutant, which is toxic to marine organisms, and a suspected link to endocrine abnormalities. Despite the wide distribution in the marine ecosystem, very little is known about the toxic impairments on marine organisms, particularly on invertebrates. Thus, we examined the adverse effects of BDE-47 on life history trait (development), oxidative markers, fatty acid composition, and lipid accumulation in response to BDE-47-induced stress in the marine copepod Paracyclopina nana. Also, activation level of mitogen-activated protein kinase (MAPK) signaling pathways along with the gene expression profile of de novo lipogenesis (DNL) pathways were addressed. As a result, BDE-47 induced oxidative stress (e.g. reactive oxygen species, ROS) mediated activation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) signaling cascades in MAPK pathways. Activated MAPK pathways, in turn, induced signal molecules that bind to the transcription factors (TFs) responsible for lipogenesis to EcR, SREBP, ChREBP promoters. Also, the stress stimulated the conversion of saturated fatty acids (SFAs) to polyunsaturated fatty acids (PUFAs), a preparedness of the organism to adapt the observed stress, which could be correlated with the elongase and desaturase gene (e.g. ELO3, Δ5-DES, Δ9-DES) expressions, and then extended to the delayed early post-embryonic development and increased accumulation of lipid droplets in P. nana. This study will provide a better understanding of how BDE-47 effects on marine invertebrates particularly on the copepods, an important link in the marine food chain.

  10. Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells.

    Science.gov (United States)

    Bradbury, C M; Locke, J E; Wei, S J; Rene, L M; Karimpour, S; Hunt, C; Spitz, D R; Gius, D

    2001-04-15

    It has been established that tumor cells develop resistance to a variety of therapeutic agents after multiple exposures to these agents/drugs. Many of these therapeutic agents also appear to increase the activity of transcription factors, such as activator protein 1 (AP-1), believed to be involved in cellular responses to oxidative stress. Therefore, we hypothesized that cellular resistance to cancer therapeutic agents may involve the increased activity of transcription factors that govern resistance to oxidative stress, such as AP-1. To investigate this hypothesis, a previously characterized cisplatin, hyperthermia, and oxidative stress-resistant Chinese hamster fibroblast cell line, OC-14, was compared to the parental HA-1 cell line. Electrophoretic mobility shift and Western blot assays performed on extracts isolated from OC-14 cells demonstrated a 10-fold increase in constitutive AP-1 DNA-binding activity as well as increased constitutive c-Fos and c-Jun immunoreactive protein relative to HA-1 cells. Treatment of OC-14 cells with indomethacin inhibited constitutive increases in AP-1 DNA-binding activity and c-Fos/c-Jun-immunoreactive protein levels. Clonogenic survival assays demonstrated that pretreatment with indomethacin, at concentrations that inhibited AP-1 activity, significantly reduced the resistance of OC-14 cells to heat-induced radiosensitization, hydrogen peroxide, and cisplatin. These results demonstrate a relationship between increases in AP-1 DNA-binding activity and increased cellular resistance to cancer therapeutic agents and oxidative stress that is inhibited by indomethacin. These results support the hypothesis that inhibition of AP-1 activity with nonsteroidal anti-inflammatory drugs, such as indomethacin, may represent a useful adjuvant to cancer therapy.

  11. Acclimation of microalgae to wastewater environments involves increased oxidative stress tolerance activity.

    Science.gov (United States)

    Osundeko, Olumayowa; Dean, Andrew P; Davies, Helena; Pittman, Jon K

    2014-10-01

    A wastewater environment can be particularly toxic to eukaryotic microalgae. Microalgae can adapt to these conditions but the specific mechanisms that allow strains to tolerate wastewater environments are unclear. Furthermore, it is unknown whether the ability to acclimate microalgae to tolerate wastewater is an innate or species-specific characteristic. Six different species of microalgae (Chlamydomonas debaryana, Chlorella luteoviridis, Chlorella vulgaris, Desmodesmus intermedius, Hindakia tetrachotoma and Parachlorella kessleri) that had never previously been exposed to wastewater conditions were acclimated over an 8-week period in secondary-treated municipal wastewater. With the exception of C. debaryana, acclimation to wastewater resulted in significantly higher growth rate and biomass productivity. With the exception of C. vulgaris, total chlorophyll content was significantly increased in all acclimated strains, while all acclimated strains showed significantly increased photosynthetic activity. The ability of strains to acclimate was species-specific, with two species, C. luteoviridis and P. kessleri, able to acclimate more efficiently to the stress than C. debaryana and D. intermedius. Metabolic fingerprinting of the acclimated and non-acclimated microalgae using Fourier transform infrared spectroscopy was able to differentiate strains on the basis of metabolic responses to the stress. In particular, strains exhibiting greater stress response and altered accumulation of lipids and carbohydrates could be distinguished. The acclimation to wastewater tolerance was correlated with higher accumulation of carotenoid pigments and increased ascorbate peroxidase activity.

  12. [Photodynamic reaction and oxidative stress - influence of the photodynamic effect on the activity antioxidant enzymes].

    Science.gov (United States)

    Romiszewska, Anna; Nowak-Stępniowska, Agata

    2014-01-01

    The interaction of light with a photosensitizer, accumulated in a tissue in the presence of oxygen, leads to formation of reactive oxygen species, mainly of singlet oxygen and free radicals. These factors react with biomolecules producing their oxidized states. Reactive oxygen species, such as singlet oxygen and free radicals are able to damage membranes, DNA, enzymes, structural peptides and other cellular structures leading to cell death. An antioxidant protection of cell is formed by enzymes belonging to the family of oxidoreductases: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Photodynamic therapy leads to the increased production of oxidizing toxic forms. It is important to analyze impact of PDT on the activity of antioxidant enzymes, such as SOD, CAT, GPx. The activity of antioxidant enzymes during the photodynamic effect is influenced by both the light energy dose and the concentration of photosensitizer. The presence only of the photosensitizer or only the light energy may also result in changes in the activity of these enzymes. The differences in changes in the activity of these enzymes depend on the type of used photosensitizer. A phenomenon of selective accumulation of photosensitizer in tumor tissues is used in the photodynamic method of tumor diagnosis and treatment.

  13. Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Tingting Yan

    2016-01-01

    Full Text Available Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer’s disease. Acetaldehyde, the most toxic metabolite of ethanol, is speculated to mediate the brain tissue damage and cognitive dysfunction induced by the chronic excessive consumption of alcohol. However, the exact mechanisms by which acetaldehyde induces neurotoxicity are not totally understood. In this study, we investigated the cytotoxic effects of acetaldehyde in SH-SY5Y cells and found that acetaldehyde induced apoptosis of SH-SY5Y cells by downregulating the expression of antiapoptotic Bcl-2 and Bcl-xL and upregulating the expression of proapoptotic Bax. Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB. In addition, acetaldehyde induced the activation of p38 mitogen-activated protein kinase (MAPK while inhibiting the activation of extracellular signal-regulated kinases (ERKs, p44/p42MAPK. Meanwhile, acetaldehyde treatment caused an increase in the production of reactive oxygen species and elevated the oxidative stress in SH-SY5Y cells. Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.

  14. Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1α complex to activate its deacetylase function.

    Science.gov (United States)

    Lee, Irene Chengjie; Ho, Xue Yan; George, Simi Elizabeth; Goh, Catherine Wenhui; Sundaram, Jeyapriya Rajameenakshi; Pang, Karen Ka Lam; Luo, Weiwei; Yusoff, Permeen; Sze, Newman Siu Kwan; Shenolikar, Shirish

    2017-10-06

    Phosphorylation of the eukaryotic translation initiation factor, eIF2α, by stress-activated protein kinases and dephosphorylation by the growth arrest and DNA damage-inducible protein (GADD34)-containing phosphatase is a central node in the integrated stress response. Mass spectrometry demonstrated GADD34 acetylation at multiple lysines. Substituting K(315) and K(322) with alanines or glutamines did not impair GADD34's ability to recruit protein phosphatase 1α (PP1α) or eIF2α, suggesting that GADD34 acetylation did not modulate eIF2α phosphatase activity. Arsenite (Ars)-induced oxidative stress increased cellular GADD34 levels and enhanced Sirtuin 1 (SIRT1) recruitment to assemble a cytoplasmic complex containing GADD34, PP1α, eIF2α and SIRT1. Induction of GADD34 in WT MEFs paralleled the dephosphorylation of eIF2α (phosphoserine-51) and SIRT1 (phosphoserine-47). By comparison, eIF2α and SIRT1 were persistently phosphorylated in Ars-treated GADD34-/- MEFs. Expressing WT GADD34, but not a mutant unable to bind PP1α in GADD34-/- MEFs restored both eIF2α and SIRT1 dephosphorylation. SIRT1 dephosphorylation increased its deacetylase activity, measured in vitro and in cells. Loss of function of GADD34 or SIRT1 enhanced cellular p-eIF2α levels and attenuated cell death following Ars exposure. These results highlighted a novel role for the GADD34/PP1α complex in coordinating the dephosphorylation and reactivation of eIF2α and SIRT1 to determine cell fate following oxidative stress.Cell Death and Differentiation advance online publication, 6 October 2017; doi:10.1038/cdd.2017.152.

  15. Toll-Like Receptor 4–Mediated Nuclear Factor Kappa B Activation Is Essential for Sensing Exogenous Oxidants to Propagate and Maintain Oxidative/Nitrosative Cellular Stress

    Science.gov (United States)

    Karki, Rajendra; Igwe, Orisa J.

    2013-01-01

    The mechanism(s) by which cells can sense exogenous oxidants that may contribute to intracellular oxidative/nitrosative stress is not clear. The objective of this study was to determine how cells might respond to exogenous oxidants to potentially initiate, propagate and/or maintain inflammation associated with many human diseases through NF-κB activation. First, we used HEK-Blue cells that are stably transfected with mouse toll-like receptor 4 (mTLR4) or mouse TLR2. These cells also express optimized secreted embryonic alkaline phosphatase (SEAP) reporter gene under the control of a promoter inducible by NF-κB transcription factor. These cells were challenged with their respective receptor-specific ligands, different pro-oxidants and/or inhibitors that act at different levels of the receptor signaling pathways. A neutralizing antibody directed against TLR4 inhibited responses to both TLR4-specific agonist and a prooxidant, which confirmed that both agents act through TLR4. We used the level of SEAP released into the culture media due to NF-κB activation as a measure of TLR4 or TLR2 stimulation. Pro-oxidants evoked increased release of SEAP from HEK-Blue mTLR4 cells at a much lower concentration compared with release from the HEK-Blue mTLR2 cells. Specific TLR4 signaling pathway inhibitors and oxidant scavengers (anti-oxidants) significantly attenuated oxidant-induced SEAP release by TLR4 stimulation. Furthermore, a novel pro-oxidant that decays to produce the same reactants as activated phagocytes induced inflammatory pain responses in the mouse orofacial region with increased TLR4 expression, and IL-1β and TNFα tissue levels. EUK-134, a synthetic serum-stable scavenger of oxidative species decreased these effects. Our data provide in vitro and related in vivo evidence that exogenous oxidants can induce and maintain inflammation by acting mainly through a TLR4-dependent pathway, with implications in many chronic human ailments. PMID:24058497

  16. Toll-like receptor 4-mediated nuclear factor kappa B activation is essential for sensing exogenous oxidants to propagate and maintain oxidative/nitrosative cellular stress.

    Science.gov (United States)

    Karki, Rajendra; Igwe, Orisa J

    2013-01-01

    The mechanism(s) by which cells can sense exogenous oxidants that may contribute to intracellular oxidative/nitrosative stress is not clear. The objective of this study was to determine how cells might respond to exogenous oxidants to potentially initiate, propagate and/or maintain inflammation associated with many human diseases through NF-κB activation. First, we used HEK-Blue cells that are stably transfected with mouse toll-like receptor 4 (mTLR4) or mouse TLR2. These cells also express optimized secreted embryonic alkaline phosphatase (SEAP) reporter gene under the control of a promoter inducible by NF-κB transcription factor. These cells were challenged with their respective receptor-specific ligands, different pro-oxidants and/or inhibitors that act at different levels of the receptor signaling pathways. A neutralizing antibody directed against TLR4 inhibited responses to both TLR4-specific agonist and a prooxidant, which confirmed that both agents act through TLR4. We used the level of SEAP released into the culture media due to NF-κB activation as a measure of TLR4 or TLR2 stimulation. Pro-oxidants evoked increased release of SEAP from HEK-Blue mTLR4 cells at a much lower concentration compared with release from the HEK-Blue mTLR2 cells. Specific TLR4 signaling pathway inhibitors and oxidant scavengers (anti-oxidants) significantly attenuated oxidant-induced SEAP release by TLR4 stimulation. Furthermore, a novel pro-oxidant that decays to produce the same reactants as activated phagocytes induced inflammatory pain responses in the mouse orofacial region with increased TLR4 expression, and IL-1β and TNFα tissue levels. EUK-134, a synthetic serum-stable scavenger of oxidative species decreased these effects. Our data provide in vitro and related in vivo evidence that exogenous oxidants can induce and maintain inflammation by acting mainly through a TLR4-dependent pathway, with implications in many chronic human ailments.

  17. Zinc oxide and titanium dioxide nanoparticles induce oxidative stress, inhibit growth, and attenuate biofilm formation activity of Streptococcus mitis.

    Science.gov (United States)

    Khan, Shams Tabrez; Ahmad, Javed; Ahamed, Maqusood; Musarrat, Javed; Al-Khedhairy, Abdulaziz A

    2016-06-01

    Streptococcus mitis from the oral cavity causes endocarditis and other systemic infections. Rising resistance against traditional antibiotics amongst oral bacteria further aggravates the problem. Therefore, antimicrobial and antibiofilm activities of zinc oxide and titanium dioxide nanoparticles (NPs) synthesized and characterized during this study against S. mitis ATCC 6249 and Ora-20 were evaluated in search of alternative antimicrobial agents. ZnO and TiO2-NPs exhibited an average size of 35 and 13 nm, respectively. The IC50 values of ZnO and TiO2-NPs against S. mitis ATCC 6249 were 37 and 77 µg ml(-1), respectively, while the IC50 values against S. mitis Ora-20 isolate were 31 and 53 µg ml(-1), respectively. Live and dead staining, biofilm formation on the surface of polystyrene plates, and extracellular polysaccharide production show the same pattern. Exposure to these nanoparticles also shows an increase (26-83 %) in super oxide dismutase (SOD) activity. Three genes, namely bapA1, sodA, and gtfB like genes from these bacteria were identified and sequenced for quantitative real-time PCR analysis. An increase in sodA gene (1.4- to 2.4-folds) levels and a decrease in gtfB gene (0.5- to 0.9-folds) levels in both bacteria following exposure to ZnO and TiO2-NPs were observed. Results presented in this study verify that ZnO-NPs and TiO2-NPs can control the growth and biofilm formation activities of these strains at very low concentration and hence can be used as alternative antimicrobial agents for oral hygiene.

  18. Oxidative Stress and HPV Carcinogenesis

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. Carbofuran induced oxidative stress mediated alterations in Na⁺-K⁺-ATPase activity in rat brain: amelioration by vitamin E.

    Science.gov (United States)

    Jaiswal, Sunil Kumar; Siddiqi, Nikhat Jamal; Sharma, Bechan

    2014-07-01

    Pesticides cause oxidative stress and adversely influence Na(+)-K(+)-ATPase activity in animals. Since impact of carbofuran has not been properly studied in the mammalian brain, the ability of carbofuran to induce oxidative stress and modulation in Na(+)-K(+)-ATPase activity and its amelioration by vitamin E was performed. The rats divided into six groups received two different doses of carbofuran (15% and 30% LD50) for 15 days. The results suggested that the carbofuran treatment caused a significant elevation in levels of malonaldehyde and reduced glutathione and sharp inhibition in the activities of super oxide dismutase, catalase, and glutathione-S-transferase; the effect being dose dependent. Carbofuran at different doses also caused sharp reduction in the activity of Na(+)-K(+)-ATPase. The pretreatment of vitamin E, however, showed a significant recovery in these indices. The pretreatment of rats with vitamin E offered protection from carbofuran-induced oxidative stress.

  1. Soyasaponins Protect Against Palmitic Acid-Induced Oxidative Stress in Primary Mouse Hepatocytes:Structure-Activity Relationship

    Institute of Scientific and Technical Information of China (English)

    Guang-zhi HE; Jia-ding CHEN; Yan-hong HU; Jin-bin CHEN; Jian-lin LV; Long-ying ZHA

    2014-01-01

    Objective To investigate the relationship between the structure and activity in protection of soyasaponins against palmitic acid (PA)-induced oxidative stress in primary mouse hepatocytes.Methods The primary mouse hepatocytes were treated with 0.05 mmol/L PA in the presence or absence of soyasaponins (10μg/ml) for 16h. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), the contents of malondialdehyde (MDA), triglyceride (TG) and reactive oxygen species (ROS) were determined.Results PA treatment significantly lowered cellular SOD and GSH-Px activities (P<0.05), increased the contents of MDA and TG (P<0.05) and the production of ROS in mitochondria was elevated (P<0.05). When compared to the treatment of PA alone, the combined treatment of soyasaponins and PA significantly increased the activities of SOD and GSH-Px (P<0.05) and decreased the contents of MDA, TG and ROS (P<0.05). It was found that soyasaponin-A1 or A2 significantly increased the cellular activities of SOD and GSH-Px (P<0.05) and decreased the contents of MDA and ROS as compared with soyasapogenol-A (P<0.05). Similarly, soyasaponin-I significantly increased activities of cellular SOD and GSH-Px (P<0.05) and decreased the content of ROS as compared with soyasapogenol-B (P<0.05).Conclusion Soyasaponins possess antioxidant activity against PA-induced oxidative stress in primary mouse hepatocytes. Soyasaponin-A1, A2 and I are stronger than their corresponding soyasapogenols (soyasapogenol-A and B) in antioxidant activity, probably due to the sugar moieties presented in their chemical structures.

  2. 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...

  3. Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and antioxidant status in diabetic rats.

    Science.gov (United States)

    Kang, Myung-Hwa; Lee, Min Sun; Choi, Mi-Kyeong; Min, Kwan-Sik; Shibamoto, Takayuki

    2012-03-14

    Diabetes mellitus, which is associated with oxidative damage, has a significant impact on health, quality of life, and life expectancy. An ethanol extract of Gymnema sylvestre leaf was examined in vitro and in vivo to investigate the role of antioxidants in diabetic rats. The extract exhibited strong antioxidant activity in the assays, including TBA (56%), SOD-like (92%), and ABTS (54%). Blood glucose levels in the diabetic rats fed G. sylvestre extract decreased to normal levels. The presence of the antihyperglycemic compounds gymnemagenin and gymnemic acids in G. sylvestre extract was detected by LC/MS analysis. Lipid peroxidation levels were decreased by 31.7% in serum, 9.9% in liver, and 9.1% in kidney in the diabetic rats fed the extract. Feeding G. sylvestre extract to the diabetic rats decreased the activity of glutathione peroxidase in cytosolic liver and glutamate pyruvate transaminase in serum to normal levels.

  4. Ziram and Sodium N,N-Dimethyldithiocarbamate Inhibit Ubiquitin Activation through Intracellular Metal Transport and Increased Oxidative Stress in HEK293 Cells

    OpenAIRE

    Dennis, Kathleen E.; Valentine, William M.

    2015-01-01

    Ubiquitin activating enzyme E1 plays a pivotal role in ubiquitin based protein signaling through regulating the initiating step of the cascade. Previous studies demonstrated that E1 is inhibited by covalent modification of reactive cysteines contained within the ubiquitin-binding groove and by conditions that increase oxidative stress and deplete cellular antioxidants. In this study, we determined the relative contribution of covalent adduction and oxidative stress to E1 inhibition produced b...

  5. 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

  6. 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.

  7. Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF-κB/p65 Activation

    Science.gov (United States)

    Jiang, Wenkai; Zhou, Lin

    2016-01-01

    Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

  8. Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF-κB/p65 Activation

    Directory of Open Access Journals (Sweden)

    Qian Liu

    2016-01-01

    Full Text Available Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2 to induce the oxidative damage on neural stem cells (NSCs. The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90 and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

  9. Effect of sodium chloride and cadmium on the growth, oxidative stress and antioxidant enzyme activities of Zygosaccharomyces rouxii

    Science.gov (United States)

    Li, Chunsheng; Xu, Ying; Jiang, Wei; Lv, Xin; Dong, Xiaoyan

    2014-06-01

    Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium (Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride (NaCl) and Cd are poorly understood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species (ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) of Z. rouxii were significantly enhanced by 2%-6% NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1 Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory effect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.

  10. Effect of Sodium Chloride and Cadmium on the Growth, Oxidative Stress and Antioxidant Enzyme Activities of Zygosaccharomyces rouxii

    Institute of Scientific and Technical Information of China (English)

    LI Chunsheng; XU Ying; JIANG Wei; LV Xin; DONG Xiaoyan

    2014-01-01

    Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium (Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride (NaCl) and Cd are poorly under-stood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species (ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) of Z. rouxii were significantly enhanced by 2%-6%NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1 Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory ef-fect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.

  11. Wnt1, FoxO3a, and NF-kappaB oversee microglial integrity and activation during oxidant stress.

    Science.gov (United States)

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

    2010-09-01

    Elucidating the underlying mechanisms that govern microglial activation and survival is essential for the development of new treatment strategies for neurodegenerative disorders, since microglia serve not only as guardian sentries of the nervous system, but also play a significant role in determining neuronal and vascular cell fate. Here we show that endogenous and exogenous Wnt1 in inflammatory microglial cells is necessary for the prevention of apoptotic early membrane phosphatidylserine exposure and later DNA degradation, since blockade of Wnt1 signaling abrogates cell survival during oxidative stress. Wnt1 prevents apoptotic demise through the post-translational phosphorylation and maintenance of FoxO3a in the cytoplasm to inhibit an apoptotic cascade that relies upon the loss of mitochondrial membrane permeability, cytochrome c release, Bad phosphorylation, and activation of caspase 3 and caspase 1 as demonstrated by complimentary gene knockdown studies of FoxO3a. Furthermore, subcellular trafficking and gene knockdown studies of NF-kappaB p65 illustrate that microglial cell survival determined by Wnt1 during oxidative stress requires NF-kappaB p65. Our work highlights Wnt1 and the control of novel downstream transcriptional pathways as critical components for the oversight of nervous system microglial cells.

  12. 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.

  13. Overexpression of plastidial thioredoxins f and m differentially alters photosynthetic activity and response to oxidative stress in tobacco plants

    Directory of Open Access Journals (Sweden)

    Pascal eREY

    2013-10-01

    Full Text Available Plants display a remarkable diversity of thioredoxins (Trxs, reductases controlling the thiol redox status of proteins. The physiological function of many of them remains elusive, particularly for plastidial Trxs f and m, which are presumed based on biochemical data to regulate photosynthetic reactions and carbon metabolism. Recent reports revealed that Trxs f and m participate in vivo in the control of starch metabolism and cyclic photosynthetic electron transfer around photosystem I, respectively. To further delineate their in planta function, we compared the photosynthetic characteristics, the level and/or activity of various Trx targets and the responses to oxidative stress in transplastomic tobacco plants overexpressing either Trx f or Trx m. We found that plants overexpressing Trx m specifically exhibit altered growth, reduced chlorophyll content, impaired photosynthetic linear electron transfer and decreased pools of glutathione and ascorbate. In both transplastomic lines, activities of two enzymes involved in carbon metabolism, NADP-malate dehydrogenase and NADP-glyceraldehyde-3-phosphate dehydrogenase are markedly and similarly altered. In contrast, plants overexpressing Trx m specifically display increased capacity for methionine sulfoxide reductases, enzymes repairing damaged proteins by regenerating methionine from oxidized methionine. Finally, we also observed that transplastomic plants exhibit distinct responses when exposed to oxidative stress conditions generated by methyl viologen or exposure to high light combined with low temperature, the plants overexpressing Trx m being notably more tolerant than Wt and those overexpressing Trx f. Altogether, these data indicate that Trxs f and m fulfill distinct physiological functions. They prompt us to propose that the m type is involved in key processes linking photosynthetic activity, redox homeostasis and antioxidant mechanisms in the chloroplast.

  14. 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.

  15. Could oxidative stress initiate programmed cell death in HIV infection? A role for plant derived metabolites having synergistic antioxidant activity.

    Science.gov (United States)

    Greenspan, H C; Aruoma, O I; Arouma, O

    1994-06-01

    Evidence supports the premise that a pro-oxidant condition exists in HIV-seropositive patients, a result of an overabundance in production of reactive oxygen forms combined with a multilevel deficiency in nutritional and metabolic sources of antioxidants. Apoptosis (a programmed cell death) is recognized as a possible pathway of immune cell loss in patients with HIV infection and AIDS. The cascade of events that results from 'oxidative stress' (OS) is markedly similar to that which can initiate apoptosis and includes oxidation of cellular membranes, alteration of metabolic pathways, disruption of electron transport systems, depletion of cellular ATP production, loss of Ca2+ homeostasis, endonuclease activation and DNA/chromatin fragmentation. Downstream events secondary to these effects may also play a role in activation of latent virus and subsequent viral replication. Primary and secondary metabolites found in plants act as synergistic antioxidants, and can protect plants from oxidation-induced cell death. Experiments have shown that some of these same metabolites can inhibit cell killing by HIV. Can these compounds be useful in inhibiting viral activation and the death of immune cells in HIV/AIDS through their synergistic antioxidant properties? A brief review of the evidence for OS in HIV is presented and the potential basis for OS playing a role in the initiation of cell death and viral replication is explored. The functional antioxidant activities of plant metabolites are illustrated and the use of these synergistic antioxidants from plants are proposed as a mechanism by which viral replication and cell killing in HIV infection can be inhibited.

  16. N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: behavioral and biochemical analyses in rats.

    Science.gov (United States)

    Smaga, Irena; Pomierny, Bartosz; Krzyżanowska, Weronika; Pomierny-Chamioło, Lucyna; Miszkiel, Joanna; Niedzielska, Ewa; Ogórka, Agata; Filip, Małgorzata

    2012-12-01

    The growing body of evidence implicates the significance of oxidative stress in the pathophysiology of depression. The aim of this paper was to examine N-acetylcysteine (NAC) - a putative precursor of the most important tissue antioxidant glutathione - in an animal model of depression and in ex vivo assays to detect oxidative stress parameters. Imipramine (IMI), a classical and clinically-approved antidepressant drug was also under investigation. Male Wistar rats which underwent either bulbectomy (BULB; removal of the olfactory bulbs) or sham surgery (SHAM; olfactory bulbs were left undestroyed) were treated acutely or repeatedly with NAC (50-100mg/kg, ip) or IMI (10mg/kg, ip). Following 10-daily injections with NAC or IMI or their solvents, or 9-daily injections with a corresponding solvent plus acute NAC or acute IMI forced swimming test on day 10, and locomotor activity were performed; immediately after behavioral tests animals were decapitated. Biochemical tests (the total antioxidant capacity - TAC and the superoxide dismutase activity - SOD) were performed on homogenates in several brain structures. In behavioral studies, chronic (but not acute) administration of NAC resulted in a dose-dependent reduction in the immobility time seen only in BULB rats while chronic IMI produced a significant decrease in this parameter in both SHAM and BULB animals. On the other hand, chronic administration of NAC and IMI resulted in a significant increase in cellular antioxidant mechanisms (SOD activity) that reversed the effects of BULB in the frontal cortex, hippocampus and striatum. Our study further supports the antidepressant-like activity of NAC and links its effect as well as IMI actions with the enhancement of brain SOD activity.

  17. Creatine and pyruvate prevent the alterations caused by tyrosine on parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex of Wistar rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Bonorino, Narielle Ferner; Costa, Bruna May Lopes; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2015-01-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II. In this disease caused by tyrosine aminotransferase deficiency, eyes, skin, and central nervous system disturbances are found. In the present study, we investigated the chronic effect of tyrosine methyl ester (TME) and/or creatine plus pyruvate on some parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex homogenates of 21-day-old Wistar. Chronic administration of TME induced oxidative stress and altered the activities of adenylate kinase and mitochondrial and cytosolic creatine kinase. Total sulfhydryls content, GSH content, and GPx activity were significantly diminished, while DCFH oxidation, TBARS content, and SOD activity were significantly enhanced by TME. On the other hand, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions but enhanced AK activity. In contrast, TME did not affect the carbonyl content and PK activity in cerebral cortex of rats. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by TME administration on the oxidative stress and the enzymes of phosphoryltransfer network, except in mitochondrial CK, AK, and SOD activities. These results indicate that chronic administration of TME may stimulate oxidative stress and alter the enzymes of phosphoryltransfer network in cerebral cortex of rats. In case this also occurs in the patients affected by these disorders, it may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias, and creatine and pyruvate supplementation could be beneficial to the patients.

  18. 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.

  19. Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress.

    Science.gov (United States)

    Rahim, Nur Syafiqah; Lim, Siong Meng; Mani, Vasudevan; Abdul Majeed, Abu Bakar; Ramasamy, Kalavathy

    2017-12-01

    Virgin coconut oil (VCO) has been reported to possess antioxidative, anti-inflammatory and anti-stress properties. Capitalizing on these therapeutic effects, this study investigated for the first time the potential of VCO on memory improvement in vivo. Thirty male Wistar rats (7-8 weeks old) were randomly assigned to five groups (n = six per group). Treatment groups were administered with 1, 5 and 10 g/kg VCO for 31 days by oral gavages. The cognitive function of treated-rats were assessed using the Morris Water Maze Test. Brains were removed, homogenized and subjected to biochemical analyses of acetylcholine (ACh) and acetylcholinesterase (AChE), antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GRx)], lipid peroxidase [malondialdehyde (MDA)] as well as nitric oxide (NO). α-Tocopherol (αT; 150 mg/kg) was also included for comparison purposes. VCO-fed Wistar rats exhibited significant (p  33%) and NO (≥ 34%). Overall, memory improvement by VCO was comparable to αT. VCO has the potential to be used as a memory enhancer, the effect of which was mediated, at least in part, through enhanced cholinergic activity, increased antioxidants level and reduced oxidative stress.

  20. Midazolam anesthesia protects neuronal cells from oxidative stress-induced death via activation of the JNK-ERK pathway.

    Science.gov (United States)

    Liu, Jing-Yu; Guo, Feng; Wu, Hong-Ling; Wang, Ying; Liu, Jin-Shan

    2017-01-01

    Midazolam is an anesthetic agent commonly used during clinical and surgical procedures, which has been shown to exert ROS‑suppressing and apoptosis‑modulating pharmacological activities in various cellular systems. However, the effects of midazolam on oxidative stress in neuronal cells require elucidation. The present study investigated the effects of midazolam on buthionine sulfoximine (BSO)‑ and hydrogen peroxide (H2O2)‑induced oxidative stress in primary cortical neuronal cells. In addition, the effects of midazolam on middle cerebral artery occlusion (MCAO) in mice and on ethanol‑induced neuroapoptosis in the brains of neonatal mice were determined. Subsequently, cell viability was detected using the MTT assay; intracellular reactive oxygen species (ROS) generation was determined using the 2',7'‑dichlorodihydrofluorescein diacetate method with confocal microscopy; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect apoptotic cells; immunohistochemistry was performed to detect activated caspase‑3; neuronal deficit and infarct volume analyses were conducted; and quantitative polymerase chain reaction and western blotting were performed to detect the expression levels of genes and proteins associated with apoptosis and cell survival pathways. The results demonstrated that BSO (10 mM) and H2O2 (1 mM) suppressed proliferation of cortical neuronal cells by inducing apoptosis. These effects were suppressed following treatment with midazolam in a dose‑dependent manner. In addition, BSO and H2O2 induced ROS generation in neuronal cells; however, this was effectively suppressed by midazolam (100 µM). Beneficial synergistic effects were detected when midazolam was used in combination with the known antioxidant trolox. BSO and H2O2 also suppressed the protein expression levels of c‑Jun N‑terminal kinases (JNK), phosphorylated (p)JNK, extracellular signal‑regulated kinases (ERK)1/2, pERK1/2, AKT and

  1. Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

    Directory of Open Access Journals (Sweden)

    Li Jin-Lian

    2012-03-01

    Full Text Available Abstract Background Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2-induced cytotoxicity in a normal human hepatocyte cell line, HL7702. Methods We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS levels, activities and protein expressions of superoxide dismutase (SOD and catalase (CAT, and malondialdehyde (MDA formation. Expressions of peroxisome proliferator-activated receptor (PPAR-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test. Results The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1 and acyl-CoA oxidase (ACOX induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886. Conclusions Taken together, our findings suggest that L-carnitine could protect HL

  2. Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

    Science.gov (United States)

    Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

    2011-04-01

    Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction.

  3. PPAR{alpha} agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Xiaoyang [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030 (United States); Shen, Ying H. [Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030 (United States); Li, Chuanbao; Wang, Fei; Zhang, Cheng [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Bu, Peili, E-mail: peilibu6320@hotmail.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Zhang, Yun [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China)

    2010-04-09

    Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors {alpha} (PPAR{alpha}) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protect against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.

  4. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ji Hye; Shin, Bo Yeon; Han, Jae Yun; Kim, Mi Gwang; Wi, Ji Eun [College of Pharmacy, Chosun University, Gwangju, 501-759 (Korea, Republic of); Kim, Young Woo; Cho, Il Je; Kim, Sang Chan [Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Shin, Sang Mi [College of Pharmacy, Chosun University, Gwangju, 501-759 (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju, 501-759 (Korea, Republic of)

    2014-01-15

    Isorhamentin is a 3′-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE-deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCδ and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes. - Highlights: • We investigated the effect of isorhamnetin on Nrf2 activation. • Isorhamnetin increased Nrf2

  5. 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.

  6. Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity.

    Science.gov (United States)

    Bukowska, Bożena; Sicińska, Paulina; Pająk, Aneta; Koceva-Chyla, Aneta; Pietras, Tadeusz; Pszczółkowska, Anna; Górski, Paweł; Koter-Michalak, Maria

    2015-12-01

    The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease.

  7. Nitro-oxidative Stress Is Involved in Anticancer Activity of 17β-Estradiol Derivative in Neuroblastoma Cells.

    Science.gov (United States)

    Gorska, Magdalena; Kuban-Jankowska, Alicja; Milczarek, Ryszard; Wozniak, Michal

    2016-04-01

    Neuroblastoma is one of the most common childhood malignancies and the primary cause of death from pediatric cancer. Derivatives of 17β-estradiol, 2-methoxyestradiol, as well as selective estrogen receptor modulators, such as fulvestrant, are novel potentially active anticancer agents. In particular, 2-methoxyestradiol is effective in treatment of numerous malignancies, including breast and prostate cancer, Ewing sarcoma, and osteosarcoma. Herein, we treated neuroblastoma SH-SY5Y cells with physiologically and pharmacologically relevant concentrations of 2-methoxyestradiol. We used flow cytometry in order to determine cell viability, cell death, level of nitric oxide and mitochondrial membrane potential. We demonstrated that at pharmacologically relevant concentrations, 2-methoxyestradiol results in induction of apoptosis of neuroblastoma SH-SY5Y cells via nitric oxide generation and reduction of mitochondrial membrane potential. Based on the obtained data, we propose that 2-methoxyestradiol may be a natural modulator of cancer cell death and survival through nitro-oxidative stress-dependent mechanisms. Moreover, the results confirm the efficiency of 2-methoxyestradiol in treatment of neuroblastoma.

  8. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Park, Ji-hoon [Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Kim, Soon Ha, E-mail: shakim@lgls.com [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of)

    2012-08-15

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

  9. Naringenin reduces oxidative stress and improves mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons.

    Science.gov (United States)

    Wang, Kaihua; Chen, Zhenzhen; Huang, Longjian; Meng, Bing; Zhou, Xinmei; Wen, Xiaodong; Ren, Ding

    2017-09-13

    Oxidative stress and mitochondrial dysfunction are considered to be major contributing factors in the development and progression of many neurodegenerative diseases. Naringenin (NAR) is an abundant flavanone in the Citrus genus and has been found to exert antioxidant, anticarcinogenic and antimutagenic effects. However, the potential underlying mechanism of its antioxidant effects remains unclear. In the present study, the authors investigated the antioxidant effect of NAR on neurons in vitro. Neurons isolated from the brains of Sprague-Dawley rats were randomly divided into a control group, model group, NAR-L group, NAR-M group and NAR-H group. The model group received hypoxia and re-oxygenation treatment, and the NAR-L, NAR-M and NAR-H groups received 20, 40 and 80 µM NAR, respectively. The levels of reactive oxygen species (ROS) in each group were detected by chloromethyl-2',7'dichlorodihydro fluorescein diacetate staining, and differences in mitochondrial dysfunction were analyzed through measurement of mitochondrial membrane potential (∆ψm), adenine nucleotide translocase transport activity and adenine nucleotide levels. MTT and flow cytometry assays were also used to analyze cell proliferation and apoptosis, and the effects of NAR on the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway were investigated using small interfering RNA methods. The authors detected an increased accumulation of ROS in the model group, and high-dose NAR could significantly reduce the levels of ROS. Furthermore, NAR could improve mitochondrial dysfunction, as indicated by increased levels of high-energy phosphates, enhanced mitochondrial ANT transport activity and increased mitochondrial membrane potential. Moreover, NAR increased cell viability and decreased the rate of cell apoptosis. NAR also increased the expression of Nrf2 and its downstream target genes. These findings demonstrated that NAR could reduce oxidative

  10. 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.

  11. Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation.

    Science.gov (United States)

    Garcia, Gonçalo; Nanni, Sara; Figueira, Inês; Ivanov, Ines; McDougall, Gordon J; Stewart, Derek; Ferreira, Ricardo B; Pinto, Paula; Silva, Rui F M; Brites, Dora; Santos, Cláudia N

    2017-01-15

    Neuroinflammation is an integral part of the neurodegeneration process inherent to several aging dysfunctions. Within the central nervous system, microglia are the effective immune cells, responsible for neuroinflammatory responses. In this study, raspberries were subjected to in vitro digestion simulation to obtain the components that result from the gastrointestinal (GI) conditions, which would be bioaccessible and available for blood uptake. Both the original raspberry extract and the gastrointestinal bioaccessible (GIB) fraction protected neuronal and microglia cells against H2O2-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammation, at low concentrations. Furthermore, this neuroprotective capacity was independent of intracellular ROS scavenging mechanisms. We show for the first time that raspberry metabolites present in the GIB fraction significantly inhibited microglial pro-inflammatory activation by LPS, through the inhibition of Iba1 expression, TNF-α release and NO production. Altogether, this study reveals that raspberry polyphenols may present a dietary route to the retardation or amelioration of neurodegenerative-related dysfunctions.

  12. Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost.

    Science.gov (United States)

    Lessiani, Gianfranco; Vazzana, Natale; Cuccurullo, Chiara; Di Michele, Dario; Laurora, Giuseppe; Sgrò, Giuseppe; Di Ruscio, Paolo; Simeone, Emilio; Di Iorio, Pierangelo; Lattanzio, Stefano; Liani, Rossella; Ferrante, Elisabetta; Davì, Giovanni

    2011-02-01

    Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB₂ and 8-iso-PGF(₂α) excretion rate, as in vivo indexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB₂ [499 (277-807) vs. 380 (189-560) pg/mg creatinine, p iloprost treatment (Rho = 0.695, p iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.

  13. 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.

  14. 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.

  15. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  16. Parathyroid Hormone-Related Protein Protects Osteoblastic Cells From Oxidative Stress by Activation of MKP1 Phosphatase.

    Science.gov (United States)

    Ardura, Juan A; Portal-Núñez, Sergio; Castelbón-Calvo, Irantzu; Martínez de Toda, Irene; De la Fuente, Mónica; Esbrit, Pedro

    2017-04-01

    Oxidative damage is an important contributor to the morphological and functional changes in osteoporotic bone. Aging increases the levels of reactive oxygen species (ROS) that cause oxidative stress and induce osteoblast apoptosis. ROS modify several signaling responses, including mitogen-activated protein kinase (MAPK) activation, related to cell survival. Both parathyroid hormone (PTH) and its bone counterpart, PTH-related protein (PTHrP), can regulate MAPK activation by modulating MAPK phosphatase-1 (MKP1). Thus, we hypothesized that PTHrP might protect osteoblasts from ROS-induced apoptosis by targeting MKP1. In osteoblastic MC3T3-E1 and MG-63 cells, H2 O2 triggered p38, JNK, ERK and p66(Shc) phosphorylation, and cell apoptosis. Meanwhile, PTHrP (1-37) rapidly but transiently increased ERK and Akt phosphorylation without affecting p38, JNK, or p66(Shc) activation. H2 O2 -induced p38 and ERK phosphorylation and apoptosis were both decreased by pre-treatment with specific kinase inhibitors or PTHrP (1-37) in both osteoblastic cell types. These dephosphorylating and prosurvival actions of PTHrP (1-37) were prevented by a phosphatase inhibitor cocktail, the phosphatase MKP1 inhibitor sanguinarine or a MKP1 siRNA. PTHrP (1-37) promptly enhanced MKP1 protein and gene expression and MKP1-dependent catalase activity in osteoblastic cells. Furthermore, exposure to PTHrP (1-37) adsorbed in an implanted hydroxyapatite-based ceramic into a tibial defect in aging rats increased MKP1 and catalase gene expression in the healing bone area. Our findings demonstrate that PTHrP counteracts the pro-apoptotic actions of ROS by a mechanism dependent on MKP1-induced dephosphorylation of MAPKs in osteoblasts. J. Cell. Physiol. 232: 785-796, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes.

    Science.gov (United States)

    Yang, Ji Hye; Shin, Bo Yeon; Han, Jae Yun; Kim, Mi Gwang; Wi, Ji Eun; Kim, Young Woo; Cho, Il Je; Kim, Sang Chan; Shin, Sang Mi; Ki, Sung Hwan

    2014-01-15

    Isorhamentin is a 3'-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE-deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCδ and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Effect of temperature on oxidative stress parameters and enzyme activity in tissues of Cape River crab (Potamanautes perlatus) following exposure to silver nanoparticles (AgNP).

    Science.gov (United States)

    Walters, Chavon R; Cheng, Paul; Pool, Edmund; Somerset, Vernon

    2016-01-01

    Biomarkers of oxidative stress have been widely used in environmental assessments to evaluate the effects of exposure of aquatic organisms to contaminants from various anthropogenic sources. Silver nanoparticles (AgNP), the most produced NP worldwide and used in several consumer products, are known to produce oxidative stress in aquatic organisms. Similarly, temperature is also known to affect reactive oxygen species (ROS) by influencing the inputs of contaminants into the environment, as well as altering behavior, fate, and transport. Aquatic ecosystems are affected by both anthropogenic releases of contaminants and increased temperature. To test this hypothesis, the influence of AgNP and temperature in the response to multiple biomarkers of oxidative stress was studied in the gills and hepatopancreas of the Cape River crab Potamonautes perlatus. Responses were assessed through activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and the nonenzymatic antioxidant glutathione S-transferase (GST). The response of the oxidative stress biomarkers analyzed was always higher in hepatopancreas than in gills. Elevated temperatures (28°C) induced oxidative stress by increasing SOD, CAT, and GST activities, particularly at 100 µg/ml AgNP. These data indicate that AgNP-mediated toxicity to P. perlatus is modulated by elevated temperatures, but this relationship is not linear. Co-effects of AgNP and temperature are reported for the first time in P. perlatus.

  3. Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stress

    Directory of Open Access Journals (Sweden)

    Melissa H Costell

    2012-07-01

    Full Text Available Soluble guanylate cyclase (sGC, the primary mediator of nitric oxide (NO bioactivity, exists as reduced (NO-sensitive and oxidized (NO-insensitive forms. We tested the hypothesis that the cardiovascular protective effects of NO-insensitive sGC activation would be potentiated under conditions of oxidative stress compared to NO-sensitive sGC stimulation. The cardiovascular effects of the NO-insensitive sGC activator GSK2181236A (a non-depressor dose and a higher dose which lowered mean arterial pressure [MAP] by 5-10mmHg and equi-efficacious doses of the NO-sensitive sGC stimulator BAY 60-4552 were assessed in Sprague Dawley rats during coronary artery ischemia/reperfusion (I/R and spontaneously hypertensive stroke prone rats (SHR-SP on a high salt/fat diet (HSFD. In I/R, neither compound reduced infarct size. In SHR-SP, HSFD increased MAP, urine output, microalbuminuria and mortality, caused left ventricular hypertrophy and impaired endothelium-dependent vasorelaxation. The low dose of BAY 60-4552 but not GSK2181236A decreased urine output and mortality. Conversely, the low dose of GSK2181236A attenuated cardiac hypertrophy. The high doses of both compounds similarly attenuated cardiac hypertrophy and mortality. In addition, the high dose of BAY 60-4552 reduced urine output, microalbuminuria and MAP. Neither compound improved endothelium-dependent vasorelaxation. In SHR-SP aorta, the vasodilatory responses to the NO-dependent compounds carbachol and sodium nitroprusside were attenuated by HSFD. In contrast, the vasodilatory responses to GSK2181236A and BAY 60-4552 were unaltered by HSFD, indicating that reduced NO-bioavailability and not changes in the sGC oxidative state is responsible for the vascular dysfunction. In summary, GSK2181236A and BAY 60-4552 provide partial benefit against hypertension-induced end organ damage. The differential beneficial effects observed between these compounds could reflect tissue-specific changes in the s

  4. Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stress.

    Science.gov (United States)

    Costell, Melissa H; Ancellin, Nicolas; Bernard, Roberta E; Zhao, Shufang; Upson, John J; Morgan, Lisa A; Maniscalco, Kristeen; Olzinski, Alan R; Ballard, Victoria L T; Herry, Kenny; Grondin, Pascal; Dodic, Nerina; Mirguet, Olivier; Bouillot, Anne; Gellibert, Francoise; Coatney, Robert W; Lepore, John J; Jucker, Beat M; Jolivette, Larry J; Willette, Robert N; Schnackenberg, Christine G; Behm, David J

    2012-01-01

    Soluble guanylate cyclase (sGC), the primary mediator of nitric oxide (NO) bioactivity, exists as reduced (NO-sensitive) and oxidized (NO-insensitive) forms. We tested the hypothesis that the cardiovascular protective effects of NO-insensitive sGC activation would be potentiated under conditions of oxidative stress compared to those of NO-sensitive sGC stimulation. The cardiovascular effects of the NO-insensitive sGC activator GSK2181236A [a low, non-depressor dose, and a high dose which lowered mean arterial pressure (MAP) by 5-10 mmHg] and those of equi-efficacious doses of the NO-sensitive sGC stimulator BAY 60-4552 were assessed in (1) Sprague Dawley rats during coronary artery ischemia/reperfusion (I/R) and (2) spontaneously hypertensive stroke prone rats (SHR-SP) on a high salt/fat diet (HSFD). In I/R, neither compound reduced infarct size 24 h after reperfusion. In SHR-SP, HSFD increased MAP, urine output, microalbuminuria, and mortality, caused left ventricular hypertrophy with preserved ejection fraction, and impaired endothelium-dependent vasorelaxation. The low dose of BAY 60-4552, but not that of GSK2181236A, decreased urine output, and improved survival. Conversely, the low dose of GSK2181236A, but not that of BAY 60-4552, attenuated the development of cardiac hypertrophy. The high doses of both compounds similarly attenuated cardiac hypertrophy and improved survival. In addition to these effects, the high dose of BAY 60-4552 reduced urine output and microalbuminuria and attenuated the increase in MAP to a greater extent than did GSK2181236A. Neither compound improved endothelium-dependent vasorelaxation. In SHR-SP isolated aorta, the vasodilatory responses to the NO-dependent compounds carbachol and sodium nitroprusside were attenuated by HSFD. In contrast, the vasodilatory responses to both GSK2181236A and BAY 60-4552 were unaltered by HSFD, indicating that reduced NO-bioavailability and not changes in the oxidative state of sGC is responsible

  5. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

    Directory of Open Access Journals (Sweden)

    Arne Trettin

    2014-01-01

    Full Text Available Paracetamol (acetaminophen is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP, cyclooxygenase (COX, and nitric oxide synthase (NOS, and this interplay may produce reactive oxygen species (ROS. We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO, and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans.

  6. Interleukin-13/Interleukin-4-induced oxidative stress contributes to death of prothrombinkringle-2 (pKr-2)-activated microglia.

    Science.gov (United States)

    Won, So-Yoon; Kim, Sang Ryong; Maeng, Sungho; Jin, Byung K

    2013-12-15

    The present study examined whether Interleukin-13 (IL-13) or IL-4, an anti-inflammatory cytokine, could induce cell death of activated microglia by prothrombin kringle-2 (pKr-2) which is a domain of prothrombin distinct from thrombin. Microglia cell death was detected at eight days after co-treatment of pKr-2 with IL-13/IL-4 in vitro. This cell death was assessed by live assay, dead assay, TUNEL and MTT assay. In parallel, reactive oxygen species (ROS) production was evident as assessed by superoxide assay, WST-1 and analyzing DCF in combination of pKr-2 and IL-13 or IL-4 treated microglia. The IL-13/IL-4-enhanced ROS production and cell death in pKr-2 activated microglia was partially inhibited by an NADPH oxidase inhibitor, apocynin and/or by several antioxidants. Moreover, Western blot analysis showed a significant increase in cyclooxygenase-2 (COX-2) expression in combination of pKr-2 and IL-13 or IL-4 treated microglia, which was partially inhibited by apocynin and an antioxidant, trolox. Additional studies demonstrated that microglia cell death was reversed by treatment with COX-2 inhibitor, NS398. Our data strongly suggest that oxidative stress and COX-2 activation through NADPH oxidase may contribute to IL-13/IL-4 induced cell death of pKr-2 activated microglia.

  7. Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

    DEFF Research Database (Denmark)

    Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon

    2015-01-01

    OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypoth......OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate...... in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT...

  8. 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.

  9. Effect of increasing temperature in the differential activity of oxidative stress biomarkers in various tissues of the Rock goby, Gobius paganellus.

    Science.gov (United States)

    Vinagre, Catarina; Madeira, Diana; Mendonça, Vanessa; Dias, Marta; Roma, Joana; Diniz, Mário S

    2014-06-01

    Oxidative stress biomarkers have been widely used in the development of ecological indices and in the assessment of exposure of aquatic organisms to contaminants from agricultural, industrial and urban pollution. However, temperature is known to also have a significant effect on oxidative stress biomarkers. This way, temperature is a confounding factor that may result in difficulties in the interpretation of oxidative stress biomarkers response patterns. Since climate change is expected to result in more frequent and intense heat wave events it is pertinent to investigate the effect of increasing temperature in the oxidative stress response of common aquatic organisms. It is also important to assess the differential response of different body tissues, given that they are differently exposed to temperature depending on their location and physiological function. This study investigates the effect of increasing temperature (20 °C-34 °C) in the response of multiple biomarkers of oxidative stress: lipid peroxidation, glutathione-S-transferase, superoxide dismutase and catalase activities, in the muscle, liver and gills of a common coastal fish, the Rock goby, Gobius paganellus. The response of the oxidative stress biomarkers analysed were always higher in the gills than in the other tissues. Muscle generally presented the lower levels of any of the biomarkers tested when compared to other tissues. Nevertheless, muscle tissue always responded significantly to temperature, as did the liver, while the gills were unresponsive in terms of lipid peroxidation and glutathione-S-transferase. Unresponsive tissues to temperature may be particularly interesting as indicators of pollution, given that temperature will not be a confounding variable in their oxidative stress response.

  10. Improvement in the electrical performance and bias-stress stability of dual-active-layered silicon zinc oxide/zinc oxide thin-film transistor

    Science.gov (United States)

    Liu, Yu-Rong; Zhao, Gao-Wei; Lai, Pai-To; Yao, Ruo-He

    2016-08-01

    Si-doped zinc oxide (SZO) thin films are deposited by using a co-sputtering method, and used as the channel active layers of ZnO-based TFTs with single and dual active layer structures. The effects of silicon content on the optical transmittance of the SZO thin film and electrical properties of the SZO TFT are investigated. Moreover, the electrical performances and bias-stress stabilities of the single- and dual-active-layer TFTs are investigated and compared to reveal the effects of the Si doping and dual-active-layer structure. The average transmittances of all the SZO films are about 90% in the visible light region of 400 nm-800 nm, and the optical band gap of the SZO film gradually increases with increasing Si content. The Si-doping can effectively suppress the grain growth of ZnO, revealed by atomic force microscope analysis. Compared with that of the undoped ZnO TFT, the off-state current of the SZO TFT is reduced by more than two orders of magnitude and it is 1.5 × 10-12 A, and thus the on/off current ratio is increased by more than two orders of magnitude. In summary, the SZO/ZnO TFT with dual-active-layer structure exhibits a high on/off current ratio of 4.0 × 106 and superior stability under gate-bias and drain-bias stress. Projected supported by the National Natural Science Foundation of China (Grant Nos. 61076113 and 61274085), the Natural Science Foundation of Guangdong Province (Grant No. 2016A030313474), and the University Development Fund (Nanotechnology Research Institute, Grant No. 00600009) of the University of Hong Kong, China.

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

    Science.gov (United States)

    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

  12. 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.

  13. 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.

  14. Sesamin imparts neuroprotection against intrastriatal 6-hydroxydopamine toxicity by inhibition of astroglial activation, apoptosis, and oxidative stress.

    Science.gov (United States)

    Baluchnejadmojarad, Tourandokht; Mansouri, Monireh; Ghalami, Jamileh; Mokhtari, Zahra; Roghani, Mehrdad

    2017-04-01

    Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry. These findings reveal the reversal effect of sesamin in 6-OHDA model of PD via attenuation of apoptosis, astrogliosis, oxidative stress, and down-regulation of α-synuclein.

  15. Citicoline protects brain against closed head injury in rats through suppressing oxidative stress and calpain over-activation.

    Science.gov (United States)

    Qian, Ke; Gu, Yi; Zhao, Yumei; Li, Zhenzong; Sun, Ming

    2014-07-01

    Citicoline, a natural compound that functions as an intermediate in the biosynthesis of cell membrane phospholipids, is essential for membrane integrity and repair. It has been reported to protect brain against trauma. This study was designed to investigate the protective effects of citicoline on closed head injury (CHI) in rats. Citicoline (250 mg/kg i.v. 30 min and 4 h after CHI) lessened body weight loss, and improved neurological functions significantly at 7 days after CHI. It markedly lowered brain edema and blood-brain barrier permeability, enhanced the activities of superoxide dismutase and the levels of glutathione, reduced the levels of malondialdehyde and lactic acid. Moreover, citicoline suppressed the activities of calpain, and enhanced the levels of calpastatin, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. Also, it attenuated the axonal and myelin sheath damage in corpus callosum and the neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. These data demonstrate the protection of citicoline against white matter and grey matter damage due to CHI through suppressing oxidative stress and calpain over-activation, providing additional support to the application of citicoline for the treatment of traumatic brain injury.

  16. 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.

  17. Oxidative Stress and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

    participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of 'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.

  19. Biochemical assessment of oxidative stress by the use of açai (Euterpe oleracea Martius gel in physically active individuals

    Directory of Open Access Journals (Sweden)

    Daniela Soares VIANA

    2016-01-01

    Full Text Available Abstract The relation between oxidative stress and inflammation induced by diseases and exercise has increased the interest in the benefits of antioxidant supplements in the improvement of health and physical and mental performance. The aim of this study was to evaluate the effectiveness of açai gel in reducing oxidative stress in individuals engaged in physical activities as well as their acceptance. Sensory evaluation was performed to determine its acceptability and the biochemical parameters related to immune profile and biomarkers of muscle, liver and oxidative stress, with and without the use of gel were evaluated. The appearance, sweetness and overall impression of the açai gel were considered good. It was observed a significant increase in CK enzyme, without the gel as well as the oxidative stress biomarkers, it was observed that the MDA (with and without gel a significant increase (p < 0.05. Through biochemical evaluation, it is concluded that the gel provided protection for some of parameters studied, since it modulated the immunological parameter reducing the lymphocyte activity and muscular stress. However, more studies must be carried out with a larger number of individuals to confirm the gel functionality.

  20. Biochemical assessment of oxidative stress by the use of açai (Euterpe oleracea Martius gel in physically active individuals

    Directory of Open Access Journals (Sweden)

    Daniela Soares VIANA

    Full Text Available Abstract The relation between oxidative stress and inflammation induced by diseases and exercise has increased the interest in the benefits of antioxidant supplements in the improvement of health and physical and mental performance. The aim of this study was to evaluate the effectiveness of açai gel in reducing oxidative stress in individuals engaged in physical activities as well as their acceptance. Sensory evaluation was performed to determine its acceptability and the biochemical parameters related to immune profile and biomarkers of muscle, liver and oxidative stress, with and without the use of gel were evaluated. The appearance, sweetness and overall impression of the açai gel were considered good. It was observed a significant increase in CK enzyme, without the gel as well as the oxidative stress biomarkers, it was observed that the MDA (with and without gel a significant increase (p < 0.05. Through biochemical evaluation, it is concluded that the gel provided protection for some of parameters studied, since it modulated the immunological parameter reducing the lymphocyte activity and muscular stress. However, more studies must be carried out with a larger number of individuals to confirm the gel functionality.

  1. Differential effects of ornithine enantiomers on the activity of anti-oxidant enzymes, polyamines content, and growth of tobacco cells under osmotic stresses.

    Science.gov (United States)

    Gholami, Morteza; Ghanati, Faezeh; Fakhari, Ali Reza; Yousefzadeh Borojeni, Laleh; Safari, Masoumeh

    2013-10-01

    Ornithine (Orn) plays an essential role in the metabolism of plant cells through incorporation in polyamines biosynthesis, the urea cycle and nitrogen metabolism. Herein, we show that Orn enantiomers have different effects on anti-oxidant enzymes activities, polyamines and proline biosynthesis and also an alleviation effect of osmotic stresses on tobacco cells. The type of stress has a significant impact on the function of L- and D-Orn for improvement of the stress effect on the cells. Under saline conditions, both enantiomers restored cell growth, though D-Orn was more beneficial to some extent. This was accompanied with a higher biosynthesis of putrescine, proline, and up-regulated activity of certain anti-oxidant enzymes by D-Orn. Under drought stress conditions, a distinct differential behavior emerged and only L-Orn showed an alleviative effect on the cell growth. Regulation of hydrogen peroxide content via the activity of catalase/peroxidase and production of osmolytes, e.g., proline and fructans, was dependent on the type of enantiomers. Activity of anti-oxidant enzymes and production of malondialdehyde from cell membranes were differently regulated following treatment with either Orn enantiomer. The results suggest that management of H2 O2 content is a determining feature of the function of Orn enantiomers in tobacco cells under salinity and drought stress conditions. © 2013 Wiley Periodicals, Inc.

  2. Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by oxidative stress induces programmed cell death

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Zadelhoff, G. van; Veldink, G.A.; Finazzi Agrò, A.

    2000-01-01

    Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive response of plants to pathogens. Here, short pulses of H2O2 are shown to cause death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA fragmentation and ladder formation, typical hallmarks of apoptosis (

  3. Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by oxidative stress induces programmed cell death

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Zadelhoff, G. van; Veldink, G.A.; Finazzi Agrò, A.

    2000-01-01

    Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive response of plants to pathogens. Here, short pulses of H2O2 are shown to cause death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA fragmentation and ladder formation, typical hallmarks of apoptosis (

  4. Increases of ferrous iron oxidation activity and arsenic stressed cell growth by overexpression of Cyc2 in Acidithiobacillus ferrooxidans ATCC19859.

    Science.gov (United States)

    Liu, Wei; Lin, Jianqun; Pang, Xin; Mi, Shuang; Cui, Shuang; Lin, Jianqiang

    2013-01-01

    Acidithiobacillus ferrooxidans plays an important role in bioleaching in reproducing the mineral oxidant of ferric iron (Fe(3+) ) by oxidization of ferrous iron (Fe(2+) ). The high-molecular-weight c-type cytochrome Cyc2 that is located in the external membrane is postulated as the first electron carrier in the Fe(2+) oxidation respiratory pathway of A. ferrooxidans. To increase ferrous iron oxidation activity, a recombinant plasmid pTCYC2 containing cyc2 gene under the control of Ptac promoter was constructed and transferred into A. ferrooxidans ATCC19859. The transcriptional level of cyc2 gene was increased by 2.63-fold and Cyc2 protein expression was observed in the recombinant strain compared with the control. The ferrous iron oxidation activity and the arsenic stressed cell growth of the recombinant strain were also elevated.

  5. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  6. Oxidative Stress and Mitogen-Activated Protein Kinase Pathways Involved in Cadmium-Induced BRL 3A Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Zhang Yiran

    2013-01-01

    Full Text Available In this study, BRL 3A cells were treated with different Cd concentrations (0, 10, 20, and 40 μmol/L for 12 h and preincubated with or without N-acetyl-L-cysteine (NAC (2 mmol/L for 30 min, and cells were treated with Cd (0 and 20 μmol/L, pretreated with p38 inhibitor (SB203580, JNK (c-Jun NH2-terminal kinases inhibitor (SP600125, and extracellular signal-regulated kinase (ERK inhibitor (U0126 for 30 min, and then treated with 20 μmol/L Cd for 12 h. Cd decreased cell viability, SOD, and GSH-Px activity in a concentration-dependent manner. Increased MDA level, ROS generation, nuclear condensation, shrinkage, and fragmentation in cell morphology were inhibited by NAC. Cd-induced apoptosis was attenuated by pretreatment with SB203580, SP600125, and U0126. The results of western blot showed that NAC preincubation affected Cd-activated MAPK pathways, p38 and ERK phosphorylation. Cd treatment elevated the mRNA levels of Bax and decreased the mRNA levels of Bcl-2, respectively. The same effect was found in their protein expression levels. These results suggest that oxidative stress and MAPK pathways participate in Cd-induced apoptosis and that the balance between pro- and antiapoptotic genes (Bax and Bcl-2 is important in Cd-induced apoptosis.

  7. Oxidative stress and mitogen-activated protein kinase pathways involved in cadmium-induced BRL 3A cell apoptosis.

    Science.gov (United States)

    Yiran, Zhang; Chenyang, Jiang; Jiajing, Wang; Yan, Yuan; Jianhong, Gu; Jianchun, Bian; Xuezhong, Liu; Zongping, Liu

    2013-01-01

    In this study, BRL 3A cells were treated with different Cd concentrations (0, 10, 20, and 40 μmol/L) for 12 h and preincubated with or without N-acetyl-L-cysteine (NAC) (2 mmol/L) for 30 min, and cells were treated with Cd (0 and 20 μmol/L), pretreated with p38 inhibitor (SB203580), JNK (c-Jun NH2-terminal kinases) inhibitor (SP600125), and extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 30 min, and then treated with 20 μmol/L Cd for 12 h. Cd decreased cell viability, SOD, and GSH-Px activity in a concentration-dependent manner. Increased MDA level, ROS generation, nuclear condensation, shrinkage, and fragmentation in cell morphology were inhibited by NAC. Cd-induced apoptosis was attenuated by pretreatment with SB203580, SP600125, and U0126. The results of western blot showed that NAC preincubation affected Cd-activated MAPK pathways, p38 and ERK phosphorylation. Cd treatment elevated the mRNA levels of Bax and decreased the mRNA levels of Bcl-2, respectively. The same effect was found in their protein expression levels. These results suggest that oxidative stress and MAPK pathways participate in Cd-induced apoptosis and that the balance between pro- and antiapoptotic genes (Bax and Bcl-2) is important in Cd-induced apoptosis.

  8. Polydatin ameliorates renal ischemia/reperfusion injury by decreasing apoptosis and oxidative stress through activating sonic hedgehog signaling pathway.

    Science.gov (United States)

    Meng, Qiu-Hong; Liu, Hong-Bao; Wang, Jian-Bo

    2016-10-01

    Polydatin, a glucoside of resveratrol, recently has been demonstrated possibly to exert its biological effects by targeting sonic hedgehog (Shh). However, whether Shh signaling pathway is involved in the therapeutic effects of polydatin for renal ischemia/reperfusion (I/R) injury has not been evaluated. Our results showed that I/R induced the secretion of Shh, upregulated Patched and Smoothened, and enhanced the nuclear translocation and target gene transcription of Glioblastoma 1 in renal I/R injury models, which were further upregulated after the administration of polydatin significantly and in turn exerted prominent nephroprotective effects against cell apoptosis and oxidative stress. The treatment with cyclopamine (a specific inhibitor of Smoothened) or 5E1 (an anti-Shh antibody) not only markedly inhibited the activation of the Shh pathway, but also dramatically suppressed the nephroprotective effects of polydatin above-mentioned. These results advance our knowledge that polydatin can provide protection for kidneys against I/R injury by enhancing antioxidant capacity and decreasing cell apoptosis through activating Shh signaling pathway.

  9. Resveratrol encapsulated in novel fusogenic liposomes activates Nrf2 and attenuates oxidative stress in cerebromicrovascular endothelial cells from aged rats.

    Science.gov (United States)

    Csiszár, Agnes; Csiszar, Anna; Pinto, John T; Gautam, Tripti; Kleusch, Christian; Hoffmann, Bernd; Tucsek, Zsuzsanna; Toth, Peter; Sonntag, William E; Ungvari, Zoltan

    2015-03-01

    Resveratrol (3,4',5-trihydroxystilbene) is a plant-derived polyphenolic trans-stilbenoid, which exerts multifaceted antiaging effects. Here, we propose a novel delivery system for resveratrol, which significantly increases its cellular uptake into aged cells. Combination of resveratrol with a positively charged lipid component to "conventional" liposomes converts these lipid vesicles to a robust fusogenic system. To study their cellular uptake and cellular effects, we treated primary cerebromicrovascular endothelial cells isolated from aged F344xBN rats with resveratrol encapsulated in fusogenic liposomes (FL-RSV). To demonstrate effective cellular uptake of FL-RSV, accumulation of the lipophilic tracer dye, DiR, and resveratrol in cerebromicrovascular endothelial cells was confirmed using flow cytometry and confocal microscopy and high-performance liquid chromatography electrochemical detection. Treatment of aged cerebromicrovascular endothelial cells with FL-RSV activated Nrf2 (assessed with a reporter gene assay), significantly decreased cellular production of reactive oxygen species (assessed by a flow cytometry-based H2DCFDA fluorescence method), and inhibited apoptosis. Taken together, encapsulation of resveratrol into novel fusogenic liposomes significantly enhances the delivery of resveratrol into aged cells, which subsequently results in rapid activation of cellular Nrf2-driven antioxidant defense mechanisms. Our studies provide proof-of-concept for the development of a novel, translationally relevant interventional strategy for prevention and/or control of oxidative stress-related pathophysiological conditions in aging.

  10. 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.

  11. Procyanidin B2 and a cocoa polyphenolic extract inhibit acrylamide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway.

    Science.gov (United States)

    Rodríguez-Ramiro, Ildefonso; Ramos, Sonia; Bravo, Laura; Goya, Luis; Martín, María Ángeles

    2011-12-01

    Humans are exposed to dietary acrylamide (AA) during their lifetime; it is therefore necessary to investigate the mechanisms associated with AA induced toxic effects. Accumulating evidence indicates that oxidative stress may contribute to AA cytotoxicity, but the link between oxidative stress and AA cytotoxicity in the gastrointestinal tract, the primary organ in contact with dietary AA, has not been described. In this study, we evaluate the alterations of the redox balance induced by AA in Caco-2 intestinal cells as well as the potential protective role of natural antioxidants such as a well-standardized cocoa polyphenolic extract (CPE) and its main polyphenol components epicatechin (EC) and procyanidin B2 (PB2). We found that AA-induced oxidative stress in Caco-2 cells is evidenced by glutathione (GSH) depletion and reactive oxygen species (ROS) overproduction. AA also activated the extracellular-regulated kinases and the c-Jun N-amino terminal kinases (JNKs) leading to an increase in caspase-3 activity and cell death. Studies with appropriate inhibitors confirmed the implication of oxidative stress and JNKs activation in AA-induced apoptosis. Additionally, AA cytotoxicity was counteracted by CPE or PB2 by inhibiting GSH consumption and ROS generation, increasing the levels of gamma-glutamyl cysteine synthase and glutathione-S-transferase and blocking the apoptotic pathways activated by AA. Therefore, AA-induced cytotoxicity and apoptosis are closely related to oxidative stress in Caco-2 cells. Interestingly, natural dietary antioxidant such as PB2 and CPE were able to suppress AA toxicity by improving the redox status of Caco-2 cells and by blocking the apoptotic pathway activated by AA.

  12. Biocompatibility of implantable materials: An oxidative stress viewpoint.

    Science.gov (United States)

    Mouthuy, Pierre-Alexis; Snelling, Sarah J B; Dakin, Stephanie G; Milković, Lidija; Gašparović, Ana Čipak; Carr, Andrew J; Žarković, Neven

    2016-12-01

    Oxidative stress occurs when the production of oxidants surpasses the antioxidant capacity in living cells. Oxidative stress is implicated in a number of pathological conditions such as cardiovascular and neurodegenerative diseases but it also has crucial roles in the regulation of cellular activities. Over the last few decades, many studies have identified significant connections between oxidative stress, inflammation and healing. In particular, increasing evidence indicates that the production of oxidants and the cellular response to oxidative stress are intricately connected to the fate of implanted biomaterials. This review article provides an overview of the major mechanisms underlying the link between oxidative stress and the biocompatibility of biomaterials. ROS, RNS and lipid peroxidation products act as chemo-attractants, signalling molecules and agents of degradation during the inflammation and healing phases. As chemo-attractants and signalling molecules, they contribute to the recruitment and activation of inflammatory and healing cells, which in turn produce more oxidants. As agents of degradation, they contribute to the maturation of the extracellular matrix at the healing site and to the degradation of the implanted material. Oxidative stress is itself influenced by the material properties, such as by their composition, their surface properties and their degradation products. Because both cells and materials produce and react with oxidants, oxidative stress may be the most direct route mediating the communication between cells and materials. Improved understanding of the oxidative stress mechanisms following biomaterial implantation may therefore help the development of new biomaterials with enhanced biocompatibility.

  13. Allium cepa Extract and Quercetin Protect Neuronal Cells from Oxidative Stress via PKC-ε Inactivation/ERK1/2 Activation

    Science.gov (United States)

    2016-01-01

    Oxidative stress plays an important role in the pathophysiology of various neurologic disorders. Allium cepa extract (ACE) and their main flavonoid component quercetin (QCT) possess antioxidant activities and protect neurons from oxidative stress. We investigated the underlying molecular mechanisms, particularly those linked to the antioxidant effects of the ACE. Primary cortical neuronal cells derived from mouse embryos were preincubated with ACE or QCT for 30 min and exposed to L-buthionine sulfoximine for 4~24 h. We found that ACE and QCT significantly decreased neuronal death and the ROS increase induced by L-buthionine-S, R-sulfoximine (BSO) in a concentration-dependent manner. Furthermore, ACE and QCT activated extracellular signal-regulated kinase 1/2 (ERK1/2), leading to downregulation of protein kinase C-ε (PKC-ε) in BSO-stimulated neuronal cells. In addition, ACE and QCT decreased the phosphorylated levels of p38 mitogen-activated protein kinase. Our results provide new insight into the protective mechanism of ACE and QCT against oxidative stress in neuronal cells. The results suggest that the inactivation of PKC-ε induced by phosphorylating ERK1/2 is responsible for the neuroprotective effect of ACE and QCT against BSO-induced oxidative stress. PMID:27668036

  14. 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.

  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. 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

  17. 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

  18. 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

  19. Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

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    Maria Letizia Taddei

    2012-01-01

    Full Text Available Increased ROS (cellular reactive oxygen species are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.

  20. Quercetin protects against aluminium induced oxidative stress and promotes mitochondrial biogenesis via activation of the PGC-1α signaling pathway.

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    Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Verma, Deepika; Priyanka, Kumari; Bal, Amanjit; Gill, Kiran Dip

    2015-12-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of PGC-1α and its downstream targets, i.e. NRF-1, NRF-2 and Tfam in mitochondrial biogenesis. Aluminium lactate (10mg/kg b.wt./day) was administered intragastrically to rats, which were pre-treated with quercetin 6h before aluminium (10mg/kg b.wt./day, intragastrically) for 12 weeks. We found a decrease in ROS levels, mitochondrial DNA oxidation and citrate synthase activity in the hippocampus (HC) and corpus striatum (CS) regions of rat brain treated with quercetin. Besides this an increase in the mRNA levels of the mitochondrial encoded subunits - ND1, ND2, ND3, Cyt b, COX1, COX3 and ATPase6 along with increased expression of nuclear encoded subunits COX4, COX5A and COX5B of electron transport chain (ETC). In quercetin treated group an increase in the mitochondrial DNA copy number and mitochondrial content in both the regions of rat brain was observed. The PGC-1α was up regulated in quercetin treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α. Electron microscopy results revealed a significant decrease in the mitochondrial cross-section area, mitochondrial perimeter length and increase in mitochondrial number in case of quercetin treated rats as compared to aluminium treated ones. Therefore it seems quercetin increases mitochondrial biogenesis and makes it an almost ideal flavanoid to control or limit the damage that has been associated with the defective mitochondrial function seen in many neurodegenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Expression of xCT and activity of system xc(-) are regulated by NRF2 in human breast cancer cells in response to oxidative stress.

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    Habib, Eric; Linher-Melville, Katja; Lin, Han-Xin; Singh, Gurmit

    2015-08-01

    Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitination. In response to oxidative stress, NRF2 dissociates from KEAP1, entering the nucleus and binding to the antioxidant response element (ARE) in the promoter of its target genes. Elevated reactive oxygen species (ROS) production may deplete GSH levels within cancer cells. System xc(-), an antiporter that exports glutamate while importing cystine to be converted into cysteine for GSH synthesis, is upregulated in cancer cells in response to oxidative stress. Here, we provided evidence that the expression of xCT, the light chain subunit of system xc(-), is regulated by NRF2 in representative human breast cancer cells. Hydrogen peroxide (H2O2) treatment increased nuclear translocation of NRF2, also increasing levels of xCT mRNA and protein and extracellular glutamate release. Overexpression of NRF2 up-regulated the activity of the xCT promoter, which contains a proximal ARE. In contrast, overexpression of KEAP1 repressed promoter activity and decreased xCT protein levels, while siRNA knockdown of KEAP1 up-regulated xCT protein levels and transporter activity. These results demonstrate the importance of the KEAP1/NRF2 pathway in balancing oxidative stress in breast cancer cells through system xc(-). We have previously shown that xCT is upregulated in various cancer cell lines under oxidative stress. In the current investigation, we focused on MCF-7 cells as a model for mechanistic studies.

  2. Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

    Science.gov (United States)

    Verma, Akhilesh Kumar; Chandra, Subhash; Singh, Rana Gopal; Singh, Tej Bali; Srivastava, Shalabh; Srivastava, Ragini

    2014-01-01

    Association of oxidative stress and serum prolidase activity (SPA) has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN) and end stage renal disease (ESRD) concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased (P < 0.001). Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2 (P < 0.001). Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1 (P < 0.001). In case-2, serum creatinine was significantly correlated with SPA only (P < 0.001). Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage. PMID:25276429

  3. Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

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    Akhilesh Kumar Verma

    2014-01-01

    Full Text Available Association of oxidative stress and serum prolidase activity (SPA has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN and end stage renal disease (ESRD concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS, total antioxidant status (TAS, and oxidative stress index (OSI were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased (P<0.001. Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2 (P<0.001. Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1 (P<0.001. In case-2, serum creatinine was significantly correlated with SPA only (P<0.001. Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage.

  4. 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.

  5. Contribution of the activated catalase to oxidative stress resistance and γ-aminobutyric acid production in Lactobacillus brevis.

    Science.gov (United States)

    Lyu, Changjiang; Hu, Sheng; Huang, Jun; Luo, Maiqi; Lu, Tao; Mei, Lehe; Yao, Shanjing

    2016-12-05

    Lactic acid bacteria (LAB) are generally sensitive to H2O2, a compound which can paradoxically produce themselves and lead to the growth arrest and cell death. To counteract the potentially toxic effects of this compound, the gene katE encoding a heme-dependent catalase (CAT) belonging to the family of monofunctional CATs was cloned from Lactobacillus brevis CGMCC1306. The enhanced homologous CAT expression was achieved using the NICE system. L. brevis cells with overexpressed CAT showed 685-fold and 823-fold higher survival when exposed to 30mmol/L of H2O2 and long-term aerated stress (after 72h), respectively, than that of the wild type cells. Furtherly, the effects of activated CAT on GABA production in L. brevis were investigated. A GABA production level of 66.4g/L was achieved using two-step biotransformation that successively employed the growing and resting cells derived from engineering L. brevis CAT. These results demonstrated clearly that overexpression of the KatE gene in L. brevis led to a marked increased survival in oxidizing environment, and shed light on a novel feasible approach to enhance the GABA production level by improving the antioxidative properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase

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    Yen Tzung-Hai

    2011-06-01

    Full Text Available Abstract Background Diabetic nephropathy (DN has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV, a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN. Methods The protective effects of RSV on DN were evaluated in streptozotocin (STZ-induced diabetic rats. Results The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys. Conclusions Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.

  7. Areca nut extract suppresses T-cell activation and interferon-gamma production via the induction of oxidative stress.

    Science.gov (United States)

    Wang, C C; Liu, T Y; Wey, S P; Wang, F I; Jan, T R

    2007-08-01

    Areca quid chewing is a major risk factor associated with oral submucous fibrosis (OSF) and oral cancer. Experimental evidence indicates that immune deterioration is associated with the pathophysiology of OSF and oral cancer. In addition, reactive oxygen species (ROS) is shown to play a role in the cytotoxic and genotoxic effect induced by areca nut extracts (ANE) in oral cells. The present studies investigated the effects of ANE on T-cell reactivity and the role of ROS in ANE effects. Treatment of splenocytes with ANE induced a marked cytotoxic effect, and suppressed the production of IL-2 and IFN-gamma, whereas the production of IL-4 was unaffected. The ANE-mediated cytotoxicity, and suppression of IFN-gamma and IL-2 production were attenuated by the presence of antioxidant N-acetyl-l-cysteine (NAC). Moreover, flow cytometric analysis demonstrated an increase in cellular ROS levels in splenic T-cells treated with ANE, which was also attenuated by the presence of NAC. Concordantly, the cellular level of glutathione was diminished by ANE in splenic T-cells pretreated with NAC. Collectively, these results demonstrated that ANE markedly suppressed T-cell activation and Th1 cytokine production, which was mediated, at least in part, by the induction of oxidative stress.

  8. Decreased antioxidase activities and oxidative stress in the spleen of chickens fed on high-fluorine diets.

    Science.gov (United States)

    Chen, Tao; Cui, Hengmin; Cui, Yun; Bai, Caimin; Gong, Tao

    2011-09-01

    Three hundred one-day-old avian broilers were divided into four equal groups of 75 animals that were fed for 42 days as follows: a control diet containing 23 mg fluorine (F)/kg and three high F diets containing 400, 800, and 1200 mg F/kg, respectively, for high F groups I, II, and III. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were greatly decreased, while the malondialdehyde (MDA) contents were markedly increased in high F groups II and III. At the same time, mitochondrial injury and expanded endocytoplasmic reticulum were obviously observed in high F groups II and III, and the fluoride contents both in spleen and serum were significantly increased in the three high F groups when compared with those of control group. The results showed that excess dietary F in the range of 800-1200 mg/kg caused obvious oxidative stress, which provided a possible pathway for the apoptosis of splenocytes in chickens.

  9. AMPK activation by isorhamnetin protects hepatocytes against oxidative stress and mitochondrial dysfunction.

    Science.gov (United States)

    Dong, Guang-Zhi; Lee, Ju-Hee; Ki, Sung Hwan; Yang, Ji Hye; Cho, Il Je; Kang, Seung Ho; Zhao, Rong Jie; Kim, Sang Chan; Kim, Young Woo

    2014-10-05

    Arachidonic acid (AA) is a ω-6 polyunsaturated fatty acid that is found in the phospholipids of membranes and released from the cellular membrane lipid bilayer by phospholipase A2. During this process, AA could produce excess reactive oxygen species and induce apoptosis and mitochondrial dysfunction by selectively inhibiting complexes I and III. Isorhamnetin, an O-methylated flavonol aglycone, has been shown to have cardio-protective, anti-adipogenic, anti-tumor, and anti-inflammatory effects. In the present study, we investigated the effects of isorhamnetin on hepatotoxicity and the underlying mechanisms involved. Our in vitro experiments showed that isorhamnetin dose-dependently blocked the hepatotoxicity induced by treatment with AA plus iron in HepG2 cells. Furthermore, isorhamnetin inhibited the AA+iron induced generation of reactive oxygen species and reduction of glutathione, and subsequently maintained mitochondria membrane potential in AA+iron treated HepG2 cells. In addition, isorhamnetin activated AMP-activated protein kinase (AMPK) by Thr-172 phosphorylation of AMPKα, and this was mediated with Ca2+/calmodulin-dependent protein kinase kinase-2 (CaMKK2), but not liver kinase B1. Experiments using CaMKK2 siRNA or its selective inhibitor, STO-609, revealed the role of CaMKK2 in the isorhamnetin-induced activation of AMPK in HepG2 cells. These results indicate isorhamnetin protects against the hepatotoxic effect of AA plus iron, and suggest that the AMPK pathway is involved in the mechanism underlying the beneficial effect of isorhamnetin in the liver.

  10. Activation of oxidative stress response by hydroxyl substituted chalcones and cyclic chalcone analogues in mitochondria.

    Science.gov (United States)

    Guzy, J; Vasková-Kubálková, J; Rozmer, Z; Fodor, K; Mareková, M; Poskrobová, M; Perjési, P

    2010-02-05

    We investigated the effect of hydroxyl substituted chalcone (1a) and some chalcone analogues (1b-d) on isolated rat liver mitochondria to gain new insights into the cytotoxic mechanism of these compounds. We observed an inhibitory effect on phosphorylation and the partial uncoupling of compounds 1a and 1d. Increased radical generation and possible covalent interaction of the compounds with cellular thiols resulted in glutathione (GSH) depletion and modulation of the investigated mitochondrial activities. Disruption of interconnected mechanisms as electron transport chain and energetic metabolism, ROS production and insufficiency of antioxidant defensive system could lead to induction of cell death.

  11. ZnO nanoparticle-induced oxidative stress triggers apoptosis by activating JNK signaling pathway in cultured primary astrocytes

    OpenAIRE

    Wang, Jieting; Deng, Xiaobei; Zhang, Fang; Chen, Deliang; Ding, Wenjun

    2014-01-01

    It has been documented in in vitro studies that zinc oxide nanoparticles (ZnO NPs) are capable of inducing oxidative stress, which plays a crucial role in ZnO NP-mediated apoptosis. However, the underlying molecular mechanism of apoptosis in neurocytes induced by ZnO NP exposure was not fully elucidated. In this study, we investigated the potential mechanisms of apoptosis provoked by ZnO NPs in cultured primary astrocytes by exploring the molecular signaling pathways triggered after ZnO NP ex...

  12. Oxidative stress, hemoglobin content, superoxide dismutase and catalase activity influenced by sulphur baths and mud packs in patients with osteoarthritis

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    Jokić Aleksandar

    2010-01-01

    Full Text Available Background/Aim. It is weel-known that sulphur baths and mud paks demonstrate beneficial effects on patients suffering from degenerative knee and hip osteoarthritis (OA through the increased activity of protective antioxidant enzymes. The aim of this study was to assess lipid peroxidation level, i.e. malondialdehyde concetration, in individuals with knee and/or hip osteoarthritis (OA, as well as to determine the influence of sulphur baths and mud packs application on the activity of superoxide dismutase (SOD and catalase (CAT in order to minimize or eliminate excessive free radical species production (oxidative stress. Methods. Thirty one patiens with knee and/or hip OA of both sexes were included in the study. All OA patients received mud pack and sulphur bath for 20 minutes a day, for 6 consecutive days a week, over 3 weeks. Blood lipid peroxidation, ie malondialdehyde concentration, superoxide dismutase and catalase activity were measured spectrophotometrically, before, on day 5 during the treatment and at the end of spa cure. Healthy volunteers (n = 31 were the controls. Results. The sulphur baths and mud packs treatment of OA patients caused a significant decrease in plasma malondialdehyde concentration compared to the controls ( p < 0.001. The mean SOD activity before the terapy was 1 836.24 U/gHb, on day 5 it rose to 1 942.15 U/gHb and after the spa cure dropped to 1 745.98 U/gHb. Catalase activity before the therapy was 20.56 kU/gHb and at the end of the terapy decreased to 16.16 kU/gHb. The difference in catalase activity before and after the therapy was significant (p < 0.001, and also significant as compared to control (p < 0.001. At the end of the treatment significant increase of hemoglobin level and significant decrease of pain intensity were noticed. Conclusion. A combined 3-week treatment by sulphur bath and mud packs led to a significant decrease of lipid peroxidation in plasma, as well as pain intensity in the patients with OA

  13. 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.

  14. Peroxidase activity and involvement in the oxidative stress response of roseobacter denitrificans truncated hemoglobin.

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    Yaya Wang

    Full Text Available Roseobacter denitrificans is a member of the widespread marine Roseobacter genus. We report the first characterization of a truncated hemoglobin from R. denitrificans (Rd. trHb that was purified in the heme-bound form from heterologous expression of the protein in Escherichia coli. Rd. trHb exhibits predominantly alpha-helical secondary structure and absorbs light at 412, 538 and 572 nm. The phylogenetic classification suggests that Rd. trHb falls into group II trHbs, whereas sequence alignments indicate that it shares certain important heme pocket residues with group I trHbs in addition to those of group II trHbs. The resonance Raman spectra indicate that the isolated Rd. trHb contains a ferric heme that is mostly 6-coordinate low-spin and that the heme of the ferrous form displays a mixture of 5- and 6-coordinate states. Two Fe-His stretching modes were detected, notably one at 248 cm-1, which has been reported in peroxidases and some flavohemoglobins that contain an Fe-His-Asp (or Glu catalytic triad, but was never reported before in a trHb. We show that Rd. trHb exhibits a significant peroxidase activity with a (kcat/Km value three orders of magnitude higher than that of bovine Hb and only one order lower than that of horseradish peroxidase. This enzymatic activity is pH-dependent with a pKa value ~6.8. Homology modeling suggests that residues known to be important for interactions with heme-bound ligands in group II trHbs from Mycobacterium tuberculosis and Bacillus subtilis are pointing toward to heme in Rd. trHb. Genomic organization and gene expression profiles imply possible functions for detoxification of reactive oxygen and nitrogen species in vivo. Altogether, Rd. trHb exhibits some distinctive features and appears equipped to help the bacterium to cope with reactive oxygen/nitrogen species and/or to operate redox biochemistry.

  15. 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.

  16. Activation of IL-11/STAT3 pathway in preconditioned human skeletal myoblasts blocks apoptotic cascade under oxidant stress.

    Science.gov (United States)

    Idris, Niagara Muhammad; Ashraf, Muhammad; Ahmed, Rafeeq P H; Shujia, Jiang; Haider, Khawaja H

    2012-01-01

    To determine whether our novel approach of diazoxide-induced stem cell preconditioning might be extrapolated to human skeletal myoblasts to support their survival under lethal oxidant stress. Using an in vitro model of H(2)O(2) treatment of human skeletal myoblasts, we report the ability of diazoxide-preconditioned human skeletal myoblasts to express cytokines and growth factors, which act in an autocrine and paracrine fashion to promote their own survival. Preconditioning of skeletal myoblasts was cytoprotective and significantly reduced their apoptotic index (p oxidant stress. The cytoprotective effect of diazoxide preconditioning was blocked by Erk1/2 inhibitor PD98059 (20-100 µM), which abrogated STAT-3 phosphorylation, thus confirming a possible involvement of Erk1/2/STAT3 signaling downstream of IL-11 in cell survival. We also investigated the time course of subcellular changes and signaling pathway of skeletal myoblasts apoptosis under oxidant stress before and after preconditioning. Apoptosis was induced in skeletal myoblasts with 100-500 µM H(2)O(2) for time points ranging from 1 to 24 h. Release of lactate dehydrogenase, disruption of the mitochondrial membrane potential and cytochrome-c translocation into cytoplasm were the earliest signs of apoptosis. Total Akt protein remained unchanged whereas marked reduction in pAkt was observed in the native skeletal myoblasts. Terminal dUTP nick end-labeling and annexin-V positivity were significantly increased after 4 h. Ultra-structure studies showed condensed chromatin, shriveled nuclei and swollen mitochondria. These data suggest that skeletal myoblasts undergo apoptosis under oxidant stress in a time-dependent manner and preconditioning of skeletal myoblasts significantly prevented their apoptosis via IL-11/STAT3 signaling.

  17. INCREASED URINARY NEOPTERIN: CREATININE RATIO AS A MARKER OF ACTIVATION OF CELL-MEDIATED IMMUNITY AND OXIDATIVE STRESS IN THE IRANIAN PATIENTS WITH MULTIPLE SCLEROSIS

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    H. Khorami

    2003-09-01

    Full Text Available Neopterin, apyrazinopyrimidine compound, is produced by macrophages after induction by interferon gamma (IFN-y and serves as a marker of cellular immune system activation followed by oxidative stress. The aim of this study was to determine urinary neopterin to creatinine ratio (UNCR as a surrogate marker of cell-mediated immune activation in multiple sclerosis (MS. Three weekly early morning urine samples were collected from 27 patients with MS and 31 age- and sex-matched apparently healthy subjects. Urinary neopterin and creatinine were determined using reversed phase high-performance liquid chromatography and Jaffe reaction, respectively. UNCR was significantly higher in patients than in healthy controls indicating IFN-y-induced cellular immunity activation and oxidative stress in multiple sclerosis. As a non-invasive method, UNCR determination may be helpful in monitoring disease progression and the effects of therapies, as well.

  18. Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway.

    Science.gov (United States)

    Park, Kwon Moo; Fogelgren, Ben; Zuo, Xiaofeng; Kim, Jinu; Chung, Daniel C; Lipschutz, Joshua H

    2010-03-01

    Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and reperfusion (I/R) injury. When cultured on plastic, Madin-Darby canine kidney (MDCK) cells overexpressing Sec10, a central exocyst component, formed domes showing increased resistance to hydrogen peroxide (H2O2). Transepithelial electric resistance (TER) of Sec10-overexpressing MDCK cells grown on Transwell filters was higher than in control MDCK cells, and the rate of TER decrease following H2O2 treatment was less in Sec10-overexpressing MDCK cells compared with control MDCK cells. After removal of H2O2, TER returned to normal more rapidly in Sec10-overexpressing compared with control MDCK cells. In collagen culture MDCK cells form cysts, and H2O2 treatment damaged Sec10-overexpressing MDCK cell cysts less than control MDCK cell cysts. The MAPK pathway has been shown to protect animals from I/R injury. Levels of active ERK, the final MAPK pathway step, were higher in Sec10-overexpressing compared with control MDCK cells. U0126 inhibited ERK activation, exacerbated the H2O2-induced decrease in TER and cyst disruption, and delayed recovery of TER following H2O2 removal. Finally, in mice with renal I/R injury, exocyst expression decreased early and returned to normal concomitant with functional recovery, suggesting that the exocyst may be involved in the recovery following I/R injury.

  19. Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity.

    Science.gov (United States)

    Bustos, Pamela Soledad; Deza-Ponzio, Romina; Páez, Paulina Laura; Albesa, Ines; Cabrera, José Luis; Virgolini, Miriam Beatriz; Ortega, María Gabriela

    2016-12-01

    We have evaluated the effect of gentamicin and gentamicin plus quercetin on ROS production, endogenous antioxidant defenses (SOD and CAT) and lipid peroxidation in vitro on human leukocytes and in vivo on whole rat blood. Gentamicin generated ROS production in human leukocytes, produced a dual effect on both enzymes dosage-dependent and generated an increase in lipid peroxidation. Quercetin, in leukocytes stimulated by gentamicin, showed more inhibitory capacity in ROS production than the reference inhibitor (vitaminC) in mononuclear cells and a similar protective behavior at this inhibitor in polymorphonuclear cells. Quercetin, in both cellular systems, tend to level SOD and CAT activities, reaching basal values and could prevent lipidic peroxidation induced by gentamicin. The results in Wistar rats confirmed that therapeutic doses of gentamicin can induce oxidative stress in whole blood and that the gentamicin treatment plus quercetin can suppress ROS generation, collaborate with SOD and CAT and diminish lipid peroxidation. Finally, flavonoid and antibiotic association was evaluated on the antimicrobial activity in S. aureus and E. coli, showing that changes were not generated in the antibacterial activity of gentamicin against E. coli strains, while for strains of S. aureus a beneficial effect observes. Therefore, we have demonstrated that gentamicin could induce oxidative stress in human leukocytes and in whole blood of Wistar rats at therapeutic doses and that quercetin may to produce a protective effect on this oxidative stress generated without substantially modifying the antibacterial activity of gentamicin against E. coli strains, and it contributes to this activity against S. aureus strains.

  20. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance.

    Science.gov (United States)

    Wenzel, Philip; Hink, Ulrich; Oelze, Matthias; Schuppan, Swaantje; Schaeuble, Karin; Schildknecht, Stefan; Ho, Kwok K; Weiner, Henry; Bachschmid, Markus; Münzel, Thomas; Daiber, Andreas

    2007-01-05

    Chronic therapy with nitroglycerin results in a rapid development of nitrate tolerance, which is associated with an increased production of reactive oxygen species. We have recently shown that mitochondria are an important source of nitroglycerin-induced oxidants and that the nitroglycerin-bioactivating mitochondrial aldehyde dehydrogenase is oxidatively inactivated in the setting of tolerance. Here we investigated the effect of various oxidants on aldehyde dehydrogenase activity and its restoration by dihydrolipoic acid. In vivo tolerance in Wistar rats was induced by infusion of nitroglycerin (6.6 microg/kg/min, 4 days). Vascular reactivity was measured by isometric tension studies of isolated aortic rings in response to nitroglycerin. Chronic nitroglycerin infusion lead to impaired vascular responses to nitroglycerin and decreased dehydrogenase activity, which was corrected by dihydrolipoic acid co-incubation. Superoxide, peroxynitrite, and nitroglycerin itself were highly efficient in inhibiting mitochondrial and yeast aldehyde dehydrogenase activity, which was restored by dithiol compounds such as dihydrolipoic acid and dithiothreitol. Hydrogen peroxide and nitric oxide were rather insensitive inhibitors. Our observations indicate that mitochondrial oxidative stress (especially superoxide and peroxynitrite) in response to organic nitrate treatment may inactivate aldehyde dehydrogenase thereby leading to nitrate tolerance. Glutathionylation obviously amplifies oxidative inactivation of the enzyme providing another regulatory pathway. Furthermore, the present data demonstrate that the mitochondrial dithiol compound dihydrolipoic acid restores mitochondrial aldehyde dehydrogenase activity via reduction of a disulfide at the active site and thereby improves nitrate tolerance.

  1. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie;

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude......, initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression. Overall, these results support the potential role of the DDR machinery as a barrier to gliomagenesis...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development....

  2. 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.

  3. The heat shock factor A4A confers salt tolerance and is regulated by oxidative stress and the mitogen-activated protein kinases MPK3 and MPK6.

    Science.gov (United States)

    Pérez-Salamó, Imma; Papdi, Csaba; Rigó, Gábor; Zsigmond, Laura; Vilela, Belmiro; Lumbreras, Victoria; Nagy, István; Horváth, Balázs; Domoki, Mónika; Darula, Zsuzsa; Medzihradszky, Katalin; Bögre, László; Koncz, Csaba; Szabados, László

    2014-05-01

    Heat shock factors (HSFs) are principal regulators of plant responses to several abiotic stresses. Here, we show that estradiol-dependent induction of HSFA4A confers enhanced tolerance to salt and oxidative agents, whereas inactivation of HSFA4A results in hypersensitivity to salt stress in Arabidopsis (Arabidopsis thaliana). Estradiol induction of HSFA4A in transgenic plants decreases, while the knockout hsfa4a mutation elevates hydrogen peroxide accumulation and lipid peroxidation. Overexpression of HSFA4A alters the transcription of a large set of genes regulated by oxidative stress. In yeast (Saccharomyces cerevisiae) two-hybrid and bimolecular fluorescence complementation assays, HSFA4A shows homomeric interaction, which is reduced by alanine replacement of three conserved cysteine residues. HSFA4A interacts with mitogen-activated protein kinases MPK3 and MPK6 in yeast and plant cells. MPK3 and MPK6 phosphorylate HSFA4A in vitro on three distinct sites, serine-309 being the major phosphorylation site. Activation of the MPK3 and MPK6 mitogen-activated protein kinase pathway led to the transcriptional activation of the HEAT SHOCK PROTEIN17.6A gene. In agreement that mutation of serine-309 to alanine strongly diminished phosphorylation of HSFA4A, it also strongly reduced the transcriptional activation of HEAT SHOCK PROTEIN17.6A. These data suggest that HSFA4A is a substrate of the MPK3/MPK6 signaling and that it regulates stress responses in Arabidopsis.

  4. 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’ ...

  5. 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.

  6. The influence of modified water chemistries on metal oxide films, activity build-up and stress corrosion cracking of structural materials in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Maekelae, K.; Laitinen, T.; Bojinov, M. [VTT Manufacturing Technology, Espoo (Finland)

    1999-03-01

    The primary coolant oxidises the surfaces of construction materials in nuclear power plants. The properties of the oxide films influence significantly the extent of incorporation of actuated corrosion products into the primary circuit surfaces, which may cause additional occupational doses for the maintenance personnel. The physical and chemical properties of the oxide films play also an important role in different forms of corrosion observed in power plants. This report gives a short overview of the factors influencing activity build-up and corrosion phenomena in nuclear power plants. Furthermore, the most recent modifications in the water chemistry to decrease these risks are discussed. A special focus is put on zinc water chemistry, and a preliminary discussion on the mechanism via which zinc influences activity build-up is presented. Even though the exact mechanisms by which zinc acts are not yet known, it is assumed that Zn may block the diffusion paths within the oxide film. This reduces ion transport through the oxide films leading to a reduced rate of oxide growth. Simultaneously the number of available adsorption sites for {sup 60}Co is also reduced. The current models for stress corrosion cracking assume that the anodic and the respective cathodic reactions contributing to crack growth occur partly on or in the oxide films. The rates of these reactions may control the crack propagation rate and therefore, the properties of the oxide films play a crucial role in determining the susceptibility of the material to stress corrosion cracking. Finally, attention is paid also on the novel techniques which can be used to mitigate the susceptibility of construction materials to stress corrosion cracking. (orig.) 127 refs.

  7. Alterations of Na(+)/K(+)-ATPase, cholinergic and antioxidant enzymes activity by protocatechuic acid in cadmium-induced neurotoxicity and oxidative stress in Wistar rats.

    Science.gov (United States)

    Adefegha, Stephen A; Oboh, Ganiyu; Omojokun, Olasunkanmi S; Adefegha, Omowunmi M

    2016-10-01

    This study assessed the possible protective mechanisms of protocatechuic acid (PCA) against cadmium (Cd)-induced oxidative stress and neurotoxicity in rats. Male wistar strain rats weighing between 150-160g were purchased and acclimatized for two weeks. The rats were divided into seven groups of seven each; NC group received normal saline, CAD group received 6mg/kg of Cd-solution, CAD+PSG group received Cd-solution and prostigmine (5mg/kg), CAD+PCA-10 and CAD+PCA-20 groups received Cd-solution and PCA (10mg/kg and 20mg/kg) respectively, PCA-10 and PCA-20 groups received 10mg/kg and 20mg/kg PCA each. Animals were administered normal saline, Cd and PCA daily by oral gavage for 21days. After which the animals were sacrificed, the brain excised, homogenized and centrifuged. The activities of enzymes (Na(+)/K(+)-ATPase, cholinesterases, catalase, glutathione peroxidase, superoxide dismutase) and levels of oxidative stress markers (lipid peroxidation and reduced glutathione) linked to neurodegeneration were subsequently assessed. Significant (penzyme activities and levels of oxidative stress markers were observed in CAD group when compared to the NC group. However, the activities of the enzymes were reversed in CAD+PSG and CAD+PCA groups. PCA may protect against cadmium-induced neurotoxicity by altering the activities of Na(+)/K(+)-ATPase, acetylcholinesterase, butyrylcholinesterase and endogenous antioxidant enzymes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. 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...

  9. 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...

  10. Chronic stress adaptation of the nitric oxide synthases and IL-1β levels in brain structures and hypothalamic-pituitary-adrenal axis activity induced by homotypic stress.

    Science.gov (United States)

    Gadek-Michalska, A; Tadeusz, J; Rachwalska, P; Bugajski, J

    2015-06-01

    The aim of this study was to determine the effect of repeated restraint stress (RS) on a single restraint (homotypic) stress-induced expression of interleukin-1β (IL-1β), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in the prefrontal cortex (PFC), hippocampus and hypothalamus and their adaptational changes in chronic stress. Also the involvement of plasma IL-1β in adrenocorticotropic hormone (ACTH) and corticosterone secretion during chronic stress was investigated. Rats were subjected to a single restraint for 10 minutes or restrained twice a day for 3, 7 and 14 consecutive days and 24 hours after the last stress period rats were restrained for 10 min and rapidly decapitated 0, 1, 2 and 3 hours later. The IL-1β, nNOS and iNOS protein levels in brain structures samples were analyzed by Western blot procedure and IL-1β, ACTH and corticosterone levels were determined in plasma. Single restraint induced a strongest decrease of iNOS protein levels (1-3 h) in the PFC and a weaker decline in the hippocampus and hypothalamus (3 h) after stress cessation. Single restraint markedly increased IL-1β protein level in PFC and hippocampus. In the PFC repeated restraint for 3 days significantly increased the homotypic stress induced iNOS and IL-1β protein levels and this increase gradually declined after 7 and 14 days of repeated restraint. Much weaker yet a parallel changes appeared with neuronal NOS level. In the hippocampus prior stress for 3, 7 and 14 days significantly increased the homotypic stress induced iNOS protein level parallel with IL-1β level which gradually declined with prolonged period of repeated restraint. In the hippocampus a longer restraint period, 7 and 14 days markedly decreased nNOS protein level evoked by homotypic stress. In the hypothalamus prior stress for 3 days strongly enhanced the homotypic stress-induced iNOS level and repeated stress for 7 and 14 days blunted this effect. Repeated stress increased IL-1

  11. Effect of the French oak wood extract Robuvit on markers of oxidative stress and activity of antioxidant enzymes in healthy volunteers: a pilot study.

    Science.gov (United States)

    Horvathova, Martina; Orszaghova, Zuzana; Laubertova, Lucia; Vavakova, Magdalena; Sabaka, Peter; Rohdewald, Peter; Durackova, Zdenka; Muchova, Jana

    2014-01-01

    We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo.

  12. 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.

  13. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons.

    Science.gov (United States)

    Singh, Shilpee; Zhuo, Ming; Gorgun, Falih M; Englander, Ella W

    2013-08-01

    Surges of nitric oxide compromise mitochondrial respiration primarily by competitive inhibition of oxygen binding to cytochrome c oxidase (complex IV) and are particularly injurious in neurons, which rely on oxidative phosphorylation for all their energy needs. Here, we show that transgenic overexpression of the neuronal globin protein, neuroglobin, helps diminish protein nitration, preserve mitochondrial function and sustain ATP content of primary cortical neurons challenged by extended nitric oxide exposure. Specifically, in transgenic neurons, elevated neuroglobin curtailed nitric oxide-induced alterations in mitochondrial oxygen consumption rates, including baseline oxygen consumption, consumption coupled with ATP synthesis, proton leak and spare respiratory capacity. Concomitantly, activation of genes involved in sensing and responding to oxidative/nitrosative stress, including the early-immediate c-Fos gene and the phase II antioxidant enzyme, heme oxygenase-1, was diminished in neuroglobin-overexpressing compared to wild-type neurons. Taken together, these differences reflect a lesser insult produced by similar concentrations of nitric oxide in neuroglobin-overexpressing compared to wild-type neurons, suggesting that abundant neuroglobin buffers nitric oxide and raises the threshold of nitric oxide-mediated injury in neurons.

  14. Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II-induced inflammation and hypertension: regulation of oxidative stress.

    Science.gov (United States)

    Ebrahimian, Talin; Li, Melissa Wei; Lemarié, Catherine A; Simeone, Stefania M C; Pagano, Patrick J; Gaestel, Matthias; Paradis, Pierre; Wassmann, Sven; Schiffrin, Ernesto L

    2011-02-01

    Vascular oxidative stress and inflammation play an important role in angiotensin II-induced hypertension, and mitogen-activated protein kinases participate in these processes. We questioned whether mitogen-activated protein kinase-activated protein kinase 2 (MK2), a downstream target of p38 mitogen-activated protein kinase, is involved in angiotensin II-induced vascular responses. In vivo experiments were performed in wild-type and Mk2 knockout mice infused intravenously with angiotensin II. Angiotensin II induced a 30 mm Hg increase in mean blood pressure in wild-type that was delayed in Mk2 knockout mice. Angiotensin II increased superoxide production and vascular cell adhesion molecule-1 in blood vessels of wild-type but not in Mk2 knockout mice. Mk2 knockdown by small interfering RNA in mouse mesenteric vascular smooth muscle cells caused a 42% reduction in MK2 protein and blunted the angiotensin II-induced 40% increase of MK2 expression. Mk2 knockdown blunted angiotensin II-induced doubling of intracellular adhesion molecule-1 expression, 2.4-fold increase of nuclear p65, and 1.4-fold increase in Ets-1. Mk2 knockdown abrogated the angiotensin II-induced 4.7-fold and 1.3-fold increase of monocyte chemoattractant protein-1 mRNA and protein. Angiotensin II enhanced reactive oxygen species levels (by 29%) and nicotinamide adenine dinucleotide phosphate oxidase activity (by 48%), both abolished by Mk2 knockdown. Reduction of MK2 blocked angiotensin II-induced p47phox translocation to the membrane, associated with a 53% enhanced catalase expression. Angiotensin II-induced increase of MK2 was prevented by the nicotinamide adenine dinucleotide phosphate oxidase inhibitor Nox2ds-tat. Mk2 small interfering RNA prevented the angiotensin II-induced 30% increase of proliferation. In conclusion, MK2 plays a critical role in angiotensin II signaling, leading to hypertension, oxidative stress via activation of p47phox and inhibition of antioxidants, and vascular inflammation

  15. Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation.

    Science.gov (United States)

    Vandresen-Filho, Samuel; Martins, Wagner C; Bertoldo, Daniela B; Mancini, Gianni; Herculano, Bruno A; de Bem, Andreza F; Tasca, Carla I

    2013-06-01

    Oxygen-glucose deprivation (OGD) in brain cells increases extracellular glutamate concentration leading to excitotoxicity. Glutamate uptake from the synaptic cleft is carried out by glutamate transporters, which are likely to be modulated by oxidative stress. Therefore, oxidative stress is associated with reduced activity of glutamate transporters and glutamine synthetase, thus increasing extracellular glutamate levels that may aggravate damage to brain cells. Atorvastatin, a cholesterol-lowering agent, has been shown to exert neuroprotective effects. The aim of this study was to investigate if in vivo atorvastatin treatment would have protective effects against hippocampal slices subjected to OGD, ex vivo. Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS). Atorvastatin pretreatment also prevented the OGD-induced decrease in glutamate uptake and glutamine synthetase activity, although it had no effect on OGD-induced excitatory aminoacids release. Addition of cholesterol before OGD and reoxygenation, abolished the protective effect of atorvastatin on cellular viability as well as on glutamate uptake and glutamine synthetase activity. Therefore, atorvastatin is capable of preventing OGD-induced cell death, an effect achieved due to modulation of glutamate uptake and glutamine synthetase activity, and associated with diminished oxidative stress. Additionally, atorvastatin effects were dependent on its action on cholesterol synthesis inhibition. Thus, atorvastatin might be a useful strategy in the prevention of glutamate exitotoxicity involved in brain injuries such as vascular disorders.

  16. 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.

  17. Arabidopsis FHY3 and FAR1 Regulate Light-Induced myo-Inositol Biosynthesis and Oxidative Stress Responses by Transcriptional Activation of MIPS1.

    Science.gov (United States)

    Ma, Lin; Tian, Tian; Lin, Rongcheng; Deng, Xing-Wang; Wang, Haiyang; Li, Gang

    2016-04-04

    myo-Inositol-1-phosphate synthase (MIPS) catalyzes the limiting step of inositol biosynthesis and has crucial roles in plant growth and development. In response to stress, the transcription of MIPS1 is induced and the biosynthesis of inositol or inositol derivatives is promoted by unknown mechanisms. Here, we found that the light signaling protein FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1) regulate light-induced inositol biosynthesis and oxidative stress responses by activating the transcription of MIPS1. Disruption of FHY3 and FAR1 caused light-induced cell death after dark-light transition, precocious leaf senescence, and increased sensitivity to oxidative stress. Reduction of salicylic acid (SA) accumulation by overexpression of SALICYLIC ACID 3-HYDROXYLASE largely suppressed the cell death phenotype of fhy3 far1 mutant plants, suggesting that FHY3- and FAR1-mediated cell death is dependent on SA. Furthermore, comparative analysis of chromatin immunoprecipitation sequencing and microarray results revealed that FHY3 and FAR1 directly target both MIPS1 and MIPS2. The fhy3 far1 mutant plants showed severely decreased MIPS1/2 transcript levels and reduced inositol levels. Conversely, constitutive expression of MIPS1 partially rescued the inositol contents, caused reduced transcript levels of SA-biosynthesis genes, and prevented oxidative stress in fhy3 far1. Taken together, our results indicate that the light signaling proteins FHY3 and FAR1 directly bind the promoter of MIPS1 to activate its expression and thereby promote inositol biosynthesis to prevent light-induced oxidative stress and SA-dependent cell death.

  18. Garlic attenuates cardiac oxidative stress via activation of PI3K/AKT/Nrf2-Keap1 pathway in fructose-fed diabetic rat.

    Directory of Open Access Journals (Sweden)

    Raju Padiya

    Full Text Available BACKGROUND: Cardiovascular complication due to diabetes has remained a major cause of death. There is an urgent need to intervene the cardiac complications in diabetes by nutritional or pharmacological agents. Thus the present study was designed to find out the effectiveness of garlic on cardiac complications in insulin-resistant diabetic rats. METHODS AND RESULTS: SD rats were fed high fructose (65% diet alone or along with raw garlic homogenate (250 mg/kg/day or nutrient-matched (65% corn starch control diet for 8 weeks. Fructose-fed diabetic rats showed cardiac hypertrophy, increased NFkB activity and increased oxidative stress. Administration of garlic significantly decreased (p<0.05 cardiac hypertrophy, NFkB activity and oxidative stress. Although we did not observe any changes in myocardial catalase, GSH and GPx in diabetic heart, garlic administration showed significant (p<0.05 increase in all three antioxidant/enzymes levels. Increased endogenous antioxidant enzymes and gene expression in garlic treated diabetic heart are associated with higher protein expression of Nrf2. Increased myocardial H2S levels, activation of PI3K/Akt pathway and decreased Keap levels in fructose-fed heart after garlic administration might be responsible for higher Nrf2 levels. CONCLUSION: Our study demonstrates that raw garlic homogenate is effective in reducing cardiac hypertrophy and fructose-induced myocardial oxidative stress through PI3K/AKT/Nrf2-Keap1 dependent pathway.

  19. Oxidative stress decreases with elevation in the lizard Psammodromus algirus.

    Science.gov (United States)

    Reguera, Senda; Zamora-Camacho, Francisco J; Trenzado, Cristina E; Sanz, Ana; Moreno-Rueda, Gregorio

    2014-06-01

    Oxidative stress is considered one of the main ecological and evolutionary forces. Several environmental stressors vary geographically and thus organisms inhabiting different sites face different oxidant environments. Nevertheless, there is scarce information about how oxidative damage and antioxidant defences vary geographically in animals. Here we study how oxidative stress varies from lowlands (300-700 m asl) to highlands (2200-2500 m asl) in the lizard Psammodromus algirus. To accomplish this, antioxidant enzymatic activity (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase, DT-diaphorase) and lipid peroxidation were assayed in tissue samples from the lizards' tail. Lipid peroxidation was higher in individuals from lowlands than from highlands, indicating higher oxidative stress in lowland lizards. These results suggest that environmental conditions are less oxidant at high elevations with respect to low ones. Therefore, our study shows that oxidative stress varies geographically, which should have important consequences for our understanding of geographic variation in physiology and life-history of organisms.

  20. 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.

  1. Increased pro-inflammatory cytokines, glial activation and oxidative stress in the hippocampus after short-term bilateral adrenalectomy

    OpenAIRE

    Hamadi, Naserddine; Sheikh, Azimullah; Madjid, Nather; Lubbad, Loai; Amir, Naheed; Shehab, Safa Al-Deen Saudi; Khelifi-Touhami, Fatima; Adem, Abdu

    2016-01-01

    Background Bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively there are few publications on the effects of short-term adrenalectomy. In the present study we aimed to investigate the effects of short-term bilateral adrenalectomy on the levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α; the response of microglia and astrocytes to neuronal cell death as well as oxidative stress markers G...

  2. Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

    Directory of Open Access Journals (Sweden)

    Tomoko Kawakami

    2012-01-01

    although, HO activity was significantly (P<0.05 attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05. CoPP, in EC-SOD(−/− mice, enhanced HO activity (P<0.05 and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/− mice.

  3. CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases

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    Arthur I. Cederbaum

    2012-01-01

    Full Text Available The mechanisms by which alcohol causes cell injury are not clear. A major mechanism is the role of lipid peroxidation and oxidative stress in alcohol toxicity. Many pathways have been suggested to play a role in how alcohol induces oxidative stress. Considerable attention has been given to alcohol elevated production of lipopolysaccharide (LPS and TNFα and to alcohol induction of CYP2E1. These two pathways are not exclusive of each other; however, interactions between them, have not been extensively evaluated. Increased oxidative stress from induction of CYP2E1 sensitizes hepatocytes to LPS and TNFα toxicity and oxidants, activation of inducible nitric oxide synthase and p38 and JNK MAP kinases, and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNFα-potentiated hepatotoxicity. This paper will summarize studies showing potentiated interactions between these two risk factors in promoting liver injury and the mechanisms involved including activation of the mitogen-activated kinase kinase kinase ASK-1. Decreasing either cytosolic or mitochondrial thioredoxin in HepG2 cells expressing CYP2E1 causes loss of cell viability and elevated oxidative stress via an ASK-1/JNK-dependent mechanism. We hypothesize that similar interactions occur as a result of ethanol induction of CYP2E1 and TNFα.

  4. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    Science.gov (United States)

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis.

  5. The role of oxidative stress in alcoholic liver injury

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    Radosavljević Tatjana

    2009-01-01

    Full Text Available Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and α-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

  6. 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.

  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. 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...

  9. 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...

  10. Impact of Oxidative Stress in Fetal Programming

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    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.

  11. Role of Lipid Peroxidation Products, Plasma Total Antioxidant Status, and Cu-, Zn-Superoxide Dismutase Activity as Biomarkers of Oxidative Stress in Elderly Prediabetics

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    Sylwia Dzięgielewska-Gęsiak

    2014-01-01

    Full Text Available The relationship between hyperglycemia and oxidative stress in diabetes is well known, but the influence of metabolic disturbances recognized as prediabetes, in elderly patients especially, awaits for an explanation. Methods. 52 elderly persons (65 years old and older with no acute or severe chronic disorders were assessed: waist circumference (WC, body mass index (BMI, percentage of body fat (FAT, and arterial blood pressure. During an oral glucose tolerance test (OGTT fasting (0′ and 120-minute (120′ glycemia and insulinemia were determined, and type 2 diabetics (n=6 were excluded. Subjects were tested for glycated hemoglobin HbA1c, plasma lipids, total antioxidant status (TAS, thiobarbituric acid-reacting substances (TBARS, and activity of erythrocyte superoxide dismutase (SOD-1. According to OGTT results, patients were classified as normoglycemics, (NGT, n=18 and prediabetics, (PRE, n=28. Results. Both groups did not differ with their lipids, FAT, and TBARS. PRE group had higher WC (P<0.002 and BMI (P<0.002. Lower SOD-1 activity (P<0.04 and TAS status (P<0.04 were found in PRE versus NGT group. Significance. In elderly prediabetics, SOD-1 and TAS seem to reflect the first symptoms of oxidative stress, while TBARS are later biomarkers of oxidative stress.

  12. Bioavailability and antioxidant activity of some food supplements in men and women using the D-Roms test as a marker of oxidative stress.

    Science.gov (United States)

    Cornelli, U; Terranova, R; Luca, S; Cornelli, M; Alberti, A

    2001-12-01

    Most antioxidants show contradictory behaviors because in the biological environment, for unpredictable reasons, they can become prooxidants. Recently, a new simple method to monitor oxidative stress in serum was developed. This test detects the derivatives of reactive oxygen metabolites (D-Roms). Hydroperoxides are converted into radicals that oxidize N,N-diethyl-para-phenylendiamine and that can be detected through spectrophotometric procedures as U.CARR. (Carratelli units). One U.CARR. corresponds to 0.8 mg/L hydrogen peroxide. In normal subjects U.CARR. values range from 250 to 300. Values outside this range indicate a modification of the prooxidant/antioxidant ratio. On the basis of this method, we tested three different formulas of antioxidants (F1, F2, F3) in 14 apparently healthy volunteers (11 men and 3 women). Formula 1 was composed of 5 mg zinc, 48 microg selenium, 400 microg vitamin A (as retinol acetate), 50 microg beta-carotene, 15 mg vitamin E (as dl-alpha-tocopheryl acetate) and 10 mg L-cysteine. Formula 2 was composed of 30 mg bioflavonoids from citrus, 30 mg vitamin C (as L-ascorbic acid), 10 mg coenzyme Q(10) and 1 mg vitamin B-6 (as pyridoxine hydrochloride). Formula 3 was composed of Formula 1 plus Formula 2. Each formula was prepared in dry capsules (formulation D1, D2, D3) or in a fluid form (formulation P1, P2, P3). Each formulation was administered for 1 wk in a crossover design. A 15% deviation of U.CARR. levels was chosen as the cut-off value for a significant change in oxidative stress. Formulas F1 and F3 reduced mean U.CARR. levels in most of the treated subjects (t test, P < 0.05), whereas F2 was not active. Fluid formulations were more active than dry formulations (chi(2) test, P < 0.05). In some cases, a slight increase in oxidative stress was detected. These minimal increases were not related to any particular antioxidant formula. In one subject only, the administration of the dry formulation (D1), increased oxidative stress to a

  13. 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.

  14. Renal Dopamine Receptors, Oxidative Stress, and Hypertension

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    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.

  15. 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.

  16. A high constitutive catalase activity confers resistance to methyl viologen-promoted oxidative stress in a mutant of the cyanobacterium Nostoc punctiforme ATCC 29133.

    Science.gov (United States)

    Moirangthem, Lakshmipyari Devi; Bhattacharya, Sudeshna; Stensjö, Karin; Lindblad, Peter; Bhattacharya, Jyotirmoy

    2014-04-01

    A spontaneous methyl viologen (MV)-resistant mutant of the nitrogen-fixing cyanobacterium Nostoc punctiforme ATCC 29133 was isolated and the major enzymatic antioxidants involved in combating MV-induced oxidative stress were evaluated. The mutant displayed a high constitutive catalase activity as a consequence of which, the intracellular level of reactive oxygen species in the mutant was lower than the wild type (N. punctiforme) in the presence of MV. The superoxide dismutase (SOD) activity that consisted of a SodA (manganese-SOD) and a SodB (iron-SOD) was not suppressed in the mutant following MV treatment. The mutant was, however, characterised by a lower peroxidase activity compared with its wild type, and its improved tolerance to externally added H₂O₂ could only be attributed to enhanced catalase activity. Furthermore, MV-induced toxic effects on the wild type such as (1) loss of photosynthetic performance assessed as maximal quantum yield of photosystem II, (2) nitrogenase inactivation, and (3) filament fragmentation and cell lysis were not observed in the mutant. These findings highlight the importance of catalase in preventing MV-promoted oxidative damage and cell death in the cyanobacterium N. punctiforme. Such oxidative stress resistant mutants of cyanobacteria are likely to be a better source of biofertilisers, as they can grow and fix nitrogen in an unhindered manner in agricultural fields that are often contaminated with the herbicide MV, also commonly known as paraquat.

  17. Coexpressed Catalase Protects Chimeric Antigen Receptor-Redirected T Cells as well as Bystander Cells from Oxidative Stress-Induced Loss of Antitumor Activity.

    Science.gov (United States)

    Ligtenberg, Maarten A; Mougiakakos, Dimitrios; Mukhopadhyay, Madhura; Witt, Kristina; Lladser, Alvaro; Chmielewski, Markus; Riet, Tobias; Abken, Hinrich; Kiessling, Rolf

    2016-01-15

    Treatment of cancer patients by adoptive T cell therapy has yielded promising results. In solid tumors, however, T cells encounter a hostile environment, in particular with increased inflammatory activity as a hallmark of the tumor milieu that goes along with abundant reactive oxygen species (ROS) that substantially impair antitumor activity. We present a strategy to render antitumor T cells more resilient toward ROS by coexpressing catalase along with a tumor specific chimeric Ag receptor (CAR) to increase their antioxidative capacity by metabolizing H2O2. In fact, T cells engineered with a bicistronic vector that concurrently expresses catalase, along with the CAR coexpressing catalase (CAR-CAT), performed superior over CAR T cells as they showed increased levels of intracellular catalase and had a reduced oxidative state with less ROS accumulation in both the basal state and upon activation while maintaining their antitumor activity despite high H2O2 levels. Moreover, CAR-CAT T cells exerted a substantial bystander protection of nontransfected immune effector cells as measured by CD3ζ chain expression in bystander T cells even in the presence of high H2O2 concentrations. Bystander NK cells, otherwise ROS sensitive, efficiently eliminate their K562 target cells under H2O2-induced oxidative stress when admixed with CAR-CAT T cells. This approach represents a novel means for protecting tumor-infiltrating cells from tumor-associated oxidative stress-mediated repression.

  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. Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

    Institute of Scientific and Technical Information of China (English)

    Okafor OY; Erukainure OL; Ajiboye JA; Adejobi RO; Owolabi FO; Kosoko SB

    2011-01-01

    Objective: To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. Methods: Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. Results: Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. Conclusions: The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.

  20. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans

    Science.gov (United States)

    Ávila, Felipe; Echeverria, Guadalupe; Perez, Druso; Trejo, Sebastian; Leighton, Federico

    2017-01-01

    This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350) produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N = 11) were randomly assigned to three experimental meals: (1) 250 g of ground turkey burger (GTB) + 500 mL of water; (2) 250 g of GTB + 500 mL of 5% BPC-350; (3) 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA), carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p < 0.05). Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p < 0.05). The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat. PMID:28243359

  1. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Ines Urquiaga

    2017-01-01

    Full Text Available This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350 produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N=11 were randomly assigned to three experimental meals: (1 250 g of ground turkey burger (GTB + 500 mL of water; (2 250 g of GTB + 500 mL of 5% BPC-350; (3 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA, carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p<0.05. Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p<0.05. The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat.

  2. Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling

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    Guo C

    2015-02-01

    Full Text Available Caixia Guo,1,2 Yinye Xia,1,2 Piye Niu,1,2 Lizhen Jiang,1,2 Junchao Duan,1,2 Yang Yu,1,2 Xianqing Zhou,1,2 Yanbo Li,1,2 Zhiwei Sun1,2 1School of Public Health, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China Abstract: Despite the widespread application of silica nanoparticles (SiNPs in industrial, commercial, and biomedical fields, their response to human cells has not been fully elucidated. Overall, little is known about the toxicological effects of SiNPs on the cardiovascular system. In this study, SiNPs with a 58 nm diameter were used to study their interaction with human umbilical vein endothelial cells (HUVECs. Dose- and time-dependent decrease in cell viability and damage on cell plasma-membrane integrity showed the cytotoxic potential of the SiNPs. SiNPs were found to induce oxidative stress, as evidenced by the significant elevation of reactive oxygen species generation and malondialdehyde production and downregulated activity in glutathione peroxidase. SiNPs also stimulated release of cytoprotective nitric oxide (NO and upregulated inducible nitric oxide synthase (NOS messenger ribonucleic acid, while downregulating endothelial NOS and ET-1 messenger ribonucleic acid, suggesting that SiNPs disturbed the NO/NOS system. SiNP-induced oxidative stress and NO/NOS imbalance resulted in endothelial dysfunction. SiNPs induced inflammation characterized by the upregulation of key inflammatory mediators, including IL-1β, IL-6, IL-8, TNFα, ICAM-1, VCAM-1, and MCP-1. In addition, SiNPs triggered the activation of the Nrf2-mediated antioxidant system, as evidenced by the induction of nuclear factor-κB and MAPK pathway activation. Our findings demonstrated that SiNPs could induce oxidative stress, inflammation, and NO/NOS system imbalance, and eventually lead to endothelial dysfunction via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling. This study indicated

  3. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    Science.gov (United States)

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID:27413419

  4. Neurological and histological consequences induced by in vivo cerebral oxidative stress: evidence for beneficial effects of SRT1720, a sirtuin 1 activator, and sirtuin 1-mediated neuroprotective effects of poly(ADP-ribose polymerase inhibition.

    Directory of Open Access Journals (Sweden)

    Cindy Gueguen

    Full Text Available Poly(ADP-ribosepolymerase and sirtuin 1 are both NAD(+-dependent enzymes. In vitro oxidative stress activates poly(ADP-ribosepolymerase, decreases NAD(+ level, sirtuin 1 activity and finally leads to cell death. Poly(ADP-ribosepolymerase hyperactivation contributes to cell death. In addition, poly(ADP-ribosepolymerase inhibition restores NAD(+ level and sirtuin 1 activity in vitro. In vitro sirtuin 1 induction protects neurons from cell loss induced by oxidative stress. In this context, the role of sirtuin 1 and its involvement in beneficial effects of poly(ADP-ribosepolymerase inhibition were evaluated in vivo in a model of cerebral oxidative stress induced by intrastriatal infusion of malonate in rat. Malonate promoted a NAD(+ decrease that was not prevented by 3-aminobenzamide, a poly(ADP-ribosepolymerase inhibitor, at 4 and 24 hours. However, 3-aminobenzamide increased nuclear SIRT1 activity/expression ratio after oxidative stress. Malonate induced a neurological deficit associated with a striatal lesion. Both were reduced by 3-aminobenzamide and SRT1720, a sirtuin 1 activator, showing beneficial effects of poly(ADP-ribosepolymerase inhibition and sirtuin 1 activation on oxidative stress consequences. EX527, a sirtuin 1 inhibitor, given alone, modified neither the score nor the lesion, suggesting that endogenous sirtuin 1 was not activated during cerebral oxidative stress. However, its association with 3-aminobenzamide suppressed the neurological improvement and the lesion reduction induced by 3-aminobenzamide. The association of 3-aminobenzamide with SRT1720, the sirtuin 1 activator, did not lead to a better protection than 3-aminobenzamide alone. The present data represent the first demonstration that the sirtuin 1 activator SRT1720 is neuroprotective during in vivo cerebral oxidative stress. Furthermore sirtuin 1 activation is involved in the beneficial effects of poly(ADP-ribosepolymerase inhibition after in vivo cerebral oxidative

  5. Activation of α7 nicotinic acetylcholine receptor protects against oxidant stress damage through reducing vascular peroxidase-1 in a JNK signaling-dependent manner in endothelial cells.

    Science.gov (United States)

    Li, Dong-Jie; Zhao, Ting; Xin, Ru-Juan; Wang, Yuan-Yuan; Fei, Yi-Bo; Shen, Fu-Ming

    2014-01-01

    Alpha7 nicotinic acetylcholine receptor (α7nAChR), a subtype of nAChR regulating neurotransmission in central nervous system, is an essential regulator of cholinergic anti-inflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endothelial cells. Cultured human umbilical vein endothelial cells were treated with H2O2 (400 µM) or H2O2 plus PNU-282987 (10 µM). Cell viability and membrane integrity were measured. Annexin V + PI assay, immunoblotting of bcl-2, bax and cleaved capase-3, and immunofluorescence of apoptosis inducing factor (AIF) were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 (VPO-1) and phosphor-JNK were measured by immunoblotting. Activation of α7nAChR by a selective agonist PNU-282987 prevented H2O2-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2O2-induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activation on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyllycaconitine blocked the cytoprotective effect of PNU-282987. These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signaling pathway-dependent manner in endothelial cells. © 2014 S. Karger AG, Basel.

  6. 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.

  7. CONCENTRATED AMBIENT AIR POLLUTION CREATES OXIDATIVE STRESS IN CNS MICROGLIA.

    Science.gov (United States)

    Nanometer size particles carry free radical activity on their surface and can produce oxidative stress (OS)-mediated damage upon impact to target cells. The initiating event of phage cell activation (i.e., the oxidative burst) is unknown, although many proximal events have been i...

  8. ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA.

    Science.gov (United States)

    Nanometer size particles carry free radical activity on their surface and can create oxidative stress (OS)-mediated inflammatory changes upon impact. The oxidative burst signals the activation of phage-lineage cells such as peripheral macrophages, Kupffer cells and CNS microgl...

  9. 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

  10. 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

  11. 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

  12. [Experimental and clinical aspects of oxidative stress and redox regulation].

    Science.gov (United States)

    Nakamura, Hajime

    2003-02-01

    Although excess amounts of oxidative stress damage proteins and nucleotides, small amounts of oxidative stress transduce intracellular signals for cellular activation, differentiation and proliferation. Reduction/oxidation(redox) regulation is defined as a biological response to maintain homeostasis against oxidative stress. Thioredoxin, a 12 kD small protein with a redox-active dithiol/disulfide in the conserved active site: -Cys-Gly-Pro-Cys-, is a key molecule for redox regulation as well as glutathione(GSH). Thioredoxin is induced by a variety of oxidative stresses and secreted from cells. Thioredoxin plays crucial roles as a redox-regulator of intracellular signal transduction and as a radical scavenger. Plasma levels of thioredoxin are good biomarkers for oxidative stress. Thioredoxin-transgenic mice are more resistant to cerebral infarction, infection or inflammation and survive longer than control mice. Administration of thioredoxin may have a good potential for anti-aging and anti-stress effects. Redox regulation mechanisms by thioredoxin and other thioredoxin family members will clarify the pathophysiology of oxidative stress-associated disorders.

  13. Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection

    Directory of Open Access Journals (Sweden)

    Daniela Surico

    2015-07-01

    Full Text Available Background/Aim: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC. Methods: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO release by hCG and its effects on cell viability, glutathione (GSH levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS, Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2 activation and markers of apoptosis were analyzed by Western Blot. Results: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. Conclusion: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders.

  14. Epigallocatechin gallate exacerbates fluoride-induced oxidative stress mediated testicular toxicity in rats through the activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    S. Thangapandiyan; S. Miltonprabu

    2015-01-01

    Objective:To explore the ameliorative potential of epigallocatechin gallate (EGCG) by evaluating markers of oxidative stress, apoptosis, and inflammation and antioxidant competence in Fl intoxicated rats.Methods:The animals were divided in to four groups that is control, EGCG alone, NaF, and EGCG with NaF. Group III animal were exposed to Fl as sodium Fluoride (NaF) (25 mg/kg BW) for 4 weeks. After the completion of the treatment, the testis tissues has been removed and used for the experimental observations.Results:Pre-administration of EGCG to Fl intoxicated rats showed a significant normalization in the levels of steroidogenic enzymes, testosterone, sperm functions, oxidative stress markers and antioxidant status. The altered levels of proinflammatory cytokines and apoptotic markers were also relapsed in close proximity to control. In addition, EGCG significantly improved antioxidant status and reduced the oxidative stress and pathological changes in testes. The mRNA and protein analysis also substantiated that EGCG pre-treatment markedly enhanced the expression of Nrf2 and its target genes HO-1, NQO1 andγGCS and suppressed the expression of Keap1 in testis.Conclusion: Altogether, our findings supports that EGCG attenuates Fl toxicity in testis through Nrf2 activation.

  15. Tat-DJ-1 enhances cell survival by inhibition of oxidative stress, NF-κB and MAPK activation in HepG2 cells.

    Science.gov (United States)

    Jo, Hyo Sang; Yeo, Eun Ji; Shin, Min Jea; Choi, Yeon Joo; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Eum, Won Sik; Choi, Soo Young

    2017-04-01

    To identify the protective effect of DJ-1 protein against oxidative stress-induced HepG2 cell death, we used cell-permeable wild type (WT) and a mutant (C106A Tat-DJ-1) protein. By using western blotting and fluorescence microscopy, we observed WT and C106A Tat-DJ-1 proteins were efficiently transduced into HepG2 cells. Transduced WT Tat-DJ-1 proteins increased cell survival and protected against DNA fragmentation and intracellular ROS generation levels in H2O2-exposed HepG2 cells. At the same time, transduced WT Tat-DJ-1 protein significantly inhibited NF-κB and MAPK (JNK and p38) activation as well as regulated the Bcl-2 and Bax expression levels. However, C106A Tat-DJ-1 protein did not show any protective effect against cell death responses in H2O2-exposed HepG2 cells. Oxidative stress-induced HepG2 cell death was significantly reduced by transduced WT Tat-DJ-1 protein, not by C106A Tat-DJ-1 protein. Thus, transduction of WT Tat-DJ-1 protein could be a novel strategy for promoting cell survival in situations of oxidative stress-induced HepG2 cell death.

  16. Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans.

    Science.gov (United States)

    Ishikado, Atsushi; Sono, Yoko; Matsumoto, Motonobu; Robida-Stubbs, Stacey; Okuno, Aya; Goto, Masashi; King, George L; Blackwell, T Keith; Makino, Taketoshi

    2013-12-01

    Willow bark extract (WBE) is listed in the European Pharmacopoeia and has been traditionally used for treating fever, pain, and inflammation. Recent studies have demonstrated its clinical usefulness. This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes heme oxygenase-1, γ-glutamylcysteine ligase modifier and catalytic subunits, and p62 and intracellular glutathione (GSH) in HUVECs. In the nematode C. elegans, WBE increased the expression of the gcs-1::green fluorescent protein reporter, a well-characterized target of the Nrf2 ortholog SKN-1, in a manner that was SKN-1-dependent. WBE increased intranuclear expression and DNA binding of Nrf2 and the activity of an antioxidant response element (ARE) reporter plasmid in HUVECs. WBE-induced expression of Nrf2-regulated genes and increased GSH levels in HUVECs were reduced by Nrf2 and p38 small interfering (si) RNAs and by the p38-specific inhibitor SB203580. Nrf2 siRNA reduced the cytoprotective effect of WBE against oxidative stress in HUVECs. Salicin, a major anti-inflammatory ingredient of WBE, failed to activate ARE-luciferase activity, whereas a salicin-free WBE fraction showed intensive activity. WBE induced antioxidant enzymes and prevented oxidative stress through activation of Nrf2 independent of salicin, providing a new potential explanation for the clinical usefulness of WBE. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect.

    Science.gov (United States)

    Picone, Pasquale; Nuzzo, Domenico; Caruana, Luca; Messina, Elisa; Barera, Annalisa; Vasto, Sonya; Di Carlo, Marta

    2015-05-01

    Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. PI-PLCβ1b affects Akt activation, cyclin E expression, and caspase cleavage, promoting cell survival in pro-B-lymphoblastic cells exposed to oxidative stress.

    Science.gov (United States)

    Piazzi, Manuela; Blalock, William L; Bavelloni, Alberto; Faenza, Irene; Raffini, Mirco; Tagliavini, Francesca; Manzoli, Lucia; Cocco, Lucio

    2015-04-01

    The phosphoinositide-dependent signal transduction pathway has been implicated in the control of a variety of biologic processes, such as the regulation of cellular metabolism and homeostasis, cell proliferation and differentiation, and apoptosis. One of the key players in the regulation of inositol lipid signaling is the phospholipase Cβ1 (PI-PLCβ1), that hydrolyzes phosphatidylinositol 4,5-bisphosphate [PtIns(4,5)P2], giving rise to the second messengers inositol triphosphate and diacylglicerol. PI-PLCβ1 has been associated with the regulation of several cellular functions, some of which have not yet been fully understood. In particular, it has been reported that PI-PLCβ1 protects murine fibroblasts from oxidative stress-induced cell death. The mediators of oxidative stress, reactive oxygen species (ROS), have been shown to regulate major epigenetic processes, causing the silencing of tumor suppressors and enhancing the proliferation of leukemic cells under oxidative stress. Investigation of the interplay between ROS, PI-PLCβ1, and their signaling mediators in leukemia might therefore reveal innovative targets of pharmacological therapy in the treatment for leukemia. In this work, we demonstrate that in pro-B-lymphoblastic cells (Ba/F3), treated with H2O2, PI-PLCβ1b conferred resistance to cell death, promoting cell cycle progression and cell proliferation and influencing the expression of cyclin A and E. Interestingly, we found that, expression of PI-PLCβ1b affects the activity of caspase-3, caspase-7, and of several protein kinases induced by oxidative stress. In particular, PI-PLCβ1b expression completely abolished the phosphorylation of Erk1/2 MAP kinases, down-regulated phosphatase and tensin homolog (PTEN), and up-regulated the phosphorylation of Akt, thereby sustaining cellular proliferation.

  19. Iron, copper, and manganese complexes with in vitro superoxide dismutase and/or catalase activities that keep Saccharomyces cerevisiae cells alive under severe oxidative stress.

    Science.gov (United States)

    Ribeiro, Thales P; Fernandes, Christiane; Melo, Karen V; Ferreira, Sarah S; Lessa, Josane A; Franco, Roberto W A; Schenk, Gerhard; Pereira, Marcos D; Horn, Adolfo

    2015-03-01

    Due to their aerobic lifestyle, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance for eliminating harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPClNOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II), and manganese(II) ions, which are also present in the active site of the above-noted metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed only SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50~0.4 μmol dm(-3)) and about 70-fold higher than those of iron. The manganese compound showed CAT activity higher than that of the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O2(•-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O2(•-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion dependent, in the order iron(III)>copper(II)>manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and the in vivo antioxidant activities. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. 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

  1. Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community.

    Science.gov (United States)

    Cui, Xiaoyi; Ohtsu, Mayumi; Mise, Nathan; Ikegami, Akihiko; Mizuno, Atsuko; Sakamoto, Takako; Ogawa, Masanori; Machida, Munehito; Kayama, Fujio

    2016-01-01

    This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard β of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging.

  2. 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....

  3. Impact of application of zinc oxide nanoparticles on callus induction, plant regeneration, element content and antioxidant enzyme activity in tomato (Solanum lycopersicum Mill. under salt stress

    Directory of Open Access Journals (Sweden)

    Alharby Hesham F.

    2016-01-01

    Full Text Available The properties of nanomaterials and their potential applications have been given considerable attention by researchers in various fields, especially agricultural biotechnology. However, not much has been done to evaluate the role or effect of zinc oxide nanoparticles (ZnO-NP in regulating physiological and biochemical processes in response to salt-induced stress. For this purpose, some callus growth traits, plant regeneration rate, mineral element (sodium, potassium, phosphorous and nitrogen contents and changes in the activity of superoxide dismutase (SOD and glutathione peroxidase (GPX in tissues of five tomato cultivars were investigated in a callus culture exposed to elevated concentrations of salt (3.0 and 6.0 g L-1NaCl, and in the presence of zinc oxide nanoparticles (15 and 30 mg L-1. The relative callus growth rate was inhibited by 3.0 g L-1 NaCl; this was increased dramatically at 6.0 g L-1. Increasing exposure to NaCl was associated with a significantly higher sodium content and SOD and GPX activities. Zinc oxide nanoparticles mitigated the effects of NaCl, and in this application of lower concentrations (15 mg L-1 was more effective than a higher concentration (30 mg L-1. This finding indicates that zinc oxide nanoparticles should be investigated further as a potential anti-stress agent in crop production. Different tomato cultivars showed different degrees of tolerance to salinity in the presence of ZnO-NP. The cultivars Edkawy, followed by Sandpoint, were less affected by salt stress than the cultivar Anna Aasa.

  4. Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

    Science.gov (United States)

    Tapia, E; Sánchez-Lozada, L G; García-Niño, W R; García, E; Cerecedo, A; García-Arroyo, F E; Osorio, H; Arellano, A; Cristóbal-García, M; Loredo, M L; Molina-Jijón, E; Hernández-Damián, J; Negrette-Guzmán, M; Zazueta, C; Huerta-Yepez, S; Reyes, J L; Madero, M; Pedraza-Chaverrí, J

    2014-11-01

    The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

  5. 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.

  6. Mixed-function oxidase enzyme activity and oxidative stress in lake trout (Salvelinus namaycush) exposed to 3,3{prime},4,4{prime}5-pentachlorobiphenyl (PCB-126)

    Energy Technology Data Exchange (ETDEWEB)

    Palace, V.P. [Univ. of Manitoba, Winnipeg, Manitoba (Canada). Dept. of Zoology; Klaverkamp, J.F.; Lockhart, W.L. [Univ. of Manitoba, Winnipeg, Manitoba (Canada). Dept. of Zoology]|[Department of Fisheries and Oceans, Winnipeg, Manitoba (Canada). Freshwater Inst.; Metner, D.A.; Muir, D.C.G.; Brown, S.B. [Department of Fisheries and Oceans, Winnipeg, Manitoba (Canada). Freshwater Inst.

    1996-06-01

    Juvenile lake trout were intraperitoneally injected with corn oil containing nominal concentrations of 0, 0.6, 6.3, or 25 {micro}g [{sup 14}C]-3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB-126) per gram of body weight. The PCB-126 accumulated in liver in a dose-dependent manner to a sustained concentration by 6 weeks and remained elevated for the 30-week experimental period. Mixed-function oxidase (MFO) enzyme activity was elevated in the two highest dose groups relative to the control group, but not in the low-dose group throughout the 30 weeks. Oxidative stress, measured by the thiobarbituric acid reactive substances test, was correlated with ethoxyresorufin O-deethylase and was elevated in liver of the two highest PCB dose groups but not the low-dose group. The activities of the enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase were unaffected by PCB-126 exposure. The nonenzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase were unaffected by PCB-126 exposure. The nonenzymatic antioxidant tocopherol was depleted to approximately 75% of the control concentration in liver of all three PCB-dosed groups. Hepatic ascorbic acid levels were not different in any of the treatment groups. Retinol was depleted by greater than an order of magnitude in liver of the two highest dose groups but not in the los-dose group. This study demonstrates a correlation between hepatic MFO activity and oxidative stress in PCB-exposed lake trout. Tocopherol and retinol may be important mediators of oxidative stress but additional study is required to confirm the antioxidant activity of retinol.

  7. Increased oxidative stress and decreased activities of Ca2+/Mg2+-ATPase and Na+/K+-ATPase in the red blood cells of the hibernating black bear

    Science.gov (United States)

    Chauhan, V.P.S.; Tsiouris, J.A.; Chauhan, A.; Sheikh, A.M.; Brown, W. Ted; Vaughan, M.

    2002-01-01

    During hibernation, animals undergo metabolic changes that result in reduced utilization of glucose and oxygen. Fat is known to be the preferential source of energy for hibernating animals. Malonyldialdehyde (MDA) is an end product of fatty acid oxidation, and is generally used as an index of lipid peroxidation. We report here that peroxidation of lipids is increased in the plasma and in the membranes of red blood cells in black bears during hibernation. The plasma MDA content was about four fold higher during hibernation as compared to that during the active, non-hibernating state (P increased during hibernation (P increased oxidative stress, and have reduced activities of membrane-bound enzymes such as Ca2+/Mg2+-ATPase and Na+/K+-ATPase. These changes can be considered part of the adaptive for survival process of metabolic depression. ?? 2002 Elsevier Science Inc. All rights reserved.

  8. 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

  9. Actively stressed marginal networks

    CERN Document Server

    Sheinman, M; MacKintosh, F C

    2012-01-01

    We study the effects of motor-generated stresses in disordered three dimensional fiber networks using a combination of a mean-field, effective medium theory, scaling analysis and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of non-affine strain fluctuations as a susceptibility to motor stress.

  10. Actively stressed marginal networks.

    Science.gov (United States)

    Sheinman, M; Broedersz, C P; MacKintosh, F C

    2012-12-07

    We study the effects of motor-generated stresses in disordered three-dimensional fiber networks using a combination of a mean-field theory, scaling analysis, and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of nonaffine strain fluctuations as a susceptibility to motor stress.

  11. Dietary grape seed proanthocyanidins inhibit UVB-induced oxidative stress and activation of mitogen-activated protein kinases and nuclear factor-kappaB signaling in in vivo SKH-1 hairless mice.

    Science.gov (United States)

    Sharma, Som D; Meeran, Syed M; Katiyar, Santosh K

    2007-03-01

    We have shown previously that dietary grape seed proanthocyanidins (GSP) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced oxidative stress and oxidative stress-mediated signaling has been implicated in photocarcinogenesis, this study was designed to investigate the effect of dietary GSPs on UVB-induced oxidative stress in in vivo SKH-1 hairless mice. Here, we report that provision of dietary GSPs (0.2 and 0.5%, w/w) to mice exposed to either acute UVB irradiation (120 mJ/cm(2)) or chronic irradiation of UVB inhibited depletion of glutathione peroxidase, catalase, and glutathione, and inhibited UVB-induced H(2)O(2), lipid peroxidation, protein oxidation, and nitric oxide in mouse skin. As UV-induced oxidative stress mediates activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) signaling pathways, we determined the effect of dietary GSPs on these pathways. We observed that dietary GSPs inhibited UVB-induced phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun-NH(2)-kinase, and p38 proteins of MAPK family, which seems to be mediated through reactivation of MAPK phosphatases. GSPs inhibited UVB-induced activation of NF-kappaB/p65 through inhibition of degradation of IkappaBalpha and activation of IkappaB kinase alpha (IKKalpha). As NF-kappaB-targeted genes play critical roles in inflammation and cellular proliferation, we assessed the effect of GSPs on proteins encoded by these genes. Dietary GSPs resulted in inhibition of the expression of proliferating cell nuclear antigen, cyclin D1, inducible nitric oxide synthase, and cyclooxygenase-2 in the skin. Collectively, our data show that GSPs have the ability to protect the skin from the adverse effects of UVB radiation via modulation of the MAPK and NF-kappaB signaling pathways and provide a molecular basis for the photoprotective effects of GSPs in an in vivo animal model.

  12. 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.

  13. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

    Directory of Open Access Journals (Sweden)

    T.I. Omotayo

    2015-04-01

    Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

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

    Science.gov (United States)

    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.

  15. Indian herb `Sanjeevani' (Selaginella bryopteris) can promote growth and protect against heat shock and apoptotic activities of ultra violet and oxidative stress

    Indian Academy of Sciences (India)

    Nand K Sah; Shyam Nandan P Singh; Sudhir Sahdev; Sharmishta Banerji; Vidyanath Jha; Zakir Khan; Seyed E Hasnain

    2005-09-01

    Selaginella bryopteris is a lithophyte with remarkable ressurection capabilities. It is full of medicinal properties, hence also known as ‘Sanjeevani’ (one that infuses life). For lack of credible scientific evidence the plant is not in active use as a medicinal herb. We provide scientific evidence for why S. bryopteris is known as ‘Sanjeevani’. The aqueous extract of S. bryopteris possesses growth-promoting activity as well as protective action against stress-induced cell death in a number of experimental cell systems including mammalian cells. Treatment of the cells in culture with 10% aqueous extract enhanced cell growth by about 41% in Sf9 cells and 78% in mammalian cells. Pre-treatment of cells with the Selaginella extract (SE) (1–2.5%) protected against oxidative stress (H2O2)-induced cell death. The killing potential of ultra violet (UV) was also significantly reduced when the cells were pre-treated with SE for 1 h. Thermal radiation suppressed cell growth by about 50%. Pre-treatment of cells with SE for 1 h afforded complete protection against heat-induced growth suppression. SE may possess anti-stress and antioxidant activities that could be responsible for the observed effects. Chemical analysis shows that SE contains hexoses and proteins. Taken together, S. bryopteris extract may help in stress-induced complications including those due to heat shock.

  16. Nitric oxide and iron modulate heme oxygenase activity as a long distance signaling response to salt stress in sunflower seedling cotyledons.

    Science.gov (United States)

    Singh, Neha; Bhatla, Satish C

    2016-02-29

    Nitric oxide is a significant component of iron signaling in plants. Heme is one of the iron sensors in plants. Free heme is highly toxic and can cause cell damage as it catalyzes the formation of reactive oxygen species (ROS). Its catabolism is carried out by heme oxygenase (HOs; EC 1.14.99.3) which uses heme both as a prosthetic group and as a substrate. Two significant events, which accompany adaptation to salt stress in sunflower seedlings, are accumulation of ROS and enhanced production of nitric oxide (NO) in roots and cotyledons. Present investigations on the immunolocalization of heme oxygenase distribution in sunflower seedling cotyledons by confocal laser scanning microscopic (CLSM) imaging provide new information on the differential spatial distribution of the inducible form of HO (HO-1) as a long distance in response to NaCl stress. The enzyme is abundantly distributed in the specialized cells around the secretory canals (SCs) in seedling cotyledons. Abundance of tyrosine nitrated proteins has also been observed in the specialized cells around the secretory canals in cotyledons derived from salt stressed seedlings. The spatial distribution of tyrosine nitrated proteins and HO-1 expression further correlates with the abundance of mitochondria in these cells. Present findings, thus, highlight a link among distribution of HO-1 expression, abundance of tyrosine nitrated proteins and mitochondria in specialized cells around the secretory canal as a long distance mechanism of salt stress tolerance in sunflower seedlings. Enhanced spatial distribution of HO-1 in response to NaCl stress in seedling cotyledons is in congruence with the observed increase in specific activity of HO-1 in NaCl stressed conditions. The enzyme activity is further enhanced by hemin (HO-1 inducer) both in the absence or presence of NaCl stress and inhibited by zinc protoporphyrin. Western blot analysis of cotyledon homogenates using anti-HO-1 polyclonal antibody shows one major band (29

  17. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Directory of Open Access Journals (Sweden)

    Fu-Wei Liu

    Full Text Available Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.

  18. Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells.

    Science.gov (United States)

    Dennis, Kathleen E; Valentine, William M

    2015-04-20

    Ubiquitin activating enzyme E1 plays a pivotal role in ubiquitin based protein signaling through regulating the initiating step of the cascade. Previous studies demonstrated that E1 is inhibited by covalent modification of reactive cysteines contained within the ubiquitin-binding groove and by conditions that increase oxidative stress and deplete cellular antioxidants. In this study, we determined the relative contribution of covalent adduction and oxidative stress to E1 inhibition produced by ziram and sodium N,N-dimethyldithiocarbamate (DMDC) in HEK293 cells. Although no dithiocarbamate-derived E1 adducts were identified on E1 using shotgun LC/MS/MS for either ziram or DMDC, both dithiocarbamates significantly decreased E1 activity, with ziram demonstrating greater potency. Ziram increased intracellular levels of zinc and copper, DMDC increased intracellular levels of only copper, and both dithiocarbamates enhanced oxidative injury evidenced by elevated levels of protein carbonyls and expression of heme oxygenase-1. To assess the contribution of intracellular copper transport to E1 inhibition, coincubations were performed with the copper chelator triethylenetetramine hydrochloride (TET). TET significantly protected E1 activity for both of the dithiocarbamates and decreased the associated oxidative injury in HEK293 cells as well as prevented dithiocarbamate-mediated lipid peroxidation assayed using an ethyl aracidonate micelle system. Because TET did not completely ameliorate intracellular transport of copper or zinc for ziram, TET apparently maintained E1 activity through its ability to diminish dithiocarbamate-mediated oxidative stress. Experiments to determine the relative contribution of elevated intracellular zinc and copper were performed using a metal free incubation system and showed that increases in either metal were sufficient to inhibit E1. To evaluate the utility of the HEK293 in vitro system for screening environmental agents, a series of additional

  19. A novel pathway links oxidative stress to loss of insulin growth factor-2 (IGF2 imprinting through NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Bing Yang

    Full Text Available Genomic imprinting is the allele-specific expression of a gene based on parental origin. Loss of imprinting(LOI of Insulin-like Growth Factor 2 (IGF2 during aging is important in tumorigenesis, yet the regulatory mechanisms driving this event are largely unknown. In this study oxidative stress, measured by increased NF-κB activity, induces LOI in both cancerous and noncancerous human prostate cells. Decreased expression of the enhancer-blocking element CCCTC-binding factor(CTCF results in reduced binding of CTCF to the H19-ICR (imprint control region, a major factor in the allelic silencing of IGF2. This ICR then develops increased DNA methylation. Assays identify a recruitment of the canonical pathway proteins NF-κB p65 and p50 to the CTCF promoter associated with the co-repressor HDAC1 explaining gene repression. An IκBα super-repressor blocks oxidative stress-induced activation of NF-κB and IGF2 imprinting is maintained. In vivo experiments using IκBα mutant mice with continuous NF-κB activation demonstrate increased IGF2 LOI further confirming a central role for canonical NF-κB signaling. We conclude CTCF plays a central role in mediating the effects of NF-κB activation that result in altered imprinting both in vitro and in vivo. This novel finding connects inflammation found in aging prostate tissues with the altered epigenetic landscape.

  20. Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue[S

    Science.gov (United States)

    Xu, X. Julia; Gauthier, Marie-Soleil; Hess, Donald T.; Apovian, Caroline M.; Cacicedo, Jose M.; Gokce, Noyan; Farb, Melissa; Valentine, Rudy J.; Ruderman, Neil B.

    2012-01-01

    We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive. However, the number of patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, and omental fat from 16 morbidly obese individuals classified as insulin sensitive or insulin resistant based on the homeostatic model assessment of insulin resistance. We confirmed that AMPK activity is diminished in the insulin resistant group. A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group. In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat. Only angiotensinogen and CD4+ mRNA levels were increased in both depots. Surprisingly, TNFα was only increased in epiploic fat, which otherwise showed very few changes. Protein carbonyl levels, a measure of oxidative stress, were increased in all depots. Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients. However, most changes in gene expression appear to be depot-specific. PMID:22323564

  1. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Nelli Giribabu

    2014-01-01

    Full Text Available P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO product, malondialdehyde (MDA, and the diminution of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.

  2. Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation.

    Science.gov (United States)

    Zheng, Fenping; Lu, Weina; Jia, Chengfang; Li, Hong; Wang, Zhou; Jia, Weiping

    2010-02-01

    The effect of glucose excursions on oxidative stress is an important topic in diabetes research. We investigated this relationship by analyzing markers of oxidative stress and glycemic data from a continuous glucose monitoring system (CGMS) in 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR), and 27 patients with newly diagnosed type 2 diabetes (T2DM). We compared the mean amplitude of glycemic excursion (MAGE), mean postprandial glucose excursion (MPPGE), and mean postprandial incremental area under the curve (IAUC) with plasma levels of oxidative stress markers 8-iso-PGF2α, 8-OH-dG, and protein carbonyl content in the study subjects. Patients with T2DM or IGR had significantly higher glucose excursions and plasma levels of oxidative stress markers compared to normal controls (P oxidative stress.

  3. [Oxidative stress in patients on regular hemodialysis and peritoneal dialysis].

    Science.gov (United States)

    Vostálová, J; Galandáková, A; Strebl, P; Zadražil, J

    2012-06-01

    Hemodialysis and peritoneal dialysis are methods of blood purification, which partially replaced excretory renal function in patients with chronic renal failure, which was depleted regime, dietary and pharmaco-therapeutic remedy, and who are not eligible for kidney transplantation. Both two methods are accompanied by increased oxidative stress. In peritoneal dialysis particularly the composition of dialysis solution contributes to oxidative stress. In extracorporeal hemodialysis the oxidative stress is associated with the character of hemodialysis membranes, non-specific loss of low molecular weight antioxidants, activation of leukocytes (oxidative burst), feroteraphy, supplementation with low molecular weight antioxidants and other factors. To improve and maintain the quality of life of dialysis patients, the continuous monitoring of oxidative stress-related parameters as non-traditional risk factors for cardiovascular complications development is suitable.

  4. Oxidative stress in deep scattering layers: Heat shock response and antioxidant enzymes activities of myctophid fishes thriving in oxygen minimum zones

    Science.gov (United States)

    Lopes, Ana Rita; Trübenbach, Katja; Teixeira, Tatiana; Lopes, Vanessa M.; Pires, Vanessa; Baptista, Miguel; Repolho, Tiago; Calado, Ricardo; Diniz, Mário; Rosa, Rui

    2013-12-01

    Diel vertical migrators, such as myctophid fishes, are known to encounter oxygen minimum zones (OMZ) during daytime in the Eastern Pacific Ocean and, therefore, have to cope with temperature and oxidative stress that arise while ascending to warmer, normoxic surface waters at night-time. The aim of this study was to investigate the antioxidant defense strategies and heat shock response (HSR) in two myctophid species, namely Triphoturus mexicanus and Benthosema panamense, at shallow and warm surface waters (21 kPa, 20-25 °C) and at hypoxic, cold (≤1 kPa, 10 °C) mesopelagic depths. More specifically, we quantified (i) heat shock protein concentrations (HSP70/HSC70) (ii) antioxidant enzyme activities [including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST)], and (iii) lipid peroxidation [malondialdehyde (MDA) levels]. HSP70/HSC70 levels increased in both myctophid species at warmer, well-oxygenated surface waters probably to prevent cellular damage (oxidative stress) due to increased oxygen demand under elevated temperatures and reactive oxygen species (ROS) formation. On the other hand, CAT and GST activities were augmented under hypoxic conditions, probably as preparatory response to a burst of oxyradicals during the reoxygenation phase (while ascending). SOD activity decreased under hypoxia in B. panamense, but was kept unchanged in T. mexicanus. MDA levels in B. panamense did not change between the surface and deep-sea conditions, whereas T. mexicanus showed elevated MDA and HSP70/HSC70 concentrations at warmer surface waters. This indicated that T. mexicanus seems to be not so well tuned to temperature and oxidative stress associated to diel vertical migrations. The understanding of such physiological strategies that are linked to oxygen deprivation and reoxygenation phases may provide valuable information about how different species might respond to the impacts of environmental stressors (e.g. expanding mesopelagic hypoxia

  5. 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.

  6. A STUDY OF OXIDATIVE STRESS IN DIABETES

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  9. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-02-03

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation.

  10. Antioxidant activity of the organotellurium compound 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid against oxidative stress in synaptosomal membrane systems and neuronal cultures.

    Science.gov (United States)

    Kanski, J; Drake, J; Aksenova, M; Engman, L; Butterfield, D A

    2001-08-17

    Antioxidant activities of 3-[4-(N,N-dimethylamino) benzenetellurenyl]propanesulfonic acid sodium salt (NDBT) were evaluated in solution, red blood cells, synaptosomal membranes, and cultured hippocampal neuronal cells after exposure to peroxynitrite (ONOO(-)) and hydroxyl radicals. The organotellurium compound NDBT possesses significant activity towards hydrogen peroxide and/or the hydroxyl radical in solution, demonstrated by inhibition of hydroxylation of terephthalic acid. In addition, the compound displayed great antioxidant abilities as shown by: reduction of ONOO(-)-induced 2,7-dichlorofluorescein (DCF) fluorescence in synaptosomes; complete prevention of lipid peroxidation in synaptosomes caused by OH radicals (TBARS), and significant prevention of protein oxidation caused by ONOO(-) and OH, indexed by the levels of protein carbonyls in synaptosomes and neuronal cells. The presence of the compound abolished neuronal cell death caused by ONOO(-). Further, the compound was effective in preventing the oxidative changes in synaptosomal membrane protein conformation and crosslinking (EPR spin labeling). Finally, the organotellurium molecule attenuated peroxynitrite-induced, luminol-dependent chemiluminescence in red blood cells--an index of cellular oxidation. These findings demonstrate the great potential of the antioxidant and are consistent with the notion that NDBT may have a role to play in modulating oxidative stress in neurodegenerative disorders, including Alzheimer's disease.

  11. Inhibition of glutathione production by L-S,R-buthionine sulfoximine activates hepatic ascorbate synthesis - A unique anti-oxidative stress mechanism in mice.

    Science.gov (United States)

    Yu, Miao; Liu, Ying; Duan, Yajun; Chen, Yuanli; Han, Jihong; Sun, Lei; Yang, Xiaoxiao

    2017-02-26

    Glutathione (GSH) and ascorbate, the cytoplasmic antioxidants, can regenerate and replace each other in scavenging reactive oxygen species reaction. Mice, but not guinea pigs, produce ascorbate endogenously. l-Buthionine-S,R-sulfoximine (L-S,R-BSO) substantially inhibited GSH production at a greater degree and caused a higher toxicity to guinea pigs than mice, implying that mice may have an additional protective mechanism against oxidative stress injury. Indeed, administration of L-S,R-BSO to mice inhibited tissue GSH production while increasing ascorbate levels. L-S,R-BSO also increased tissue ascorbate levels in mice fed a ascorbate and dehydroascorbate-free diet suggesting activation of ascorbate synthesis, which was further confirmed by increased urinary ascorbate excretion. Other reagents inhibiting GSH production also increased tissue ascorbate levels. The results of Northern blot and promoter assay showed that L-S,R-BSO increased mRNA expression and promoter activity of mouse liver L-gulono-γ-lactone oxidase, the critical enzyme for ascorbate synthesis. Taken together, our study demonstrates that inhibition of GSH production activates ascorbate synthesis to protect mice against oxidative stress injury, the mechanism which is not present in guinea pigs or humans.

  12. 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.

  13. Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress by activating LKB1-AMPK-FoxO1 signal pathway.

    Science.gov (United States)

    Lee, Jihyun; Yang, Goowon; Kim, Young-Joo; Tran, Quynh Hoa; Choe, Wonchae; Kang, Insug; Kim, Sung Soo; Ha, Joohun

    2017-09-23

    Persistent oxidative stress is recognized as a major cause of many pathological conditions as well as ageing. However, most clinical trials of dietary antioxidants have failed to produce successful outcomes in treating oxidative stress-induced diseases. Molecular hydrogen (H2) has recently received considerable attention as a therapeutic agent owing to its novel antioxidant properties, a selective scavenger of hydroxyl and peroxynitrite radicals. Beyond this, numerous reports support that H2 can modulate the activity of various cellular signal pathways. However, its effect on AMP-activated protein kinase (AMPK) signal pathway, a central regulator of energy hemostasis, has remained almost elusive. Here, we report that hydrogen-rich medium activated LKB1-AMPK signal pathway without ATP depletion, which in turn induced FoxO1-dependent transcription of manganese superoxide dismutase and catalase in mouse embryonic fibroblasts. Moreover, hydrogen-rich media effectively reduced the level of reactive oxygen species in cells treated with hydrogen peroxide and protected these cells from apoptosis in an AMPK-dependent manner. These results suggest that the LKB1-AMPK-FoxO1 signaling pathway is a critical mediator of the antioxidant properties of H2, further supporting the idea that H2 acts as a signaling molecule to serve various physiological functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Activation of Na(+)-K(+)-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na(+)-K(+)-ATPase/Src/Ros amplifier.

    Science.gov (United States)

    Yan, Xiaofei; Xun, Meng; Dou, Xiaojuan; Wu, Litao; Zhang, Fujun; Zheng, Jin

    2017-04-01

    Reduced Na(+)-K(+)-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na(+)-K(+)-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na(+)/K(+)-ATPase's DR-region specific monoclonal antibody and direct activator, could disrupt Na(+)-K(+)-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H2O2)-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of H2O2 on inhibition of Na(+)-K(+)-ATPase activity, Na(+)-K(+)-ATPase cell surface expression, and Src phosphorylation. H2O2-treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca(2+), mitochondrial Ca(2+) overload. DRm217 closed Na(+)-K(+)-ATPase/ROS amplifier, alleviated Ca(2+) accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na(+)-K(+)-ATPase in oxidative stress and oxidative stress-related disease.

  15. Linoleic acid derivative DCP-LA protects neurons from oxidative stress-induced apoptosis by inhibiting caspase-3/-9 activation.

    Science.gov (United States)

    Yaguchi, Takahiro; Fujikawa, Hirokazu; Nishizaki, Tomoyuki

    2010-05-01

    The present study aimed at understanding the effect of the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on oxidative stress-induced neuronal death. Sodium nitroprusside (SNP; 1 mM) reduced viability of cultured rat cerebral cortical neurons to 50% of basal levels, but DCP-LA significantly prevented the SNP effect in a concentration (1-100 nM)-dependent manner. In addition, DCP-LA (100 nM) rescued neurons from SNP-induced degradation. SNP (1 mM) activated caspase-3 and -9 in cultured rat cerebral cortical neurons, but DCP-LA (100 nM) abolished the caspase activation. For a mouse model of middle cerebral artery occlusion, oral administration with DCP-LA (1 mg/kg) significantly diminished degraded area due to cerebral infarction. The results of the present study, thus, demonstrate that DCP-LA protects neurons at least in part from oxidative stress-induced apoptosis by inhibiting activation of caspase-3/-9.

  16. Chronic oxidative stress after irradiation: an unproven hypothesis

    Science.gov (United States)

    Cohen, Samuel R; Cohen, Eric P

    2012-01-01

    Injury and organ failure after irradiation of late-responding tissues is a substantial problem in radiation oncology and a major threat after accidental or belligerent exposures. The mechanisms of injury may include death of clonogens, vascular injury, activation of cytokine networks, and/or chronic oxidative stress. Knowledge of mechanisms may guide optimal use of mitigators. The hypothesis of chronic oxidative stress as a mechanism of late radiation injury has received much attention. We review herein the published evidence for chronic oxidative stress in vivo, and for use of antioxidants as mitigators of normal tissue radiation injury. We conclude that there is only indirect evidence for chronic oxidative stress after irradiation, and there are only limited published reports of mitigation by antioxidants. We did not find a differentiation of persistent markers of oxidative stress from an ongoing production of oxygen radicals. It is thus unproven that chronic oxidative stress plays a major role in causing radiation injury and organ failure in late-responding tissues. Further investigation is justified, to identify persistent oxidative stress and to identify optimal mitigators of radiation injury. PMID:23245910

  17. 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...

  18. 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.

  19. A meta-analysis of oxidative stress markers in schizophrenia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Oxidative stress has been identified as a possible element in the neuropathological processes of schizophrenia(SCZ).Alteration of oxidative stress markers has been reported in SCZ studies,but with inconsistent results.To evaluate the risk of oxidative stress to schizophrenia,a meta-analysis was conducted,including five markers of oxidative stress [thiobarbituric reactive substances(TBARS),nitric oxide(NO),catalase(CAT),glutathione peroxidase(GP) and superoxide dismutase(SOD)] in SCZ patients versus healthy controls.This study showed that TBARS and NO significantly increased in SCZ,while SOD activity significantly decreased in the disorganized type of SCZ patients.No significant effect size was found for the activities of GP and CAT in SCZ patients(P>0.05).Egger’s regression test observed no significant publication bias across the oxidative stress markers,but found high heterogeneities in all the 5 markers.The subgroup analysis suggested that the ethnicity,sample size of patients and sample sources may contribute to the heterogeneity of the results for TBARS,NO and SOD.The result further demonstrated the involvement of oxidative stress in the pathophysiology of schizophrenia.

  20. Potential role of punicalagin against oxidative stress induced testicular damage

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    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  1. Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.

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    Santosh Singh

    Full Text Available BACKGROUND AND PURPOSE: Liver dysfunction led hyperammonemia (HA causes a nervous system disorder; hepatic encephalopathy (HE. In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF. METHODS: ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS and glutaminase (GA, the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats. RESULTS: The ALF rats showed significantly increased levels of ammonia in the blood (HA but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats. CONCLUSION: ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.

  2. Effect of virgin coconut oil enriched diet on the antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats - a comparative study.

    Science.gov (United States)

    Arunima, S; Rajamohan, T

    2013-09-01

    Virgin coconut oil (VCO) extracted by wet processing is popular among the scientific field and society nowadays. The present study was carried out to examine the comparative effect of VCO with copra oil (CO), olive oil (OO) and sunflower oil (SFO) on endogenous antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats. Male Sprague-Dawley rats were fed different oils at 8% level for 45 days along with the synthetic diet. Results revealed that dietary VCO improved the antioxidant status compared to other three oil fed groups (P oil fed groups (P oil fed rats (P oil) and tocopherols (33.12 μg per 100 g oil) etc. compared to other oils (P < 0.05). From these observations, it is concluded that VCO has a beneficial role in improving antioxidant status and hence preventing lipid and protein oxidation.

  3. 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.

  4. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease.

    Science.gov (United States)

    Ojha, Shreesh; Javed, Hayate; Azimullah, Sheikh; Haque, M Emdadul

    2016-07-01

    Parkinson disease (PD) is a neurodegenerative disease characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta (SNc) area. The present study was undertaken to evaluate the neuroprotective effect of β-caryophyllene (BCP) against rotenone-induced oxidative stress and neuroinflammation in a rat model of PD. In the present study, BCP was administered once daily for 4 weeks at a dose of 50 mg/kg body weight prior to a rotenone (2.5 mg/kg body weight) challenge to mimic the progressive neurodegenerative nature of PD. Rotenone administration results in oxidative stress as evidenced by decreased activities of superoxide dismutase, catalase, and depletion of glutathione with a concomitant rise in lipid peroxidation product, malondialdehyde. Rotenone also significantly increased pro-inflammatory cytokines in the midbrain region and elevated the inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Further, immunohistochemical analysis revealed loss of dopaminergic neurons in the SNc area and enhanced expression of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), indicators of microglia activation, and astrocyte hypertrophy, respectively, as an index of inflammation. However, treatment with BCP rescued dopaminergic neurons and decreased microglia and astrocyte activation evidenced by reduced Iba-1 and GFAP expression. BCP in addition to attenuation of pro-inflammatory cytokines and inflammatory mediators such as COX-2 and iNOS, also restored antioxidant enzymes and inhibited lipid peroxidation as well as glutathione depletion. The findings demonstrate that BCP provides neuroprotection against rotenone-induced PD and the neuroprotective effects can be ascribed to its potent antioxidant and anti-inflammatory activities.

  5. Melamine Induces Oxidative Stress in Mouse Ovary.

    Science.gov (United States)

    Dai, Xiao-Xin; Duan, Xing; Cui, Xiang-Shun; Kim, Nam-Hyung; Xiong, Bo; Sun, Shao-Chen

    2015-01-01

    Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were analyzed, and the concentration of malondialdehyde (MDA) were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway.

  6. Melamine Induces Oxidative Stress in Mouse Ovary.

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    Xiao-Xin Dai

    Full Text Available Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GPX were analyzed, and the concentration of malondialdehyde (MDA were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway.

  7. 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.

  8. Flavonoids and oxidative stress in Drosophila melanogaster.

    Science.gov (United States)

    Sotibrán, América Nitxin Castañeda; Ordaz-Téllez, María Guadalupe; Rodríguez-Arnaiz, Rosario

    2011-11-27

    Flavonoids are a family of antioxidants that are widely represented in fruits, vegetables, dry legumes, and chocolate, as well as in popular beverages, such as red wine, coffee, and tea. The flavonoids chlorogenic acid, kaempferol, quercetin and quercetin 3β-d-glycoside were investigated for genotoxicity using the wing somatic mutation and recombination test (SMART). This test makes use of two recessive wing cell markers: multiple wing hairs (mwh) and flare (flr(3)), which are mutations located on the left arm of chromosome 3 of Drosophila melanogaster and are indicative of both mitotic recombination and various types of mutational events. In order to test the antioxidant capacities of the flavonoids, experiments were conducted with various combinations of oxidants and polyphenols. Oxidative stress was induced using hydrogen peroxide, the Fenton reaction and paraquat. Third-instar transheterozygous larvae were chronically treated for all experiments. The data obtained in this study showed that, at the concentrations tested, the flavonoids did not induce somatic mutations or recombination in D. melanogaster with the exception of quercetin, which proved to be genotoxic at only one concentration. The oxidants hydrogen peroxide and the Fenton reaction did not induce mutations in the wing somatic assay of D. melanogaster, while paraquat and combinations of flavonoids produced significant numbers of small single spots. Quercetin 3β-d-glycoside mixed with paraquat was shown to be desmutagenic. Combinations of the oxidants with the other flavonoids did not show any antioxidant activity.

  9. Menopause as risk factor for oxidative stress.

    Science.gov (United States)

    Sánchez-Rodríguez, Martha A; Zacarías-Flores, Mariano; Arronte-Rosales, Alicia; Correa-Muñoz, Elsa; Mendoza-Núñez, Víctor Manuel

    2012-03-01

    The aim of this study was to determine the influence of menopause (hypoestrogenism) as a risk factor for oxidative stress. We carried out a cross-sectional study with 187 perimenopausal women from Mexico City, including 94 premenopausal (mean ± SD age, 44.9 ± 4.0 y; estrogen, 95.8 ± 65.7 pg/mL; follicle-stimulating hormone, 13.6 ± 16.9 mIU/mL) and 93 postmenopausal (mean ± SD age, 52.5 ± 3.3 y; estrogen, 12.8 ± 6.8 pg/mL; follicle-stimulating hormone, 51.4 ± 26.9 mIU/mL) women. We measured lipoperoxides using a thiobarbituric acid-reacting substance assay, erythrocyte superoxide dismutase and glutathione peroxidase activities, and the total antioxidant status with the Randox kit. An alternative cutoff value for lipoperoxide level of 0.320 μmol/L or higher was defined on the basis of the 90th percentile of young healthy participants. All women answered the Menopause Rating Scale, the Athens Insomnia Scale, and a structured questionnaire about pro-oxidant factors, that is, smoking, consumption of caffeinated and alcoholic beverages, and physical activity. Finally, we measured weight and height and calculated body mass index. The lipoperoxide levels were significantly higher in the postmenopausal group than in the premenopausal group (0.357 ± 0.05 vs 0.331 ± 0.05 μmol/L, P = 0.001). Using logistic regression to control pro-oxidant variables, we found that menopause was the main risk factor for oxidative stress (odds ratio, 2.62; 95% CI, 1.35-5.11; P menopause rating score, insomnia score, and lipoperoxides, and this relationship was most evident in the postmenopausal group (menopause scale, r = 0.327 [P = 0.001]; insomnia scale, r = 0.209 [P < 0.05]). Our findings suggest that the depletion of estrogen in postmenopause could cause oxidative stress in addition to the known symptoms.

  10. Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcoholinduced oxidative stressed rats

    Institute of Scientific and Technical Information of China (English)

    Okafor; OY; Erukainure; OL; Ajiboye; JA; Adejobi; RO; Owolabi; FO; Kosoko; SB

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation,changes in catalase activities and hepatic biochemical marker levels in blood plasma.Methods:Oxidative stress was induced by oral administration of ethanol(20%w/v) at a dosage of 5 niL/kg bw in rats.After 28 days of treatment,the rats were fasted overnight and sacrificed by cervical dislocation.Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min.The plasma was analyzed to evaluate malondialdehyde(MDA),catalase activity,aspartate aminotransferase(AST),alkaline phosphatase(ALP) and alanine aminotransferase(ALT) concentrations.Results:Administration of alcohol caused a drastic increase(87.74%) in MDA level compared with the control.Pineapple peel extract significantly reduced the MDA level by 60.16%at 2.S mL/kg bw.Rats fed alcohol only had the highest catalase activity,treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity.Increased AST,ALP and ALT activities were observed in rats fed alcohol only respectively,treatment with pineapple peel extract drastically reduced their activities. Conclusions:The positive modulation of lipid peroxidation,catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcoholinduced oxidative stress is an indication of its protective ability in the management of alcoholinduced toxicity.

  11. Peroxisome Proliferator Activator Receptor (PPAR-γ Ligand, but Not PPAR-α, Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver

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    Azza A. K. El-Sheikh

    2014-01-01

    Full Text Available Hepatoprotective potential of peroxisome proliferator activator receptor (PPAR-α and -γ agonists, fenofibrate (FEN, and pioglitazone (PIO, respectively, against cyclophosphamide (CP-induced toxicity has been investigated in rat. FEN and PIO (150 and 10 mg/kg/day, resp. were given orally for 4 weeks. In separate groups, CP (150 mg/kg, i.p. was injected as a single dose 5 days before the end of experiment, with or without either PPAR agonist. CP induced hepatotoxicity, as it caused histopathological alterations, with increased serum alanine and aspartate transaminases, total bilirubin, albumin, alkaline phosphatase and lactate dehydrogenase. CP caused hepatic oxidative stress, indicated by decrease in tissue reduced glutathione, with increase in malondialdehyde and nitric oxide levels. CP also caused decrease in hepatic antioxidant enzyme levels, including catalase, superoxide dismutase, glutathione peroxidase, and glutathione S-transferase. Furthermore, CP increased serum and hepatic levels of the inflammatory marker tumor necrosis factor (TNF-α, evaluated using ELISA. Preadministration of PIO, but not FEN, prior to CP challenge improved hepatic function and histology, and significantly reversed oxidative and inflammatory parameters. In conclusion, activation of PPAR-γ, but not PPAR-α, conferred protection against CP-induced hepatotoxicity, via activation of antioxidant and anti-inflammatory mechanisms, and may serve as supplement during CP chemotherapy.

  12. Salvianolic Acid B (Sal B Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1

    Directory of Open Access Journals (Sweden)

    Xiaobin Liu

    2016-11-01

    Full Text Available Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG between cysteine residues and glutathione (GSH, can lead to cell death. Glutaredoxin 1 (Grx1 is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B, a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H2O2-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2, the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H2O2-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

  13. Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

    Science.gov (United States)

    Liu, Xiaobin; Xavier, Christy; Jann, Jamieson; Wu, Hongli

    2016-11-03

    Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

  14. Curcumin Pretreatment Prevents Potassium Dichromate-Induced Hepatotoxicity, Oxidative Stress, Decreased Respiratory Complex I Activity, and Membrane Permeability Transition Pore Opening

    Directory of Open Access Journals (Sweden)

    Wylly Ramsés García-Niño

    2013-01-01

    Full Text Available Curcumin is a polyphenol derived from turmeric with recognized antioxidant properties. Hexavalent chromium is an environmental toxic and carcinogen compound that induces oxidative stress. The objective of this study was to evaluate the potential protective effect of curcumin on the hepatic damage generated by potassium dichromate (K2Cr2O7 in rats. Animals were pretreated daily by 9-10 days with curcumin (400 mg/kg b.w. before the injection of a single intraperitoneal of K2Cr2O7 (15 mg/kg b.w.. Groups of animals were sacrificed 24 and 48 h later. K2Cr2O7-induced damage to the liver was evident by histological alterations and increase in the liver weight and in the activity of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase in plasma. In addition, K2Cr2O7 induced oxidative damage in liver and isolated mitochondria, which was evident by the increase in the content of malondialdehyde and protein carbonyl and decrease in the glutathione content and in the activity of several antioxidant enzymes. Moreover, K2Cr2O7 induced decrease in mitochondrial oxygen consumption, in the activity of respiratory complex I, and permeability transition pore opening. All the above-mentioned alterations were prevented by curcumin pretreatment. The beneficial effects of curcumin against K2Cr2O7-induced liver oxidative damage were associated with prevention of mitochondrial dysfunction.

  15. 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...

  16. Iron-induced oxidative stress activates AKT and ERK1/2 and decreases Dyrk1B and PRMT1 in neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Bautista, Elizabeth; Vergara, Paula; Segovia, José

    2016-03-01

    Iron is essential for proper neuronal functioning; however, excessive accumulation of brain iron is reported in Parkinson's, Alzheimer's, Huntington's diseases and amyotrophic lateral sclerosis. This indicates that dysregulated iron homeostasis is involved in the pathogenesis of these diseases. To determinate the effect of iron on oxidative stress and on cell survival pathways, such as AKT, ERK1/2 and DyrK1B, neuroblastoma SH-SY5Y cells were exposed to different concentration of FeCl2 (iron). We found that iron induced cell death in SH-SY5Y cells in a concentration-dependent manner. Detection of iNOS and 3-nitrotyrosine confirms the presence of increased nitrogen species. Furthermore, we found a decrease of catalase and protein arginine methyl-transferase 1 (PRMT1). Interestingly, iron increased the activity of ERK and AKT and reduced DyrK1B. Moreover, after FeCl2 treatment, the transcription factors c-Jun and pSmad1/5 were activated. These results indicate that the presence of high levels of iron increase the vulnerability of neurons to oxidative stress.

  17. 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

  18. Activation of Nrf2-Antioxidant Signaling by 1,25-Dihydroxycholecalciferol Prevents Leptin-Induced Oxidative Stress and Inflammation in Human Endothelial Cells.

    Science.gov (United States)

    Teixeira, Thaisa M; da Costa, Danielly C; Resende, Angela C; Soulage, Christophe O; Bezerra, Flavia F; Daleprane, Julio B

    2017-04-01

    Background: Obesity is associated with hyperleptinemia and endothelial dysfunction. Hyperleptinemia has been reported to induce both oxidative stress and inflammation by increasing reactive oxygen species production.Objective: The objective of this study was to determine the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] against leptin-induced oxidative stress and inflammation in human endothelial cells.Methods: Small interfering RNA (siRNA) were used to knock down the expression of vitamin D receptor (VDR) in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 4 h with physiologic (10(-10) M) or supraphysiologic (10(-7) M) concentrations of 1,25(OH)2D3 and exposed to leptin (10 ng/mL). Superoxide anion production and translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and nuclear transcription factor κB (NF-κB) subunit p65 to the nucleus and the activation of their target genes were quantified.Results: Pretreatment of HUVECs with 1,25(OH)2D3 prevented the leptin-induced increase in superoxide anion production (P Leptin doubled the translocation of NF-κB (P leptin has a beneficial effect on HUVECs through the regulation of mediators of antioxidant activity and inflammation. © 2017 American Society for Nutrition.

  19. Fipronil insecticide toxicology: oxidative stress and metabolism.

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. Isolated and combined exposure to ammonia and nitrite in giant freshwater pawn (Macrobrachium rosenbergii): effects on the oxidative stress, antioxidant enzymatic activities and apoptosis in haemocytes.

    Science.gov (United States)

    Zhang, Yufan; Ye, Chaoxia; Wang, Anli; Zhu, Xuan; Chen, Changhong; Xian, Jianan; Sun, Zhenzhu

    2015-10-01

    The residual contaminators such as ammonia and nitrite are widely considered as relevant sources of aquatic environmental pollutants, posing a great threat to shrimp survival. To study the toxicological effects of ammonia and nitrite exposure on the innate immune response in invertebrates, we investigated the oxidative stress and apoptosis in haemocytes of freshwater prawn (Macrobrachium rosenbergii) under isolated and combined exposure to ammonia and nitrite in order to provide useful information about adult prawn immune responses. M. rosenbergii (13.44 ± 2.75 g) were exposed to 0, 5, and 25 mg/L total ammonia-N (TAN) and 0, 5, and 20 mg/L nitrite-N for 24 h. All ammonia concentrations were combined with all nitrite concentrations, making a total of nine treatments studied. Following the exposure treatment, antioxidant enzyme activity, reactive oxygen species (ROS) generation, nitric oxide (NO) generation, and apoptotic cell ratio of haemocytes were measured using flow cytometry. Results indicated that ROS generation was sensitive to the combined effect of ammonia and nitrite, which subsequently affected the Cu-Zn SOD activity. In addition, CAT showed the highest activity at 5 mg/L TAN while GPx decreased at 5 mg/L TAN and returned towards baseline at 25 mg/L. NO generation synchronized with the apoptotic cell ratio in haemocytes, indicating that NO production was closely associated with programmed cell death. Both NO production and apoptotic ratios significantly decreased following 25 mg/L TAN, which may be due to the antagonistic regulation of NO and GPx. We hypothesized that the toxicological effect of nitrite exhibited less change in physiological changes compared to that of ammonia, because of the high tolerance to nitrite exposure in mature M. rosenbergii and/or the competitive effects of chloride ions. Taken together, these results showed that ammonia and nitrite caused a series of combined oxidative stress and apoptosis in M. rosenbergi, but further

  3. Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: antioxidative systems, peroxide elimination, radical generation, lipid peroxidation.

    Science.gov (United States)

    Röhl, Claudia; Armbrust, Elisabeth; Herbst, Eva; Jess, Anne; Gülden, Michael; Maser, Edmund; Rimbach, Gerald; Bösch-Saadatmandi, Christine

    2010-05-01

    Microglia and astrocytes are the cellular key players in many neurological disorders associated with oxidative stress and neuroinflammation. Previously, we have shown that microglia activated by lipopolysaccharides (LPS) induce the expression of antioxidative enzymes in astrocytes and render them more resistant to hydrogen peroxide (H2O2). In this study, we examined the mechanisms involved with respect to the cellular action of different peroxides, the ability to detoxify peroxides, and the status of further antioxidative systems. Astrocytes were treated for 3 days with medium conditioned by purified quiescent (microglia-conditioned medium, MCM[-]) or LPS-activated (MCM[+]) microglia. MCM[+] reduced the cytotoxicity of the organic cumene hydroperoxide in addition to that of H2O2. Increased peroxide resistance was not accompanied by an improved ability of astrocytes to remove H2O2 or an increased expression/activity of peroxide eliminating antioxidative enzymes. Neither peroxide-induced radical generation nor lipid peroxidation were selectively affected in MCM[+] treated astrocytes. The glutathione content of peroxide resistant astrocytes, however, was increased and superoxide dismutase and heme oxygenase were found to be upregulated. These changes are likely to contribute to the higher peroxide resistance of MCM[+] treated astrocytes by improving their ability to detoxify reactive oxygen radicals and oxidation products. For C6 astroglioma cells a protective effect of microglia-derived factors could not be observed, underlining the difference of primary cells and cell lines concerning their mechanisms of oxidative stress resistance. Our results indicate the importance of microglial-astroglial cell interactions during neuroinflammatory processes.

  4. 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.

  5. Intense and exhaustive exercise induce oxidative stress in skeletal muscle

    Directory of Open Access Journals (Sweden)

    T Thirumalai

    2011-03-01

    Full Text Available Objective: To assess the oxidative stress and antioxidant defense system in the skeletal muscle of male albino rats subjected to strenuous exercise programme. Methods: Wistar strain albino rats were subjected to exhaustive swimming exercise programme daily for a period of five days. The thiobarbituric acid reactive substances (TBARS, conjugated dienes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase were measured in the gastrocnemius muscle of the exercised animals. Results: The elevated levels of TBARS and conjugated dienes indicated the oxidative stress in the gastrocemius muscle of the exercised animals. The depleted activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the exercise animals indicated the increased oxidative stress and decreased antioxidative defense system in the muscle. Conclusions: The study suggests that prolonged strenuous exercise programme can induce oxidative stress and therefore an optimal level of exercise schedule should be advocated to obtain the maximum benefit of exercise programme.

  6. Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies

    Directory of Open Access Journals (Sweden)

    Xinyu Yang

    2017-08-01

    Full Text Available Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS, nitrogen (RNS and halogen species, non-radical as well as free radical species. This occurrence results in cell injury due to direct oxidation of cellular protein, lipid, and DNA or via cell death signaling pathways responsible for accelerating atherogenesis. This paper discusses inflammation, mitochondria, autophagy, apoptosis, and epigenetics as they induce oxidative stress in atherosclerosis, as well as various treatments for antioxidative stress that may prevent atherosclerosis.

  7. 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

  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 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.

  10. 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.

  11. Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Zhenying Han

    Full Text Available Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1 and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, α-7 nAchR agonist, methyllycaconitine (MLA, nAchR antagonist, or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO. Behavior test, lesion volume, CD68(+, M1 (CD11b(+/Iba1(+ and M2 (CD206/Iba1+ microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68(+ and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in α-7 nAchR neuro-protective effect.

  12. Nitric oxide stress and activation of AMP-activated protein kinase impair β-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.

    Science.gov (United States)

    Tong, X; Kono, T; Evans-Molina, C

    2015-06-18

    The sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) concentration gradient between the cytosol and ER lumen in the pancreatic β-cell, and the integrity of this gradient has a central role in regulated insulin production and secretion, maintenance of ER function and β-cell survival. We have previously demonstrated loss of β-cell SERCA2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1β (IL-1β) combined with or without cycloheximide or actinomycin D. IL-1β treatment led to increased inducible nitric oxide synthase (iNOS) gene and protein expression, which occurred concurrently with the activation of AMP-activated protein kinase (AMPK). IL-1β led to decreased SERCA2b mRNA and protein expression, whereas time-course experiments revealed a reduction in protein half-life with no change in mRNA stability. Moreover, SERCA2b protein but not mRNA levels were rescued by treatment with the NOS inhibitor l-NMMA (NG-monomethyl L-arginine), whereas the NO donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) and the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) recapitulated the effects of IL-1β on SERCA2b protein stability. Similarly, IL-1β-induced reductions in SERCA2b expression were rescued by pharmacological inhibition of AMPK with compound C or by transduction of a dominant-negative form of AMPK, whereas β-cell death was prevented in parallel. Finally, to determine a functional relationship between NO and AMPK signaling and SERCA2b activity, fura-2/AM (fura-2-acetoxymethylester) Ca(2+) imaging experiments were performed in INS-1 cells. Consistent with observed changes in SERCA2b expression, IL-1β, SNAP and AICAR increased cytosolic Ca(2+) and decreased ER Ca(2+) levels, suggesting congruent modulation of SERCA activity under these conditions. In aggregate, these results show that SERCA2b

  13. Oxidized Extracellular DNA as a Stress Signal in Human Cells

    Directory of Open Access Journals (Sweden)

    Aleksei V. Ermakov

    2013-01-01

    Full Text Available The term “cell-free DNA” (cfDNA was recently coined for DNA fragments from plasma/serum, while DNA present in in vitro cell culture media is known as extracellular DNA (ecDNA. Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that promotes irradiation-induced bystander effect. Evidence points to TLR9 as a possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA stimulates a synthesis of reactive oxygen species (ROS that evokes an adaptive response that includes transposition of the homologous loci within the nucleus, polymerization and the formation of the stress fibers of the actin, as well as activation of the ribosomal gene expression, and nuclear translocation of NF-E2 related factor-2 (NRF2 that, in turn, mediates induction of phase II detoxifying and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal released in response to oxidative stress in the cultured cells and, possibly, in the human body; in particular, it might contribute to systemic abscopal effects of localized irradiation treatments.

  14. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  15. PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

    Science.gov (United States)

    Pacak, Karel

    2012-01-01

    -oncogene activation, tumor suppressor gene inactivation, DNA damage, and genomic instability. Since the mitochondria serves as the main source of prooxidants, any mitochondrial impairment leads to severe oxidative stress, a major outcome of which is tumor development. In terms of cancer pathogenesis, pheochromocytomas and paragangliomas represent tumors where the oxidative phosphorylation defect due to the mutation of succinate dehydrogenase is the cause, not a consequence, of tumor development. Any succinate dehydrogenase pathogenic mutation results in the shift from oxidative phosphorylation to aerobic glycolysis in the cytoplasm (also called anaerobic glycolysis if hypoxia is the main cause of such a shift). This phenomenon, also called the Warburg effect, is well demonstrated by a positive [18F]-fluorodeoxyglycose positron emission tomography scan. Microarray studies, genome-wide association studies, proteomics and protein arrays, metabolomics, transcriptomics, and bioinformatics approaches will remain powerful tools to further uncover the pathogenesis of these tumors and their unique markers, with the ultimate goal to introduce new therapeutic options for those with metastatic or malignant pheochromocytoma and paraganglioma. Soon oxidative stress will be tightly linked to a multistep cancer process in which the mutation of various genes (perhaps in a logistic way) ultimately results in uncontrolled growth, proliferation, and metastatic potential of practically any cell. Targeting the mTORC, IGF-1, HIF and other pathways, topoisomerases, protein degradation by proteosomes, balancing the activity of protein kinases and phosphatases or even synchronizing the cell cycle before any exposure to any kind of therapy will soon become a reality. Facing such a reality today will favor our chances to “beat” this disease tomorrow. PMID:21615192

  16. 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...

  17. 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 ...

  18. 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 ...

  19. 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

  20. Suppression of oxidative stress and 5-lipoxygenase activation by edaravone improves depressive-like behavior after concussion.

    Science.gov (United States)

    Higashi, Youichirou; Hoshijima, Michihiro; Yawata, Toshio; Nobumoto, Atsuya; Tsuda, Masayuki; Shimizu, Takahiro; Saito, M