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Sample records for angiogenesis oxidative stress

  1. Relationships between Cycling Hypoxia, HIF-1, Angiogenesis and Oxidative Stress

    PubMed Central

    Dewhirst, Mark W.

    2009-01-01

    This Failla Lecture focused on the inter-relationships between tumor angiogenesis, HIF-1 expression and radiotherapy responses. A common thread that bonds all of these factors together is microenvironmental stress caused by reactive oxygen and nitrogen species formed during tumor growth and angiogenesis or in response to cytotoxic treatment. In this review we focus on one aspect of the crossroad between oxidative stress and angiogenesis, namely cycling hypoxia. Understanding of the relative importance of this feature of the tumor microenvironment has recently expanded; it influences tumor biology in ways that are separate from chronic hypoxia. Cycling hypoxia can influence angiogenesis, treatment responses and metastatic behavior. It represents an important and relatively less well understood feature of tumor biology that requires additional research. PMID:19929412

  2. Role of EC-SOD Overexpression in Preserving Pulmonary Angiogenesis Inhibited by Oxidative Stress

    PubMed Central

    Perveen, Shahana; Patel, Hardik; Arif, Arslan; Younis, Sharif; Codipilly, Champa N.; Ahmed, Mohamed

    2012-01-01

    Angiogenesis is one of the most important processes for normal lung development. Oxidative stress can impair the pulmonary angiogenesis, leading to chronic lung disease or Bronchopulmonary dysplasia (BPD). Objective To investigate the protective effects of EC-SOD overexpression on pulmonary angiogenesis on neonates following exposure to acute hyperoxia. Design/Methods Transgenic (TG) and wild-type (WT) neonatal mice (10 mice per group) were exposed either to air (control group) or 95% O2 for 7 days starting at birth. After exposure, all animals were sacrificed. ROS concentration was measured in lung homogenates using OxiSelect ROS assay kit. Mean vascular density (MVD) was measured using anti CD34 staining. RNA was extracted and the angiogenesis markers, VEGF, VEGFR1 and VEGFR2 and PECAM-1 were analyzed by RT-q PCR. VGEF protein was measured using Western blots. Endothelial progenitor cells (EPCs) was assayed by flow cytometer. Results There was a significant reduction of ROS in TG hyperoxic neonate group (156±14.2) compared to WT hyperoxic animals (255±35.1). Evaluation of MVD, using anti-CD34, showed marked significant increase of MVD in the TG group following hyperoxic exposure (85±12) in comparison to the WT hyperoxic group (62±8.4), (P<0.05). Among the hyperoxic groups, both RNA and protein of VEGF expression were significantly reduced in the WT animals compared to the TG group (P<0.05). The same trend was found in VEGFR 1 and 2 which were significantly reduced in WT group compared to the TG group (P<0.05). There was no significant difference between hyperoxia TG and control group (P>0.05). PECAM expression was significantly reduced in both hyperoxic compared to normoxic groups (P<0.05). EPC’s showed significant reduction in WT hyperoxic group compared to others (P>0.05). Conclusions EC-SOD plays a key role in preserving angiogenesis by scavenging free radicals which has an inhibitory effect on angiogenesis process in neonatal mice lung following

  3. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells.

    PubMed

    Atienzar-Aroca, Sandra; Flores-Bellver, Miguel; Serrano-Heras, Gemma; Martinez-Gil, Natalia; Barcia, Jorge M; Aparicio, Silvia; Perez-Cremades, Daniel; Garcia-Verdugo, Jose M; Diaz-Llopis, Manuel; Romero, Francisco J; Sancho-Pelluz, Javier

    2016-08-01

    The retinal pigment epithelium (RPE), a monolayer located between the photoreceptors and the choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species (ROS). As the RPE, because of its physiological functions, is essential for the survival of the retina, any sustained damage may consequently lead to loss of vision. Exosomes are small membranous vesicles released into the extracellular medium by numerous cell types, including RPE cells. Their cargo includes genetic material and proteins, making these vesicles essential for cell-to-cell communication. Exosomes may fuse with neighbouring cells influencing their fate. It has been observed that RPE cells release higher amounts of exosomes when they are under oxidative stress. Exosomes derived from cultured RPE cells were isolated by ultracentrifugation and quantified by flow cytometry. VEGF receptors (VEGFR) were analysed by both flow cytometry and Western blot. RT-PCR and qPCR were conducted to assess mRNA content of VEGFRs in exosomes. Neovascularization assays were performed after applying RPE exosomes into endothelial cell cultures. Our results showed that stressed RPE cells released a higher amount of exosomes than controls, with a higher expression of VEGFR in the membrane, and enclosed an extra cargo of VEGFR mRNA. Angiogenesis assays confirmed that endothelial cells increased their tube formation capacity when exposed to stressed RPE exosomes. PMID:26999719

  4. Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice

    PubMed Central

    JIN, PENG; LI, TAO; LI, XUEQI; SHEN, XINGHUA; ZHAO, YANRU

    2016-01-01

    Myocardial infarction is a major contributor to morbidity and mortality in diabetes, which is characterized by inadequate angiogenesis and consequent poor blood reperfusion in the diabetic ischemic heart. The aim of the present study was to investigate the effect that oxidative stress in endothelial progenitor cells (EPCs) has on cardiac angiogenesis in diabetic mice. EPCs derived from diabetic mice revealed reductions in superoxide dismutase (SOD) expression levels and activity compared with those from normal mice. An endothelial tube formation assay showed that angiogenesis was markedly delayed for diabetic EPCs, compared with normal controls. EPCs subjected to various pretreatments were tested as a cell therapy in a diabetic mouse model of myocardial infarction. Induction of oxidative stress in normal EPCs by H2O2 or small interfering RNA-mediated knockdown of SOD reduced their angiogenic activity in the ischemic myocardium of the diabetic mice. Conversely, cell therapy using EPCs from diabetic mice following SOD gene overexpression or treatment with the antioxidant Tempol normalized their ability to promote angiogenesis. These results indicate that decreased expression levels of SOD in EPCs contribute to impaired angiogenesis. In addition, normalization of diabetic EPCs by ex vivo SOD gene therapy accelerates the ability of the EPCs to promote angiogenesis and improve cardiac function when used as a cell therapy following myocardial infarction in diabetic mice. PMID:27284297

  5. D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects.

    PubMed

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Yorita, K; Chung, S P; Tran, D H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-10-01

    Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells. PMID:22802136

  6. Oxidative stress, polarization of macrophages and tumour angiogenesis: Efficacy of caffeic acid.

    PubMed

    Oršolić, Nada; Kunštić, Martina; Kukolj, Marina; Gračan, Romana; Nemrava, Johann

    2016-08-25

    Macrophage polarization is a process when macrophage expresses different functional programs in response to microenvironmental signals and two extreme forms exist; M1 and M2 macrophages. M1 macrophages are highly microbicidal and anticancer with enhanced ability to kill and phagocytose pathogens, upregulate pro-inflammatory cytokines and reactive molecular species, and present antigens; M2 macrophages and the related tumour associated macrophages (TAMs) regulate tissue remodelling and promote tissue repair and angiogenesis and can amplification of metabolic pathways that can suppress adaptive immune responses. It is demonstrated that ROS production, critical for the activation and functions of M1 macrophages, is necessary for the differentiation of M2 macrophages and TAMs, and that antioxidant therapy blocks TAMs differentiation and tumorigenesis in mouse models of cancer. In order to study how caffeic acid (CA), a natural antioxidant, affects macrophage function, polarization, angiogenesis and tumour growth we injected mice with Ehrlich ascites tumour (EAT) cells and treated them for 10 days with CA in a dose of 40 and/or 80 mg kg(-1.) Macrophage polarization was further characterized by quantifying secreted pro- and anti-inflammatory cytokines, nitric oxide and arginase 1 activity. CA may increase the cytotoxic actions of M1 macrophages and inhibit tumour growth; inhibitory activity on TAMs may be mediated through its antioxidative activity. Taken together, we conclude that the antitumour activity of CA was the result of the synergistic activities of different mechanisms by which CA acts on proliferation, angiogenesis, immunomodulation and survival. The continuous administration of CA efficiently blocked the occurrence of TAMs and markedly suppressed tumorigenesis in mouse cancer models. Targeting TAMs by antioxidants can be a potentially effective method for cancer treatment. PMID:27378625

  7. Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis.

    PubMed

    Henning, Susanne M; Wang, Piwen; Said, Jonathan; Magyar, Clara; Castor, Brandon; Doan, Ngan; Tosity, Carmen; Moro, Aune; Gao, Kun; Li, Luyi; Heber, David

    2012-11-01

    It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice. PMID:22405694

  8. Long-term progestin contraceptives (LTPOC) induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humans

    PubMed Central

    2010-01-01

    Background Irregular uterine bleeding is the major side effect of, and cause for, discontinuation of long-term progestin-only contraceptives (LTPOCs). The endometria of LTPOC-treated women display abnormally enlarged, fragile blood vessels (BV), decreased endometrial blood flow and oxidative stress. However, obtaining sufficient, good quality tissues have precluded elucidation of the mechanisms underlying these morphological and functional vascular changes. Methods The current study assessed the suitability of the guinea pig (GP) as a model for evaluating the uterine effects of LTPOC administration. Thus GPs were treated with a transdermal pellet for 21 days and examined for endometrial histology, angiogenic markers as well as markers of oxidative stress and apoptosis. Results and Discussion We now demonstrate that GP uteri were enlarged by both estradiol (E2) and medroxyprogesterone acetate (MPA) (p < 0.001). Effects of MPA on uterine weight differed significantly depending on E2 levels (p < 0.001), where MPA opposed the E2 effect in combined treatments. Angiogenesis parameters were similarly impacted upon: MPA alone increased BV density (p = 0.036) and BV average area (p = 0.002). The presence of E2 significantly decreased these parameters. These changes were associated with highly elevated of the lipid peroxidation product, 8-isoprostane (8-isoP) content in E2+MPA-treated and by nuclear 8-OH-deoxyguanosine (8oxoG) staining compared to all other groups (p < 0.001). Abnormalities in the E2+MPA group were consistent with chromatin redistribution, nuclear pyknosis, karyolysis and increased apoptosis as observed by a marked increase in TUNEL labeling. Conclusions LTPOC exposure alters endometrial vascular and tissue morphology consistent with oxidative stress and apoptosis in a complex interplay with endogenous estrogens. These findings are remarkably similar to in vivo change observed in the human uterus following LTPOC administration. Hence, the GP is an excellent

  9. Chemoprevention of rat mammary carcinogenesis by black tea polyphenols: modulation of xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation, apoptosis, and angiogenesis.

    PubMed

    Kumaraguruparan, R; Seshagiri, P B; Hara, Y; Nagini, S

    2007-09-01

    Chemoprevention of dietary constituents has emerged as a cost-effective approach to control the incidence of breast cancer. The present study was therefore designed to evaluate the chemopreventive efficacy of black tea polyphenols (Polyphenon-B) during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis using xenobiotic-metabolizing enzymes, cellular redox status, cell proliferation, apoptosis, and angiogenesis as biomarkers of chemoprevention. Intragastric administration of DMBA induced adenocarcinomas that showed enhanced activities of phase I carcinogen activation and phase II detoxification enzymes with increased lipid and protein oxidation and decrease in antioxidant status. This was associated with increased cell proliferation, angiogenesis, and evasion of apoptosis as revealed by upregulation of proliferating cell nuclear antigen (PCNA), Bcl-2, and vascular endothelial growth factor (VEGF), and downregulation of Bax, caspase 3, and poly(ADP-ribose) polymerase (PARP). Dietary administration of Polyphenon-B effectively suppressed the incidence of mammary tumors as evidenced by modulation of xenobiotic-metabolizing enzymes and oxidant-antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. The present study provides evidence that Polyphenon-B exerts multifunctional inhibitory effects on DMBA-induced mammary carcinogenesis and suggests that it can be developed as a potential chemopreventive agent. PMID:17415784

  10. Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1.

    PubMed

    El-Sayed, R M; Moustafa, Y M; El-Azab, M F

    2014-10-01

    Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis. PMID:24664592

  11. Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment

    PubMed Central

    Agostini, Silvia; Chiavacci, Elena; Matteucci, Marco; Torelli, Michele; Pitto, Letizia; Lionetti, Vincenzo

    2015-01-01

    Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) β-d-glucan (β-d-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of β-d-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v β-d-glucan significantly increased the level of MnSOD by 200% ± 2% compared to control and by 50% ± 4% compared to untreated H2O2-stressed cells. β-d-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24 hrs-treatment with 3% w/v β-d-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2−) and an increased survival under oxidative stress. In addition, β-d-glucan prevented the rise of hypoxia inducible factor (HIF)1-α under oxidative stress. The level of histone H4 acetylation was significantly increased by β-d-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair β-d-glucan effects. In conclusion, 3% w/v β-d-glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O2−, cell survival and angiogenic response to oxidative stress. The identification of dietary β-d-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodelling and heart failure. PMID:25388628

  12. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

    PubMed Central

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-01-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  13. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

    PubMed

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-12-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  14. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    NASA Astrophysics Data System (ADS)

    Reinhart-King, Cynthia

    2010-03-01

    Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

  15. Oxidative Stress in Placenta: Health and Diseases.

    PubMed

    Wu, Fan; Tian, Fu-Ju; Lin, Yi

    2015-01-01

    During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. PMID:26693479

  16. Oxidative Stress in Placenta: Health and Diseases

    PubMed Central

    Wu, Fan; Tian, Fu-Ju; Lin, Yi

    2015-01-01

    During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. PMID:26693479

  17. Staphylococcal response to oxidative stress

    PubMed Central

    Gaupp, Rosmarie; Ledala, Nagender; Somerville, Greg A.

    2012-01-01

    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. PMID:22919625

  18. Oxidative stress in psoriasis and potential therapeutic use of antioxidants.

    PubMed

    Lin, Xiran; Huang, Tian

    2016-06-01

    The pathophysiology of psoriasis is complex and dynamic. Recently, the involvement of oxidative stress in the pathogenesis of psoriasis has been proposed. Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage. In this article, the published studies on the role of oxidative stress in psoriasis pathogenesis are reviewed, focusing on the impacts of oxidative stress on dendritic cells, T lymphocytes, and keratinocytes, on angiogenesis and on inflammatory signaling (mitogen-activated protein kinase, nuclear factor-κB, and Janus kinase/signal transducer and activator of transcription). As there is compelling evidence that oxidative stress is involved in the pathogenesis of psoriasis, the possibility of using this information to develop novel strategies for treatment of patients with psoriasis is of considerable interest. In this article, we also review the published studies on treating psoriasis with antioxidants and drugs with antioxidant activity. PMID:27098416

  19. Oxidative stress in autism.

    PubMed

    Chauhan, Abha; Chauhan, Ved

    2006-08-01

    Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed. PMID:16766163

  20. Oxidative Stress and Psychological Disorders

    PubMed Central

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined. Another critical aspect that needs much attention and effort is our understanding of the association between cellular oxidative stress and emotional stress. This review examines some of the recent discoveries that link oxidative status with anxiety, depression, schizophrenia and bipolar disorder. A discussion of published results and questions that currently exist in the field regarding a causal relationship between oxidative and emotional stress is also provided. PMID:24669208

  1. Cutaneous oxidative stress.

    PubMed

    Polefka, Thomas G; Meyer, Thomas A; Agin, Patricia P; Bianchini, Robert J

    2012-03-01

    The earliest known microfossil records suggest that microorganisms existed on the earth approximately 3.8 billion years ago. Not only did sunlight drive this evolutionary process, but it also allowed photosynthetic organisms to elaborate oxygen and fundamentally change the earth's atmosphere and subsequent evolution. Paradoxically, however, an atmosphere of 20% oxygen offers aerobic organisms both benefits and some key challenges, particularly, to the external integument. This mini-review summarizes almost 40 years of research and provides a "60 000-foot" perspective on cutaneous oxidative stress. Topics reviewed include the following: What are free radicals and reactive oxygen species? Where do they come from? What is their chemistry? What are their roles and/or impact on the skin? What antioxidant defenses are available to mitigate oxidative stress. PMID:22360336

  2. Oxidative Stress in Malaria

    PubMed Central

    Percário, Sandro; Moreira, Danilo R.; Gomes, Bruno A. Q.; Ferreira, Michelli E. S.; Gonçalves, Ana Carolina M.; Laurindo, Paula S. O. C.; Vilhena, Thyago C.; Dolabela, Maria F.; Green, Michael D.

    2012-01-01

    Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. PMID:23208374

  3. Oxidative Stress in Myopia

    PubMed Central

    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. PMID:25922643

  4. Dimethylarginine dimethylaminohydrolase: a new therapeutic target for the modulation of nitric oxide and angiogenesis.

    PubMed

    Singh, Jai Pal

    2007-09-01

    Nitric oxide (NO) has a key role in promoting angiogenesis by increasing vasodilation, vascular permeability, endothelial cell proliferation and migration, and by modifying the activities of angiogenic mediators. NO is also critical for the mobilization of endothelial progenitor cells from the bone marrow which promotes vasculogenesis and angiogenesis. Studies have shown that the enzymes catalyzing NO synthesis are inhibited by the endogenously generated inhibitor asymmetric dimethylarginine (ADMA). Pharmacological agents targeted to modulate dimethyl-arginine dimethylaminohydrolase, the key enzyme metabolizing ADMA, may offer a potential strategy for developing novel pro- and anti-angiogenic therapies. PMID:17729185

  5. Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling pathway.

    PubMed

    Ha, Jung Min; Jin, Seo Yeon; Lee, Hye Sun; Shin, Hwa Kyoung; Lee, Dong Hyung; Song, Sang Heon; Kim, Chi Dae; Bae, Sun Sik

    2016-09-01

    Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis. PMID:27610040

  6. Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling pathway

    PubMed Central

    Ha, Jung Min; Jin, Seo Yeon; Lee, Hye Sun; Shin, Hwa Kyoung; Lee, Dong Hyung; Song, Sang Heon; Kim, Chi Dae

    2016-01-01

    Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis. PMID:27610040

  7. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1

    PubMed Central

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L.; Li, Jun

    2016-01-01

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals. PMID:26932825

  8. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1.

    PubMed

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L; Li, Jun

    2016-01-01

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals. PMID:26932825

  9. Oxidative stress by inorganic nanoparticles.

    PubMed

    Tee, Jie Kai; Ong, Choon Nam; Bay, Boon Huat; Ho, Han Kiat; Leong, David Tai

    2016-05-01

    Metallic and metallic oxide nanoparticles (NPs) have been increasingly used for various bio-applications owing to their unique physiochemical properties in terms of conductivity, optical sensitivity, and reactivity. With the extensive usage of NPs, increased human exposure may cause oxidative stress and lead to undesirable health consequences. To date, various endogenous and exogenous sources of oxidants contributing to oxidative stress have been widely reported. Oxidative stress is generally defined as an imbalance between the production of oxidants and the activity of antioxidants, but it is often misrepresented as a single type of cellular stress. At the biological level, NPs can initiate oxidative stress directly or indirectly through various mechanisms, leading to profound effects ranging from the molecular to the disease level. Such effects of oxidative stress have been implicated owing to their small size and high biopersistence. On the other hand, cellular antioxidants help to counteract oxidative stress and protect the cells from further damage. While oxidative stress is commonly known to exert negative biological effects, measured and intentional use of NPs to induce oxidative stress may provide desirable effects to either stimulate cell growth or promote cell death. Hence, NP-induced oxidative stress can be viewed from a wide paradigm. Because oxidative stress is comprised of a wide array of factors, it is also important to use appropriate assays and methods to detect different pro-oxidant and antioxidant species at molecular and disease levels. WIREs Nanomed Nanobiotechnol 2016, 8:414-438. doi: 10.1002/wnan.1374 For further resources related to this article, please visit the WIREs website. PMID:26359790

  10. BRCA1 and Oxidative Stress

    PubMed Central

    Yi, Yong Weon; Kang, Hyo Jin; Bae, Insoo

    2014-01-01

    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. PMID:24704793

  11. Oxidative stress in Alzheimer disease

    PubMed Central

    Durany, Nuria

    2009-01-01

    Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production. PMID:19372765

  12. Oxidant stress in the vasculature.

    PubMed

    Maytin, M; Leopold, J; Loscalzo, J

    1999-09-01

    Vascular disease and vasomotor responses are largely influenced by oxidant stress. Superoxide is generated via the cellular oxidase systems, xanthine oxidase, and NADH/NADPH oxidases. Once formed, superoxides participate in a number of reactions, yielding various free radicals such as hydrogen peroxide, peroxynitrite, oxidized low-density lipoprotein, or hypochlorous acid. Numerous cellular antioxidant systems exist to defend against oxidant stress; glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell. However, the redox state is disrupted by certain vascular diseases. It appears that oxidant stress both promotes and is induced by diseases such as hypertension, atherosclerosis, and restenosis as well as by certain risk factors for coronary artery disease including hyperlipidemia, diabetes, and cigarette smoking. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, namely adverse vessel reactivity, vascular smooth muscle cell proliferation, macrophage adhesion, platelet activation, and lipid peroxidation. PMID:11122705

  13. Magnesium Corrosion Triggered Spontaneous Generation of H2O2 on Oxidized Titanium for Promoting Angiogenesis.

    PubMed

    Park, Jimin; Du, Ping; Jeon, Jin-Kyung; Jang, Gun Hyuk; Hwang, Mintai Peter; Han, Hyung-Seop; Park, Kwideok; Lee, Kwan Hyi; Lee, Jee-Wook; Jeon, Hojeong; Kim, Yu-Chan; Park, Jong Woong; Seok, Hyun-Kwang; Ok, Myoung-Ryul

    2015-12-01

    Although the use of reactive oxygen species (ROS) has been extensively studied, current systems employ external stimuli such as light or electrical energy to produce ROS, which limits their practical usage. In this report, biocompatible metals were used to construct a novel electrochemical system that can spontaneously generate H2O2 without any external light or voltage. The corrosion of Mg transfers electrons to Au-decorated oxidized Ti in an energetically favorable process, and the spontaneous generation of H2O2 in an oxygen reduction reaction was revealed to occur at titanium by combined spectroscopic and electrochemical analyses. The controlled release of H2O2 noticeably enhanced in vitro angiogenesis even in the absence of growth factors. Finally, a new titanium implant prototype was developed by Mg incorporation, and its potential for promoting angiogenesis was demonstrated. PMID:26482466

  14. Oxidative Stress and Insulin Resistance

    PubMed Central

    Park, Kyong; Gross, Myron; Lee, Duk-Hee; Holvoet, Paul; Himes, John H.; Shikany, James M.; Jacobs, David R.

    2009-01-01

    OBJECTIVE Although cumulative evidence suggests that increased oxidative stress may lead to insulin resistance in vivo or in vitro, community-based studies are scarce. This study examined the longitudinal relationships of oxidative stress biomarkers with the development of insulin resistance and whether these relationships were independent of obesity in nondiabetic young adults. RESEARCH DESIGN AND METHODS Biomarkers of oxidative stress (F2-isoprostanes [F2Isop] and oxidized LDL [oxLDL]), insulin resistance (the homeostasis model assessment of insulin resistance [HOMA-IR]), and various fatness measures (BMI, waist circumference, and estimated percent fat) were obtained in a population-based observational study (Coronary Artery Risk Development in Young Adults) and its ancillary study (Young Adult Longitudinal Trends in Antioxidants) during 2000–2006. RESULTS There were substantial increases in estimated mean HOMA-IR over time. OxLDL and F2Isop showed little association with each other. Mean evolving HOMA-IR increased with increasing levels of oxidative stress markers (P < 0.001 for oxLDL and P = 0.06 for F2Isop), measured in 2000–2001. After additional adjustment for adiposity, a positive association between oxLDL and HOMA-IR was strongly evident, whereas the association between F2Isop and HOMA-IR was not. CONCLUSIONS We observed positive associations between each of two oxidative stress markers and insulin resistance. The association with oxidized LDL was independent of obesity, but that with F2Isop was not. PMID:19389821

  15. [Heme metabolism and oxidative stress].

    PubMed

    Kaliman, P A; Barannik, T B

    2001-01-01

    The role of heme metabolism in oxidative stress development and defense reactions formation in mammals under different stress factors are discussed in the article. Heme metabolism is considered as the totality of synthesis, degradation, transport and exchange processes of exogenous heme and heme liberated from erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data presented display normal heme metabolism including mammals heme-binding proteins and intracellular free heme pool and heme metabolism alterations under oxidative stress development. The main attention is focused to the prooxidant action of heme, the interaction of heme transport and lipid exchange, and to the heme metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum heme-binding protein hemopexin and intracellular heme-binding proteins participating in metabolism adaptation under the action of factors, which cause oxidative stress. PMID:11599427

  16. Oxidative Stress Markers in Sputum

    PubMed Central

    Antus, Balazs

    2016-01-01

    Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases. PMID:26885248

  17. Phagocytes and oxidative stress.

    PubMed

    Babior, B M

    2000-07-01

    Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one-electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large number of highly reactive microbicidal oxidants are formed, including HOCl (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction between O(2)(-) and NO(*); and many others. These reactive oxidants are manufactured for the purpose of killing invading microorganisms, but they also inflict damage on nearby tissues, and are thought to be of pathogenic significance in a large number of diseases. Included among these are emphysema, acute respiratory distress syndrome, atherosclerosis, reperfusion injury, malignancy and rheumatoid arthritis. PMID:10936476

  18. Oxidative Stress in Atopic Dermatitis

    PubMed Central

    Ji, Hongxiu; Li, Xiao-Kang

    2016-01-01

    Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients. PMID:27006746

  19. Ethanol and oxidative stress.

    PubMed

    Sun, A Y; Ingelman-Sundberg, M; Neve, E; Matsumoto, H; Nishitani, Y; Minowa, Y; Fukui, Y; Bailey, S M; Patel, V B; Cunningham, C C; Zima, T; Fialova, L; Mikulikova, L; Popov, P; Malbohan, I; Janebova, M; Nespor, K; Sun, G Y

    2001-05-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun. PMID:11391077

  20. Hemoglobin oxidative stress

    NASA Astrophysics Data System (ADS)

    Croci, S.; Ortalli, I.; Pedrazzi, G.; Passeri, G.; Piccolo, P.

    2000-07-01

    Venous blood obtained from healthy donors and from patients suffering from breast cancer have been treated with acetylphenylhydrazine (APH) for different time. Mössbauer 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.

  1. Cuprous oxide nanoparticles inhibit angiogenesis via down regulation of VEGFR2 expression

    NASA Astrophysics Data System (ADS)

    Song, Hongyuan; Wang, Wenbo; Zhao, Ping; Qi, Zhongtian; Zhao, Shihong

    2014-02-01

    Angiogenesis is a process that forms new blood capillaries from existing vessels, which is of great physiological and pathological significance. Although recent studies provide evidence that cuprous oxide nanoparticles (CO-NPs) may have biomedical potential, the mechanisms of CO-NPs in angiogenesis have not been investigated to date. We have studied the anti-angiogenic properties of CO-NPs on primary human umbilical vein endothelial cells (HUVECs). We found that CO-NPs were able to induce cell morphology changes and suppress cell proliferation, migration and tube formation in vitro and in vivo dose dependently. Furthermore, CO-NPs could induce cell apoptosis both at the early and late apoptotic stage and induce cell cycle arrest at S phase in a dose dependent manner. As signalling via the vascular endothelial growth factor receptor-2 (VEGFR2) is critical for angiogenic responses, we further explored the expression of VEGFR2 after the treatment of CO-NPs. They were found to inhibit VEGFR2 expression dose and time dependently both at the protein and mRNA level while had no effect on VEGF and VEGFR1 expression. Together, we report for the first time that CO-NPs can act as an anti-angiogenic agent by suppressing VEGFR2 expression, which may be a potential nanomedicine for angiogenesis therapy.Angiogenesis is a process that forms new blood capillaries from existing vessels, which is of great physiological and pathological significance. Although recent studies provide evidence that cuprous oxide nanoparticles (CO-NPs) may have biomedical potential, the mechanisms of CO-NPs in angiogenesis have not been investigated to date. We have studied the anti-angiogenic properties of CO-NPs on primary human umbilical vein endothelial cells (HUVECs). We found that CO-NPs were able to induce cell morphology changes and suppress cell proliferation, migration and tube formation in vitro and in vivo dose dependently. Furthermore, CO-NPs could induce cell apoptosis both at the early and

  2. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

    Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

    2013-01-01

    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. PMID:24351827

  3. Nitric oxide mediates bleomycin-induced angiogenesis and pulmonary fibrosis via regulation of VEGF.

    PubMed

    Iyer, Anand Krishnan V; Ramesh, Vani; Castro, Carlos A; Kaushik, Vivek; Kulkarni, Yogesh M; Wright, Clayton A; Venkatadri, Rajkumar; Rojanasakul, Yon; Azad, Neelam

    2015-11-01

    Pulmonary fibrosis is a progressive lung disease hallmarked by increased fibroblast proliferation, amplified levels of extracellular matrix deposition and increased angiogenesis. Although dysregulation of angiogenic mediators has been implicated in pulmonary fibrosis, the specific rate-limiting angiogenic markers involved and their role in the progression of pulmonary fibrosis remains unclear. We demonstrate that bleomycin treatment induces angiogenesis, and inhibition of the central angiogenic mediator VEGF using anti-VEGF antibody CBO-P11 significantly attenuates bleomycin-induced pulmonary fibrosis in vivo. Bleomycin-induced nitric oxide (NO) was observed to be the key upstream regulator of VEGF via the PI3k/Akt pathway. VEGF regulated other important angiogenic proteins including PAI-1 and IL-8 in response to bleomycin exposure. Inhibition of NO and VEGF activity significantly mitigated bleomycin-induced angiogenic and fibrogenic responses. NO and VEGF are key mediators of bleomycin-induced pulmonary fibrosis, and could serve as important targets against this debilitating disease. Overall, our data suggests an important role for angiogenic mediators in the pathogenesis of bleomycin-induced pulmonary fibrosis. PMID:25919965

  4. Space flight and oxidative stress.

    PubMed

    Stein, T P

    2002-10-01

    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. PMID:12361781

  5. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    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.

  6. Oxidative stress and alopecia areata

    PubMed Central

    Prie, BE; Voiculescu, VM; Ionescu-Bozdog, OB; Petrutescu, B; Iosif, L; Gaman, LE; Clatici, VG; Stoian, I; Giurcaneanu, C

    2015-01-01

    Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. Abbreviations: AA = alopecia areata, ROS = reactive oxygen species, H2O2 = hydrogen peroxide, TBARS = thiobarbituric acid rective substances, MDA = malondialdehyde, TBARS = thiobarbituric acid-reactive substances, SOD = superoxide dismutase, CAT = catalase, GSH-Px = glutathione peroxidase, PON1 = paraoxonase 1, HO-1 = hemoxigenase 1, TrxR = thioredoxin reductase, GSH = glutathione PMID:26361510

  7. Marine carotenoids and oxidative stress.

    PubMed

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  8. Marine Carotenoids and Oxidative Stress

    PubMed Central

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  9. [Statins and oxidative stress].

    PubMed

    Filip-Ciubotaru, Florina; Foia, Liliana; Manciuc, Carmen

    2009-01-01

    Statins, as inhibitors of the first regulatory enzyme in cholesterol biosynthesis --HMG-CoA reductase--have a special impact in medical practice. Given their therapeutic efficacy, statins are believed to be the strongest class of agents in the treatment of cardiovascular disorders. Moreover, besides decreasing total cholesterol and C-LDL levels, numerous fundamental and clinical researches suggest that statins also have an antiinflammatory effect. Inflammation is closely related to the production of oxygen-derived reactive species (ROS). The antioxidant effects of statins associated with their ability to block the formation and/or action of ROS may add up their therapeutic efficacy. Within this context, the present paper presents data in literature related to the effect of statins on the expression and activity of NAD(P)H oxidase, activity of the enzymes involved in the antioxidative defence (SOD, GPx, catalase, paraoxonase), and their ability to act as free radical scavengers and oxidized-LDL inhibitors. By their antioxidant properties statins may decrease the atherogenic potential of lipoproteins. PMID:21495335

  10. Hypoxia, Oxidative Stress and Fat.

    PubMed

    Netzer, Nikolaus; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Martin; Pramsohler, Stephan; Pesta, Dominik

    2015-01-01

    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. PMID:26061760

  11. Nitric Oxide-Driven Hypoxia Initiates Synovial Angiogenesis, Hyperplasia and Inflammatory Lesions in Mice

    PubMed Central

    Bao, Fei; Wu, Pei; Xiao, Na; Qiu, Frank; Zeng, Qing-Ping

    2012-01-01

    Background Rheumatoid arthritis (RA) is an inflammatory articular disease with cartilage and bone damage due to hyperplasic synoviocyte invasion and subsequent matrix protease digestion. Although monoclonal antibodies against tumor necrosis factor alpha (TNFα) have been approved for clinical use in patients with RA, desired therapeutic regimens suitable for non-responders are still unavailable because etiological initiators leading to RA remain enigmatic and unidentified. Methodology/Principal Findings Bacteria-induced arthritis (BIA) that simulates collagen-induced arthritis (CIA) is developed in mice upon daily live bacterial feeding. The morphological lesions of paw erythema and edema together with the histological alterations of synovial hyperplasia and lymphocytic infiltration emerge as the early-phase manifestations of BIA and CIA. Bacteria- or collagen-mediated global upregulation of pro-inflammatory cytokines is accompanied by the burst of nitric oxide (NO). Elevation of the serum NO level is correlated with decline of the blood oxygen saturation percentage (SpO2), reflecting a hypoxic consequence during development towards arthritis. NO-driven hypoxia is further evident from a positive relationship between NO and lactic acid (LA), an end product from glycolysis. Upregulation of hypoxia inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) validates hypoxia-induced angiogenesis in the inflamed synovium of modeling mice. Administration of the NO donor compound sodium nitroprusside (SNP) causes articular inflammation by inducing synovial hypoxia. Anti-bacteria by the antibiotic cefotaxime and/or the immunosuppressant rapamycin or artesunate that also inhibits nitric oxide synthase (NOS) can abrogate NO production, mitigate hypoxia, and considerably ameliorate or even completely abort synovitis, hence highlighting that NO may serve as an initiator of inflammatory arthritis. Conclusions/Significance Like collagen, bacteria also

  12. Oxidative stress and adrenocortical insufficiency

    PubMed Central

    Prasad, R; Kowalczyk, J C; Meimaridou, E; Storr, H L; Metherell, L A

    2014-01-01

    Maintenance of redox balance is essential for normal cellular functions. Any perturbation in this balance due to increased reactive oxygen species (ROS) leads to oxidative stress and may lead to cell dysfunction/damage/death. Mitochondria are responsible for the majority of cellular ROS production secondary to electron leakage as a consequence of respiration. Furthermore, electron leakage by the cytochrome P450 enzymes may render steroidogenic tissues acutely vulnerable to redox imbalance. The adrenal cortex, in particular, is well supplied with both enzymatic (glutathione peroxidases and peroxiredoxins) and non-enzymatic (vitamins A, C and E) antioxidants to cope with this increased production of ROS due to steroidogenesis. Nonetheless oxidative stress is implicated in several potentially lethal adrenal disorders including X-linked adrenoleukodystrophy, triple A syndrome and most recently familial glucocorticoid deficiency. The finding of mutations in antioxidant defence genes in the latter two conditions highlights how disturbances in redox homeostasis may have an effect on adrenal steroidogenesis. PMID:24623797

  13. Oxidative stress in prostate cancer.

    PubMed

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

    2009-09-18

    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 and play vital roles in stimulation of signaling pathways in response to changing intra- and extracellular environmental conditions. Chronic increases in ROS over time are known to induce somatic mutations and neoplastic transformation. In this review we summarize the causes for increased ROS generation and its potential role in etiology and progression of prostate cancer. PMID:19185987

  14. Lectin-Like Oxidized LDL Receptor-1 Is an Enhancer of Tumor Angiogenesis in Human Prostate Cancer Cells

    PubMed Central

    González-Chavarría, Iván; Cerro, Rita P.; Parra, Natalie P.; Sandoval, Felipe A.; Zuñiga, Felipe A.; Omazábal, Valeska A.; Lamperti, Liliana I.; Jiménez, Silvana P.; Fernandez, Edelmira A.; Gutiérrez, Nicolas A.; Rodriguez, Federico S.; Onate, Sergio A.; Sánchez, Oliberto; Vera, Juan C.; Toledo, Jorge R.

    2014-01-01

    Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells. PMID:25170920

  15. Oxidative Stress and Major Depression

    PubMed Central

    Verma, Akhilesh Kumar; Srivastava, Mona; Srivastava, Ragini

    2014-01-01

    Background: Major causative factor for major depression is inflammation, autoimmune tissue damage and prolonged psychological stress, which leads to oxidative stress. The aim of this study was to know the association of free radicals and antioxidant status in subjects suffering from major depression. Materials and Methods: Sixty patients diagnosed as a case of unipolar depression as per DSM IV, fulfilling the inclusion and exclusion criteria were compared with 40 healthy age and sex matched controls. The sera of both the groups were collected taking aseptic precautions and were evaluated for the markers of oxidative stress and for the antioxidants. The age group of the sample and the controls was between 18-60 y, both males and females were equally represented in the groups. Results: A significantly high level of malondialdehyde (MDA) was found in the patients with major depression (1.95 ± 1.04 mmol/L) as compared to healthy controls (0.366 ± 0.175 mmol/L) (p < 0.0001). The serum level of nitrite was found to be lower in cases (23.18 ± 12.08 μmol/L) in comparison to controls (26.18 ± 8.68 μmol/L) (p = 0.1789). Similarly the serum level of ascorbic acid and superoxide dismutase (SOD) were significantly below as compared to healthy controls (all p < 0.0001). Ceruloplasmin levels were also depressed in cases (p = 0.3943). Conclusion: The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression. PMID:25653939

  16. Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses.

    PubMed

    Mohamad Shalan, Nor Aijratul Asikin; Mustapha, Noordin M; Mohamed, Suhaila

    2016-12-01

    Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery. PMID:27374554

  17. Sepiapterin improves angiogenesis of pulmonary artery endothelial cells with in utero pulmonary hypertension by recoupling endothelial nitric oxide synthase

    PubMed Central

    Du, Jianhai; Xu, Hao; Bakhutashvili, Ivane; Eis, Annie; Shi, Yang; Pritchard, Kirkwood A.; Konduri, Girija G.

    2011-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is associated with decreased blood vessel density that contributes to increased pulmonary vascular resistance. Previous studies showed that uncoupled endothelial nitric oxide (NO) synthase (eNOS) activity and increased NADPH oxidase activity resulted in marked decreases in NO bioavailability and impaired angiogenesis in PPHN. In the present study, we hypothesize that loss of tetrahydrobiopterin (BH4), a critical cofactor for eNOS, induces uncoupled eNOS activity and impairs angiogenesis in PPHN. Pulmonary artery endothelial cells (PAEC) isolated from fetal lambs with PPHN (HTFL-PAEC) or control lambs (NFL-PAEC) were used to investigate the cellular mechanisms impairing angiogenesis in PPHN. Cellular mechanisms were examined with respect to BH4 levels, GTP-cyclohydrolase-1 (GCH-1) expression, eNOS dimer formation, and eNOS-heat shock protein 90 (hsp90) interactions under basal conditions and after sepiapterin (Sep) supplementation. Cellular levels of BH4, GCH-1 expression, and eNOS dimer formation were decreased in HTFL-PAEC compared with NFL-PAEC. Sep supplementation decreased apoptosis and increased in vitro angiogenesis in HTFL-PAEC and ex vivo pulmonary artery sprouting angiogenesis. Sep also increased cellular BH4 content, NO production, eNOS dimer formation, and eNOS-hsp90 association and decreased the superoxide formation in HTFL-PAEC. These data demonstrate that Sep improves NO production and angiogenic potential of HTFL-PAEC by recoupling eNOS activity. Increasing BH4 levels via Sep supplementation may be an important therapy for improving eNOS function and restoring angiogenesis in PPHN. PMID:21622842

  18. Oxidative Stress in Neurodegenerative Diseases.

    PubMed

    Niedzielska, Ewa; Smaga, Irena; Gawlik, Maciej; Moniczewski, Andrzej; Stankowicz, Piotr; Pera, Joanna; Filip, Małgorzata

    2016-08-01

    The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction. PMID:26198567

  19. Oxidative stress in cardiovascular disease.

    PubMed

    Csányi, Gábor; Miller, Francis J

    2014-01-01

    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. PMID:24722571

  20. Oxidative Stress in Cardiovascular Disease

    PubMed Central

    Csányi, Gábor; Miller, Francis J.

    2014-01-01

    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. PMID:24722571

  1. Oxidative stress in inherited mitochondrial diseases.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2015-11-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for "oxidative stress" citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia. PMID:26073122

  2. Oxidative stress in oral diseases.

    PubMed

    Kesarwala, A H; Krishna, M C; Mitchell, J B

    2016-01-01

    Oxidative species, including reactive oxygen species (ROS), are components of normal cellular metabolism and are required for intracellular processes as varied as proliferation, signal transduction, and apoptosis. In the situation of chronic oxidative stress, however, ROS contribute to various pathophysiologies and are involved in multiple stages of carcinogenesis. In head and neck cancers specifically, many common risk factors contribute to carcinogenesis via ROS-based mechanisms, including tobacco, areca quid, alcohol, and viruses. Given their widespread influence on the process of carcinogenesis, ROS and their related pathways are attractive targets for intervention. The effects of radiation therapy, a central component of treatment for nearly all head and neck cancers, can also be altered via interfering with oxidative pathways. These pathways are also relevant to the development of many benign oral diseases. In this review, we outline how ROS contribute to pathophysiology with a focus toward head and neck cancers and benign oral diseases, describing potential targets and pathways for intervention that exploit the role of oxidative species in these pathologic processes. PMID:25417961

  3. Analysis of Oxidative Stress in Zebrafish Embryos

    PubMed Central

    Mugoni, Vera; Camporeale, Annalisa; Santoro, Massimo M.

    2014-01-01

    High levels of reactive oxygen species (ROS) may cause a change of cellular redox state towards oxidative stress condition. This situation causes oxidation of molecules (lipid, DNA, protein) and leads to cell death. Oxidative stress also impacts the progression of several pathological conditions such as diabetes, retinopathies, neurodegeneration, and cancer. Thus, it is important to define tools to investigate oxidative stress conditions not only at the level of single cells but also in the context of whole organisms. Here, we consider the zebrafish embryo as a useful in vivo system to perform such studies and present a protocol to measure in vivo oxidative stress. Taking advantage of fluorescent ROS probes and zebrafish transgenic fluorescent lines, we develop two different methods to measure oxidative stress in vivo: i) a “whole embryo ROS-detection method” for qualitative measurement of oxidative stress and ii) a “single-cell ROS detection method” for quantitative measurements of oxidative stress. Herein, we demonstrate the efficacy of these procedures by increasing oxidative stress in tissues by oxidant agents and physiological or genetic methods. This protocol is amenable for forward genetic screens and it will help address cause-effect relationships of ROS in animal models of oxidative stress-related pathologies such as neurological disorders and cancer. PMID:25046434

  4. VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle

    NASA Astrophysics Data System (ADS)

    Sun, Zhongchan; Huang, Peng; Tong, Guang; Lin, Jing; Jin, Albert; Rong, Pengfei; Zhu, Lei; Nie, Liming; Niu, Gang; Cao, Feng; Chen, Xiaoyuan

    2013-07-01

    Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease.Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01573d

  5. Etiologies of sperm oxidative stress

    PubMed Central

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-01-01

    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. PMID:27351024

  6. Etiologies of sperm oxidative stress.

    PubMed

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-04-01

    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. PMID:27351024

  7. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

    Peroxisomes are ubiquitous and multifunctional organelles that are primarily known for their role in cellular lipid metabolism. As many peroxisomal enzymes catalyze redox reactions as part of their normal function, these organelles are also increasingly recognized as potential regulators of oxidative stress-related signaling pathways. This in turn suggests that peroxisome dysfunction is not only associated with rare inborn errors of peroxisomal metabolism, but also with more common age-related diseases such as neurodegeneration, type 2 diabetes, and cancer. This review intends to provide a comprehensive picture of the complex role of mammalian peroxisomes in cellular redox metabolism. We highlight how peroxisomal metabolism may contribute to the bioavailability of important mediators of oxidative stress, with particular emphasis on reactive oxygen species. In addition, we review the biological properties of peroxisome-derived signaling messengers and discuss how these molecules may mediate various biological responses. Furthermore, we explore the emerging concepts that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. This is particularly relevant to the observed demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases. PMID:23933092

  8. Inflammation, Oxidative Stress, and Obesity

    PubMed Central

    Fernández-Sánchez, Alba; Madrigal-Santillán, Eduardo; Bautista, Mirandeli; Esquivel-Soto, Jaime; Morales-González, Ángel; Esquivel-Chirino, Cesar; Durante-Montiel, Irene; Sánchez-Rivera, Graciela; Valadez-Vega, Carmen; Morales-González, José A.

    2011-01-01

    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. PMID:21686173

  9. Oxidative Stress in Cystinosis Patients

    PubMed Central

    Vaisbich, Maria Helena; Pache de Faria Guimaraes, Luciana; Shimizu, Maria Heloisa Mazzola; Seguro, Antonio Carlos

    2011-01-01

    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 < 0.0001). We detected no significant correlation between plasma TBARS levels and renal function. 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. PMID:22470381

  10. Serum vascular endothelial growth factor is related to systemic oxidative stress in patients with lung cancer.

    PubMed

    Katsabeki-Katsafli, A; Kerenidi, T; Kostikas, K; Dalaveris, E; Kiropoulos, T S; Gogou, E; Papaioannou, A I; Gourgoulianis, K I

    2008-05-01

    Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer. PMID:18242763

  11. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    PubMed Central

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  12. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy.

    PubMed

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen; Chen, Gang

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  13. A differential role for nitric oxide in two forms of physiological angiogenesis in mouse

    PubMed Central

    Williams, James L; Cartland, David; Hussain, Arif; Egginton, Stuart

    2006-01-01

    NO plays a role in a variety of in vitro models of angiogenesis, although confounding effects of NO on non-endothelial tissues make its role during in vivo angiogenesis unclear. We therefore examined the effects of NO on two physiological models of angiogenesis in mouse skeletal muscle: (1) administration of prazosin (50 mg l−1) thereby increasing blood flow; and (2) muscle overload from surgical ablation of a functional synergist. These models induce angiogenesis via longitudinal splitting and capillary sprouting, respectively. Administration of NG-nitro-l-arginine (l-NNA) abolished the increase in capillary to fibre ratio (C:F) in response to prazosin administration, along with the increases in luminal filopodia and large endothelial vacuoles. l-NNA prevented luminal filopodia and vacuolisation in response to extirpation, but had no effect on abluminal sprouting, and little effect on C:F. Comparison of mice lacking endothelial (eNOS−/−) and neuronal NO synthase (nNOS−/−) showed that longitudinal splitting is eNOS-dependent, and Western blotting demonstrated an increase in eNOS but not inducible NOS (iNOS) expression. These data show that there are two pathways of physiological angiogenesis in skeletal muscle characterised by longitudinal splitting and capillary sprouting, respectively. NO generated by eNOS plays an essential role in splitting but not in sprouting angiogenesis, which has important implications for angiogenic therapies that target NO. PMID:16293647

  14. Induction of Oxidative Stress in Kidney

    PubMed Central

    Ozbek, Emin

    2012-01-01

    Oxidative stress has a critical role in the pathophysiology of several kidney diseases, and many complications of these diseases are mediated by oxidative stress, oxidative stress-related mediators, and inflammation. Several systemic diseases such as hypertension, diabetes mellitus, and hypercholesterolemia; infection; antibiotics, chemotherapeutics, and radiocontrast agents; and environmental toxins, occupational chemicals, radiation, smoking, as well as alcohol consumption induce oxidative stress in kidney. We searched the literature using PubMed, MEDLINE, and Google scholar with “oxidative stress, reactive oxygen species, oxygen free radicals, kidney, renal injury, nephropathy, nephrotoxicity, and induction”. The literature search included only articles written in English language. Letters or case reports were excluded. Scientific relevance, for clinical studies target populations, and study design, for basic science studies full coverage of main topics, are eligibility criteria for articles used in this paper. PMID:22577546

  15. Primary and secondary oxidative stress in Bacillus.

    PubMed

    Mols, Maarten; Abee, Tjakko

    2011-06-01

    Coping with oxidative stress originating from oxidizing compounds or reactive oxygen species (ROS), associated with the exposure to agents that cause environmental stresses, is one of the prerequisites for an aerobic lifestyle of Bacillus spp. such as B. subtilis, B. cereus and B. anthracis. This minireview highlights novel insights in the primary oxidative stress response caused by oxidizing compounds including hydrogen peroxide and the secondary oxidative stress responses apparent upon exposure to a range of agents and conditions leading to environmental stresses such as antibiotics, heat and acid. Insights in the pathways and damaging radicals involved have been compiled based among others on transcriptome studies, network analyses and fluorescence techniques for detection of ROS at single cell level. Exploitation of the current knowledge for the control of spoilage and pathogenic bacteria is discussed. PMID:21352461

  16. Role of oxidative stress and nitric oxide in atherothrombosis

    PubMed Central

    Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

    2008-01-01

    During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

  17. Clinical Relevance of Biomarkers of Oxidative Stress

    PubMed Central

    Frijhoff, Jeroen; Winyard, Paul G.; Zarkovic, Neven; Davies, Sean S.; Stocker, Roland; Cheng, David; Knight, Annie R.; Taylor, Emma Louise; Oettrich, Jeannette; Ruskovska, Tatjana; Gasparovic, Ana Cipak; Cuadrado, Antonio; Weber, Daniela; Poulsen, Henrik Enghusen; Grune, Tilman; Schmidt, Harald H.H.W.

    2015-01-01

    Abstract 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 using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170. PMID:26415143

  18. Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma.

    PubMed

    Marrogi, A J; Travis, W D; Welsh, J A; Khan, M A; Rahim, H; Tazelaar, H; Pairolero, P; Trastek, V; Jett, J; Caporaso, N E; Liotta, L A; Harris, C C

    2000-12-01

    We have investigated the hypothesis that nitric oxide synthase (NOS2), cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) protein levels individually demonstrate a direct correlation with microvessel density (MVD) and clinical outcome in human non-small cell lung cancer (NSCLC). Furthermore, we hypothesized that MVD may explain the propensity of certain histological lung cancer subtypes for early metastasis via a hematological route. Immunohistochemically, we studied the protein expression levels of NOS2, COX2, and VEGF and MVD by counting CD31-reactive blood vessels (BVs) in 106 surgically resected NSCLC specimens. NOS2, COX2, and VEGF immunoreactivity were observed in 48, 48, and 58%, respectively, of the study subjects, and their levels correlated with MVD at the tumor-stromal interphase (P < or = 0.001). More adenocarcindmas and large cell carcinomas displayed overexpression of NOS2 when compared with squamous cell carcinoma (SCC; r = 0.44; P < 0.001). NOS2 and COX2 levels were found to correlate positively with VEGF status (r = 0.44; P < 0.001, 0.01, and 0.03, respectively). These results attest to the significant interaction of these factors in the angiogenesis of NSCLC. Although neither angiogenic factors nor MVD correlated with patient survival, the latter correlated with tumor clinical stage in both squamous (SCC; 73 BVs/mm2) and non-SCC (78 BVs/mm2) tumors. These results indicate that angiogenesis is a complex process that involves multiple factors including NOS2, COX2, and VEGF. Furthermore, the role of angiogenesis in the biology of various histological lung cancer types may be different. The complexity of angiogenesis may explain the modest results observed in antiangiogenesis therapy that target a single protein. PMID:11156228

  19. Oxidative Stress Related Diseases in Newborns.

    PubMed

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

    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. PMID:27403229

  20. Oxidative Stress Related Diseases in Newborns

    PubMed Central

    Aykac, Kubra

    2016-01-01

    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. PMID:27403229

  1. Oxidative Stress, Lens Gap Junctions, and Cataracts

    PubMed Central

    Beyer, Eric C.

    2009-01-01

    Abstract The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation. Antioxid. Redox Signal. 11, 339–353. PMID:18831679

  2. Mitochondrial Oxidative Stress in Temporal Lobe Epilepsy

    PubMed Central

    Waldbaum, Simon; Patel, Manisha

    2011-01-01

    Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy. Mitochondrial oxidative stress and dysfunction are emerging as key factors that not only result from seizures, but may also contribute to epileptogenesis. The occurrence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, suggesting a further involvement of mitochondrial dysfunction in seizure generation. Mitochondria have critical cellular functions that effect neuronal excitability including production of adenosine triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis, regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation of cytosolic Ca2+ homeostasis. Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis and seizure initiation. PMID:19850449

  3. Oxidative stress and oxidative damage in chemical carcinogenesis

    SciTech Connect

    Klaunig, James E. Wang Zemin; Pu Xinzhu; Zhou Shaoyu

    2011-07-15

    Reactive oxygen species (ROS) are induced through a variety of endogenous and exogenous sources. Overwhelming of antioxidant and DNA repair mechanisms in the cell by ROS may result in oxidative stress and oxidative damage to the cell. This resulting oxidative stress can damage critical cellular macromolecules and/or modulate gene expression pathways. Cancer induction by chemical and physical agents involves a multi-step process. This process includes multiple molecular and cellular events to transform a normal cell to a malignant neoplastic cell. Oxidative damage resulting from ROS generation can participate in all stages of the cancer process. An association of ROS generation and human cancer induction has been shown. It appears that oxidative stress may both cause as well as modify the cancer process. Recently association between polymorphisms in oxidative DNA repair genes and antioxidant genes (single nucleotide polymorphisms) and human cancer susceptibility has been shown.

  4. Nitric Oxide Synthase Inhibition by NG-Nitro-l-Arginine Methyl Ester Inhibits Tumor-Induced Angiogenesis in Mammary Tumors

    PubMed Central

    Jadeski, Lorraine C.; Lala, Peeyush K.

    1999-01-01

    Using a murine breast cancer model, we earlier found a positive correlation between the expression of nitric oxide synthase (NOS) and tumor progression; treatment with inhibitors of NOS, NG-methyl-l-arginine (NMMA) and NG-nitro-l-arginine methyl ester (L-NAME), had antitumor and antimetastatic effects that were partly attributed to reduced tumor cell invasiveness. In the present study, we used a novel in vivo model of tumor angiogenesis using subcutaneous implants of tumor cells suspended in growth factor-reduced Matrigel to examine the angiogenic role of NO in a highly metastatic murine mammary adenocarcinoma cell line. This cell line, C3L5, expresses endothelial (e) NOS in vitro and in vivo, and inducible (i) NOS in vitro on stimulation with lipopolysaccharide and interferon-γ. Female C3H/HeJ mice received subcutaneous implants of growth factor-reduced Matrigel inclusive of C3L5 cells on one side, and on the contralateral side, Matrigel alone; L-NAME and D-NAME (inactive enantiomer) were subsequently administered for 14 days using osmotic minipumps. Immediately after sacrifice, implants were removed and processed for immunolocalization of eNOS and iNOS proteins, and measurement of angiogenesis. Neovascularization was quantified in sections stained with Masson’s trichrome or immunostained for the endothelial cell specific CD31 antigen. While most tumor cells and endothelial cells expressed immunoreactive eNOS protein, iNOS was localized in endothelial cells and some macrophages within the tumor-inclusive implants. Measurable angiogenesis occurred only in implants containing tumor cells. Irrespective of the method of quantification used, tumor-induced neovascularization was significantly reduced in L-NAME-treated mice relative to those treated with D-NAME. The quantity of stromal tissue was lower, but the quantity of necrotic tissue higher in L-NAME relative to D-NAME-treated animals. The total mass of viable tissue (ie, stroma and tumor cells) was lower in L

  5. p66Shc, oxidative stress and aging

    PubMed Central

    Pinton, Paolo; Rizzuto, Rosario

    2009-01-01

    The 66 KDa isoform of Shc and its signalling properties have attracted in the past years major interest in aging research. Here, we summarize p66Shc functions and outline a specific signalling route leading to mitochondrial import, that accounts for its pro-apoptotic activity upon oxidative stress. This model, that could explain the alterations of mitochondrial Ca2+ homeostasis observed after oxidative stress, highlights novel pharmacological targets in age-related disorders. PMID:18235239

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

    PubMed Central

    Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d’Hellencourt, Christian; Ravanan, Palaniyandi

    2014-01-01

    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 disturbs 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 have 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. PMID:25120434

  7. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay

    PubMed Central

    Rahal, Anu; Kumar, Amit; Singh, Vivek; Yadav, Brijesh

    2014-01-01

    Oxidative stress is a normal phenomenon in the body. Under normal conditions, the physiologically important intracellular levels of reactive oxygen species (ROS) are maintained at low levels by various enzyme systems participating in the in vivo redox homeostasis. Therefore, oxidative stress can also be viewed as an imbalance between the prooxidants and antioxidants in the body. For the last two decades, oxidative stress has been one of the most burning topics among the biological researchers all over the world. Several reasons can be assigned to justify its importance: knowledge about reactive oxygen and nitrogen species production and metabolism; identification of biomarkers for oxidative damage; evidence relating manifestation of chronic and some acute health problems to oxidative stress; identification of various dietary antioxidants present in plant foods as bioactive molecules; and so on. This review discusses the importance of oxidative stress in the body growth and development as well as proteomic and genomic evidences of its relationship with disease development, incidence of malignancies and autoimmune disorders, increased susceptibility to bacterial, viral, and parasitic diseases, and an interplay with prooxidants and antioxidants for maintaining a sound health, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. PMID:24587990

  8. Oxidative Stress in Aging Human Skin

    PubMed Central

    Rinnerthaler, Mark; Bischof, Johannes; Streubel, Maria Karolin; Trost, Andrea; Richter, Klaus

    2015-01-01

    Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis. PMID:25906193

  9. Oxidative stress in developmental brain disorders.

    PubMed

    Hayashi, Masaharu; Miyata, Rie; Tanuma, Naoyuki

    2012-01-01

    In order to examine the involvement of oxidative stress in developmental brain disorders, we have performed immunohistochemistry in autopsy brains and enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid and urines of patients. Here, we review our data on the hereditary DNA repair disorders, congenital metabolic errors and childhood-onset neurodegenerative disorders. First, in our studies on hereditary DNA repair disorders, increased oxidative DNA damage and lipid peroxidation were carried out in the degeneration of basal ganglia, intracerebral calcification and cerebellar degeneration in patients with xeroderma pigmentosum, Cockayne syndrome and ataxia-telangiectasia-like disorder, respectively. Next, congenital metabolic errors, apoptosis due to lipid peroxidation seemed to cause neuronal damage in neuronal ceroid-lipofuscinosis. Oxidative stress of DNA combined with reduced expression of antioxidant enzymes occurred in the lesion of the cerebral cortex in mucopolysaccharidoses and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. In childhood-onset neurodegenerative disorders, increased oxidative DNA damage and lipid peroxidation may lead to motor neuron death in spinal muscular atrophy like in amyotrophic lateral sclerosis. In patients with dentatorubral-pallidoluysian atrophy, a triplet repeat disease, deposition of oxidative products of nucleosides and reduced expression of antioxidant enzymes were found in the lenticular nucleus. In contrast, the involvement of oxidative stress is not definite in patients with Lafora disease. Rett syndrome patients showed changes of oxidative stress markers and antioxidant power in urines, although the changes may be related to systemic complications. PMID:22411250

  10. Oxidative Stress Resistance in Deinococcus radiodurans†

    PubMed Central

    Slade, Dea; Radman, Miroslav

    2011-01-01

    Summary: Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health. PMID:21372322

  11. Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers.

    PubMed

    Zuo, Tao; Zhu, Minghui; Xu, Wenming

    2016-01-01

    Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%-12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic. PMID:26770659

  12. Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers

    PubMed Central

    Zuo, Tao; Zhu, Minghui; Xu, Wenming

    2016-01-01

    Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%–12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic. PMID:26770659

  13. CYP1B1 and endothelial nitric oxide synthase combine to sustain proangiogenic functions of endothelial cells under hyperoxic stress

    PubMed Central

    Tang, Yixin; Scheef, Elizabeth A.; Gurel, Zafer; Sorenson, Christine M.; Jefcoate, Colin R.

    2010-01-01

    We have recently shown that deletion of constitutively expressed CYP1B1 is associated with attenuation of retinal endothelial cell (EC) capillary morphogenesis (CM) in vitro and angiogenesis in vivo. This was largely caused by increased intracellular oxidative stress and increased production of thrombospondin-2, an endogenous inhibitor of angiogenesis. Here, we demonstrate that endothelium nitric oxide synthase (eNOS) expression is dramatically decreased in the ECs prepared from retina, lung, heart, and aorta of CYP1B1-deficient (CYP1B1−/−) mice compared with wild-type (CYP1B1+/+) mice. The eNOS expression was also decreased in retinal vasculature of CYP1B1−/− mice. Inhibition of eNOS activity in cultured CYP1B1+/+ retinal ECs blocked CM and was concomitant with increased oxidative stress, like in CYP1B1−/− retinal ECs. In addition, expression of eNOS in CYP1B1−/− retinal ECs or their incubation with a nitric oxide (NO) donor enhanced NO levels, lowered oxidative stress, and improved cell migration and CM. Inhibition of CYP1B1 activity in the CYP1B1+/+ retinal ECs resulted in reduced NO levels and attenuation of CM. In contrast, expression of CYP1B1 increased NO levels and enhanced CM of CYP1B1−/− retinal ECs. Furthermore, attenuation of CYP1B1 expression with small interfering RNA proportionally lowered eNOS expression and NO levels in wild-type cells. Together, our results link CYP1B1 metabolism in retinal ECs with sustained eNOS activity and NO synthesis and/or bioavailability and low oxidative stress and thrombospondin-2 expression. Thus CYP1B1 and eNOS cooperate in different ways to lower oxidative stress and thereby to promote CM in vitro and angiogenesis in vivo. PMID:20032512

  14. Sustained stress response after oxidative stress in trabecular meshwork cells

    PubMed Central

    Li, Guorong; Luna, Coralia; Liton, Paloma B.; Navarro, Iris; Epstein, David L.

    2007-01-01

    Purpose To investigate the mechanisms by which chronic oxidative stress may lead to a sustained stress response similar to that previously observed in the trabecular meshwork (TM) of glaucoma donors. Methods Porcine TM cells were treated with 200 μM H2O2 twice a day for four days and were allowed to recover for three additional days. After the treatment, TM cells were analyzed for generation of intracellular reactive oxygen species (iROS), mitochondrial potential, activation of NF-κB, and the expression of inflammatory markers IL-1α, IL-6, IL-8, and ELAM-1. Potential sources of iROS were evaluated using inhibitors for nitric oxide, nitric oxide synthetase, cyclooxygenase, xanthine oxidase, NADPH oxidase, mitochondrial ROS, and PKC. The role of NF-κB activation in the induction of inflammatory markers was evaluated using the inhibitors Lactacystin and BAY11–7082. Results Chronic oxidative stress simulated by H2O2 exposure of porcine TM cells resulted in the sustained production of iROS by the mitochondria. Inhibition of mitochondrial iROS had a significant inhibitory effect on the activation of NF-κB and the induction of IL-1α, IL-6, IL-8, and ELAM-1 triggered by chronic oxidative stress. Inhibition of NF-κB partially prevented the induction of IL-1α, IL-8, and ELAM-1, but not IL-6. Conclusions Chronic oxidative stress in TM cells induced iROS production in mitochondria. This increase in iROS may contribute to the pathogenesis of the TM in glaucoma by inducing the expression of inflammatory mediators previously observed in glaucoma donors as well as the levels of oxidative damage in the tissue. PMID:18199969

  15. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    PubMed Central

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

    2015-01-01

    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. PMID:26512646

  16. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  17. The impact of oxidative stress on hair.

    PubMed

    Trüeb, R M

    2015-12-01

    Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to detoxify the reactive intermediates or to repair the resulting damage. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage lipids, proteins, and DNA. They are generated by a multitude of endogenous and environmental challenges, while the body possesses endogenous defense mechanisms. With age, production of free radicals increases, while the endogenous defense mechanisms decrease. This imbalance leads to progressive damage of cellular structures, presumably resulting in the aging phenotype. While the role of oxidative stress has been widely discussed in skin aging, little focus has been placed on its impact on hair condition. Moreover, most literature on age-related hair changes focuses on alopecia, but it is equally important that the hair fibers that emerge from the scalp exhibit significant age-related changes that have equal impact on the overall cosmetic properties of hair. Sources of oxidative stress with impact on the pre-emerging fiber include: oxidative metabolism, smoking, UVR, and inflammation from microbial, pollutant, or irritant origins. Sources of oxidative stress with impact on the post-emerging fiber include: UVR (enhanced by copper), chemical insults, and oxidized scalp lipids. The role of the dermatologist is recognition and treatment of pre- and post-emerging factors for lifetime scalp and hair health. PMID:26574302

  18. Drug-Induced Oxidative Stress and Toxicity

    PubMed Central

    Deavall, Damian G.; Martin, Elizabeth A.; Horner, Judith M.; Roberts, Ruth

    2012-01-01

    Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. PMID:22919381

  19. Oxidative stress, mitochondrial damage and neurodegenerative diseases

    PubMed Central

    Guo, Chunyan; Sun, Li; Chen, Xueping; Zhang, Danshen

    2013-01-01

    Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases. PMID:25206509

  20. Oxidative stress and antioxidant strategies in dermatology.

    PubMed

    Baek, Jinok; Lee, Min-Geol

    2016-07-01

    Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology. PMID:26020527

  1. Oxidative Stress in Schizophrenia: An Integrated Approach

    PubMed Central

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

    2010-01-01

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

  2. Potential Modulation of Sirtuins by Oxidative Stress

    PubMed Central

    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

  3. Potential Modulation of Sirtuins by Oxidative Stress.

    PubMed

    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

  4. Mitochondrial oxidative stress promotes atrial fibrillation

    PubMed Central

    Xie, Wenjun; Santulli, Gaetano; Reiken, Steven R.; Yuan, Qi; Osborne, Brent W.; Chen, Bi-Xing; Marks, Andrew R.

    2015-01-01

    Oxidative stress has been suggested to play a role in the pathogenesis of atrial fibrillation (AF). Indeed, the prevalence of AF increases with age as does oxidative stress. However, the mechanisms linking redox state to AF are not well understood. In this study we identify a link between oxidative stress and aberrant intracellular Ca2+ release via the type 2 ryanodine receptor (RyR2) that promotes AF. We show that RyR2 are oxidized in the atria of patients with chronic AF compared with individuals in sinus rhythm. To dissect the molecular mechanism linking RyR2 oxidation to AF we used two murine models harboring RyR2 mutations that cause intracellular Ca2+ leak. Mice with intracellular Ca2+ leak exhibited increased atrial RyR2 oxidation, mitochondrial dysfunction, reactive oxygen species (ROS) production and AF susceptibility. Both genetic inhibition of mitochondrial ROS production and pharmacological treatment of RyR2 leakage prevented AF. Collectively, our results indicate that alterations of RyR2 and mitochondrial ROS generation form a vicious cycle in the development of AF. Targeting this previously unrecognized mechanism could be useful in developing effective interventions to prevent and treat AF. PMID:26169582

  5. Oxidative stress, NADPH oxidases, and arteries.

    PubMed

    Sun, Qi-An; Runge, Marschall S; Madamanchi, Nageswara R

    2016-05-10

    Atherosclerosis and its major complications - myocardial infarction and stroke - remain major causes of death and disability in the United States and world-wide. Indeed, with dramatic increases in obesity and diabetes mellitus, the prevalence and public health impact of cardiovascular diseases (CVD) will likely remain high. Major advances have been made in development of new therapies to reduce the incidence of atherosclerosis and CVD, in particular for treatment of hypercholesterolemia and hypertension. Oxidative stress is the common mechanistic link for many CVD risk factors. However, only recently have the tools existed to study the interface between oxidative stress and CVD in animal models. The most important source of reactive oxygen species (and hence oxidative stress) in vascular cells are the multiple forms of enzymes nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Recently published and emerging studies now clearly establish that: 1) NADPH oxidases are of critical importance in atherosclerosis and hypertension in animal models; 2) given the tissue-specific expression of key components of NADPH oxidase, it may be possible to target vascular oxidative stress for prevention of CVD. PMID:25649240

  6. Oxidative Stress Control by Apicomplexan Parasites

    PubMed Central

    Izui, Natália M.; Schettert, Isolmar; Liebau, Eva

    2015-01-01

    Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis. PMID:25722976

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

    PubMed

    Busch, Andrea W U; Montgomery, Beronda L

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

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

    PubMed Central

    Busch, Andrea W.U.; Montgomery, Beronda L.

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

  9. Thiol specific oxidative stress response in Mycobacteria.

    PubMed

    Dosanjh, Nirpjit S; Rawat, Mamta; Chung, Ji-Hae; Av-Gay, Yossef

    2005-08-01

    The cellular response of mycobacteria to thiol specific oxidative stress was studied in Mycobacterium bovis BCG cultures. Two-dimensional gel electrophoresis revealed that upon diamide treatment at least 60 proteins were upregulated. Fourteen of these proteins were identified by MALDI-MS; four proteins, AhpC, Tpx, GroEL2, and GroEL1 are functionally related to oxidative stress response; eight proteins, LeuC, LeuD, Rv0224c, Rv3029c, AsnB, Rv2971, PheA and HisH are classified as part of the bacterial intermediary metabolism and respiration pathways; protein EchA14 belong to lipid metabolism, and NrdE, belongs to the mycobacterial information pathway category. Reverse transcription followed by quantitative real time PCR in response to diamide stress demonstrated that protein expression is directly proportional to the corresponding gene transcription. PMID:16006064

  10. Protein Quality Control Under Oxidative Stress Conditions

    PubMed Central

    Dahl, Jan-Ulrik; Gray, Michael J.; Jakob, Ursula

    2015-01-01

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the E. coli protein RidA, and the mammalian protein α2-macroglobin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and of how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  11. Protein quality control under oxidative stress conditions.

    PubMed

    Dahl, Jan-Ulrik; Gray, Michael J; Jakob, Ursula

    2015-04-10

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and we will review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the Escherichia coli protein RidA, and the mammalian protein α2-macroglobulin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  12. Inflammatory and oxidative stress in rotavirus infection.

    PubMed

    Guerrero, Carlos A; Acosta, Orlando

    2016-05-12

    Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. PMID:27175349

  13. Inflammatory and oxidative stress in rotavirus infection

    PubMed Central

    Guerrero, Carlos A; Acosta, Orlando

    2016-01-01

    Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. PMID:27175349

  14. Cofactor binding protects flavodoxin against oxidative stress.

    PubMed

    Lindhoud, Simon; van den Berg, Willy A M; van den Heuvel, Robert H H; Heck, Albert J R; van Mierlo, Carlo P M; van Berkel, Willem J H

    2012-01-01

    In organisms, various protective mechanisms against oxidative damaging of proteins exist. Here, we show that cofactor binding is among these mechanisms, because flavin mononucleotide (FMN) protects Azotobacter vinelandii flavodoxin against hydrogen peroxide-induced oxidation. We identify an oxidation sensitive cysteine residue in a functionally important loop close to the cofactor, i.e., Cys69. Oxidative stress causes dimerization of apoflavodoxin (i.e., flavodoxin without cofactor), and leads to consecutive formation of sulfinate and sulfonate states of Cys69. Use of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) reveals that Cys69 modification to a sulfenic acid is a transient intermediate during oxidation. Dithiothreitol converts sulfenic acid and disulfide into thiols, whereas the sulfinate and sulfonate forms of Cys69 are irreversible with respect to this reagent. A variable fraction of Cys69 in freshly isolated flavodoxin is in the sulfenic acid state, but neither oxidation to sulfinic and sulfonic acid nor formation of intermolecular disulfides is observed under oxidising conditions. Furthermore, flavodoxin does not react appreciably with NBD-Cl. Besides its primary role as redox-active moiety, binding of flavin leads to considerably improved stability against protein unfolding and to strong protection against irreversible oxidation and other covalent thiol modifications. Thus, cofactors can protect proteins against oxidation and modification. PMID:22829943

  15. Oxidative stress induced carbonylation in human plasma.

    PubMed

    Madian, Ashraf G; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E

    2011-10-19

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  16. Oxidative stress induced carbonylation in human plasma

    PubMed Central

    Madian, Ashraf G.; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E.

    2011-01-01

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  17. Oxidative stress and mitochondrial dysfunction in fibromyalgia.

    PubMed

    Cordero, Mario D; de Miguel, Manuel; Carmona-López, Inés; Bonal, Pablo; Campa, Francisco; Moreno-Fernández, Ana María

    2010-01-01

    Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and pathophysiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM. Furthermore, it is controversial the role of mitochondria in the oxidant imbalance documented in FM. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with FM. To this respect, Coenzyme Q10 (CoQ10) deficiency, an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant, alters mitochondria function and mitochondrial respiratory complexes organization and leading to increased ROS generation. Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease. PMID:20424583

  18. Selected oxidative stress markers in gynecological laparoscopy

    PubMed Central

    Koźlik, Jacek; Przybyłowska, Joanna; Mikrut, Kinga; Zwoliński, Jacek; Piątek, Jacek; Sobczak, Paweł

    2014-01-01

    Introduction The surgical stress response after laparoscopy is smaller when compared with open surgery, and it is expected that after minimally invasive surgery the possible development of oxidative stress will be less severe. Aim To evaluate markers of pro-oxidant activity – levels of lipid peroxides and malondialdehyde – and activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase in the perioperative period in patients undergoing gynecological laparoscopy and to determine whether the duration of laparoscopy can affect these changes. Material and methods The study included 64 patients, divided into two groups: group 1 with duration of laparoscopy up to 20 min, and group 2 with duration of the operation over 40 min. Blood samples were collected before anesthesia, 5 min after release of pneumoperitoneum, and 10 h after surgery. Results A statistically significant increase in the levels of lipid peroxides and malondialdehyde in samples collected after surgery was found in comparison with values obtained before surgery. Also statistically significant differences existed between groups of patients with different duration of surgery. Superoxide dismutase and glutathione peroxidase activity values were significantly decreased. They were also significantly different between the two groups with different duration of surgery. Conclusions In our study, levels of the markers of pro-oxidant activity increased and levels of the markers of antioxidant enzymes decreased, suggesting development of oxidative stress. The duration of laparoscopic procedures affects the severity of the presented changes. PMID:25960799

  19. Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

    PubMed Central

    Consales, Claudia; Merla, Caterina; Marino, Carmela; Benassi, Barbara

    2012-01-01

    Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system. PMID:22991514

  20. Angiogenesis in the Placenta: The Role of Reactive Oxygen Species Signaling

    PubMed Central

    Pereira, Robyn D.; De Long, Nicole E.; Wang, Ruijun C.; Yazdi, Fereshteh T.; Holloway, Alison C.; Raha, Sandeep

    2015-01-01

    Proper placental development and function are central to the health of both the mother and the fetus during pregnancy. A critical component of healthy placental function is the proper development of its vascular network. Poor vascularization of the placenta can lead to fetal growth restriction, preeclampsia, and in some cases fetal death. Therefore, understanding the mechanisms by which uterine stressors influence the development of the placental vasculature and contribute to placental dysfunction is of central importance to ensuring a healthy pregnancy. In this review we discuss how oxidative stress observed in maternal smoking, maternal obesity, and preeclampsia has been associated with aberrant angiogenesis and placental dysfunction resulting in adverse pregnancy outcomes. We also highlight that oxidative stress can influence the expression of a number of transcription factors important in mediating angiogenesis. Therefore, understanding how oxidative stress affects redox-sensitive transcription factors within the placenta may elucidate potential therapeutic targets for correcting abnormal placental angiogenesis and function. PMID:25705690

  1. Airway oxidative stress in chronic cough

    PubMed Central

    2013-01-01

    Background The mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases. Methods Exhaled breath condensate samples were obtained in 43 non-smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria included a doctor’s diagnosis of any lung disorders and any abnormality in lung x-ray. The concentration of 8-isoprostane was measured. In addition, the patients filled in Leicester Cough Questionnaire and underwent hypertonic saline cough provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, and histamine airway challenge. In a subgroup of patients the measurements were repeated during 12 weeks’ treatment with inhaled budesonide, 800 ug/day. Results The 8-isoprostane concentrations were higher in the cough patients than in the healthy subjects (24.6 ± 1.2 pg/ml vs. 10.1 ± 1.7 pg/ml, p = 0.045). The 8-isoprostane concentration was associated with the Leicester Cough Questionnaire total score (p = 0.044) but not with the cough sensitivity to saline or other tests. Budesonide treatment did not affect the 8-isoprostane concentrations. Conclusions Chronic cough seems to be associated with airway oxidative stress in subjects with chronic cough but without chronic lung diseases. This finding may help to develop novel antitussive drugs. Trial registration The study was registered in ClinicalTrials.gov database (KUH5801112), identifier NCT00859274. PMID:24294924

  2. Oxidative stress and immunotoxicity induced by graphene oxide in zebrafish.

    PubMed

    Chen, Minjie; Yin, Junfa; Liang, Yong; Yuan, Shaopeng; Wang, Fengbang; Song, Maoyong; Wang, Hailin

    2016-05-01

    Graphene oxide (GO) has been extensively explored as a promising nanomaterial for applications in biology because of its unique properties. Therefore, systematic investigation of GO toxicity is essential to determine its fate in the environment and potential adverse effects. In this study, acute toxicity, oxidative stress and immunotoxicity of GO were investigated in zebrafish. No obvious acute toxicity was observed when zebrafish were exposed to 1, 5, 10 or 50mg/L GO for 14 days. However, a number of cellular alterations were detected by histological analysis of the liver and intestine, including vacuolation, loose arrangement of cells, histolysis and disintegration of cell boundaries. As evidence for oxidative stress, malondialdehyde levels and superoxide dismutase and catalase activities were increased and glutathione content was decreased in the liver after treatment with GO. GO treatment induced an immune response in zebrafish, as demonstrated by increased expression of tumor necrosis factor α, interleukin-1 β, and interleukin-6 in the spleen. Our findings demonstrated that GO administration in an aquatic system can cause oxidative stress and immune toxicity in adult zebrafish. To our knowledge, this is the first report of immune toxicity of GO in zebrafish. PMID:26921726

  3. Modulation of functional responses of endothelial cells linked to angiogenesis and inflammation by shear stress: differential effects of the mechanotransducer CD31.

    PubMed

    Glen, Katie; Luu, N Thin; Ross, Ewan; Buckley, Chris D; Rainger, G Ed; Egginton, Stuart; Nash, Gerard B

    2012-06-01

    We investigated the roles of the "mechanotransducer" CD31 in the effects of shear stress on endothelial gene expression and functional responses relevant to angiogenesis and inflammation. Human or murine endothelial cells (hEC or mEC) were exposed to different levels of shear stress, while expression of CD31 was modified using siRNA in the hEC, or mEC from CD31(-/-) mice. Quantitation of expression of genes linked to inflammation or angiogenesis showed several were sensitive to shear. In a "wound" assay, exposure of endothelial cells (EC) to shear stress tended to align migration with the direction of flow and decrease the rate of closure compared to static cultures. When EC were cultured on filters, shear stress promoted migration away from the luminal surface. EC conditioned by shear stress recruited fewer flowing neutrophils, and showed reduced up-regulation of E-selectin after stimulation with tumor necrosis factor-α (TNF). Use of siRNA against CD31 in the hEC, or testing of mEC from mice lacking CD31, indicated that expression of CD31 was not required for the shear-induced modification of wound closure. However, shear modulation of response to TNF was less effective in the absence of CD31, while reduction of CD31 reduced shear-sensitivity in some genes (e.g., eNOS), but not others (e.g., KLF-2). Thus, CD31 played a role in shear-sensitivity of some genes and of neutrophil recruitment, but not in modulation of endothelial migration. Different mechanotransducers may mediate different functional effects of shear stress. Hence, identification of the specific pathways may provide targets for therapeutic manipulation of angiogenesis or inflammation. PMID:21898411

  4. Oxidative Stress and Air Pollution Exposure

    PubMed Central

    Lodovici, Maura; Bigagli, Elisabetta

    2011-01-01

    Air pollution is associated with increased cardiovascular and pulmonary morbidity and mortality. The mechanisms of air pollution-induced health effects involve oxidative stress and inflammation. As a matter of fact, particulate matter (PM), especially fine (PM2.5, PM < 2.5 μm) and ultrafine (PM0.1, PM < 0.1 μm) particles, ozone, nitrogen oxides, and transition metals, are potent oxidants or able to generate reactive oxygen species (ROS). Oxidative stress can trigger redox-sensitive pathways that lead to different biological processes such as inflammation and cell death. However, it does appear that the susceptibility of target organ to oxidative injury also depends upon its ability to upregulate protective scavenging systems. As vehicular traffic is known to importantly contribute to PM exposure, its intensity and quality must be strongly relevant determinants of the qualitative characteristics of PM spread in the atmosphere. Change in the composition of this PM is likely to modify its health impact. PMID:21860622

  5. Oxidative Stress and Periodontal Disease in Obesity

    PubMed Central

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

    2016-01-01

    Abstract Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women. Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated. Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P < 0.05 for all). GCF TOS was higher in the obese women (P < 0.05), whereas there was a nonsignificant trend for higher serum TOS in obese women (P = 0.074). GCF TAOC values showed a negative correlation with body mass index, whereas GCF OSI was positively correlated with fasting insulin and low-density lipoprotein-cholesterol levels (P < 0.05 for all). Clinical periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status

  6. Oxidative Stress and Periodontal Disease in Obesity.

    PubMed

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

    2016-03-01

    Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women.Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated.Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P < 0.05 for all). GCF TOS was higher in the obese women (P < 0.05), whereas there was a nonsignificant trend for higher serum TOS in obese women (P = 0.074). GCF TAOC values showed a negative correlation with body mass index, whereas GCF OSI was positively correlated with fasting insulin and low-density lipoprotein-cholesterol levels (P < 0.05 for all). Clinical periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status markers

  7. Oxidative stress and Parkinson’s disease

    PubMed Central

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

    2015-01-01

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

  8. ALS and Oxidative Stress: The Neurovascular Scenario

    PubMed Central

    Thakur, Keshav; Gupta, Pawan Kumar

    2013-01-01

    Oxidative stress and angiogenic factors have been placed as the prime focus of scientific investigations after an establishment of link between vascular endothelial growth factor promoter (VEGF), hypoxia, and amyotrophic lateral sclerosis (ALS) pathogenesis. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter and mutant superoxide dismutase 1 (SOD1) which are characterised by atrophy and muscle weakness resulted in phenotype resembling human ALS in mice. This results in lower motor neurodegeneration thus establishing an important link between motor neuron degeneration, vasculature, and angiogenic molecules. In this review, we have presented human, animal, and in vitro studies which suggest that molecules like VEGF have a therapeutic, diagnostic, and prognostic potential in ALS. Involvement of vascular growth factors and hypoxia response elements also highlights the converging role of oxidative stress and neurovascular network for understanding and treatment of various neurodegenerative disorders like ALS. PMID:24367722

  9. Oxidative stress in coronary artery bypass surgery

    PubMed Central

    Dias, Amaury Edgardo Mont’Serrat Ávila Souza; Melnikov, Petr; Cônsolo, Lourdes Zélia Zanoni

    2015-01-01

    Objective The aim of this prospective study was to assess the dynamics of oxidative stress during coronary artery bypass surgery with cardiopulmonary bypass. Methods Sixteen patients undergoing coronary artery bypass grafting were enrolled. Blood samples were collected from the systemic circulation during anesthesia induction (radial artery - A1), the systemic venous return (B1 and B2) four minutes after removal of the aortic cross-clamping, of the coronary sinus (CS1 and CS2) four minutes after removal of the aortic cross-clamping and the systemic circulation four minutes after completion of cardiopulmonary bypass (radial artery - A2). The marker of oxidative stress, malondialdehyde, was measured using spectrophotometry. Results The mean values of malondialdehyde were (ng/dl): A1 (265.1), B1 (490.0), CS1 (527.0), B2 (599.6), CS2 (685.0) and A2 (527.2). Comparisons between A1/B1, A1/CS1, A1/B2, A1/CS2, A1/A2 were significant, with ascending values (P<0.05). Comparisons between the measurements of the coronary sinus and venous reservoir after the two moments of reperfusion (B1/B2 and CS1/CS2) were higher when CS2 (P<0.05). Despite higher values ​​after the end of cardiopulmonary bypass (A2), when compared to samples of anesthesia (A1), those show a downward trend when compared to the samples of the second moment of reperfusion (CS2) (P<0.05). Conclusion The measurement of malondialdehyde shows that coronary artery bypass grafting with cardiopulmonary bypass is accompanied by increase of free radicals and this trend gradually decreases after its completion. Aortic clamping exacerbates oxidative stress but has sharper decline after reperfusion when compared to systemic metabolism. The behavior of thiobarbituric acid species indicates that oxidative stress is an inevitable pathophysiological component. PMID:27163415

  10. Renal oxidative stress, oxygenation, and hypertension.

    PubMed

    Palm, Fredrik; Nordquist, Lina

    2011-11-01

    Hypertension is closely associated with progressive kidney dysfunction, manifested as glomerulosclerosis, interstitial fibrosis, proteinuria, and eventually declining glomerular filtration. The postulated mechanism for development of glomerulosclerosis is barotrauma caused by increased capillary pressure, but the reason for development of interstitial fibrosis and the subsequently reduced kidney function is less clear. However, it has been hypothesized that tissue hypoxia induces fibrogenesis and progressive renal failure. This is very interesting, since recent reports highlight several different mechanisms resulting in altered oxygen handling and availability in the hypertensive kidney. Such mechanisms include decreased renal blood flow due to increased vascular tone induced by ANG II that limits oxygen delivery and increases oxidative stress, resulting in increased mitochondrial oxygen usage, increased oxygen usage for tubular electrolyte transport, and shunting of oxygen from arterial to venous blood in preglomerular vessels. It has been shown in several studies that interventions to prevent oxidative stress and to restore kidney tissue oxygenation prevent progression of kidney dysfunction. Furthermore, inhibition of ANG II activity, by either blocking ANG II type 1 receptors or angiotensin-converting enzyme, or by preventing oxidative stress by administration of antioxidants also results in improved blood pressure control. Therefore, it seems likely that tissue hypoxia in the hypertensive kidney contributes to progression of kidney damage, and perhaps also persistence the high blood pressure. PMID:21832206

  11. Oxidative Stress in Patients With Acne Vulgaris

    PubMed Central

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

    2005-01-01

    Acne vulgaris is one of the common dermatological diseases and its pathogenesis is multifactorial. In this study, we aim to determine the effects of oxidative stress in acne vulgaris. Forty-three consecutive acne patients and 46 controls were enrolled. The parameters of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood of cases were measured spectrophotometrically. The values compared with control group, the relation between the severity and distribution of acne, and the correlation of each enzyme level were researched. CAT and G6PD levels in patients were found to be statistically decreased, and SOD and MDA levels were found to be statistically increased (P < .001). However, any statistical difference and correlation could not be found between the severity and distribution of lesions and the mean levels of enzymes. In addition, we found that each enzyme is correlated with one another. Our findings show that oxidative stress exists in the acne patients. It will be useful to apply at least one antioxidant featured drug along with the combined acne treatment. PMID:16489259

  12. Lamins as mediators of oxidative stress

    SciTech Connect

    Sieprath, Tom; Darwiche, Rabih; De Vos, Winnok H.

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer The nuclear lamina defines structural and functional properties of the cell nucleus. Black-Right-Pointing-Pointer Lamina dysfunction leads to a broad spectrum of laminopathies. Black-Right-Pointing-Pointer Recent data is reviewed connecting laminopathies to oxidative stress. Black-Right-Pointing-Pointer A framework is proposed to explain interactions between lamins and oxidative stress. -- Abstract: The nuclear lamina defines both structural and functional properties of the eukaryotic cell nucleus. Mutations in the LMNA gene, encoding A-type lamins, lead to a broad spectrum of diseases termed laminopathies. While different hypotheses have been postulated to explain disease development, there is still no unified view on the mechanistic basis of laminopathies. Recent observations indicate that laminopathies are often accompanied by altered levels of reactive oxygen species and a higher susceptibility to oxidative stress at the cellular level. In this review, we highlight the role of reactive oxygen species for cell function and disease development in the context of laminopathies and present a framework of non-exclusive mechanisms to explain the reciprocal interactions between a dysfunctional lamina and altered redox homeostasis.

  13. Chrononutrition against Oxidative Stress in Aging

    PubMed Central

    Garrido, M.; Terrón, M. P.; Rodríguez, A. B.

    2013-01-01

    Free radicals and oxidative stress have been recognized as important factors in the biology of aging and in many age-associated degenerative diseases. Antioxidant systems deteriorate during aging. It is, thus, considered that one way to reduce the rate of aging and the risk of chronic disease is to avoid the formation of free radicals and reduce oxidative stress by strengthening antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and other foodstuffs have been linked to reducing the risk of major oxidative stress-induced diseases. Some dietary components of foods possess biological activities which influence circadian rhythms in humans. Chrononutrition studies have shown that not only the content of food, but also the time of ingestion contributes to the natural functioning of the circadian system. Dietary interventions with antioxidant-enriched foods taking into account the principles of chrononutrition are of particular interest for the elderly since they may help amplify the already powerful benefits of phytochemicals as natural instruments with which to prevent or delay the onset of common age-related diseases. PMID:23861994

  14. Asthmatic cough and airway oxidative stress.

    PubMed

    Koskela, Heikki O; Purokivi, Minna K; Nieminen, Riina M; Moilanen, Eeva

    2012-05-31

    The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma. PMID:22546340

  15. Angiogenesis Inhibitors

    MedlinePlus

    ... of anticancer agents that target the VEGF pathway. Nature Reviews Clinical Oncology 2009; 6(8):465–477. [ ... mechanisms involved in the toxicity of angiogenesis inhibition. Nature Reviews Cancer 2007; 7(6):475–485. [PubMed ...

  16. Role of oxidative stress in Alzheimer's disease

    PubMed Central

    HUANG, WEN-JUAN; ZHANG, XIA; CHEN, WEI-WEI

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD is characterized by the abnormal deposition of amyloid β (Aβ) peptide, and intracellular accumulation of neurofibrillary tangles of hyperphosphorylated τ protein and dementia. The neurotoxic oligomer Aβ peptide, which is the neuropathological diagnostic criterion of the disease, together with τ protein, are mediators of the neurodegeneration that is among the main causative factors. However, these phenomena are mainly initiated and enhanced by oxidative stress, a process referring to an imbalance between antioxidants and oxidants in favour of oxidants. This imbalance can occur as a result of increased free radicals or a decrease in antioxidant defense, free radicals being a species that contains one or more unpaired electrons in its outer shell. The major source of potent free radicals is the reduction of molecular oxygen in water, that initially yields the superoxide radical, which produces hydrogen peroxide by the addition of an electron. The reduction of hydrogen peroxide produces highly reactive hydroxyl radicals, termed reactive oxygen species (ROS) that can react with lipids, proteins, nucleic acids, and other molecules and may also alter their structures and functions. Thus, tissues and organs, particularly the brain, a vulnerable organ, are affected by ROS due to its composition. The brain is largely composed of easily oxidizable lipids while featuring a high oxygen consumption rate. The current review examined the role of oxidative stress in AD. PMID:27123241

  17. Ferritin and the response to oxidative stress.

    PubMed Central

    Orino, K; Lehman, L; Tsuji, Y; Ayaki, H; Torti, S V; Torti, F M

    2001-01-01

    Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron levels. Chief among these is the sequestration of iron in ferritin. Ferritin is a 24 subunit protein composed of two subunit types, termed H and L. The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability. In the present study we report that increased synthesis of both subunits of ferritin occurs in HeLa cells exposed to oxidative stress. An increase in the activity of iron responsive element binding proteins in response to oxidative stress was also observed. However, this activation was transient, allowing ferritin protein induction to subsequently proceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferritin H or ferritin L cDNA under control of a tetracycline-responsive promoter. We observed that overexpression of either ferritin H or ferritin L reduced the accumulation of ROS in response to oxidant challenge. PMID:11415455

  18. Nitric oxide, stomatal closure, and abiotic stress.

    PubMed

    Neill, Steven; Barros, Raimundo; Bright, Jo; Desikan, Radhika; Hancock, John; Harrison, Judith; Morris, Peter; Ribeiro, Dimas; Wilson, Ian

    2008-01-01

    Various data indicate that nitric oxide (NO) is an endogenous signal in plants that mediates responses to several stimuli. Experimental evidence in support of such signalling roles for NO has been obtained via the application of NO, usually in the form of NO donors, via the measurement of endogenous NO, and through the manipulation of endogenous NO content by chemical and genetic means. Stomatal closure, initiated by abscisic acid (ABA), is effected through a complex symphony of intracellular signalling in which NO appears to be one component. Exogenous NO induces stomatal closure, ABA triggers NO generation, removal of NO by scavengers inhibits stomatal closure in response to ABA, and ABA-induced stomatal closure is reduced in mutants that are impaired in NO generation. The data indicate that ABA-induced guard cell NO generation requires both nitric oxide synthase-like activity and, in Arabidopsis, the NIA1 isoform of nitrate reductase (NR). NO stimulates mitogen-activated protein kinase (MAPK) activity and cGMP production. Both these NO-stimulated events are required for ABA-induced stomatal closure. ABA also stimulates the generation of H2O2 in guard cells, and pharmacological and genetic data demonstrate that NO accumulation in these cells is dependent on such production. Recent data have extended this model to maize mesophyll cells where the induction of antioxidant defences by water stress and ABA required the generation of H2O2 and NO and the activation of a MAPK. Published data suggest that drought and salinity induce NO generation which activates cellular processes that afford some protection against the oxidative stress associated with these conditions. Exogenous NO can also protect cells against oxidative stress. Thus, the data suggest an emerging model of stress responses in which ABA has several ameliorative functions. These include the rapid induction of stomatal closure to reduce transpirational water loss and the activation of antioxidant defences

  19. Melanocytes as instigators and victims of oxidative stress.

    PubMed

    Denat, Laurence; Kadekaro, Ana L; Marrot, Laurent; Leachman, Sancy A; Abdel-Malek, Zalfa A

    2014-06-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis, and to the intrinsic antioxidant defenses that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment. PMID:24573173

  20. Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

    PubMed Central

    Takaki, Akinobu; Yamamoto, Kazuhide

    2015-01-01

    Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma. PMID:25954479

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

    PubMed Central

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

    2010-01-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is lifespan, i.e., does altering oxidative stress/damage change lifespan? Mice with genetic manipulations in the antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in lifespan. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory; increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean a) oxidative stress plays a very limited, if any, role in aging but a major role in healthspan; and/or b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an “anti-aging” action, leading to changes in lifespan, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging. PMID:20036736

  2. Extract of Meretrix meretrix Linnaeus induces angiogenesis in vitro and activates endothelial nitric oxide synthase

    NASA Astrophysics Data System (ADS)

    Liu, Ming; Wei, Jianteng; Wang, Hui; Ding, Lili; Zhang, Yuyan; Lin, Xiukun

    2012-09-01

    Meretrix meretrix Linnaeus has long been used as traditional Chinese medicine in oriental medicine. The angiogentic activity of the extract of M. meretrix was investigated in this study, using human umbilical vein endothelial cells (HUVECs). Extract of M. meretrix Linnaeus (AFG-25) was prepared with acetone and ethanol precipitation, and further separated by Sephadex G-25 column. The results show that AFG-25 promoted proliferation, migration, and capillary-like tube formation in HUVECs, and in the presence of eNOS inhibitor NMA, the tube formation induced by AFG-25 is inhibited significantly. Moreover, AFG-25 could also promote the activation of endothelial nitric oxide synthase (eNOS) and the resultant elevation of nitric oxide (NO) production. The results suggested that M. meretrix contains active ingredients with angiogentic activity and eNOS/NO signal pathway is in part involved in the proangiogenesis effect induced by AFG-25.

  3. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    PubMed Central

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio

    2014-01-01

    Abstract Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both transcriptional and post-translational events. This cross talk, in turn, regulates the structural integrity of cardiomyocytes, promotes proteostasis, and reduces inflammation, events critical to disease pathogenesis. Critical Issues: Dysregulation of either autophagy or redox state has been implicated in many cardiovascular diseases. Cardiomyocytes are rich in mitochondria, which make them particularly sensitive to oxidative damage. Maintenance of mitochondrial homeostasis and elimination of defective mitochondria are each critical to the maintenance of redox homeostasis. Future Directions: The complex interplay between autophagy and oxidative stress underlies a wide range of physiological and pathological events and its elucidation holds promise of potential clinical applicability. Antioxid. Redox Signal. 20, 507–518. PMID:23641894

  4. Oxidative stress, thyroid dysfunction & Down syndrome

    PubMed Central

    Campos, Carlos; Casado, Ángela

    2015-01-01

    Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1) is coded on chromosome 21 and it is overexpressed (~50%) resulting in an increase of reactive oxygen species (ROS) due to overproduction of hydrogen peroxide (H2O2). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS. PMID:26354208

  5. Blood oxidative stress markers after ultramarathon swimming.

    PubMed

    Kabasakalis, Athanasios; Kyparos, Antonios; Tsalis, Georgios; Loupos, Dimitrios; Pavlidou, Anastasia; Kouretas, Dimitrios

    2011-03-01

    Data on redox balance in response to marathon swimming are lacking, whereas findings from studies using other types of ultraendurance exercise are controversial. The aim of the present study was to investigate the effect of ultramarathon swimming on selective blood oxidative stress markers. Five well-trained male swimmers aged 28.8 (6.0) years participated in the study. Blood samples were obtained before and after the ultramarathon swimming, for full blood count analysis and determination of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and total antioxidant capacity (TAC). The swimmers swam 19.4 (3.4) hours, covering 50.5 (15.0) km. Hematocrit and erythrocyte count, and leukocyte, neutrophil and monocyte counts were significantly elevated after swimming, whereas protein carbonyls, TBARS and TAC did not significantly change. The findings of the present study indicate that well-trained swimmers were able to regulate a redox homeostasis during ultra-long duration swimming. It is also postulated that the relatively low intensity of marathon swimming may not be a sufficient stimulus to induce oxidative stress in well-trained swimmers. The fact that low-intensity long-duration exercise protocols are not associated with oxidative damage is useful knowledge for coaches and athletes in scheduling the content of the training sessions that preceded and followed these exercise protocols. PMID:20613649

  6. Oxidative stress in haemodialysis--intradialytic changes.

    PubMed

    Srinivasa Rao, P V; Dakshinamurty, K V; Saibaba, K S; Raghavan, M S; Vijayabhaskar, M; Sreekrishna, V; Ambekar, J G; Jayaseelan, L

    2001-01-01

    Oxidative stress is likely to be involved in the development of complications due to haemodialysis. Though there is evidence for production of oxygen free radicals during haemodialysis, reports on net oxidative imbalance due to a single dialysis session are conflicting. Hence, a time-course analysis of changes in lipid peroxides (LPO) along with antioxidant enzymes and vitamins was carried out. Hourly changes in LPO and antioxidants were studied during a first-use cuprophan membrane and acetate dialysis in 20 patients on regular haemodialysis treatment. Data were corrected for haemoconcentration and standardised to measure the rate of change before statistical evaluation using analysis of variance for repeated measures. The results of the study showed a net oxidative stress due to a single dialysis session in the form of increased plasma and erythrocyte lipid peroxidation, decrease in plasma vitamin E, slight increase in plasma superoxide dismutase and erythrocyte glutathione peroxidase and no change in plasma glutathione peroxidase. erythrocyte superoxide dismutase and plasma vitamin A levels. The oxygen radical production was found to be maximum in the first hour of dialysis. PMID:11778848

  7. Oxidative stress-mediated HMGB1 biology

    PubMed Central

    Yu, Yan; Tang, Daolin; Kang, Rui

    2015-01-01

    High mobility group box 1 (HMGB1) is a widely-expressed and highly-abundant protein that acts as an extracellular signal upon active secretion by immune cells or passive release by dead, dying, and injured cells. Both intracellular and extracellular HMGB1 play pivotal roles in regulation of the cellular response to stress. Targeting the translocation, release, and activity of HMGB1 can limit inflammation and reduce tissue damage during infection and sterile inflammation. Although the mechanisms contributing to HMGB1 biology are still under investigation, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in inflammation and cell death (e.g., necrosis, apoptosis, autophagic cell death, pyroptosis, and NETosis). Thus, targeting HMGB1 with antioxidant compounds may be an attractive therapeutic strategy for inflammation-associated diseases such as sepsis, ischemia and reperfusion injury, arthritis, diabetes, and cancer. PMID:25904867

  8. Oxidative stress in prostate hyperplasia and carcinogenesis.

    PubMed

    Udensi, Udensi K; 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 antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment. PMID:27609145

  9. Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension

    PubMed Central

    Crosswhite, Patrick; Sun, Zhongjie

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH. PMID:20051913

  10. Air pollution and circulating biomarkers of oxidative stress

    PubMed Central

    Staimer, Norbert; Vaziri, Nosratola D.

    2013-01-01

    Chemical components of air pollutant exposures that induce oxidative stress and subsequent inflammation may be partly responsible for associations of cardiovascular morbidity and mortality with airborne particulate matter and combustion-related pollutant gasses. However, epidemiologic evidence regarding this is limited. An exposure-assessment approach is to measure the oxidative potential of particle mixtures because it is likely that hundreds of correlated chemicals are involved in overall effects of air pollution on health. Oxidative potential likely depends on particle composition and size distribution, especially ultrafine particle concentration, and on transition metals and certain semivolatile and volatile organic chemicals. For health effects, measuring systemic oxidative stress in the blood is one feasible approach, but there is no universal biomarker of oxidative stress and there are many potential target molecules (lipids, proteins, DNA, nitric oxide, etc.), which may be more or less suitable for specific study goals. Concurrent with the measurement of oxidative stress, it is important to measure gene and/or protein expression of endogenous antioxidant enzymes because they can modify relations between oxidative stress biomarkers and air pollutants. Conversely, the expression and activities of these enzymes are modified by oxidative stress. This interplay will likely determine the observed effects of air pollutants on systemic inflammatory and thrombotic mediators and related clinical outcomes. Studies are needed to assess the reliability and validity of oxidative stress biomarkers, evaluate differences in associations between oxidative stress biomarkers and various pollutant measurements (mass, chemical components, and oxidative potential), and evaluate impacts of antioxidant responses on these relations. PMID:23626660

  11. Molecular magnetic resonance imaging of angiogenesis in vivo using polyvalent cyclic RGD-iron oxide microparticle conjugates.

    PubMed

    Melemenidis, Stavros; Jefferson, Andrew; Ruparelia, Neil; Akhtar, Asim M; Xie, Jin; Allen, Danny; Hamilton, Alastair; Larkin, James R; Perez-Balderas, Francisco; Smart, Sean C; Muschel, Ruth J; Chen, Xiaoyuan; Sibson, Nicola R; Choudhury, Robin P

    2015-01-01

    Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule α(v)β(3) integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for α(v)β(3), to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 μm MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre- and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A significantly greater volume of MPIO-induced hypointensities were found in c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater reduction in mean tumour T(2)* relaxation times than the control agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed

  12. Molecular Magnetic Resonance Imaging of Angiogenesis In Vivo using Polyvalent Cyclic RGD-Iron Oxide Microparticle Conjugates

    PubMed Central

    Melemenidis, Stavros; Jefferson, Andrew; Ruparelia, Neil; Akhtar, Asim M; Xie, Jin; Allen, Danny; Hamilton, Alastair; Larkin, James R; Perez-Balderas, Francisco; Smart, Sean C; Muschel, Ruth J; Chen, Xiaoyuan; Sibson, Nicola R; Choudhury, Robin P

    2015-01-01

    Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule αvβ3 integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for αvβ3, to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 μm MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre- and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A significantly greater volume of MPIO-induced hypointensities were found in c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater reduction in mean tumour T2* relaxation times than the control agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed immunohistochemically was

  13. Diversity in Robustness of Lactococcus lactis Strains during Heat Stress, Oxidative Stress, and Spray Drying Stress

    PubMed Central

    Dijkstra, Annereinou R.; Setyawati, Meily C.; Bayjanov, Jumamurat R.; Alkema, Wynand; van Hijum, Sacha A. F. T.; Hugenholtz, Jeroen

    2014-01-01

    In this study we tested 39 Lactococcus lactis strains isolated from diverse habitats for their robustness under heat and oxidative stress, demonstrating high diversity in survival (up to 4 log units). Strains with an L. lactis subsp. lactis phenotype generally displayed more-robust phenotypes than strains with an L. lactis subsp. cremoris phenotype, whereas the habitat from which the strains had been isolated did not appear to influence stress survival. Comparison of the stress survival phenotypes with already available comparative genomic data sets revealed that the absence or presence of specific genes, including genes encoding a GntR family transcriptional regulator, a manganese ABC transporter permease, a cellobiose phosphotransferase system (PTS) component, the FtsY protein, and hypothetical proteins, was associated with heat or oxidative stress survival. Finally, 14 selected strains also displayed diversity in survival after spray drying, ranging from 20% survival for the most robust strains, which appears acceptable for industrial application, to 0.1% survival for the least-tolerant strains. The high and low levels of survival upon spray drying correlated clearly with the combined robustness under heat and oxidative stress. These results demonstrate the relevance of screening culture collections for robustness under heat and oxidative stress on top of the typical screening for acidifying and flavor-forming properties. PMID:24212574

  14. Melamine Induces Oxidative Stress in Mouse Ovary

    PubMed Central

    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 glutathi-one 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. PMID:26545251

  15. Oxidative stress induction by nanoparticles in THP-1 cells with 4-HNE production: stress biomarker or oxidative stress signalling molecule?

    PubMed

    Foucaud, L; Goulaouic, S; Bennasroune, A; Laval-Gilly, P; Brown, D; Stone, V; Falla, J

    2010-09-01

    The aim of this study was to investigate whether carbon black (CB) nanoparticles might induce toxicity to monocytic cells in vitro via an oxidative stress mechanism involving formation of the lipid peroxidation product 4-hydroxynonenal (4-HNE) and the subsequent role of 4-HNE in inducing further cytotoxic effects. ROS production in cells by CB nanoparticles was shown by the oxidation of DCFH after a short time exposure. These particles induced the formation of 4-HNE-protein adducts and significant modification of glutathione content corresponding to an increase of oxidized glutathione form (GSSG) and a decrease of total glutathione (GSX) content. These results attest to an oxidative stress induced by the carbon black nanoparticles, although no induction of HO-1 protein expression was detected. Concerning the effects of a direct exposure to 4-HNE, our results showed that 4-HNE is not cytotoxic for concentrations lower than 12.5 microM. By contrast, it provokes a very high cytotoxicity for concentrations above 25 microM. An induction of HO-1 expression was observed from concentrations above 5 microM of 4-HNE. Finally, glutathione content decreased significantly from 5 microM of 4-HNE but no modification was observed under this concentration. The discrepancy between effects of carbon black nanoparticles and 4-HNE on the intracellular markers of oxidative stress suggests that 4-HNE is not directly implied in the signalling of oxidative toxicity of nanoparticles but is an effective biomarker of oxidative effects of nanoparticles. PMID:20638469

  16. Chasing great paths of Helmut Sies "Oxidative Stress".

    PubMed

    Majima, Hideyuki J; Indo, Hiroko P; Nakanishi, Ikuo; Suenaga, Shigeaki; Matsumoto, Ken-Ichiro; Matsui, Hirofumi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Yen, Hsiu-Chuan; Hawkins, Clare L; Davies, Michael J; Ozawa, Toshihiko; St Clair, Daret K

    2016-04-01

    Prof. Dr. Helmut Sies is a pioneer of "Oxidative Stress", and has published over 18 papers with the name of "Oxidative Stress" in the title. He has been Editor-in-Chief of the journal "Archives of Biochemistry and Biophysics" for many years, and is a former Editor-in-Chief of the journal "Free Radical Research". He has clarified our understanding of the causes of chronic developing diseases, and has studied antioxidant factors. In this article, importance of "Oxidative Stress" and our mitochondrial oxidative stress studies; roles of mitochondrial ROS, effects of vitamin E and its homologues in oxidative stress-related diseases, effects of antioxidants in vivo and in vitro, and a mitochondrial superoxide theory for oxidative stress diseases and aging are introduced, and some of our interactions with Helmut are described, congratulating and appreciating his great path. PMID:27095216

  17. Going retro: Oxidative stress biomarkers in modern redox biology.

    PubMed

    Margaritelis, N V; Cobley, J N; Paschalis, V; Veskoukis, A S; Theodorou, A A; Kyparos, A; Nikolaidis, M G

    2016-09-01

    The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting. PMID:26855421

  18. A Nucleocytoplasmic Shuttling Protein in Oxidative Stress Tolerance

    SciTech Connect

    Ow, David W.; Song, Wen

    2003-03-26

    Plants for effective extraction of toxic metals and radionuclides must tolerate oxidative stress. To identify genes that enhance oxidative stress tolerance, an S. pombe cDNA expression plasmid library was screened for the ability to yield hypertolerant colonies. Here, we report on the properties of one gene that confers hypertolerance to cadmium and oxidizing chemicals. This gene appears to be conserved in other organisms as homologous genes are found in human, mouse, fruitfly and Arabidopsis. The fruitfly and Arabidopsis genes likewise enhance oxidative stress tolerance in fission yeast. During oxidative stress, the amount of mRNA does not change, but protein fusions to GFP relocate from the cytoplasm to the nucleus. The same pattern is observed with the Arabidopsis homologue-GFP fusion protein. This behavior suggests a signaling role in oxidative stress tolerance and these conserved proteins may be targets for engineering stress tolerant plants for phytoremediation.

  19. Oxidative Stress in Genetic Mouse Models of Parkinson's Disease

    PubMed Central

    Varçin, Mustafa; Bentea, Eduard; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    There is extensive evidence in Parkinson's disease of a link between oxidative stress and some of the monogenically inherited Parkinson's disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson's disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson's disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson's disease, gene-environment interactions in genetically engineered mouse models of Parkinson's disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson's disease. PMID:22829959

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

    PubMed Central

    Muriach, María; Flores-Bellver, Miguel; Romero, Francisco J.; Barcia, Jorge M.

    2014-01-01

    Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation. PMID:25215171

  1. FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs

    PubMed Central

    Nakayoshi, Takaharu; Sasaki, Ken-ichiro; Kajimoto, Hidemi; Koiwaya, Hiroshi; Ohtsuka, Masanori; Ueno, Takafumi; Chibana, Hidetoshi; Itaya, Naoki; Sasaki, Masahiro; Yokoyama, Shinji; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

    2014-01-01

    The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. PMID:24663349

  2. Management of multicellular senescence and oxidative stress.

    PubMed

    Haines, David D; Juhasz, Bela; Tosaki, Arpad

    2013-08-01

    Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs' apoptosis, necrosis, autophagy and 'necroapoptophagy'. The concept of 'necroapoptophagy' is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a unique form of

  3. Management of multicellular senescence and oxidative stress

    PubMed Central

    Haines, David D; Juhasz, Bela; Tosaki, Arpad

    2013-01-01

    Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs’ apoptosis, necrosis, autophagy and ‘necroapoptophagy’. The concept of ‘necroapoptophagy’ is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a

  4. Oxidative stress modulates theophylline effects on steroid responsiveness.

    PubMed

    Marwick, John A; Wallis, Gillian; Meja, Koremu; Kuster, Bernhard; Bouwmeester, Tewis; Chakravarty, Probir; Fletcher, Danielle; Whittaker, Paul A; Barnes, Peter J; Ito, Kazuhiro; Adcock, Ian M; Kirkham, Paul A

    2008-12-19

    Oxidative stress is a central factor in many chronic inflammatory diseases such as severe asthma and chronic obstructive pulmonary disease (COPD). Oxidative stress reduces the anti-inflammatory corticosteroid action and may therefore contribute to the relative corticosteroid insensitivity seen in these diseases. Low concentrations of theophylline can restore the anti-inflammatory action of corticosteroids in oxidant exposed cells, however the mechanism remains unknown. Here, we demonstrate that a low concentration of theophylline restores corticosteroid repression of pro-inflammatory mediator release and histone acetylation in oxidant exposed cells. Global gene expression analysis shows that theophylline regulates distinct pathways in naïve and oxidant exposed cells and reverses oxidant mediated modulated of pathways. Furthermore, quantitative chemoproteomics revealed that theophylline has few high affinity targets in naive cells but an elevated affinity in oxidant stressed cells. In conclusion, oxidative stress alters theophylline binding profile and gene expression which may result in restoration of corticosteroid function. PMID:18951874

  5. Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion

    PubMed Central

    Ishii, Takamasa; Miyazawa, Masaki; Takanashi, Yumi; Tanigawa, Maya; Yasuda, Kayo; Onouchi, Hiromi; Kawabe, Noboru; Mitsushita, Junji; Hartman, Phil S.; Ishii, Naoaki

    2014-01-01

    Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence relating to the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. Recently, we have established Tet-mev-1 conditional transgenic mice, which can express the doxycycline-induced mutant SDHCV69E transgene and experience mitochondrial respiratory chain dysfunction leading to intracellular oxidative stress. In this report, we demonstrate that this kind of abnormal mitochondrial respiratory chain-induced chronic oxidative stress affects fertility, pregnancy and delivery rates as well as causes recurrent abortions, occasionally resulting in maternal death. Despite this, spermatogenesis and early embryogenesis are completely normal, indicating the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as placental angiodysplasia with reduced Flt-1 protein leading to hypoxic conditions, which could contribute to placental inflammation and fetal abnormal angiogenesis. Collectively these data strongly suggest that chronic oxidative stress caused by mitochondrial mutations provokes spontaneous abortions and recurrent miscarriage resulting in age-related female infertility. PMID:24936442

  6. Effects of oxidative stress on erythrocyte deformability

    NASA Astrophysics Data System (ADS)

    Bayer, Rainer; Wasser, Gerd

    1996-05-01

    Hemolysis as a consequence of open heart surgery is well investigated and explained by the oxidative and/or mechanical stress produced, e.g. by the heart lung machine. In Europe O3 is widely used by physicians, dedicated to alternative medicine. They apply O3 mostly by means of the Major Autohematotherapy (MAH, a process of removing 50 - 100 ml of blood, adding O3 gas to it and returning it to the patient's body). No controlled studies on the efficacy of O3 are available so far, but several anecdotal cases appear to confirm that MAH improves microcirculation, possibly due to increased RBC flexibility. Most methods established to estimate RBC deformability are hard to standardize and include high error of measurement. For our present investigation we used the method of laser diffraction in combination with image analysis. The variation coefficient of the measurement is less than 1%. Previous investigations of our group have shown, that mechanical stress decreases deformability, already at rather low levels of mechanical stress which do not include hemolysis. On the other hand exposure to O2, H2O2 or O3 does not alter the deformability of RBC and--except O3--does not induce considerably hemolysis. However this only holds true if deformability (shear rates 36/s - 2620/s) is determined in isotonic solutions. In hypertonic solutions O3 decreases RBC deformability, but improves it in hypotonic solutions. The results indicate that peroxidative stress dehydrates RBC and reduces their size. To explain the positive effect of O3 on the mechanical fragility of RBC we tentatively assume, that the reduction of RBC size facilitates the feed through small pore filters. In consequence, the size reduction in combination with undisturbed deformability at iso-osmolarity may have a beneficial effect on microcirculation.

  7. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration.

    PubMed

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L; Kamei, Motohiro

    2012-05-15

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  8. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration

    PubMed Central

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L.; Kamei, Motohiro

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  9. Amyloids, Melanins and Oxidative Stress in Melanomagenesis

    PubMed Central

    Liu-Smith, Feng; Poe, Carrie; Farmer, Patrick J.; Meyskens, Frank L.

    2015-01-01

    Melanoma has traditionally been viewed as an ultra-violet (UV) radiation induced malignancy. While UV is a common inducing factor, other endogenous stresses such as metal ion accumulation or the melanin pigment itself, may provide alternative pathways to melanoma progression. Eumelanosomes within melanoma often exhibit disrupted membranes and fragmented pigment which may be due to alterations in their amyloid-based striatial matrix. The melanosomal amyloid can itself be toxic, especially in combination with reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by endogenous NADPH oxidase (NOX) and nitric oxide synthase (NOS) enzymes; a toxic mix that may initiate melanomagenesis. Further understanding of the loss of the melanosomal organization, the behavior of the exposed melanin, and the induction of ROS/RNS in melanomas may provide critical insights into this deadly disease. PMID:25271672

  10. Thyroid Hormones, Oxidative Stress, and Inflammation.

    PubMed

    Mancini, Antonio; Di Segni, Chantal; Raimondo, Sebastiano; Olivieri, Giulio; Silvestrini, Andrea; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases. PMID:27051079

  11. Oxidative stress in normal and diabetic rats.

    PubMed

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (p<0.001) greater than the control levels. The diabetic animals presented an amount of vitamin E far greater (p<0.0001) than the controls, as was also the case for the vitaminE/polyunsaturated fatty acid (PUFA) and vitaminE/linoleic acid (C18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected. PMID:10523056

  12. The Oxygen Paradox, oxidative stress, and ageing.

    PubMed

    Davies, Kelvin J A

    2016-04-01

    Professor Helmut Sies is being lauded in this special issue of Archives of Biochemistry & Biophysics, on the occasion of his retirement as Editor-in-Chief. There is no doubt that Helmut has exerted an enormously positive influence on this journal, the fields of Biochemistry & Biophysics in general, and the areas of free radical and redox biology & medicine in particular. Helmut Sies' many discoveries about peroxide metabolism, glutathione, glutathione peroxidases, singlet oxygen, carotenoids in general and lycopene in particular, and flavonoids, fill the pages of his more than 600 publications. In addition, he will forever be remembered for coining the term 'oxidative stress' that is so widely used (and sometimes abused) by most of his colleagues. PMID:27095211

  13. Glutamate neurotoxicity, oxidative stress and mitochondria.

    PubMed

    Atlante, A; Calissano, P; Bobba, A; Giannattasio, S; Marra, E; Passarella, S

    2001-05-18

    The excitatory neurotransmitter glutamate plays a major role in determining certain neurological disorders. This situation, referred to as 'glutamate neurotoxicity' (GNT), is characterized by an increasing damage of cell components, including mitochondria, leading to cell death. In the death process, reactive oxygen species (ROS) are generated. The present study describes the state of art in the field of GNT with a special emphasis on the oxidative stress and mitochondria. In particular, we report how ROS are generated and how they affect mitochondrial function in GNT. The relationship between ROS generation and cytochrome c release is described in detail, with the released cytochrome c playing a role in the cell defense mechanism against neurotoxicity. PMID:11376653

  14. Thyroid Hormones, Oxidative Stress, and Inflammation

    PubMed Central

    Raimondo, Sebastiano; Olivieri, Giulio; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases. PMID:27051079

  15. The natriuretic peptide/guanylyl cyclase--a system functions as a stress-responsive regulator of angiogenesis in mice.

    PubMed

    Kuhn, Michaela; Völker, Katharina; Schwarz, Kristine; Carbajo-Lozoya, Javier; Flögel, Ulrich; Jacoby, Christoph; Stypmann, Jörg; van Eickels, Martin; Gambaryan, Stepan; Hartmann, Michael; Werner, Matthias; Wieland, Thomas; Schrader, Jürgen; Baba, Hideo A

    2009-07-01

    Cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) modulate blood pressure and volume by activation of the receptor guanylyl cyclase-A (GC-A) and subsequent intracellular cGMP formation. Here we report what we believe to be a novel function of these peptides as paracrine regulators of vascular regeneration. In mice with systemic deletion of the GC-A gene, vascular regeneration in response to critical hind limb ischemia was severely impaired. Similar attenuation of ischemic angiogenesis was observed in mice with conditional, endothelial cell-restricted GC-A deletion (here termed EC GC-A KO mice). In contrast, smooth muscle cell-restricted GC-A ablation did not affect ischemic neovascularization. Immunohistochemistry and RT-PCR revealed BNP expression in activated satellite cells within the ischemic muscle, suggesting that local BNP elicits protective endothelial effects. Since within the heart, BNP is mainly induced in cardiomyocytes by mechanical load, we investigated whether the natriuretic peptide/GC-A system also regulates angiogenesis accompanying load-induced cardiac hypertrophy. EC GC-A KO hearts showed diminished angiogenesis, mild fibrosis, and diastolic dysfunction. In vitro BNP/GC-A stimulated proliferation and migration of cultured microvascular endothelia by activating cGMP-dependent protein kinase I and phosphorylating vasodilator-stimulated phosphoprotein and p38 MAPK. We therefore conclude that BNP, produced by activated satellite cells within ischemic skeletal muscle or by cardiomyocytes in response to pressure load, regulates the regeneration of neighboring endothelia via GC-A. This paracrine communication might be critically involved in coordinating muscle regeneration/hypertrophy and angiogenesis. PMID:19487812

  16. Traumatic stress, oxidative stress and posttraumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may play in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. PMID:25245500

  17. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    PubMed Central

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-01-01

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID:26540040

  18. [Carbonyl stress and oxidatively modified proteins in chronic renal failure].

    PubMed

    Bargnoux, A-S; Morena, M; Badiou, S; Dupuy, A-M; Canaud, B; Cristol, J-P

    2009-01-01

    Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis. PMID:19297289

  19. Oxidative and nitrative stress in neurodegeneration.

    PubMed

    Cobb, Catherine A; Cole, Marsha P

    2015-12-01

    Aerobes require oxygen for metabolism and normal free radical formation. As a result, maintaining the redox homeostasis is essential for brain cell survival due to their high metabolic energy requirement to sustain electrochemical gradients, neurotransmitter release, and membrane lipid stability. Further, brain antioxidant levels are limited compared to other organs and less able to compensate for reactive oxygen and nitrogen species (ROS/RNS) generation which contribute oxidative/nitrative stress (OS/NS). Antioxidant treatments such as vitamin E, minocycline, and resveratrol mediate neuroprotection by prolonging the incidence of or reversing OS and NS conditions. Redox imbalance occurs when the antioxidant capacity is overwhelmed, consequently leading to activation of alternate pathways that remain quiescent under normal conditions. If OS/NS fails to lead to adaptation, tissue damage and injury ensue, resulting in cell death and/or disease. The progression of OS/NS-mediated neurodegeneration along with contributions from microglial activation, dopamine metabolism, and diabetes comprise a detailed interconnected pathway. This review proposes a significant role for OS/NS and more specifically, lipid peroxidation (LPO) and other lipid modifications, by triggering microglial activation to elicit a neuroinflammatory state potentiated by diabetes or abnormal dopamine metabolism. Subsequently, sustained stress in the neuroinflammatory state overwhelms cellular defenses and prompts neurotoxicity resulting in the onset or amplification of brain damage. PMID:26024962

  20. Chronic obstructive pulmonary disease and oxidative stress.

    PubMed

    Domej, W; Földes-Papp, Z; Flögel, E; Haditsch, B

    2006-04-01

    The respiratory tract as the main entrance for various inhalative substances has great potential to generate reactive species directly or indirectly in excess. Thus, heavy smokers are at high risk for development, impairment and failed response to treatment of chronic obstructive pulmonary disease (COPD). The article is an update regarding the influence of reactive oxygen (ROS) and nitrogen (RNS) species on COPD; however, we do not intend to describe ROS and RNS actions on the entire lung tissue. Here, we focus on the airways, because in human most of the described effects of ROS and RNS species are measured on respiratory epithelial cells obtained by bronchoscopy. ROS and RNS species are physiological compounds in cells and risk factors for several respiratory diseases. In general, both kinds of species are thermodynamically stabile, but their reaction behaviors in cellular environments are very different. For example, the life times of the superoxide anion radical range from micro/milliseconds up to minutes and even hours in in-vitro model systems. Oxidative stress by cigarette smoke was investigated in detail by the authors of this article. In addition, original studies by the authors on the amount of fine particulate matter and trace elements in lung biopsies after defined inhalation indicate a distortion of the equilibrium between oxidants and antioxidants. We also try to present some modern views with respect to genomic medicine for future therapeutic perspectives, although this is an upcoming sector of COPD therapy. PMID:16724946

  1. Correlation of Zinc with Oxidative Stress Biomarkers

    PubMed Central

    Morales-Suárez-Varela, María; Llopis-González, Agustín; González-Albert, Verónica; López-Izquierdo, Raúl; González-Manzano, Isabel; Cháves, Javier; Huerta-Biosca, Vicente; Martin-Escudero, Juan C.

    2015-01-01

    Hypertension and smoking are related with oxidative stress (OS), which in turn reports on cellular aging. Zinc is an essential element involved in an individual’s physiology. The aim of this study was to evaluate the relation of zinc levels in serum and urine with OS and cellular aging and its effect on the development of hypertension. In a Spanish sample with 1500 individuals, subjects aged 20–59 years were selected, whose zinc intake levels fell within the recommended limits. These individuals were classified according to their smoking habits and hypertensive condition. A positive correlation was found (Pearson’s C = 0.639; p = 0.01) between Zn serum/urine quotient and oxidized glutathione levels (GSSG). Finally, risk of hypertension significantly increased when the GSSG levels exceeded the 75 percentile; OR = 2.80 (95%CI = 1.09–7.18) and AOR = 3.06 (95%CI = 0.96–9.71). Low zinc levels in serum were related with OS and cellular aging and were, in turn, to be a risk factor for hypertension.  PMID:25774936

  2. Oxidative stress in atherosclerosis and diabetes.

    PubMed

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

    2005-07-01

    We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus. PMID:16254616

  3. Influence of Oxidative Stress on Stored Platelets

    PubMed Central

    2016-01-01

    Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS) is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions. PMID:26949396

  4. Testosterone and oxidative stress: the oxidation handicap hypothesis

    PubMed Central

    Alonso-Alvarez, Carlos; Bertrand, Sophie; Faivre, Bruno; Chastel, Olivier; Sorci, Gabriele

    2006-01-01

    Secondary sexual traits (SST) are usually thought to have evolved as honest signals of individual quality during mate choice. Honesty of SST is guaranteed by the cost of producing/maintaining them. In males, the expression of many SST is testosterone-dependent. The immunocompetence handicap hypothesis has been proposed as a possible mechanism ensuring honesty of SST on the basis that testosterone, in addition to its effect on sexual signals, also has an immunosuppressive effect. The immunocompetence handicap hypothesis has received mixed support. However, the cost of testosterone-based signalling is not limited to immunosuppression and might involve other physiological functions such as the antioxidant machinery. Here, we tested the hypothesis that testosterone depresses resistance to oxidative stress in a species with a testosterone-dependent sexual signal, the zebra finch. Male zebra finches received subcutaneous implants filled with flutamide (an anti-androgen) or testosterone, or kept empty (control). In agreement with the prediction, we found that red blood cell resistance to a free radical attack was the highest in males implanted with flutamide and the lowest in males implanted with testosterone. We also found that cell-mediated immune response was depressed in testosterone-treated birds, supporting the immunocompetence handicap hypothesis. The recent finding that red blood cell resistance to free radicals is negatively associated with mortality in this species suggests that benefits of sexual signalling might trade against the costs derived from oxidation. PMID:17251089

  5. Testosterone and oxidative stress: the oxidation handicap hypothesis.

    PubMed

    Alonso-Alvarez, Carlos; Bertrand, Sophie; Faivre, Bruno; Chastel, Olivier; Sorci, Gabriele

    2007-03-22

    Secondary sexual traits (SST) are usually thought to have evolved as honest signals of individual quality during mate choice. Honesty of SST is guaranteed by the cost of producing/maintaining them. In males, the expression of many SST is testosterone-dependent. The immunocompetence handicap hypothesis has been proposed as a possible mechanism ensuring honesty of SST on the basis that testosterone, in addition to its effect on sexual signals, also has an immunosuppressive effect. The immunocompetence handicap hypothesis has received mixed support. However, the cost of testosterone-based signalling is not limited to immunosuppression and might involve other physiological functions such as the antioxidant machinery. Here, we tested the hypothesis that testosterone depresses resistance to oxidative stress in a species with a testosterone-dependent sexual signal, the zebra finch. Male zebra finches received subcutaneous implants filled with flutamide (an anti-androgen) or testosterone, or kept empty (control). In agreement with the prediction, we found that red blood cell resistance to a free radical attack was the highest in males implanted with flutamide and the lowest in males implanted with testosterone. We also found that cell-mediated immune response was depressed in testosterone-treated birds, supporting the immunocompetence handicap hypothesis. The recent finding that red blood cell resistance to free radicals is negatively associated with mortality in this species suggests that benefits of sexual signalling might trade against the costs derived from oxidation. PMID:17251089

  6. Angiogenesis Assays.

    PubMed

    Nambiar, Dhanya K; Kujur, Praveen K; Singh, Rana P

    2016-01-01

    Neoangiogenesis constitutes one of the first steps of tumor progression beyond a critical size of tumor growth, which supplies a dormant mass of cancerous cells with the required nutrient supply and gaseous exchange through blood vessels essentially needed for their sustained and aggressive growth. In order to understand any biological process, it becomes imperative that we use models, which could mimic the actual biological system as closely as possible. Hence, finding the most appropriate model is always a vital part of any experimental design. Angiogenesis research has also been much affected due to lack of simple, reliable, and relevant models which could be easily quantitated. The angiogenesis models have been used extensively for studying the action of various molecules for agonist or antagonistic behaviour and associated mechanisms. Here, we have described two protocols or models which have been popularly utilized for studying angiogenic parameters. Rat aortic ring assay tends to bridge the gap between in vitro and in vivo models. The chorioallantoic membrane (CAM) assay is one of the most utilized in vivo model system for angiogenesis-related studies. The CAM is highly vascularized tissue of the avian embryo and serves as a good model to study the effects of various test compounds on neoangiogenesis. PMID:26608294

  7. Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress

    EPA Science Inventory

    Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ)induce oxidative stress by redox cycling, which generates hydrogen peroxide (H202). Cysteinylthio...

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

    PubMed

    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. PMID:27423629

  9. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  10. Antioxidant status and biomarkers of oxidative stress in canine lymphoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background – Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly-diagnosed lymphoma prior to treatm...

  11. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    SciTech Connect

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  12. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    PubMed Central

    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

  13. ROS Function in Redox Signaling and Oxidative Stress

    PubMed Central

    Schieber, Michael; Chandel, Navdeep S.

    2014-01-01

    Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS are also signaling molecules i.e. redox biology that maintain physiological functions. In this review we discuss the two faces of ROS, redox signaling and oxidative stress, and their contribution to both physiological and pathological conditions. Redox biology refers to low levels of ROS that activate signaling pathways to initiate biological processes while oxidative stress denotes high levels of ROS that incur damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis. The In this review, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions. PMID:24845678

  14. Nanoparticles, lung injury, and the role of oxidant stress.

    PubMed

    Madl, Amy K; Plummer, Laurel E; Carosino, Christopher; Pinkerton, Kent E

    2014-01-01

    The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion. PMID:24215442

  15. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology.

    PubMed

    Denu, Ryan A; Hematti, Peiman

    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

  16. Nanoparticles, Lung Injury, and the Role of Oxidant Stress

    PubMed Central

    Madl, Amy K.; Plummer, Laurel E.; Carosino, Christopher; Pinkerton, Kent E.

    2015-01-01

    The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties, which have been shown to induce inflammation and oxidative stress in biologic systems. Oxidative stress reflects the imbalance between the generation of reaction oxygen species (ROS) and the biochemical mechanisms to detoxify and repair resulting damage of reactive intermediates. This review examines current research incidental and engineered nanoparticles in terms of their health effects on the lungs and mechanisms by which oxidative stress via physicochemical characteristics influence toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review will also briefly discuss some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site specific fashion. PMID:24215442

  17. Oxidized LDL at low concentration promotes in-vitro angiogenesis and activates nitric oxide synthase through PI3K/Akt/eNOS pathway in human coronary artery endothelial cells

    SciTech Connect

    Yu, Shan; Wong, Siu Ling; Lau, Chi Wai; Huang, Yu; Yu, Cheuk-Man

    2011-04-01

    Research highlights: {yields} Low-concentration oxidized LDL enhances angiogenesis through nitric oxide (NO). {yields} Oxidized LDL increases intracellular NO levels via eNOS phosphorylation. {yields} Akt/PI3K signaling mediates oxidized LDL-induced eNOS phosphorylation. -- Abstract: It has long been considered that oxidized low-density lipoprotein (oxLDL) causes endothelial dysfunction and is remarkably related to the development of atherosclerosis. However, the effect of oxLDL at very low concentration (<10 {mu}g/ml) on the endothelial cells remains speculative. Nitric oxide (NO) has a crucial role in the endothelial cell function. In this study, we investigated the effect of oxLDL at low concentration on NO production and proliferation, migration, tube formation of the human coronary artery endothelial cells (HCAEC). Results showed that oxLDL at 5 {mu}g/ml enhanced HCAEC proliferation, migration and tube formation. These phenomena were accompanied by an increased intracellular NO production. L-NAME (a NOS inhibitor), LY294002 and wortmannin (PI3K inhibitors) could abolish oxLDL-induced angiogenic effects and prevent NO production in the HCAEC. The phosphorylation of Akt, PI3K and eNOS were up-regulated by oxLDL, which was attenuated by LY294002. Our results suggested that oxLDL at low concentration could promote in-vitro angiogenesis and activate nitric oxide synthesis through PI3K/Akt/eNOS pathway in HCAEC.

  18. Clinical Perspective of Oxidative Stress in Sporadic ALS

    PubMed Central

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  19. TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis

    PubMed Central

    Arimoto-Matsuzaki, Kyoko; Saito, Haruo; Takekawa, Mutsuhiro

    2016-01-01

    Cytoplasmic stress granules (SGs) are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of misfolded proteins, and that are formed in response to certain types of stress including ER stress. SG formation contributes to cell survival not only by suppressing translation but also by sequestering some apoptosis regulatory factors. Because cells can be exposed to various stresses simultaneously in vivo, the regulation of SG assembly under multiple stress conditions is important but unknown. Here we report that reactive oxygen species (ROS) such as H2O2 oxidize the SG-nucleating protein TIA1, thereby inhibiting SG assembly. Thus, when cells are confronted with a SG-inducing stress such as ER stress caused by protein misfolding, together with ROS-induced oxidative stress, they cannot form SGs, resulting in the promotion of apoptosis. We demonstrate that the suppression of SG formation by oxidative stress may underlie the neuronal cell death seen in neurodegenerative diseases. PMID:26738979

  20. Hypertension and physical exercise: The role of oxidative stress.

    PubMed

    Korsager Larsen, Monica; Matchkov, Vladimir V

    2016-01-01

    Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress. PMID:26987496

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

    PubMed

    Liu, Fu-Wei; Liu, Fu-Chao; Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    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. PMID:26637174

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

    PubMed Central

    Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    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. PMID:26637174

  3. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress.

    PubMed

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Chen, Ying; Jackson, Brian C; Matsumoto, Akiko; Thompson, David C; Vasiliou, Vasilis

    2013-03-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single-celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors such as dehydration and ultraviolet radiation. The ability to act as an "aldehyde scavenger" during lipid peroxidation is another ostensibly universal ALDH function found across species. Upregulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity, and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation), and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane, and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, highlighting the fundamental importance of these enzymes in physiological and pathological processes. PMID:23195683

  4. Oxidative Stress-Mediated Regulation of Proteasome Complexes*

    PubMed Central

    Aiken, Charity T.; Kaake, Robyn M.; Wang, Xiaorong; Huang, Lan

    2011-01-01

    Oxidative stress has been implicated in aging and many human diseases, notably neurodegenerative disorders and various cancers. The reactive oxygen species that are generated by aerobic metabolism and environmental stressors can chemically modify proteins and alter their biological functions. Cells possess protein repair pathways to rescue oxidized proteins and restore their functions. If these repair processes fail, oxidized proteins may become cytotoxic. Cell homeostasis and viability are therefore dependent on the removal of oxidatively damaged proteins. Numerous studies have demonstrated that the proteasome plays a pivotal role in the selective recognition and degradation of oxidized proteins. Despite extensive research, oxidative stress-triggered regulation of proteasome complexes remains poorly defined. Better understanding of molecular mechanisms underlying proteasome function in response to oxidative stress will provide a basis for developing new strategies aimed at improving cell viability and recovery as well as attenuating oxidation-induced cytotoxicity associated with aging and disease. Here we highlight recent advances in the understanding of proteasome structure and function during oxidative stress and describe how cells cope with oxidative stress through proteasome-dependent degradation pathways. PMID:21543789

  5. Tyrphostins protect neuronal cells from oxidative stress.

    PubMed

    Sagara, Yutaka; Ishige, Kumiko; Tsai, Cindy; Maher, Pamela

    2002-09-27

    Tyrphostins are a family of tyrosine kinase inhibitors originally synthesized as potential anticarcinogenic compounds. Because tyrphostins have chemical structures similar to those of the phenolic antioxidants, we decided to test the protective efficacy of tyrphostins against oxidative stress-induced nerve cell death (oxytosis). Many commercially available tyrphostins, at concentrations ranging from 0.5 to 200 microm, protect both HT-22 hippocampal cells and rat primary neurons from oxytosis brought about by treatment with glutamate, as well as by treatment with homocysteic acid and buthionine sulfoximine. The tyrphostins protect nerve cells by three distinct mechanisms. Some tyrphostins, such as A25, act as antioxidants and eliminate the reactive oxygen species that accumulate as a result of glutamate treatment. These tyrphostins also protect cells from hydrogen peroxide and act as antioxidants in an in vitro assay. In contrast, tyrphostins A9 and AG126 act as mitochondrial uncouplers, collapsing the mitochondrial membrane potential and thereby reducing the generation of reactive oxygen species from mitochondria during glutamate toxicity. Finally, the third group of tyrphostins does not appear to be effective as antioxidants but rather protects cells by increasing the basal level of cellular glutathione. Therefore, the effects of tyrphostins on cells are not limited to their ability to inhibit tyrosine kinases. PMID:12121989

  6. Effect of Oxidative Stress on Male Reproduction

    PubMed Central

    Virk, Gurpriya; Ong, Chloe; du Plessis, Stefan S

    2014-01-01

    Infertility affects approximately 15% of couples trying to conceive, and a male factor contributes to roughly half of these cases. Oxidative stress (OS) has been identified as one of the many mediators of male infertility by causing sperm dysfunction. OS is a state related to increased cellular damage triggered by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). During this process, augmented production of ROS overwhelms the body's antioxidant defenses. While small amounts of ROS are required for normal sperm functioning, disproportionate levels can negatively impact the quality of spermatozoa and impair their overall fertilizing capacity. OS has been identified as an area of great attention because ROS and their metabolites can attack DNA, lipids, and proteins; alter enzymatic systems; produce irreparable alterations; cause cell death; and ultimately, lead to a decline in the semen parameters associated with male infertility. This review highlights the mechanisms of ROS production, the physiological and pathophysiological roles of ROS in relation to the male reproductive system, and recent advances in diagnostic methods; it also explores the benefits of using antioxidants in a clinical setting. PMID:24872947

  7. Oxidative stress: the special case of diabetes.

    PubMed

    Wiernsperger, N F

    2003-01-01

    The implication of oxidative stress (OS) in diabetes is a major concern for the development of therapeutics aimed at improving the metabolic and/or vascular dysfunctions of this burdening disease. Ample evidence is available suggesting that OS is present in essentially all tissues and can even be observed in prediabetic states. This raises the question of the origin of OS and suggests that, although hyperglycemia is largely linked with free radical production, its role may mainly be the aggravation of a preexisting state. Indeed other factors are also causally linked to OS, such as hormones and lipids. The main debate is about the pertinence of antioxidant therapy since the large scale clinical trials performed recently have essentially failed to show any significant improvement in metabolic or vascular disturbances of diabetic patients. However this conclusion must be tempered by the fact that they have mainly been using vitamin E +/-C; indeed many arguments suggest that either the choice or the application modalities of these substances may have been inadequate. Potential reasons for the actual failure of antioxidant therapy in diabetes are discussed; the indisputable involvement of OS in this disease still leaves hope for alternative therapeutic approaches. PMID:14757973

  8. Aldose reductase, oxidative stress, and diabetic mellitus.

    PubMed

    Tang, Wai Ho; Martin, Kathleen A; Hwa, John

    2012-01-01

    Diabetes mellitus (DM) is a complex metabolic disorder arising from lack of insulin production or insulin resistance (Diagnosis and classification of diabetes mellitus, 2007). DM is a leading cause of morbidity and mortality in the developed world, particularly from vascular complications such as atherothrombosis in the coronary vessels. Aldose reductase (AR; ALR2; EC 1.1.1.21), a key enzyme in the polyol pathway, catalyzes nicotinamide adenosine dinucleotide phosphate-dependent reduction of glucose to sorbitol, leading to excessive accumulation of intracellular reactive oxygen species (ROS) in various tissues of DM including the heart, vasculature, neurons, eyes, and kidneys. As an example, hyperglycemia through such polyol pathway induced oxidative stress, may have dual heart actions, on coronary blood vessel (atherothrombosis) and myocardium (heart failure) leading to severe morbidity and mortality (reviewed in Heather and Clarke, 2011). In cells cultured under high glucose conditions, many studies have demonstrated similar AR-dependent increases in ROS production, confirming AR as an important factor for the pathogenesis of many diabetic complications. Moreover, recent studies have shown that AR inhibitors may be able to prevent or delay the onset of cardiovascular complications such as ischemia/reperfusion injury, atherosclerosis, and atherothrombosis. In this review, we will focus on describing pivotal roles of AR in the pathogenesis of cardiovascular diseases as well as other diabetic complications, and the potential use of AR inhibitors as an emerging therapeutic strategy in preventing DM complications. PMID:22582044

  9. Mitochondrial oxidative stress in aging and healthspan

    PubMed Central

    2014-01-01

    The free radical theory of aging proposes that reactive oxygen species (ROS)-induced accumulation of damage to cellular macromolecules is a primary driving force of aging and a major determinant of lifespan. Although this theory is one of the most popular explanations for the cause of aging, several experimental rodent models of antioxidant manipulation have failed to affect lifespan. Moreover, antioxidant supplementation clinical trials have been largely disappointing. The mitochondrial theory of aging specifies more particularly that mitochondria are both the primary sources of ROS and the primary targets of ROS damage. In addition to effects on lifespan and aging, mitochondrial ROS have been shown to play a central role in healthspan of many vital organ systems. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and dysfunction in aging and healthspan, including cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging, neurodegenerative diseases, insulin resistance and diabetes as well as age-related cancers. The crosstalk of mitochondrial ROS, redox, and other cellular signaling is briefly presented. Potential therapeutic strategies to improve mitochondrial function in aging and healthspan are reviewed, with a focus on mitochondrial protective drugs, such as the mitochondrial antioxidants MitoQ, SkQ1, and the mitochondrial protective peptide SS-31. PMID:24860647

  10. Oxidative Stress and Neurobiology of Demyelination.

    PubMed

    Ljubisavljevic, Srdjan

    2016-01-01

    Despite a large amount of research which aims at defining the pathophysiology of human demyelination (i.e., multiple sclerosis), etiological bases of disease have been unknown so far. The point of intersection of all assumed etiological factors, which are mainly based upon immunological cascades, is neuroinflammation. The precise definition of the place and role of all pathogenetic factors in the occurrence and development of the disease is of crucial importance for understanding the clinical nature and for finding more effective therapeutic options. There are few studies whose results give more precise data about the role and the importance of other factors in neuroinflammation, besides immunological ones, with regard to clinical and paraclinical correlates of the disease. The review integrates results found in previously performed studies which have evaluated oxidative stress participation in early and late neuroinflammation. The largest number of studies indicates that the use of antioxidants affects the change of neuroinflammation course under experimental conditions, which is reflected in the reduction of the severity and the total reversibility in clinical presentation of the disease, the faster achieving of remission, and the delayed and slow course of neuroinflammation. Therapies based on the knowledge of redox biology targeting free radical generation hold great promise in modulation of the neuroinflammation and its clinical presentations. PMID:25502298

  11. Effect of thyroid hormone-nitric oxide interaction on tumor growth, angiogenesis, and aminopeptidase activity in mice.

    PubMed

    Carmona-Cortés, Javier; Rodríguez-Gómez, Isabel; Wangensteen, Rosemary; Banegas, Inmaculada; García-Lora, Ángel M; Quesada, Andrés; Osuna, Antonio; Vargas, Félix

    2014-06-01

    This study evaluated the effects of thyroid hormone-NO interaction on tumor development, vascularization, vascular endothelial growth factor (VEGF), and aminopeptidase (AP) activity in a murine model of implanted Lewis's carcinoma. Experiments were performed in male CBA-C57 mice. Animals were untreated (controls) or treated with: T4, the antithyroid drug methimazole, the NO inhibitor L-NAME, T4+L-NAME, methimazole+NAME, the αvß3 integrin antagonist tetrac, T4+tetrac, the iNOS inhibitor aminoguanidine (AG), and T4 + AG; all treatments were for 6 weeks except for tetrac, administered for the last 11 days. Mice were subcutaneously inoculated with 1 × 10(6) exponentially growing Lewis carcinoma 3LL cells into the dorsum. Study variables 9 days later were tumor weight (TW), Hb content, an index of tumor vascularization, VEGF, and AP activity. T4 produced parallel increases in TW and angiogenesis. L-NAME reduced TW and angiogenesis in control, hyperthyroid, and hypothyroid mice, whereas AG had no effect on these variables. Tetrac arrested TW in normal and T4-treated mice but did not decrease angiogenesis in T4-treated animals. Negative correlations were found between TW and AP activity in tumors from control hyper- and hypothyroid groups and an inverse relationship was observed between TW and AP activities in tetrac-treated mice. T4 enhances TW and angiogenesis, in which NO participates, but requires activation of integrin αvß3 to promote carcinogenesis. NO blockade reduces TW, regardless of the thyroid status. Thyroid hormone negatively modulates AP activity in the tumor. Accordingly, blockade of the membrane TH receptor αvß3 integrin reduces TW associated with an increase in AP activity. PMID:24549786

  12. Boolean modeling and fault diagnosis in oxidative stress response

    PubMed Central

    2012-01-01

    Background Oxidative stress is a consequence of normal and abnormal cellular metabolism and is linked to the development of human diseases. The effective functioning of the pathway responding to oxidative stress protects the cellular DNA against oxidative damage; conversely the failure of the oxidative stress response mechanism can induce aberrant cellular behavior leading to diseases such as neurodegenerative disorders and cancer. Thus, understanding the normal signaling present in oxidative stress response pathways and determining possible signaling alterations leading to disease could provide us with useful pointers for therapeutic purposes. Using knowledge of oxidative stress response pathways from the literature, we developed a Boolean network model whose simulated behavior is consistent with earlier experimental observations from the literature. Concatenating the oxidative stress response pathways with the PI3-Kinase-Akt pathway, the oxidative stress is linked to the phenotype of apoptosis, once again through a Boolean network model. Furthermore, we present an approach for pinpointing possible fault locations by using temporal variations in the oxidative stress input and observing the resulting deviations in the apoptotic signature from the normally predicted pathway. Such an approach could potentially form the basis for designing more effective combination therapies against complex diseases such as cancer. Results In this paper, we have developed a Boolean network model for the oxidative stress response. This model was developed based on pathway information from the current literature pertaining to oxidative stress. Where applicable, the behaviour predicted by the model is in agreement with experimental observations from the published literature. We have also linked the oxidative stress response to the phenomenon of apoptosis via the PI3k/Akt pathway. Conclusions It is our hope that some of the additional predictions here, such as those pertaining to the

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

    PubMed Central

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    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. PMID:26763544

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

    PubMed

    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. PMID:26851532

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

    PubMed

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    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. PMID:26763544

  16. Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

    PubMed Central

    Jaquet, Vincent; Trabace, Luigia; Krause, Karl-Heinz

    2013-01-01

    Abstract Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues. Antioxid. Redox Signal. 18, 1475–1490. PMID:22746161

  17. The Role of Flavonoids on Oxidative Stress in Epilepsy

    PubMed Central

    Diniz, Tâmara Coimbra; Silva, Juliane Cabral; de Lima-Saraiva, Sarah Raquel Gomes; Ribeiro, Fernanda Pires Rodrigues de Almeida; Pacheco, Alessandra Gomes Marques; de Freitas, Rivelilson Mendes; Quintans-Júnior, Lucindo José; Quintans, Jullyana de Souza Siqueira; Mendes, Rosemairy Luciane; Almeida, Jackson Roberto Guedes da Silva

    2015-01-01

    Backgrounds. Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. Objective. This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. Results/Conclusions. There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy. PMID:25653736

  18. Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans.

    PubMed

    Crombie, Timothy A; Tang, Lanlan; Choe, Keith P; Julian, David

    2016-07-15

    It has long been recognized that simultaneous exposure to heat stress and oxidative stress shows a synergistic interaction that reduces organismal fitness, but relatively little is known about the mechanisms underlying this interaction. We investigated the role of molecular stress responses in driving this synergistic interaction using the nematode Caenorhabditis elegans To induce oxidative stress, we used the pro-oxidant compounds acrylamide, paraquat and juglone. As expected, we found that heat stress and oxidative stress interact synergistically to reduce survival. Compared with exposure to each stressor alone, during simultaneous sublethal exposure to heat stress and oxidative stress the normal induction of key oxidative-stress response (OxSR) genes was generally inhibited, whereas the induction of key heat-shock response (HSR) genes was not. Genetically activating the SKN-1-dependent OxSR increased a marker for protein aggregation and decreased whole-worm survival during heat stress alone, with the latter being independent of HSF-1. In contrast, compared with wild-type worms, inactivating the HSR by HSF-1 knockdown, which would be expected to decrease basal heat shock protein expression, increased survival during oxidative stress alone. Taken together, these data suggest that, in C. elegans, the HSR and OxSR cannot be simultaneously activated to the same extent that each can be activated during a single stressor exposure. We conclude that the observed synergistic reduction in survival during combined exposure to heat stress and oxidative stress is due, at least in part, to inhibition of the OxSR during activation of the HSR. PMID:27207646

  19. Protective mechanisms of Cucumis sativus in diabetes-related modelsof oxidative stress and carbonyl stress

    PubMed Central

    Heidari, Himan; Kamalinejad, Mohammad; Noubarani, Maryam; Rahmati, Mokhtar; Jafarian, Iman; Adiban, Hasan; Eskandari, Mohammad Reza

    2016-01-01

    Introduction: Oxidative stress and carbonyl stress have essential mediatory roles in the development of diabetes and its related complications through increasing free radicals production and impairing antioxidant defense systems. Different chemical and natural compounds have been suggested for decreasing such disorders associated with diabetes. The objectives of the present study were to investigate the protective effects of Cucumis sativus (C. sativus) fruit (cucumber) in oxidative and carbonyl stress models. These diabetes-related models with overproduction of reactive oxygen species (ROS) and reactive carbonyl species (RCS) simulate conditions observed in chronic hyperglycemia. Methods: Cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonyl stress model) were measured and the protective effects of C. sativus were evaluated using freshly isolated rat hepatocytes. Results: Aqueous extract of C. sativus fruit (40 μg/mL) prevented all cytotoxicity markers in both the oxidative and carbonyl stress models including cell lysis, ROS formation, membrane lipid peroxidation, depletion of glutathione, mitochondrial membrane potential decline, lysosomal labialization, and proteolysis. The extract also protected hepatocytes from protein carbonylation induced by glyoxal. Our results indicated that C. sativus is able to prevent oxidative stress and carbonyl stress in the isolated hepatocytes. Conclusion: It can be concluded that C. sativus has protective effects in diabetes complications and can be considered a safe and suitable candidate for decreasing the oxidative stress and carbonyl stress that is typically observed in diabetes mellitus. PMID:27340622

  20. Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

    PubMed

    Zimmer, Cédric; Spencer, Karen A

    2015-05-01

    Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. PMID:25542633

  1. Increased oxidative stress in foam cells obtained from hemodialysis patients.

    PubMed

    Gonçalves, Marlene S B; Fabris, Bruno A; Brinholi, Francis F; Bortolasci, Chiara C; Watanabe, Maria A E; Oliveira, Karen B; Delfino, Vinícius D A; Lavado, Edson L; Barbosa, Décio S

    2013-04-01

    Premature atherosclerosis represents the main cause of mortality among end-stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor-α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by-products were measured in the supernatants of macrophage-derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by-products, inducible nitric oxide synthase activity, and tumor necrosis factor-α between patients and controls. Our results, obtained with human macrophages and macrophage-derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions. PMID:22928784

  2. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

    PubMed Central

    Satapati, Santhosh; Kucejova, Blanka; Duarte, Joao A.G.; Fletcher, Justin A.; Reynolds, Lacy; Sunny, Nishanth E.; He, Tianteng; Nair, L. Arya; Livingston, Kenneth; Fu, Xiaorong; Merritt, Matthew E.; Sherry, A. Dean; Malloy, Craig R.; Shelton, John M.; Lambert, Jennifer; Parks, Elizabeth J.; Corbin, Ian; Magnuson, Mark A.; Browning, Jeffrey D.; Burgess, Shawn C.

    2015-01-01

    Mitochondria are critical for respiration in all tissues; however, in liver, these organelles also accommodate high-capacity anaplerotic/cataplerotic pathways that are essential to gluconeogenesis and other biosynthetic activities. During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance. Here, we provide several lines of evidence indicating that induction of biosynthesis through hepatic anaplerotic/cataplerotic pathways is energetically backed by elevated oxidative metabolism and hence contributes to oxidative stress and inflammation during NAFLD. First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid–induced rise in oxidative flux, oxidative stress, and inflammation. Flux appeared to be regulated by redox state, energy charge, and metabolite concentration, which may also amplify antioxidant pathways. Third, preventing elevated oxidative metabolism with metformin also normalized hepatic anaplerosis/cataplerosis and reduced markers of inflammation. Finally, independent histological grades in human NAFLD biopsies were proportional to oxidative flux. Thus, hepatic oxidative stress and inflammation are associated with elevated oxidative metabolism during an obesogenic diet, and this link may be provoked by increased work through anabolic pathways. PMID:26571396

  3. Oxidative stress induces senescence in human mesenchymal stem cells

    SciTech Connect

    Brandl, Anita; Meyer, Matthias; Bechmann, Volker; Nerlich, Michael; Angele, Peter

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  4. Macrophage Migration Inhibitory Factor Secretion Is Induced by Ionizing Radiation and Oxidative Stress in Cancer Cells

    PubMed Central

    Du, Weinan; Welford, Scott M.

    2016-01-01

    The macrophage migration inhibitory factor (MIF) has been increasingly implicated in cancer development and progression by promoting inflammation, angiogenesis, tumor cell survival and immune suppression. MIF is overexpressed in a variety of solid tumor types in part due to its responsiveness to hypoxia inducible factor (HIF) driven transcriptional activation. MIF secretion, however, is a poorly understood process owing to the fact that MIF is a leaderless polypeptide that follows a non-classical secretory pathway. Better understanding of MIF processing and release could have therapeutic implications. Here, we have discovered that ionizing radiation (IR) and other DNA damaging stresses can induce robust MIF secretion in several cancer cell lines. MIF secretion by IR appears independent of ABCA1, a cholesterol efflux pump that has been implicated previously in MIF secretion. However, MIF secretion is robustly induced by oxidative stress. Importantly, MIF secretion can be observed both in cell culture models as well as in tumors in mice in vivo. Rapid depletion of MIF from tumor cells observed immunohistochemically is coincident with elevated circulating MIF detected in the blood sera of irradiated mice. Given the robust tumor promoting activities of MIF, our results suggest that an innate host response to genotoxic stress may mitigate the beneficial effects of cancer therapy, and that MIF inhibition may improve therapeutic responses. PMID:26741693

  5. Oxidized Extracellular DNA as a Stress Signal in Human Cells

    PubMed Central

    Ermakov, Aleksei V.; Konkova, Marina S.; Kostyuk, Svetlana V.; Izevskaya, Vera L.; Veiko, Natalya N.

    2013-01-01

    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. PMID:23533696

  6. Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?

    PubMed Central

    Al-Smadi, Ahmed Mohammad; Ashour, Ala Fawzi; Al-Awaida, Wajdy

    2016-01-01

    Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Results Although stress and anxiety were correlated. No significant correlation exists between salivary nitrate and daily psychological stress and anxiety in the study's participants. Conclusion While all previous studies focused NOx levels in acute stress models. This is the first study to investigate the correlation between salivary nitrates and daily psychological stress and anxiety. Although stress and anxiety were correlated, there is no correlation between salivary nitrates and daily psychological stress and anxiety. Further studies are required to investigate this correlation using other biological samples such as plasma. PMID:27247597

  7. Oxidative stress in juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum)

    USGS Publications Warehouse

    Welker, T.L.; Congleton, J.L.

    2004-01-01

    Juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum), were held in 8-11??C freshwater, starved for 3 days and subjected to a low-water stressor to determine the relationship between the general stress response and oxidative stress. Lipid peroxidation (LPO) levels (lipid hydroperoxides) were measured in kidney, liver and brain samples taken at the beginning of the experiment (0-h unstressed controls) and at 6, 24 and 48 h after application of a continuous low-water stressor. Tissue samples were also taken at 48 h from fish that had not been exposed to the stressor (48-h unstressed controls). Exposure to the low-water stressor affected LPO in kidney and brain tissues. In kidney, LPO decreased 6 h after imposition of the stressor; similar but less pronounced decreases also occurred in the liver and brain. At 48 h, LPO increased (in comparison with 6-h stressed tissues) in the kidney and brain. In comparison with 48-h unstressed controls, LPO levels were higher in the kidney and brain of stressed fish. Although preliminary, results suggest that stress can cause oxidative tissue damage in juvenile chinook salmon. Measures of oxidative stress have shown similar responses to stress in mammals; however, further research is needed to determine the extent of the stress-oxidative stress relationship and the underlying physiological mechanisms in fish.

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

    PubMed Central

    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

  9. Role of sulfiredoxin in systemic diseases influenced by oxidative stress

    PubMed Central

    Ramesh, Asha; Varghese, Sheeja S.; Doraiswamy, Jayakumar; Malaiappan, Sankari

    2014-01-01

    Sulfiredoxin is a recently discovered member of the oxidoreductases family which plays a crucial role in thiol homoeostasis when under oxidative stress. A myriad of systemic disorders have oxidative stress and reactive oxygen species as the key components in their etiopathogenesis. Recent studies have evaluated the role of this enzyme in oxidative stress mediated diseases such as atherosclerosis, chronic obstructive pulmonary disease and a wide array of carcinomas. Its action is responsible for the normal functioning of cells under oxidative stress and the promotion of cell survival in cancerous cells. This review will highlight the cumulative effects of sulfiredoxin in various systemic disorders with a strong emphasis on its target activity and the factors influencing its expression in such conditions. PMID:25460739

  10. OXIDATIVE STRESS STATUS IN HUMANS WITH METABOLIC SYNDROME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Each component of the constellation of Metabolic Syndrome signs - dyslipidemia, hyperglycemia, hypertension, and obesity - has been associated, though not unequivocally, with an elevation of oxidative stress. Moreover, reductions in these conditions appear generally associated with attenuation of b...

  11. The Role of Oxidative Stress in Neurodegenerative Diseases

    PubMed Central

    Kim, Geon Ha; Kim, Jieun E.; Rhie, Sandy Jeong

    2015-01-01

    Oxidative stress is induced by an imbalanced redox states, involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system. The brain is one of organs especially vulnerable to the effects of ROS because of its high oxygen demand and its abundance of peroxidation-susceptible lipid cells. Previous studies have demonstrated that oxidative stress plays a central role in a common pathophysiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases, although the results with regard to their efficacy of treating neurodegenerative disease have been inconsistent. In this review, we will discuss the role of oxidative stress in the pathophysiology of neurodegenerative diseases and in vivo measurement of an index of damage by oxidative stress. Moreover, the present knowledge on antioxidant in the treatment of neurodegenerative diseases and future directions will be outlined. PMID:26713080

  12. Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition.

    PubMed

    Yu, Su Jong; Yoon, Jung-Hwan; Yang, Jong-In; Cho, Eun Ju; Kwak, Min Sun; Jang, Eun Sun; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Hyo-Suk; Kim, Chung Yong

    2012-02-01

    3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs. PMID:22350012

  13. Introduction to Oxidative Stress in Biomedical and Biological Research

    PubMed Central

    Breitenbach, Michael; Eckl, Peter

    2015-01-01

    Oxidative stress is now a well-researched area with thousands of new articles appearing every year. We want to give the reader here an overview of the topics in biomedical and basic oxidative stress research which are covered by the authors of this thematic issue. We also want to give the newcomer a short introduction into some of the basic concepts, definitions and analytical procedures used in this field. PMID:26117854

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

    PubMed

    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. PMID:27185188

  15. Ubiquitin-proteasome pathway and cellular responses to oxidative stress

    PubMed Central

    Taylor, Allen

    2011-01-01

    The ubiquitin-proteasome pathway (UPP) is the primary cytosolic proteolytic machinery for the selective degradation of various forms of damaged proteins. Thus, the UPP is an important protein quality control mechanism. In the canonical UPP, both ubiquitin and the 26S proteasome are involved. Substrate proteins of the canonical UPP are first tagged by multiple ubiquitin molecules and then degraded by the 26S proteasome. However, in non-canonical UPP, proteins can be degraded by the 26S or the 20S proteasome without being ubiquitinated. It is clear that a proteasome is responsible for selective degradation of oxidized proteins, but the extent to which ubiquitination is involved in this process remains a subject of debate. While many publications suggest that the 20S proteasome degrades oxidized proteins independent of ubiquitin, there is also solid evidence indicating that ubiquitin and ubiquitination are involved in degradation of some forms of oxidized proteins. A fully functional UPP is required for cells to cope with oxidative stress and the activity of the UPP is also modulated by cellular redox status. Mild or transient oxidative stress up-regulates the ubiquitination system and proteasome activity in cells and tissues and transiently enhances intracellular proteolysis. Severe or sustained oxidative stress impairs the function of the UPP and decreases intracellular proteolysis. Both the ubiquitin conjugation enzymes and the proteasome can be inactivated by sustained oxidative stress, especially the 26S proteasome. Differential susceptibilities of the ubiquitin conjugation enzymes and the 26S proteasome to oxidative damage lead to an accumulation of ubiquitin conjugates in cells in response to mild oxidative stress. Thus, increased levels of ubiquitin conjugates in cells appear to be an indicator of mild oxidative stress. PMID:21530648

  16. Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

    PubMed Central

    Fournier, Margot; Ferrari, Carina; Baumann, Philipp S.; Polari, Andrea; Monin, Aline; Bellier-Teichmann, Tanja; Wulff, Jacob; Pappan, Kirk L.; Cuenod, Michel; Conus, Philippe; Do, Kim Q.

    2014-01-01

    Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients’ fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors. PMID:24687046

  17. Oxidative Stress in Niemann-Pick Disease, Type C

    PubMed Central

    Fu, Rao; Yanjanin, Nicole M.; Bianconi, Simona; Pavan, William J.; Porter, Forbes D.

    2010-01-01

    Niemann-Pick Disease, type C (NPC) is a neurodegenerative lysosomal storage disorder due to impaired intracellular cholesterol and lipid transport. Increased oxidative stress has been reported in human NPC1 mutant fibroblasts and in tissues from Npc1 mutant mice. However, oxidative stress in NPC patients has not been established. In this study, we demonstrated increased oxidative stress in NPC patients. Evaluation of serum from 37 NPC patients, compared to control values, showed significant decreases (p<0.01) in both the fraction of reduced coenzyme Q10 (CoQ10) and trolox equivalent antioxidant capacity (TEAC). Both findings are consistent with increased oxidative stress in NPC. Supplementation with CoQ10 was not effective in correcting the decreased fraction of reduced CoQ10. Increased oxidative stress may be a contributing factor to the pathology of NPC, and demonstration of increased oxidative stress in NPC patients provides both a rationale and the biomarkers necessary to test the efficacy of antioxidant therapy in NPC. PMID:20667755

  18. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.

    PubMed

    Sanchez-Padilla, Javier; Guzman, Jaime N; Ilijic, Ema; Kondapalli, Jyothisri; Galtieri, Daniel J; Yang, Ben; Schieber, Simon; Oertel, Wolfgang; Wokosin, David; Schumacker, Paul T; Surmeier, D James

    2014-06-01

    Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approaches in ex vivo mouse brain slices. We found that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca(2+) concentration that were attributable to the opening of L-type Ca(2+) channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide increased the spike rate but differentially affected mitochondrial oxidant stress. Oxidant stress was also increased in an animal model of PD. Thus, our results point to activity-dependent Ca(2+) entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  19. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase

    PubMed Central

    Sanchez–Padilla, J.; Guzman, J.N.; Ilijic, E.; Kondapalli, J.; Galtieri, D.J.; Yang, B.; Schieber, S.; Oertel, W.; Wokosin, D.; Schumacker, P. T.; Surmeier, D. J.

    2014-01-01

    Summary Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging–related neurodegenerative diseases, like Parkinson’s disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, LC neurons were studied using electrophysiological and optical approaches in ex vivo mouse brain slices. These studies revealed that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca2+ concentration attributable to opening of L–type Ca2+ channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide, each increased the spike rate, but differentially affected mitochondrial oxidant stress. Oxidant stress also was increased in an animal model of PD. Thus, our results point to activity–dependent Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  20. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide.

    PubMed

    Ozgocmen, Salih; Ozyurt, Huseyin; Sogut, Sadik; Akyol, Omer

    2006-05-01

    Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder. PMID:16328420

  1. Oxidation stress evolution and relaxation of oxide film/metal substrate system

    NASA Astrophysics Data System (ADS)

    Dong, Xuelin; Feng, Xue; Hwang, Keh-Chih

    2012-07-01

    Stresses in the oxide film/metal substrate system are crucial to the reliability of the system at high temperature. Two models for predicting the stress evolution during isothermal oxidation are proposed. The deformation of the system is depicted by the curvature for single surface oxidation. The creep strain of the oxide and metal, and the lateral growth strain of the oxide are considered. The proposed models are compared with the experimental results in literature, which demonstrates that the elastic model only considering for elastic strain gives an overestimated stress in magnitude, but the creep model is consistent with the experimental data and captures the stress relaxation phenomenon during oxidation. The effects of the parameter for the lateral growth strain rate are also analyzed.

  2. Oxidative stress: new approaches to diagnosis and prognosis in atherosclerosis.

    PubMed

    Heinecke, Jay W

    2003-02-01

    Oxidative modifications of low-density lipoprotein (LDL) have been proposed to play a critical role in atherogenesis. To test the role of proposed antioxidants in inhibiting LDL oxidation and vascular disease, it is important to identify the biologically relevant sources of oxidative stress in the human arterial wall. Mass spectrometric (MS) quantification of oxidized amino acids in proteins was used as a "molecular fingerprint" to identify the pathways that inflict oxidative damage in vivo. For example, myeloperoxidase is expressed in macrophages in human atherosclerotic lesions, and immunohistochemical studies suggest that it might be a pathway for LDL oxidation. We found that hypochlorous acid, tyrosyl radical, and reactive nitrogen species generated by myeloperoxidase each yielded a unique pattern of protein oxidation products in vitro. MS analysis of human atherosclerotic tissue revealed a similar pattern of oxidation products. This strategy has pinpointed myeloperoxidase as a pathway that promotes LDL oxidation in the human artery wall. It is noteworthy that vitamin E fails to inhibit LDL oxidation by myeloperoxidase in vitro. Because the utility of an antioxidant depends critically on the nature of the oxidant that inflicts tissue damage, interventions that specifically inhibit physiologically relevant pathways would be logical candidates for clinical trials of antioxidants. Such a rational approach to therapy is likely to accelerate progress against oxidative stress and coronary artery disease. PMID:12645639

  3. Infrared Dielectric Properties of Low-Stress Silicon Oxide

    NASA Technical Reports Server (NTRS)

    Cataldo, Giuseppe; Wollack, Edward J.; Brown, Ari D.; Miller, Kevin H.

    2016-01-01

    Silicon oxide thin films play an important role in the realization of optical coatings and high-performance electrical circuits. Estimates of the dielectric function in the far- and mid-infrared regime are derived from the observed transmittance spectrum for a commonly employed low-stress silicon oxide formulation. The experimental, modeling, and numerical methods used to extract the dielectric function are presented.

  4. Residual stress distribution in oxide films formed on Zircaloy-2

    NASA Astrophysics Data System (ADS)

    Sawabe, T.; Sonoda, T.; Furuya, M.; Kitajima, S.; Takano, H.

    2015-11-01

    In order to evaluate residual the stress distribution in oxides formed on zirconium alloys, synchrotron X-ray diffraction (XRD) was performed on the oxides formed on Zircaloy-2 after autoclave treatment at a temperature of 360° C in pure water. The use of a micro-beam XRD and a micro-sized cross-sectional sample achieved the detailed local characterization of the oxides. The oxide microstructure was observed by TEM following the micro-beam XRD measurements. The residual compressive stress increased in the vicinity of the oxide/metal interface of the pre-transition oxide. Highly oriented columnar grains of a monoclinic phase were observed in that region. Furthermore, at the interface of the post-first transition oxide, there was only a small increase in the residual compressive stress and the columnar grains had a more random orientation. The volume fraction of the tetragonal phase increased with the residual compressive stress. The results are discussed in terms of the formation and transition of the protective oxide.

  5. ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA.

    EPA Science Inventory

    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...

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

    EPA Science Inventory

    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...

  7. 99mTc-Labeled Iron Oxide Nanoparticles for Dual-Contrast (T1/T2) Magnetic Resonance and Dual-Modality Imaging of Tumor Angiogenesis.

    PubMed

    Xue, Sihan; Zhang, Chunfu; Yang, Yi; Zhang, Lu; Cheng, Dengfeng; Zhang, Jianping; Shi, Hongcheng; Zhang, Yingjian

    2015-06-01

    Multi functional probes possessing magnetic resonance imaging and single-photon emission computed tomography properties are favorable for the molecular imaging of cancers. In this study, ultra small super paramagnetic iron oxide nanoparticles, about 3.5 nm in size, were synthesized by the polyol method. The particles were functionalized using c(RGDyC) peptides and labeled with 99mTc to prepare molecular imaging probes for detecting tumor angiogenesis. The probes demonstrated good T1 (r1 = 8.2 s(-1) mM(-1)) and reasonable T2 contrast effects (r2 = 20.1 s(-1) mM(-1)) and could specifically target avβ3-positive cells, inducing more cell ingestion, unlike that in case of the control probes [functionalized with scrambled c(RADyC) peptides]. After the probes were injected into the mice bearing H1299 lung tumors, T1/T2-weighted magnetic resonance imaging and single-photon emission computed tomography revealed that they addressed tumor angiogenic vessels, which were distributed mainly in the peripheral region of tumors. Biodistribution studies indicated that tumor accumulation of the probes was significant [13.8 ± 9.6%ID/g (p < 0.01), which is more than that of the control probes, 4.5 ± 1.9%ID/g], and could be inhibited by free RGD peptides (6.0 ± 2.8%ID/g, p < 0.01). Our study demonstrated that the dual-contrast (T1/T2) magnetic resonance and dual-modal imaging probe based on ultra small superparamagnetic iron oxide nanoparticles is very promising for the molecular imaging of tumor angiogenesis. PMID:26353592

  8. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease.

    PubMed

    Mota, Sandra I; Costa, Rui O; Ferreira, Ildete L; Santana, Isabel; Caldeira, Gladys L; Padovano, Carmela; Fonseca, Ana C; Baldeiras, Inês; Cunha, Catarina; Letra, Liliana; Oliveira, Catarina R; Pereira, Cláudia M F; Rego, Ana Cristina

    2015-07-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells. PMID:25857617

  9. Metallothionein Alleviates Oxidative Stress-Induced Endoplasmic Reticulum Stress and Myocardial Dysfunction

    PubMed Central

    Guo, Rui; Ma, Heng; Gao, Feng; Zhong, Li; Ren, Jun

    2009-01-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been implicated in cardiovascular diseases although the interplay between the two is not clear. This study was designed to examine the influence of oxidative stress through glutathione depletion on myocardial ER stress and contractile function in the absence or presence of the heavy metal scavenger antioxidant metallothionein (MT). FVB and MT overexpression transgenic mice received the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM) in drinking water for 2 weeks. Oxidative stress, ER stress, apoptosis, cardiac function and ultrastructure were assessed using GSH/GSSG assay, reactive oxygen species (ROS), immunoblotting, caspase-3 activity, Langendorff perfused heart function (LVDP and ± dP/dt), and transmission electron microscopy. BSO led to a robust decrease in the GSH/GSSG ratio and increased ROS production, consolidating oxidative stress. Cardiac function and ultrastructure were compromised following BSO treatment, the effect of which was obliterated by MT. BSO promoted overt ER stress as evidenced by upregulated BiP, calregulin, phospho-IRE1α and phospho-eIF2α without affecting total IRE1α and eIF2α. BSO treatment led to apoptosis manifested as elevated expression of CHOP/GADD153, caspase-12 and Bax as well as caspase-3 activity, reduced Bcl-2 expression and JNK phosphorylation, all of which was ablated by MT. Moreover, both antioxidant N-acetylcysteine and the ER stress inhibitor tauroursodeoxycholic acid reversed the oxidative stress inducer menadione-elicited depression in cardiomyocyte contractile function. Taken together, these data suggested that ER stress occurs likely downstream of oxidative stress en route to cardiac dysfunction. PMID:19344729

  10. Oxidative stress contributes to autophagy induction in response to endoplasmic reticulum stress in Chlamydomonas reinhardtii.

    PubMed

    Pérez-Martín, Marta; Pérez-Pérez, María Esther; Lemaire, Stéphane D; Crespo, José L

    2014-10-01

    The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes. PMID:25143584

  11. Oxidative stress in β-thalassaemia and sickle cell disease.

    PubMed

    Voskou, S; Aslan, M; Fanis, P; Phylactides, M; Kleanthous, M

    2015-12-01

    Sickle cell disease and β-thalassaemia are inherited haemoglobinopathies resulting in structural and quantitative changes in the β-globin chain. These changes lead to instability of the generated haemoglobin or to globin chain imbalance, which in turn impact the oxidative environment both intracellularly and extracellularly. The ensuing oxidative stress and the inability of the body to adequately overcome it are, to a large extent, responsible for the pathophysiology of these diseases. This article provides an overview of the main players and control mechanisms involved in the establishment of oxidative stress in these haemoglobinopathies. PMID:26285072

  12. Oxidative stress in β-thalassaemia and sickle cell disease

    PubMed Central

    Voskou, S.; Aslan, M.; Fanis, P.; Phylactides, M.; Kleanthous, M.

    2015-01-01

    Sickle cell disease and β-thalassaemia are inherited haemoglobinopathies resulting in structural and quantitative changes in the β-globin chain. These changes lead to instability of the generated haemoglobin or to globin chain imbalance, which in turn impact the oxidative environment both intracellularly and extracellularly. The ensuing oxidative stress and the inability of the body to adequately overcome it are, to a large extent, responsible for the pathophysiology of these diseases. This article provides an overview of the main players and control mechanisms involved in the establishment of oxidative stress in these haemoglobinopathies. PMID:26285072

  13. Oxidative stress and autophagy: Crucial modulators of kidney injury

    PubMed Central

    Sureshbabu, Angara; Ryter, Stefan W.; Choi, Mary E.

    2015-01-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) that lead to diminished kidney function are interdependent risk factors for increased mortality. If untreated over time, end stage renal disease (ESRD) is an inevitable outcome. Acute and chronic kidney diseases occur partly due to imbalance between the molecular mechanisms that govern oxidative stress, inflammation, autophagy and cell death. Oxidative stress refers to the cumulative effects of highly reactive oxidizing molecules that cause cellular damage. Autophagy removes damaged organelles, protein aggregates and pathogens by recruiting these substrates into double membrane vesicles called autophagosomes which subsequently fuse with lysosomes. Mounting evidence suggests that both oxidative stress and autophagy are significantly involved in kidney health and disease. However, very little is known about the signaling processes that link them. This review is focused on understanding the role of oxidative stress and autophagy in kidney diseases. In this review, we also discuss the potential relationships between oxidative stress and autophagy that may enable the development of better therapeutic intervention to halt the progression of kidney disease and promote its repair and resolution. PMID:25613291

  14. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  15. Heat Stress and Hormetin-Induced Hormesis in Human Cells: Effects on Aging, Wound Healing, Angiogenesis, and Differentiation

    PubMed Central

    Rattan, Suresh I. S.; Fernandes, Ricardo A.; Demirovic, Dino; Dymek, Barbara; Lima, Cristovao F.

    2009-01-01

    Accumulation of molecular damage and increased molecular heterogeneity are hallmarks of cellular aging. Mild stress-induced hormesis can be an effective way for reducing the accumulation of molecular damage, and thus slowing down aging from within. We have shown that repeated mild heat stress (RMHS) has anti-aging effects on growth and various other cellular and biochemical characteristics of normal human skin fibroblasts and keratinocytes undergoing aging in vitro. RMHS given to human cells increased the basal levels of various chaperones, reduced the accumulation of damaged proteins, stimulated proteasomal activities, increased the cellular resistance to other stresses, enhanced the levels of various antioxidant enzymes, enhanced the activity and amounts of sodium-potassium pump, and increased the phosphorylation-mediated activities of various stress kinases. We have now observed novel hormetic effects of mild heat stress on improving the wound healing capacity of skin fibroblasts and on enhancing the angiogenic ability of endothelial cells. We have also tested potential hormetins, such as curcumin and rosmarinic acid in bringing about their beneficial effects in human cells by inducing stress response pathways involving heat shock proteins and hemeoxygenase HO-1. These data further support the view that mild stress-induced hormesis can be applied for the modulation, intervention and prevention of aging and age-related impairments. PMID:19343114

  16. Stressed Oxidation of C/SiC Composites

    NASA Technical Reports Server (NTRS)

    Halbig, Michael C.; Brewer, David N.; Eckel, Andrew J.; Cawley, James D.

    1997-01-01

    Constant load, stressed oxidation testing was performed on T-300 C/SiC composites with a SiC seal coat. Test conditions included temperatures ranging from 350 C to 1500 C at stresses of 69 MPa and 172 MPa (10 and 25 ksi). The coupon subjected to stressed oxidation at 550 C/69 MPa for 25 hours had a room temperature residual strength one-half that of the as-received coupons. The coupon tested at the higher stress and all coupons tested at higher temperatures failed in less than 25 hr. Microstructural analysis of the fracture surfaces, using SEM (scanning electron microscopy), revealed the formation of reduced cross-sectional fibers with pointed tips. Analysis of composite cross-sections show pathways for oxygen ingress. The discussion will focus on fiber/matrix interphase oxidation and debonding as well as the formation and implications of the fiber tip morphology.

  17. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    PubMed

    Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

    2011-01-01

    Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. PMID:21422516

  18. General approach on chemistry and stress coupling effects during oxidation

    NASA Astrophysics Data System (ADS)

    Suo, Yaohong; Shen, Shengping

    2013-10-01

    In this paper, the mechanism of growth strain is discussed based on the irreversible evolving equations by considering the coupling effects of stress and chemical reaction during isothermal oxidation, and a simple model relating the growth strain and the oxide thickness is developed. If the effect of the stress on the chemical reaction is not taken into account, the model reduces to the Clarke assumption. The expression of Dox is exhibited, and its value can be determined by experiments. The stress evolving equations are derived, where the viscoplastic strain of the oxide and metal and the growth strain of the oxide are considered. Numerical results are given and compared with results from experiments and the existing model. There is good agreement between the proposed model and the experimental data.

  19. Markers of Oxidative Stress and Neuroprogression in Depression Disorder

    PubMed Central

    Vaváková, Magdaléna; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. PMID:26078821

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

    PubMed Central

    Tangvarasittichai, Surapon

    2015-01-01

    Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. PMID:25897356

  1. Retinopathy of prematurity: an oxidative stress neonatal disease.

    PubMed

    Stone, William L; Shah, Darshan; Hollinger, Shawn M

    2016-01-01

    Proteomics is the global study of proteins in an organism or a tissue/fluid and is clinically relevant since most disease states are accompanied by specific alterations in an organism's proteome. This review focuses on the application of proteomics to neonatology with particular emphasis on retinopathy of prematurity (ROP), which is a disease in which oxidative stress plays a key pathophysiological role. Oxidative stress is a physiologically relevant redox imbalance caused by an excess of reactive oxygen (ROS) or reactive nitrogen oxide species (RNOS). A major conclusion of this review is that proteomics may be the optimal technology for studying neonatal diseases such as ROP, particularly in the setting of a neonatal intensive care unit (NICU). Proteomics has already identified a number of ROP serum biomarkers. This review will also suggest novel therapeutic approaches to ROP and other neonatal oxidative stress diseases (NOSDs) based on a systems medicine approach. PMID:26709767

  2. OXIDATIVE STRESS 3 Is a Chromatin-Associated Factor Involved in Tolerance to Heavy Metals and Oxidative Stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A cDNA expression library from Brassica juncea was introduced into the fission yeast Schizosaccharomyces pombe to select for transformants tolerant to cadmium. Transformants expressing OXIDATIVE STRESS 3 (OXS3) or OXS3-Like cDNA exhibited enhanced tolerance to a range of metals and oxidizing chemica...

  3. Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

    PubMed Central

    Wang, Xinglong; Wang, Wenzhang; Li, Li; Perry, George; Lee, Hyoung-gon; Zhu, Xiongwei

    2013-01-01

    Alzheimer’s disease (AD) exhibits extensive oxidative stress throughout the body, being detected peripherally as well as associated with the vulnerable regions of the brain affected in disease. Abundant evidence not only demonstrates the full spectrum of oxidative damage to neuronal macromolecules, but also reveals the occurrence of oxidative events early in the course of the disease and prior to the formation of the pathology, which support an important role of oxidative stress in AD. As a disease of abnormal aging, AD demonstrats oxidative damage at levels that significantly surpass that of elderly controls, which suggests the involvement of additional factor(s). Structurally and functionally damaged mitochondria, which are more proficient at producing reactive oxygen species but less so in ATP, are also an early and prominent feature of the disease. Since mitochondria are also vulnerable to oxidative stress, it is likely that a vicious downward spiral involving the interactions between mitochondrial dysfunction and oxidative stress contributes to the initiation and/or amplification of reactive oxygen species that is critical to the pathogenesis of AD. PMID:24189435

  4. Contaminant-induced oxidative stress in fish: a mechanistic approach.

    PubMed

    Lushchak, Volodymyr I

    2016-04-01

    The presence of reactive oxygen species (ROS) in living organisms was described more than 60 years ago and virtually immediately it was suggested that ROS were involved in various pathological processes and aging. The state when ROS generation exceeds elimination leading to an increased steady-state ROS level has been called "oxidative stress." Although ROS association with many pathological states in animals is well established, the question of ROS responsibility for the development of these states is still open. Fish represent the largest group of vertebrates and they inhabit a broad range of ecosystems where they are subjected to many different aquatic contaminants. In many cases, the deleterious effects of contaminants have been connected to induction of oxidative stress. Therefore, deciphering of molecular mechanisms leading to such contaminant effects and organisms' response may let prevent or minimize deleterious impacts of oxidative stress. This review describes general aspects of ROS homeostasis, in particular highlighting its basic aspects, modification of cellular constituents, operation of defense systems and ROS-based signaling with an emphasis on fish systems. A brief introduction to oxidative stress theory is accompanied by the description of a recently developed classification system for oxidative stress based on its intensity and time course. Specific information on contaminant-induced oxidative stress in fish is covered in sections devoted to such pollutants as metal ions (particularly iron, copper, chromium, mercury, arsenic, nickel, etc.), pesticides (insecticides, herbicides, and fungicides) and oil with accompanying pollutants. In the last section, certain problems and perspectives in studies of oxidative stress in fish are described. PMID:26607273

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

    PubMed Central

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

    2015-01-01

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = −0.32, p < 0.0001 for MDA; r = −0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = −0.13, p = 0.04 for MDA; r = −0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental “programming” the vulnerability to metabolic syndrome related disorders remain to be elucidated. PMID:26643495

  6. Are metallothioneins equally good biomarkers of metal and oxidative stress?

    PubMed

    Figueira, Etelvina; Branco, Diana; Antunes, Sara C; Gonçalves, Fernando; Freitas, Rosa

    2012-10-01

    Several researchers investigated the induction of metallothioneins (MTs) in the presence of metals, namely Cadmium (Cd). Fewer studies observed the induction of MTs due to oxidizing agents, and literature comparing the sensitivity of MTs to different stressors is even more scarce or even nonexistent. The role of MTs in metal and oxidative stress and thus their use as a stress biomarker, remains to be clearly elucidated. To better understand the role of MTs as a biomarker in Cerastoderma edule, a bivalve widely used as bioindicator, a laboratory assay was conducted aiming to assess the sensitivity of MTs to metal and oxidative stressors. For this purpose, Cd was used to induce metal stress, whereas hydrogen peroxide (H2O2), being an oxidizing compound, was used to impose oxidative stress. Results showed that induction of MTs occurred at very different levels in metal and oxidative stress. In the presence of the oxidizing agent (H2O2), MTs only increased significantly when the degree of oxidative stress was very high, and mortality rates were higher than 50 percent. On the contrary, C. edule survived to all Cd concentrations used and significant MTs increases, compared to the control, were observed in all Cd exposures. The present work also revealed that the number of ions and the metal bound to MTs varied with the exposure conditions. In the absence of disturbance, MTs bound most (60-70 percent) of the essential metals (Zn and Cu) in solution. In stressful situations, such as the exposure to Cd and H2O2, MTs did not bind to Cu and bound less to Zn. When organisms were exposed to Cd, the total number of ions bound per MT molecule did not change, compared to control. However the sort of ions bound per MT molecule differed; part of the Zn and all Cu ions where displaced by Cd ions. For organisms exposed to H2O2, each MT molecule bound less than half of the ions compared to control and Cd conditions, which indicates a partial oxidation of thiol groups in the cysteine

  7. Oxidative stress in patients with obstructive sleep apnoea syndrome.

    PubMed

    Passali, D; Corallo, G; Yaremchuk, S; Longini, M; Proietti, F; Passali, G C; Bellussi, L

    2015-12-01

    Obstructive sleep apnoea syndrome (OSAS) is a disorder that leads to metabolic abnormalities and increased cardiovascular risk. The aim of this study was to identify early laboratory markers of cardiovascular disease through analysis of oxidative stress in normal subjects and patients with OSAS. A prospective study was designed to compare outcomes of oxidative stress laboratory tests in 20 adult patients with OSAS and a control group of 20 normal subjects. Laboratory techniques for detecting and quantifying free radical damage must be targeted to assess the pro-oxidant component and the antioxidant in order to obtain an overall picture of oxidative balance. No statistical differences in age, sex distribution, or BMI were found between the two groups (p>0.05). There were significant differences in the apnoea/hypopnoea index (AHI) between OSAS patients and the control group (p<0.05). Statistically significant differences in isoprostane, advanced oxidation protein products (AOPP) and non-protein bound iron (NPBI) levels were found between the study and control groups. No significant difference in the levels of thiol biomarkers was found between the two groups. The main finding of the present study was increased production of oxidative stress biomarkers in OSAS patients. The major difference between thiols and other oxidative stress biomarkers is that thiols are antioxidants, while the others are expressions of oxidative damage. The findings of the present study indicate that biomarkers of oxidative stress in OSAS may be used as a marker of upper airway obstructive episodes due to mechanical trauma, as well as a marker of hypoxaemia causing local oropharyngeal inflammation. PMID:26900248

  8. A Meta-Analysis of Oxidative Stress Markers in Depression

    PubMed Central

    Liu, Tao; Zhong, Shuming; Liao, Xiaoxiao; Chen, Jian; He, Tingting; Lai, Shunkai; Jia, Yanbin

    2015-01-01

    Object Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls. Methods A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted. Results 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers. Conclusion This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication

  9. Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress.

    PubMed

    Schiavone, Stefania; Colaianna, Marilena; Curtis, Logos

    2015-01-01

    Stress is an inevitable part of human life and it is experienced even before birth. Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. Recent studies have attempted to clarify how the human central nervous system (CNS) reacts to early life stress, focusing mainly on neurobiological modifications. Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders. PMID:25564385

  10. Role of Nrf2 in Oxidative Stress and Toxicity

    PubMed Central

    Ma, Qiang

    2015-01-01

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

  11. Characterization of RNA damage under oxidative stress in Escherichia coli

    PubMed Central

    Liu, Min; Gong, Xin; Alluri, Ravi Kumar; Wu, Jinhua; Sablo, Tene’; Li, Zhongwei

    2012-01-01

    We have examined the level of 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine, in RNA in Escherichia coli under normal and oxidative stress conditions. The level of 8-oxo-G in RNA rises rapidly and remains high for hours in response to hydrogen peroxide (H2O2) challenge in a dose-dependent manner. H2O2 induced elevation of 8-oxo-G content is much higher in RNA than that of 8-hydroxydeoxyguanosine (8-oxo-dG) in DNA. Under normal conditions, the 8-oxo-G level is low in RNA isolated from the ribosome and it is nearly three times higher in non-ribosomal RNAs. In contrast, 8-oxo-G generated by a short exposure to H2O2 is almost equally distributed in various RNA species, suggesting that although ribosomal RNAs are normally less oxidized, they are not protected against exogenous H2O2. Interestingly, highly folded RNA is not protected from oxidation because 8-oxo-G generated by H2O2 treatment in vitro increases to approximately the same levels in tRNA and rRNA in both native and denatured forms. Lastly, increased RNA oxidation is closely associated with cell death by oxidative stress. Our data suggests that RNA is a primary target for reactive oxygen species and RNA oxidation is part of the paradox that cells have to deal with under oxidative stress. PMID:22718628

  12. Mild oxidative stress is beneficial for sperm telomere length maintenance

    PubMed Central

    Mishra, Swetasmita; Kumar, Rajeev; Malhotra, Neena; Singh, Neeta; Dada, Rima

    2016-01-01

    AIM: To evaluate telomere length in sperm DNA and its correlation with oxidative stress (normal, mild, severe). METHODS: The study included infertile men (n = 112) and age matched fertile controls (n = 102). The average telomere length from the sperm DNA was measured using a quantitative real time PCR based assay. Seminal reactive oxygen species (ROS) and 8-Isoprostane (8-IP) levels were measured by chemiluminescence assay and ELISA respectively. RESULTS: Average sperm telomere length in infertile men and controls was 0.609 ± 0.15 and 0.789 ± 0.060, respectively (P < 0.0001). Seminal ROS levels in infertile was higher [66.61 ± 28.32 relative light units (RLU)/s/million sperm] than in controls (14.04 ± 10.67 RLU/s/million sperm) (P < 0.0001). The 8-IP level in infertile men was significantly higher (421.55 ± 131.29 pg/mL) than in controls (275.94 ± 48.13 pg/mL) (P < 0.001). When correlated to oxidative stress, in normal range of oxidative stress (ROS, 0-21.3 RLU/s/million sperm) the average telomere length in cases was 0.663 ± 0.14, in mild oxidative stress (ROS, 21.3-35 RLU/s/million sperm) it was elevated (0.684 ± 0.12) and in severe oxidative stress (ROS > 35 RLU/s/million sperm) average telomere length was decreased to 0.595 ± 0.15. CONCLUSION: Mild oxidative stress results in lengthening of telomere length, but severe oxidative stress results in shorter telomeres. Although telomere maintenance is a complex trait, the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological levels. Detailed molecular evaluation of telomere structure, its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition. PMID:27376021

  13. OGG1 is essential in oxidative stress induced DNA demethylation.

    PubMed

    Zhou, Xiaolong; Zhuang, Ziheng; Wang, Wentao; He, Lingfeng; Wu, Huan; Cao, Yan; Pan, Feiyan; Zhao, Jing; Hu, Zhigang; Sekhar, Chandra; Guo, Zhigang

    2016-09-01

    DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes. PMID:27251462

  14. Cellular Mechanisms of Oxidative Stress and Action in Melanoma.

    PubMed

    Venza, Mario; Visalli, Maria; Beninati, Concetta; De Gaetano, Giuseppe Valerio; Teti, Diana; Venza, Isabella

    2015-01-01

    Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment. PMID:26064422

  15. Role of oxidative stress in Deoxynivalenol induced toxicity.

    PubMed

    Mishra, Sakshi; Dwivedi, Premendra D; Pandey, Haushila P; Das, Mukul

    2014-10-01

    Deoxynivalenol (DON) is a Fusarium toxin that causes a variety of toxic effects with symptoms such as diarrhoea and low weight gain. To date, no review has addressed the toxicity of DON in relation to oxidative stress. The focus of this article is primarily intended to summarize the information associated with oxidative stress as a plausible mechanism for DON-induced toxicity. The present review shows that over the past two decades, several investigators have documented the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in oxidative stress as a result of DON treatment and have correlated them with various types of toxicity. The evidence for induction of an oxidative stress response resulting from DON exposure has been more focused on in vitro models and is relatively lacking in in vivo studies. Hence, more emphasis should be laid on in vivo investigations with doses that are commonly encountered in food products. Since DON is commonly found in food and feed, the cellular effects of this toxin in relation to oxidative stress, as well as effective measures to combat its toxicity, are important aspects to be considered for future studies. PMID:25010452

  16. Phloroglucinol Attenuates Free Radical-induced Oxidative Stress

    PubMed Central

    So, Mi Jung; Cho, Eun Ju

    2014-01-01

    The protective role of phloroglucinol against oxidative stress and stress-induced premature senescence (SIPS) was investigated in vitro and in cell culture. Phloroglucinol had strong and concentration-dependent radical scavenging effects against nitric oxide (NO), superoxide anions (O2−), and hydroxyl radicals. In this study, free radical generators were used to induce oxidative stress in LLC-PK1 renal epithelial cells. Treatment with phloroglucinol attenuated the oxidative stress induced by peroxyl radicals, NO, O2−, and peroxynitrite. Phloroglucinol also increased cell viability and decreased lipid peroxidation in a concentration-dependent manner. WI-38 human diploid fibroblast cells were used to investigate the protective effect of phloroglucinol against hydrogen peroxide (H2O2)-induced SIPS. Phloroglucinol treatment attenuated H2O2-induced SIPS by increasing cell viability and inhibited lipid peroxidation, suggesting that treatment with phloroglucinol should delay the aging process. The present study supports the promising role of phloroglucinol as an antioxidative agent against free radical-induced oxidative stress and SIPS. PMID:25320709

  17. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    SciTech Connect

    Lefevre, Sophie; Sliwa, Dominika; Rustin, Pierre; Camadro, Jean-Michel; Santos, Renata

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  18. Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against oxidative stress.

    PubMed

    Yoo, Hee Geun; Lee, Bong Han; Kim, Wooki; Lee, Jong Suk; Kim, Gun Hee; Chun, Ock K; Koo, Sung I; Kim, Dae-Ok

    2014-11-01

    Oxidative stress damages dermal and epidermal cells and degrades extracellular matrix proteins, such as collagen, ultimately leading to skin aging. The present study evaluated the potential protective effect of the aqueous methanolic extract obtained from Lithospermum erythrorhizon (LE) against oxidative stress, induced by H2O2 and ultraviolet (UV) irradiation, on human keratinocyte (HaCaT) and human dermal fibroblast-neonatal (HDF-n) cells. Exposure of cells to H2O2 or UVB irradiation markedly increased oxidative stress and reduced cell viability. However, pretreatment of cells with the LE extract not only increased cell viability (up to 84.5%), but also significantly decreased oxidative stress. Further, the LE extract downregulated the expression of matrix metalloproteinase-1, an endopeptidase that degrades extracellular matrix collagen. In contrast, treatment with the LE extract did not affect the expression of procollagen type 1 in HDF-n cells exposed to UVA irradiation. Thirteen phenolic compounds, including derivatives of shikonin and caffeic acid, were identified by ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. These results suggest that LE-derived extracts may protect oxidative-stress-induced skin aging by inhibiting degradation of skin collagen, and that this protection may derive at least in part from the antioxidant phenolics present in these extracts. Further studies are warranted to determine the potential utility of LE-derived extracts in both therapeutic and cosmetic applications. PMID:25136892

  19. (+)-Catechin protects dermal fibroblasts against oxidative stress-induced apoptosis

    PubMed Central

    2014-01-01

    Background Oxidative stress has been suggested as a mechanism underlying skin aging, as it triggers apoptosis in various cell types, including fibroblasts, which play important roles in the preservation of healthy, youthful skin. Catechins, which are antioxidants contained in green tea, exert various actions such as anti-inflammatory, anti-bacterial, and anti-cancer actions. In this study, we investigated the effect of (+)-catechin on apoptosis induced by oxidative stress in fibroblasts. Methods Fibroblasts (NIH3T3) under oxidative stress induced by hydrogen peroxide (0.1 mM) were treated with either vehicle or (+)-catechin (0–100 μM). The effect of (+)-catechin on cell viability, apoptosis, phosphorylation of c-Jun terminal kinases (JNK) and p38, and activation of caspase-3 in fibroblasts under oxidative stress were evaluated. Results Hydrogen peroxide induced apoptotic cell death in fibroblasts, accompanied by induction of phosphorylation of JNK and p38 and activation of caspase-3. Pretreatment of the fibroblasts with (+)-catechin inhibited hydrogen peroxide-induced apoptosis and reduced phosphorylation of JNK and p38 and activation of caspase-3. Conclusion (+)-Catechin protects against oxidative stress-induced cell death in fibroblasts, possibly by inhibiting phosphorylation of p38 and JNK. These results suggest that (+)-catechin has potential as a therapeutic agent for the prevention of skin aging. PMID:24712558

  20. Oxidative stress modulation in hepatitis C virus infected cells

    PubMed Central

    Lozano-Sepulveda, Sonia A; Bryan-Marrugo, Owen L; Cordova-Fletes, Carlos; Gutierrez-Ruiz, Maria C; Rivas-Estilla, Ana M

    2015-01-01

    Hepatitis C virus (HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system (GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants (vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells. PMID:26692473

  1. Cellular Mechanisms of Oxidative Stress and Action in Melanoma

    PubMed Central

    Venza, Mario; Visalli, Maria; Beninati, Concetta; De Gaetano, Giuseppe Valerio; Teti, Diana; Venza, Isabella

    2015-01-01

    Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment. PMID:26064422

  2. Arterial Stiffness, Oxidative Stress, and Smoke Exposure in Wildland Firefighters

    PubMed Central

    Gaughan, Denise M.; Siegel, Paul D.; Hughes, Michael D.; Chang, Chiung-Yu; Law, Brandon F.; Campbell, Corey R.; Richards, Jennifer C.; Kales, Stefanos F.; Chertok, Marcia; Kobzik, Lester; Nguyen, Phuongson; O’Donnell, Carl R.; Kiefer, Max; Wagner, Gregory R.; Christiani, David C.

    2015-01-01

    Objectives To assess the association between exposure, oxidative stress, symptoms, and cardiorespiratory function in wildland firefighters. Methods We studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the smoke exposure marker (urinary levoglucosan). Arterial stiffness was assessed by examining levels of the aortic augmentation index, expressed as a percentage. An oxidative stress score comprising the average of z-scores created for 8-OHdG and 8-isoprostane was calculated. Results Mean augmentation index % was higher for participants with higher oxidative stress scores after adjusting for smoking status. Specifically for every one unit increase in oxidative stress score the augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower respiratory symptom score was associated with lower percent predicted forced expiratory volume in one second/forced vital capacity. Conclusions Biomarkers of oxidative stress may serve as indicators of arterial stiffness in wildland firefighters. PMID:24909863

  3. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    PubMed

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention. PMID:26596837

  4. Diaphragmatic breathing reduces exercise-induced oxidative stress.

    PubMed

    Martarelli, Daniele; Cocchioni, Mario; Scuri, Stefania; Pompei, Pierluigi

    2011-01-01

    Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1 h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals. PMID:19875429

  5. Plasma levels of oxidative stress-responsive apoptosis inducing protein (ORAIP) in rats subjected to physicochemical oxidative stresses.

    PubMed

    Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Seko, Yoshinori

    2016-01-01

    Oxidative stress is known to play a pivotal role in the pathogenesis of various disorders including atherosclerosis, aging and especially ischaemia/reperfusion injury. It causes cell damage that leads to apoptosis. However, the precise mechanism has been uncertain. Recently, we identified an apoptosis-inducing humoral factor in a hypoxia/reoxygenated medium of cardiac myocytes. We named this novel post-translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) as oxidative stress-responsive apoptosis inducing protein (ORAIP). We developed a sandwich ELISA and confirmed that myocardial ischaemia/reperfusion markedly increased plasma levels of ORAIP. To investigate whether the role of ORAIP is common to various types of oxidative stress, we measured plasma ORAIP levels in rats subjected to three physicochemical models of oxidative stress including N2/O2 inhalation, cold/warm-stress (heat shock) and blood acidification. In all three models, plasma ORAIP levels significantly increased and reached a peak level at 10-30 min after stimulation, then decreased within 60 min. The (mean±S.E.M.) plasma ORAIP levels before and after (peak) stimulation were (16.4±9.6) and (55.2±34.2) ng/ml in N2/O2 inhalation, (14.1±12.4) and (34.3±14.6) ng/ml in cold/warm-stress, and (18.9±14.3) and (134.0±67.2) ng/ml in blood acidification study. These data strongly suggest that secretion of ORAIP in response to oxidative stress is universal mechanism and plays an essential role. ORAIP will be an important novel biomarker as well as a specific therapeutic target of these oxidative stress-induced cell injuries. PMID:26934977

  6. Acute exercise and oxidative stress: a 30 year history

    PubMed Central

    Fisher-Wellman, Kelsey; Bloomer, Richard J

    2009-01-01

    The topic of exercise-induced oxidative stress has received considerable attention in recent years, with close to 300 original investigations published since the early work of Dillard and colleagues in 1978. Single bouts of aerobic and anaerobic exercise can induce an acute state of oxidative stress. This is indicated by an increased presence of oxidized molecules in a variety of tissues. Exercise mode, intensity, and duration, as well as the subject population tested, all can impact the extent of oxidation. Moreover, the use of antioxidant supplements can impact the findings. Although a single bout of exercise often leads to an acute oxidative stress, in accordance with the principle of hormesis, such an increase appears necessary to allow for an up-regulation in endogenous antioxidant defenses. This review presents a comprehensive summary of original investigations focused on exercise-induced oxidative stress. This should provide the reader with a well-documented account of the research done within this area of science over the past 30 years. PMID:19144121

  7. Causes and consequences of oxidative stress in spermatozoa.

    PubMed

    Aitken, Robert John; Gibb, Zamira; Baker, Mark A; Drevet, Joel; Gharagozloo, Parviz

    2015-02-01

    Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent. PMID:27062870

  8. [Characteristics of oxidative stress in mental maladaptation].

    PubMed

    Smirnova, L P; Ivanova, S A; Krotenko, N M; Levchuk, L A; Gutkevich, E V; Semke, V Ia

    2012-01-01

    Changes in the balance of pro and antioxidant systems were studied in persons in state of mental maladaptation, developed under the influence of emotional stress. Activation of lipid peroxidation has been revealed associated with increase of amount of malondialdehyde in erythrocytes and blood serum in persons surveyed. Activity of catalase and glutathione peroxidase in erythrocytes in persons in state of mental stress was increased and glutathione preductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase has been reliably reduced as compared with group of healthy people. Comparative chemiluminiscent analysis of common antioxidant properties of serum of blood of studied groups has also revealed decrease of antioxidant properties of blood under influence of mental stress. PMID:23101248

  9. Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress

    PubMed Central

    Wages, Phillip A.; Lavrich, Katelyn S.; Zhang, Zhenfa; Cheng, Wan-Yun; Corteselli, Elizabeth; Gold, Avram; Bromberg, Philip; Simmons, Steven O.; Samet, James M.

    2016-01-01

    Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ) induce oxidative stress by redox cycling, which generates hydrogen peroxide (H2O2). Cysteinyl thiolate residues on regulatory proteins are subjected to oxidative modification by H2O2 in physiological contexts and are also toxicological targets of oxidant stress induced by environmental contaminants. We investigated whether exposure to environmentally relevant concentrations of 1,2-NQ can induce H2O2-dependent oxidation of cysteinyl thiols in regulatory proteins as a readout of oxidant stress in human airway epithelial cells. BEAS-2B cells were exposed to 0–1000 μM 1,2-NQ for 0–30 min, and levels of H2O2 were measured by ratiometric spectrofluorometry of HyPer. H2O2-dependent protein sulfenylation was measured using immunohistochemistry, immunoblotting, and isotopic mass spectrometry. Catalase overexpression was used to investigate the relationship between H2O2 generation and protein sulfenylation in cells exposed to 1,2-NQ. Multiple experimental approaches showed that exposure to 1,2-NQ at concentrations as low as 3 μM induces H2O2-dependent protein sulfenylation in BEAS-2B cells. Moreover, the time of onset and duration of 1,2-NQ-induced sulfenylation of the regulatory proteins GAPDH and PTP1B showed significant differences. Oxidative modification of regulatory cysteinyl thiols in human lung cells exposed to relevant concentrations of an ambient air contaminant represents a novel marker of oxidative environmental stress. PMID:26605980

  10. Oxidative stress and life histories: unresolved issues and current needs.

    PubMed

    Speakman, John R; Blount, Jonathan D; Bronikowski, Anne M; Buffenstein, Rochelle; Isaksson, Caroline; Kirkwood, Tom B L; Monaghan, Pat; Ozanne, Susan E; Beaulieu, Michaël; Briga, Michael; Carr, Sarah K; Christensen, Louise L; Cochemé, Helena M; Cram, Dominic L; Dantzer, Ben; Harper, Jim M; Jurk, Diana; King, Annette; Noguera, Jose C; Salin, Karine; Sild, Elin; Simons, Mirre J P; Smith, Shona; Stier, Antoine; Tobler, Michael; Vitikainen, Emma; Peaker, Malcolm; Selman, Colin

    2015-12-01

    Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting

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

    PubMed

    Alan, Rebecca R; McWilliams, Scott R

    2013-03-01

    Oxidative stress is an unavoidable consequence of metabolism and increases during intensive exercise. This is especially problematic for migratory birds that metabolize fat to fuel long-distance flight. Birds can mitigate damage by increasing endogenous antioxidants (e.g. uric acid) or by consuming dietary antioxidants (e.g. tocopherol). During flight, birds may increase protein catabolism of lean tissue which may increase circulating uric acid and many birds also consume an antioxidant-rich frugivorous diet during autumn migration. We evaluated three related hypotheses in a migratory passerine: (1) protein consumption is positively related to circulating antioxidants, (2) a dietary oxidative stressor [i.e. polyunsaturated fatty acid (PUFA)] influences antioxidant capacity and oxidative damage, and (3) oxidative stress influences dietary antioxidant preferences. White-throated Sparrows (Zonotrichia albicollis) consuming a high protein diet increased circulating uric acid; however, uric acid, antioxidant capacity, and oxidative stress did not differ between birds consuming a high PUFA versus a low PUFA diet, despite increased oxidative damage in high PUFA birds. Birds did not prefer antioxidant-rich diets even when fed high PUFA, low protein. We conclude that White-throated Sparrows successfully mitigated oxidative damage associated with a high PUFA diet and mounted an endogenous antioxidant response independent of uric acid, other circulating antioxidants, and dietary antioxidants. PMID:23270695

  12. Novel biomarker pipeline to probe the oxidation sites and oxidation degrees of hemoglobin in bovine erythrocytes exposed to oxidative stress.

    PubMed

    Zong, Wansong; Wang, Xiaoning; Yang, Chuanxi; Du, Yonggang; Sun, Weijun; Xu, Zhenzhen

    2016-06-01

    Research on biomarkers for protein oxidation might give insight into the mechanistic mode of oxidative stress. In the work present here, a novel pipeline was established to probe the oxidation mechanism of bovine hemoglobin (Hb) with its oxidation products serving as the biomarkers. Reactive oxygen species generated by irradiation were used to mimic oxidative stress conditions to oxidize Hb in bovine erythrocytes. After Hb extraction and digestion, oxidized peptides in the tryptic fragments were assigned by comparison with the extracted ion chromatography spectra of native peptide from the control sample. Subsequent tandem mass spectrometry analysis of these peptides proved that oxidation was limited to partially exposed amino acid residues (α-Phe36 , β-Met1 , β-Trp14 , for instance) in Hb. Quantitation analysis on these oxidized peptides showed that oxidation degrees of target sites had positive correlations with the extended oxidation dose and the oxidation processes were also controlled by residues types. Compared with the conventional protein carbonyl assay, the identified oxidized products were feasibility biomarkers for Hb oxidation, indicating that the proposed biomarker pipeline was suitable to provide specific and valid information for protein oxidation. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26348117

  13. Oxidative stress and therapeutic implications in psychiatric disorders.

    PubMed

    Zhang, Xiang Yang; Yao, Jeffrey K

    2013-10-01

    Increasing evidence indicates that disturbances of antioxidant defense system and presence of oxidative stress can play a part in a wide range of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and major depression, as well as antipsychotic-induced tardive dyskinesia (TD). Moreover, researchers have embarked on using antioxidant treatment as adjunct therapy for psychiatry disorders. Evidence from clinical, pre-clinical and epidemiological studies suggests that a benefit of using antioxidant compounds should be considered as an adjunctive therapy in these patients. These are some of the main perspectives that are reviewed by four articles in this special section. Overall, there has been growing recognition of the importance of oxidative stress in the pathophysiology of psychiatric disorders and the development of TD. The collection of articles in this special section will contribute to providing more efficacious treatments arising from a better appreciation of the roles of oxidative stress in these psychiatric disorders. PMID:23523744

  14. Discovery of biomarkers for oxidative stress based on cellular metabolomics.

    PubMed

    Wang, Ningli; Wei, Jianteng; Liu, Yewei; Pei, Dong; Hu, Qingping; Wang, Yu; Di, Duolong

    2016-07-01

    Oxidative stress has a close relationship with various pathologic physiology phenomena and the potential biomarkers of oxidative stress may provide evidence for clinical diagnosis or disease prevention. Metabolomics was employed to identify the potential biomarkers of oxidative stress. High-performance liquid chromatography-diode array detector, mass spectrometry and partial least squares discriminate analysis were used in this study. The 10, 15 and 13 metabolites were considered to discriminate the model group, vitamin E-treated group and l-glutathione-treated group, respectively. Some of them have been identified, namely, malic acid, vitamin C, reduced glutathione and tryptophan. Identification of other potential biomarkers should be conducted and their physiological significance also needs to be elaborated. PMID:27168482

  15. Does aspirin-induced oxidative stress cause asthma exacerbation?

    PubMed Central

    Kacprzak, Dorota

    2015-01-01

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism. PMID:26170841

  16. Uremic toxins, oxidative stress, and renal fibrosis: an interwined complex.

    PubMed

    Chao, Chia-Ter; Chiang, Chih-Kang

    2015-03-01

    The prevalence of end-stage renal diseases is currently on the rise globally, and finding the way to curb this tide is urgently needed. Tubulointerstitial fibrosis is a common pathway for essentially all the nephropathy categories known to date, and the manifestations of renal fibrosis include excessive deposition of extracellular matrix with distortion of renal microstructures and functional deterioration. Uremic toxins have been gradually found to play an important role in the development of progressive renal fibrosis, with protein-bound indoxyl sulfate, p-cresol, and p-cresyl sulfate receiving the most attention. However, the contribution of oxidative stress among the pathogenesis of uremic toxins and renal fibrosis has not been evaluated much until recently. In this review, we will discuss about the nature and sources of oxidative stress in the kidney and how uremic toxins use oxidative stress to orchestrate the processes of renal fibrosis. PMID:25511523

  17. Transketolase counteracts oxidative stress to drive cancer development

    PubMed Central

    Xu, Iris Ming-Jing; Lai, Robin Kit-Ho; Lin, Shu-Hai; Tse, Aki Pui-Wah; Chiu, David Kung-Chun; Koh, Hui-Yu; Law, Cheuk-Ting; Wong, Chun-Ming; Cai, Zongwei; Wong, Carmen Chak-Lui; Ng, Irene Oi-Lin

    2016-01-01

    Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants. PMID:26811478

  18. Transketolase counteracts oxidative stress to drive cancer development.

    PubMed

    Xu, Iris Ming-Jing; Lai, Robin Kit-Ho; Lin, Shu-Hai; Tse, Aki Pui-Wah; Chiu, David Kung-Chun; Koh, Hui-Yu; Law, Cheuk-Ting; Wong, Chun-Ming; Cai, Zongwei; Wong, Carmen Chak-Lui; Ng, Irene Oi-Lin

    2016-02-01

    Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants. PMID:26811478

  19. Iron-Deficiency Anemia Enhances Red Blood Cell Oxidative Stress

    PubMed Central

    Nagababu, Enika; Gulyani, Seema; Earley, Christopher J.; Cutler, Roy G.; Mattson, Mark P.; Rifkind, Joseph M.

    2009-01-01

    Oxidative stress associated with iron deficiency anemia in a murine model was studied feeding an iron deficient diet. Anemia was monitored by a decrease in hematocrit and hemoglobin. For the 9 week study an increase in total iron binding capacity was also demonstrated. Anemia resulted in an increase in red blood cells (RBC) oxidative stress as indicated by increased levels of fluorescent heme degradation products (1.24 fold after 5 weeks; 2.1 fold after 9 weeks). The increase in oxidative stress was further confirmed by elevated levels of methemoglobin for mice fed an iron deficient diet. Increased hemoglobin autoxidation and subsequent generation of ROS can account for the shorter RBC lifespan and other pathological changes associated with iron deficiency anemia. PMID:19051108

  20. Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials

    EPA Science Inventory

    Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanoma...

  1. Maillard reaction, mitochondria and oxidative stress: potential role of antioxidants.

    PubMed

    Edeas, M; Attaf, D; Mailfert, A-S; Nasu, M; Joubet, R

    2010-06-01

    Glycation and oxidative stress are two important processes known to play a key role in complications of many disease processes. Oxidative stress, either via increasing reactive oxygen species (ROS), or by depleting the antioxidants may modulate the genesis of early glycated proteins in vivo. Maillard Reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes, aging and age-related diseases. Hyperglycaemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes facilitate the generation of reactive oxygen species and decrease the activity of antioxidant enzymes such as Cu,Zn-superoxide dismutase, resulting in a remarkable increase of oxidative stress. A large body of evidence indicates that mitochondria alteration is involved and plays a central role in various oxidative stress-related diseases. The damaged mitochondria produce more ROS (increase oxidative stress) and less ATP (cellular energy) than normal mitochondria. As they are damaged, they cannot burn or use glucose or lipid and cannot provide cell with ATP. Further, glucose, amino acids and lipid will not be correctly used and will accumulate outside the mitochondria; they will undergo more glycation (as observed in diabetes, obesity, HIV infection and lipodystrophia). The objective of this paper is to discuss how to stop the vicious circle established between oxidative stress, Maillard Reaction and mitochondria. The potential application of some antioxidants to reduce glycation phenomenon and to increase the antioxidant defence system by targeting mitochondria will be discussed. Food and pharmaceutical companies share the same challenge, they must act now, urgently and energetically. PMID:20031340

  2. Work at high altitude and oxidative stress: antioxidant nutrients.

    PubMed

    Askew, E W

    2002-11-15

    A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. Some investigators have linked the development of these symptoms with the condition of altered blood-brain barrier permeability, possibly related to hypoxia induced free radical formation. The burden of oxidative stress increases during the time spent at altitude and may even persist for some time upon return to sea level. The physiological and medical consequences of increased oxidative stress engendered by altitude is unclear; indeed, hypoxia is believed to be the trigger for the cascade of signaling events that ultimately leads to adaptation to altitude. These signaling events include the generation of reactive oxygen species (ROS) that may elicit important adaptive responses. If produced in excess, however, these ROS may contribute to impaired muscle function and reduced capillary perfusion at altitude or may even play a role in precipitating more serious neurological and pulmonary crisis. Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is

  3. IRON OXIDE NANOPARTICLE-INDUCED OXIDATIVE STRESS AND INFLAMMATION

    EPA Science Inventory

    1. Nanoparticle Physicochemical Characterizations
    2. We first focused on creating NP systems that could be used to test our hypotheses and assessing their stability in aqueous media. The iron oxide NP systems were not stable in cell culture medium o...

    3. Oxidative Stress and Ca2+ Release Events in Mouse Cardiomyocytes

      PubMed Central

      Shirokova, Natalia; Kang, Chifei; Fernandez-Tenorio, Miguel; Wang, Wei; Wang, Qiongling; Wehrens, Xander H.T.; Niggli, Ernst

      2014-01-01

      Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca2+ signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca2+ release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxidation of RyR2s was found to increase the open probability of the channel, whereas CaMKII can be activated independent of Ca2+ through oxidation. Here, we investigated how oxidative stress affects RyR2 function and SR Ca2+ signaling in situ, by analyzing Ca2+ sparks in permeabilized mouse cardiomyocytes under a broad range of oxidative conditions. The results show that with increasing oxidative stress Ca2+ spark duration is prolonged. In addition, long and very long-lasting (up to hundreds of milliseconds) localized Ca2+ release events started to appear, eventually leading to sarcoplasmic reticulum (SR) Ca2+ depletion. These changes of release duration could be prevented by the CaMKII inhibitor KN93 and did not occur in mice lacking the CaMKII-specific S2814 phosphorylation site on RyR2. The appearance of long-lasting Ca2+ release events was paralleled by an increase of RyR2 oxidation, but also by RyR-S2814 phosphorylation, and by CaMKII oxidation. Our results suggest that in a strongly oxidative environment oxidation-dependent activation of CaMKII leads to RyR2 phosphorylation and thereby contributes to the massive prolongation of SR Ca2+ release events. PMID:25517148

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

      PubMed Central

      Spiers, Jereme G.; Chen, Hsiao-Jou Cortina; Sernia, Conrad; Lavidis, Nickolas A.

      2015-01-01

      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. PMID:25646076

    5. Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

      PubMed Central

      Kurita-Ochiai, Tomoko; Jia, Ru; Cai, Yu; Yamaguchi, Yohei; Yamamoto, Masafumi

      2015-01-01

      Periodontal disease is a highly prevalent disorder affecting up to 80% of the global population. Recent epidemiological studies have shown an association between periodontal disease and cardiovascular disease, as oxidative stress plays an important role in chronic inflammatory diseases such as periodontal disease and cardiovascular disease. In this review, we focus on the mechanisms by which periodontopathic bacteria cause chronic inflammation through the enhancement of oxidative stress and accelerate cardiovascular disease. Furthermore, we comment on the antioxidative activity of catechin in atherosclerosis accelerated by periodontitis. PMID:26783845

    6. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

      Technology Transfer Automated Retrieval System (TEKTRAN)

      Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

    7. Severe physical exertion, oxidative stress, and acute lung injury.

      PubMed

      Shah, Nikunj R; Iqbal, M Bilal; Barlow, Andrew; Bayliss, John

      2011-11-01

      We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID:22064719

    8. Haptoglobin Is Required to Prevent Oxidative Stress and Muscle Atrophy

      PubMed Central

      Lo Verso, Francesca; Santini, Ferruccio; Vitti, Paolo; Chisari, Carmelo; Sandri, Marco; Maffei, Margherita

      2014-01-01

      Background Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. Results We used Hp knockout mice (Hp-/-) to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD), OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. Conclusions Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges. PMID:24959824

    9. Overexpression of calreticulin sensitizes SERCA2a to oxidative stress.

      PubMed

      Ihara, Yoshito; Kageyama, Kan; Kondo, Takahito

      2005-04-22

      Calreticulin (CRT), a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac disorder in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In this study, the effect of overexpression of CRT on sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2a under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. The in vitro activity of SERCA2a and uptake of (45)Ca(2+) into isolated microsomes were suppressed by H(2)O(2) in CRT-overexpressing cells compared with controls. Moreover, SERCA2a protein was degraded via a proteasome-dependent pathway following the formation of a complex with CRT under the stress with H(2)O(2). Thus, we conclude that overexpression of CRT enhances the inactivation and degradation of SERCA2a in the cells under oxidative stress, suggesting some pathophysiological functions of CRT in Ca(2+) homeostasis of myocardiac disease. PMID:15766574

    10. Tyrosine phosphorylation of clathrin heavy chain under oxidative stress.

      PubMed

      Ihara, Yoshito; Yasuoka, Chie; Kageyama, Kan; Wada, Yoshinao; Kondo, Takahito

      2002-09-20

      In mouse pancreatic insulin-producing betaTC cells, oxidative stress due to H(2)O(2) causes tyrosine phosphorylation in various proteins. To identify proteins bearing phosphotyrosine under stress, the proteins were affinity purified using an anti-phosphotyrosine antibody-conjugated agarose column. A protein of 180kDa was identified as clathrin heavy chain (CHC) by electrophoresis and mass spectrometry. Immunoprecipitated CHC showed tyrosine phosphorylation upon H(2)O(2) treatment and the phosphorylation was suppressed by the Src kinase inhibitor, PP2. The phosphorylation status of CHC affected the intracellular localization of CHC and the clathrin-dependent endocytosis of transferrin under oxidative stress. In conclusion, CHC is a protein that is phosphorylated at tyrosine by H(2)O(2) and this phosphorylation status is implicated in the intracellular localization and functions of CHC under oxidative stress. The present study demonstrates that oxidative stress affects intracellular vesicular trafficking via the alteration of clathrin-dependent vesicular trafficking. PMID:12237126

    11. Oxidative stress: a concept in redox biology and medicine

      PubMed Central

      Sies, Helmut

      2015-01-01

      Oxidative stress” as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term. This concept has its merits and its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance and (ii) the associated potential strains in the balance as denoted by the term, stress, evoking biological stress responses. Current research on molecular redox switches governing oxidative stress responses is in full bloom. The fundamental importance of linking redox shifts to phosphorylation/dephosphorylation signaling is being more fully appreciated, thanks to major advances in methodology. Among the pitfalls is the fact that the underlying molecular details are to be worked out in each particular case, which is bvious for a global concept, but which is sometimes overlooked. This can lead to indiscriminate use of the term, oxidative stress, without clear relation to redox chemistry. The major role in antioxidant defense is fulfilled by antioxidant enzymes, not by small-molecule antioxidant compounds. The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research. PMID:25588755

    12. Oxidative-stress-induced epigenetic changes in chronic diabetic complications.

      PubMed

      Feng, Biao; Ruiz, Michael Anthony; Chakrabarti, Subrata

      2013-03-01

      Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations. PMID:23537434

    13. Proteomic analysis of seminal fluid from men exhibiting oxidative stress

      PubMed Central

      2013-01-01

      Background Seminal plasma serves as a natural reservoir of antioxidants. It helps to remove excessive formation of reactive oxygen species (ROS) and consequently, reduce oxidative stress. Proteomic profiling of seminal plasma proteins is important to understand the molecular mechanisms underlying oxidative stress and sperm dysfunction in infertile men. Methods This prospective study consisted of 52 subjects: 32 infertile men and 20 healthy donors. Once semen and oxidative stress parameters were assessed (ROS, antioxidant concentration and DNA damage), the subjects were categorized into ROS positive (ROS+) or ROS negative (ROS-). Seminal plasma from each group was pooled and subjected to proteomics analysis. In-solution digestion and protein identification with liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by bioinformatics analyses was used to identify and characterize potential biomarker proteins. Results A total of 14 proteins were identified in this analysis with 7 of these common and unique proteins were identified in both the ROS+ and ROS- groups through MASCOT and SEQUEST analyses, respectively. Prolactin-induced protein was found to be more abundantly present in men with increased levels of ROS. Gene ontology annotations showed extracellular distribution of proteins with a major role in antioxidative activity and regulatory processes. Conclusions We have identified proteins that help protect against oxidative stress and are uniquely present in the seminal plasma of the ROS- men. Men exhibiting high levels of ROS in their seminal ejaculate are likely to exhibit proteins that are either downregulated or oxidatively modified, and these could potentially contribute to male infertility. PMID:24004880

    14. Muscle Aging and Oxidative Stress in Wild-Caught Shrews

      PubMed Central

      Hindle, Allyson G.; Lawler, John M.; Campbell, Kevin L.; Horning, Markus

      2010-01-01

      Red-toothed shrews (Soricidae, subfamily Soricinae) are an intriguing model system to examine the free radical theory of aging in wild mammals, given their short (<18 month) lifespan and high mass-specific metabolic rates. As muscle performance underlies both foraging ability and predator avoidance, any age-related decline should be detrimental to fitness and survival. Muscle samples of water shrews (Sorex palustris) and sympatrically distributed short-tailed shrews (Blarina brevicauda) were therefore assessed for oxidative stress markers, protective antioxidant enzymes and apoptosis. Activity levels of catalase and glutathione peroxidase increased with age in both species. Similarly, Cu,Zn-superoxide dismutase isoform content was elevated significantly in older animals of both species (increases of 60% in the water shrew, 25% in the short-tailed shrew). Only one oxidative stress marker (lipid peroxidation) was age-elevated; the others were stable or declined (4-hydroxynonenal adducts and dihydroethidium oxidation). Glutathione peroxidase activity was significantly higher in the short-tailed shrew, while catalase activity was 2× higher in water shrews. Oxidative stress indicators were on average higher in short-tailed shrews. Apoptosis occurred in <1% of myocytes examined, and did not increase with age. Within the constraints of the sample size we found evidence of protection against elevated oxidative stress in wild-caught shrews. PMID:20109576

    15. Epigenetic Regulation of Oxidative Stress in Ischemic Stroke

      PubMed Central

      Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin

      2016-01-01

      The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844

    16. Oxidative stress--assassin behind the ischemic stroke.

      PubMed

      Pradeep, Hanumanthappa; Diya, Joseph B; Shashikumar, Shivaiah; Rajanikant, Golgodu K

      2012-01-01

      Ischemic stroke is the second leading cause of death and disability worldwide and is associated with significant clinical and socioeconomic implications, emphasizing the need for effective therapies. Several neuroprotective strategies have failed in clinical trials because of poor knowledge of the molecular processes flanked with ischemic stroke. Therefore, uncovering the molecular processes involved in ischemic brain injury is of critical importance. Therapeutic strategies for ischemic stroke remain ineffective, though rapid advances occur in understanding the pathophysiology of the disease. The oxidative stress is one such high-potential phenomenon, the precise role of which needs to be understood during ischemic events. Nevertheless, the studies carried out in preclinical models of ischemic stroke have pointed to the major role of oxidative stress in exacerbating the ischemic injury. Oxidative stress leading to cell death requires generation of free radicals through multiple mechanisms, such as respiratory inhibition, Ca(2+) imbalance, excitotoxicity, reperfusion injury and inflammation. Free radicals are highly reactive to all the molecular targets: lipids, proteins and nucleic acids, modifying their chemical structure and generating oxidation-derived products. This review discusses molecular aspects of oxidative stress in ischemic stroke and catastrophes that set up as an aftermath of the trauma. PMID:23023336

    17. Muscle aging and oxidative stress in wild-caught shrews.

      PubMed

      Hindle, Allyson G; Lawler, John M; Campbell, Kevin L; Horning, Markus

      2010-04-01

      Red-toothed shrews (Soricidae, subfamily Soricinae) are an intriguing model system to examine the free-radical theory of aging in wild mammals, given their short (<18months) lifespan and high mass-specific metabolic rates. As muscle performance underlies both foraging ability and predator avoidance, any age-related decline should be detrimental to fitness and survival. Muscle samples of water shrews (Sorex palustris) and sympatrically distributed short-tailed shrews (Blarina brevicauda) were therefore assessed for oxidative stress markers, protective antioxidant enzymes and apoptosis. Activity levels of catalase and glutathione peroxidase increased with age in both species. Similarly, Cu,Zn-superoxide dismutase isoform content was elevated significantly in older animals of both species (increases of 60% in the water shrew, 25% in the short-tailed shrew). Only one oxidative stress marker (lipid peroxidation) was age-elevated; the others were stable or declined (4-hydroxynonenal adducts and dihydroethidium oxidation). Glutathione peroxidase activity was significantly higher in the short-tailed shrew, while catalase activity was 2x higher in water shrews. Oxidative stress indicators were on average higher in short-tailed shrews. Apoptosis occurred in <1% of myocytes examined, and did not increase with age. Within the constraints of the sample size we found evidence of protection against elevated oxidative stress in wild-caught shrews. PMID:20109576

    18. Fungicide prochloraz induces oxidative stress and DNA damage in vitro.

      PubMed

      Lundqvist, J; Hellman, B; Oskarsson, A

      2016-05-01

      Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties. PMID:26945613

    19. Environmental-induced oxidative stress in neurodegenerative disorders and aging.

      PubMed

      Migliore, Lucia; Coppedè, Fabio

      2009-03-31

      The aetiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. Free radicals derived primarily from molecular oxygen have been implicated and considered as associated risk factors for a variety of human disorders including neurodegenerative diseases and aging. Damage to tissue biomolecules, including lipids, proteins and DNA, by free radicals is postulated to contribute importantly to the pathophysiology of oxidative stress. The potential of environmental exposure to metals, air pollution and pesticides as well as diet as risk factors via the induction of oxidative stress for neurodegenerative diseases and aging is discussed. The role of genetic background is discussed on the light of the oxidative stress implication, focusing on both complex neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis) and monogenic neurological disorders (Huntington's disease, Ataxia telangiectasia, Friedreich Ataxia and others). Emphasis is given to role of the repair mechanisms of oxidative DNA damage in delaying aging and protecting against neurodegeneration. The emerging interplay between environmental-induced oxidative stress and epigenetic modifications of critical genes for neurodegeneration is also discussed. PMID:18952194

  1. In vitro model suggests oxidative stress involved in keratoconus disease

    NASA Astrophysics Data System (ADS)

    Karamichos, D.; Hutcheon, A. E. K.; Rich, C. B.; Trinkaus-Randall, V.; Asara, J. M.; Zieske, J. D.

    2014-04-01

    Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype.

  2. Fluorescence lifetime imaging of endogenous biomarker of oxidative stress.

    PubMed

    Datta, Rupsa; Alfonso-García, Alba; Cinco, Rachel; Gratton, Enrico

    2015-01-01

    Presence of reactive oxygen species (ROS) in excess of normal physiological level results in oxidative stress. This can lead to a range of pathological conditions including inflammation, diabetes mellitus, cancer, cardiovascular and neurodegenerative disease. Biomarkers of oxidative stress play an important role in understanding the pathogenesis and treatment of these diseases. A number of fluorescent biomarkers exist. However, a non-invasive and label-free identification technique would be advantageous for in vivo measurements. In this work we establish a spectroscopic method to identify oxidative stress in cells and tissues by fluorescence lifetime imaging (FLIM). We identified an autofluorescent, endogenous species with a characteristic fluorescent lifetime distribution as a probe for oxidative stress. To corroborate our hypothesis that these species are products of lipid oxidation by ROS, we correlate the spectroscopic signals arising from lipid droplets by combining FLIM with THG and CARS microscopy which are established techniques for selective lipid body imaging. Further, we performed spontaneous Raman spectral analysis at single points of the sample which provided molecular vibration information characteristics of lipid droplets. PMID:25993434

  3. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    SciTech Connect

    David Henry, M. Wolfley, Steve; Monson, Todd; Clark, Blythe G.; Shaner, Eric; Jarecki, Robert

    2014-02-28

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, T{sub c}. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb{sub 2}O{sub 5}, consumed the top 6–10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. T{sub c} measurements using a SQUID magnetometer indicate that the tensile films maintained a T{sub c} approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere.

  4. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    NASA Astrophysics Data System (ADS)

    David Henry, M.; Wolfley, Steve; Monson, Todd; Clark, Blythe G.; Shaner, Eric; Jarecki, Robert

    2014-02-01

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, Tc. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb2O5, consumed the top 6-10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. Tc measurements using a SQUID magnetometer indicate that the tensile films maintained a Tc approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere.

  5. Oxidative stress in MeHg-induced neurotoxicity

    SciTech Connect

    Farina, Marcelo; Aschner, Michael; Rocha, Joao B.T.

    2011-11-15

    Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

  6. Stress generation in thermally grown oxide films. [oxide scale spalling from superalloy substrates

    NASA Technical Reports Server (NTRS)

    Kumnick, A. J.; Ebert, L. J.

    1981-01-01

    A three dimensional finite element analysis was conducted, using the ANSYS computer program, of the stress state in a thin oxide film thermally formed on a rectangular piece of NiCrAl alloy. The analytical results indicate a very high compressive stress in the lateral directions of the film (approximately 6200 MPa), and tensile stresses in the metal substrate that ranged from essentially zero to about 55 MPa. It was found further that the intensity of the analytically determined average stresses could be approximated reasonably well by the modification of an equation developed previously by Oxx for stresses induced into bodies by thermal gradients.

  7. Statins Decrease Oxidative Stress and ICD Therapies

    PubMed Central

    Bloom, Heather L.; Shukrullah, Irfan; Veledar, Emir; Gutmann, Rebecca; London, Barry; Dudley, Samuel C.

    2010-01-01

    Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD) patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs) and interleukin-6 (IL-6). Results. Subjects included 252 (83%) men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF) 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r = 0.12, P = .02). Subjects on statins had lower hsCRP (5.2 versus 6.3; P = .05) and DROM levels (373 versus 397; P = .03). Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation. PMID:20369058

  8. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration

    PubMed Central

    Patra, R. C.; Rautray, Amiya K.; Swarup, D.

    2011-01-01

    Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects. PMID:21547215

  9. Oxidative stress and the pathogenesis of Parkinson's disease.

    PubMed

    Jenner, P; Olanow, C W

    1996-12-01

    Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to substantia nigra pars compacta. Extensive postmortem studies have provided evidence to support the involvement of oxidative stress in the pathogenesis of PD; in particular, these include alterations in brain iron content, impaired mitochondrial function, alterations in the antioxidant protective systems (most notably superoxide dismutase [SOD] and reduced glutathione [GSH]), and evidence of oxidative damage to lipids, proteins, and DNA. Iron can induce oxidative stress, and intranigral injections have been shown to induce a model of progressive parkinsonism. A loss of GSH is associated with incidental Lewy body disease and may represent the earliest biochemical marker of nigral cell loss. GSH depletion alone may not result in damage to nigral neurons but may increase susceptibility to subsequent toxic or free radical exposure. The nature of the free radical species responsible for cell death in PD remains unknown, but there is evidence of involvement of hydroxyl radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite formation may be critically dependent on nitric oxide formation. Central to many of the processes involved in oxidative stress and oxidative damage in PD are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion of dopamine to hydrogen peroxide (H2O2), and for the activation of other potential toxins such as isoquinolines and beta-carbolines. Thus, the inhibition of MAO-B by drugs such as selegiline may protect against activation of some toxins and free radicals formed from the MAO-B oxidation of dopamine. In addition, selegiline may act through a mechanism unrelated to MAO-B to increase neurotrophic

  10. The plant Apolipoprotein D ortholog protects Arabidopsis against oxidative stress

    PubMed Central

    Charron, Jean-Benoit F; Ouellet, Francois; Houde, Mario; Sarhan, Fathey

    2008-01-01

    Background Lipocalins are a large and diverse family of small, mostly extracellular proteins implicated in many important functions. This family has been studied in bacteria, invertebrate and vertebrate animals but little is known about these proteins in plants. We recently reported the identification and molecular characterization of the first true lipocalins from plants, including the Apolipoprotein D ortholog AtTIL identified in the plant model Arabidopsis thaliana. This study aimed to determine its physiological role in planta. Results Our results demonstrate that the AtTIL lipocalin is involved in modulating tolerance to oxidative stress. AtTIL knock-out plants are very sensitive to sudden drops in temperature and paraquat treatment, and dark-grown plants die shortly after transfer to light. These plants accumulate a high level of hydrogen peroxide and other ROS, which causes an oxidative stress that is associated with a reduction in hypocotyl growth and sensitivity to light. Complementation of the knock-out plants with the AtTIL cDNA restores the normal phenotype. On the other hand, overexpression enhances tolerance to stress caused by freezing, paraquat and light. Moreover, this overexpression delays flowering and maintains leaf greenness. Microarray analyses identified several differentially-regulated genes encoding components of oxidative stress and energy balance. Conclusion This study provides the first functional evidence that a plant lipocalin is involved in modulating tolerance to oxidative stress. These findings are in agreement with recently published data showing that overexpression of ApoD enhances tolerance to oxidative stress and increases life span in mice and Drosophila. Together, the three papers strongly support a similar function of lipocalins in these evolutionary-distant species. PMID:18671872

  11. Abnormal Oxidative Stress Responses in Fibroblasts from Preeclampsia Infants

    PubMed Central

    Yang, Penghua; Dai, Aihua; Alexenko, Andrei P.; Liu, Yajun; Stephens, Amanda J.; Schulz, Laura C.; Schust, Danny J.; Roberts, R. Michael; Ezashi, Toshihiko

    2014-01-01

    Background Signs of severe oxidative stress are evident in term placentae of infants born to mothers with preeclampsia (PE), but it is unclear whether this is a cause or consequence of the disease. Here fibroblast lines were established from umbilical cords (UC) delivered by mothers who had experienced early onset PE and from controls with the goal of converting these primary cells to induced pluripotent stem cells and ultimately trophoblast. Contrary to expectations, the oxidative stress responses of these non-placental cells from PE infants were more severe than those from controls. Methods and Findings Three features suggested that UC-derived fibroblasts from PE infants responded less well to oxidative stressors than controls: 1) While all UC provided outgrowths in 4% O2, success was significantly lower for PE cords in 20% O2; 2) PE lines established in 4% O2 proliferated more slowly than controls when switched to 20% O2; 3) PE lines were more susceptible to the pro-oxidants diethylmaleate and tert-butylhydroquinone than control lines, but, unlike controls, were not protected by glutathione. Transcriptome profiling revealed only a few genes differentially regulated between PE lines and controls in 4% O2 conditions. However, a more severely stressed phenotype than controls, particularly in the unfolded protein response, was evident when PE lines were switched suddenly to 20% O2, thus confirming the greater sensitivity of the PE fibroblasts to acute changes in oxidative stress. Conclusions UC fibroblasts derived from PE infants are intrinsically less able to respond to acute oxidative stress than controls, and this phenotype is retained over many cell doublings. Whether the basis of this vulnerability is genetic or epigenetic and how it pertains to trophoblast development remains unclear, but this finding may provide a clue to the basis of the early onset, usually severe, form of PE. PMID:25058409

  12. Enterobactin as Part of the Oxidative Stress Response Repertoire

    PubMed Central

    Corbalán, Natalia S.; Paz García, Enrique Carlos; Pomares, María Fernanda; Vincent, Paula A.

    2016-01-01

    Microorganisms produce siderophores to facilitate iron uptake and even though this trait has been extensively studied, there is growing evidence suggesting that siderophores may have other physiological roles aside from iron acquisition. In support of this notion, we previously linked the archetypal siderophore enterobactin with oxidative stress alleviation. To further characterize this association, we studied the sensitivity of Escherichia coli strains lacking different components of the enterobactin system to the classical oxidative stressors hydrogen peroxide and paraquat. We observed that strains impaired in enterobactin production, uptake and hydrolysis were more susceptible to the oxidative damage caused by both compounds than the wild-type strain. In addition, meanwhile iron supplementation had little impact on the sensitivity, the reducing agent ascorbic acid alleviated the oxidative stress and therefore significantly decreased the sensitivity to the stressors. This indicated that the enterobactin-mediated protection is independent of its ability to scavenge iron. Furthermore, enterobactin supplementation conferred resistance to the entE mutant but did not have any protective effect on the fepG and fes mutants. Thus, we inferred that only after enterobactin is hydrolysed by Fes in the cell cytoplasm and iron is released, the free hydroxyl groups are available for radical stabilization. This hypothesis was validated testing the ability of enterobactin to scavenge radicals in vitro. Given the strong connection between enterobactin and oxidative stress, we studied the transcription of the entE gene and the concomitant production of the siderophore in response to such kind of stress. Interestingly, we observed that meanwhile iron represses the expression and production of the siderophore, hydrogen peroxide and paraquat favour these events even if iron is present. Our results support the involvement of enterobactin as part of the oxidative stress response and

  13. Identification of the Oxidative Stress Proteome in the Brain

    PubMed Central

    Sultana, Rukhsana; Butterfield, D. Allan

    2011-01-01

    The redox proteomics technique normally combines two-dimensional gel electrophoresis, mass spectrometry and protein databases to analyze the cell proteome from different samples, thereby leading to the identification of specific targets of oxidative modification. Oxidative stress that occurs due to increased levels of reactive oxygen species and reactive nitrogen species can target most biomolecules, consequently leading to altered physiological function of the cells. Redox proteomics has identified oxidatively modified protein targets in different pathological conditions, consequently providing insight into the pathways involved in pathogenesis of these conditions. This approach also can be used to identify possible protective mechanisms to prevent or delay these disorders. PMID:21111808

  14. Oxidation induced stress-rupture of fiber bundles

    SciTech Connect

    Lara-Curzio, E.

    1997-03-01

    The effect of oxidation on the stress-rupture behavior of fiber bundles was modeled. It is shown that oxidation-induced fiber strength degradation results in the delayed failure of the associated fiber bundle and that the fiber bundle strength decreases with time as t{sup {minus}1/4}. It is also shown that the temperature dependence of the bundle loss of strength reflects the thermal dependence of the mechanism controlling the oxidation of the fibers. The effect of gauge length on the fiber bundle strength was also analyzed. Numerical examples are presented for the special case of Nicalon{trademark} fibers.

  15. Specioside ameliorates oxidative stress and promotes longevity in Caenorhabditis elegans.

    PubMed

    Asthana, Jyotsna; Yadav, A K; Pant, Aakanksha; Pandey, Swapnil; Gupta, M M; Pandey, Rakesh

    2015-03-01

    Specioside (6-O-coumaroylcatalpol) is an iridoid glucoside which possesses multifunctional activities viz. analgesic, antidyspeptic, astringent, liver stimulating and wound healing properties. The present study for the first time delineates stress alleviating and lifespan prolonging action of specioside (SPC), isolated from Stereospermum suaveolens in the free living, multicellular nematode model Caenorhabditis elegans. A strong correlation between lifespan extension and stress modulation in adult worms was established in a dose dependent manner. The dietary intake of this phytomolecule elevated juglone induced oxidative and heat induced thermal stress tolerance in C. elegans. On evaluation, it was found that 25 μM dose of SPC significantly extended lifespan by 15.47% (P≤0.0001) with reduction in stress level. Furthermore, SPC enhanced mean survival in mev-1 mutant suggesting its oxidative stress reducing potential. Furthermore, SPC augmented stress modulatory enzymes superoxide dismutase (SOD) and catalase (CAT) level in C. elegans. Altogether, these findings broaden current perspectives concerning stress alleviating potentials of SPC and have implications in development of therapeutics for curing age related disorders. PMID:25619942

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  17. Dynamic Contrast-Enhanced Magnetic Resonance Imaging Reveals Stress-Induced Angiogenesis in MCF7 Human Breast Tumors

    NASA Astrophysics Data System (ADS)

    Furman-Haran, Edna; Margalit, Raanan; Grobgeld, Dov; Degani, Hadassa

    1996-06-01

    The mechanism of contrast enhancement of tumors using magnetic resonance imaging was investigated in MCF7 human breast cancer implanted in nude mice. Dynamic contrast-enhanced images recorded at high spatial resolution were analyzed by an image analysis method based on a physiological model, which included the blood circulation, the tumor, the remaining tissues, and clearance via the kidneys. This analysis enabled us to map in rapidly enhancing regions within the tumor, the capillary permeability factor (capillary permeability times surface area per voxel volume) and the fraction of leakage space. Correlation of these maps with T2-weighted spin echo images, with histopathology, and with immunohistochemical staining of endothelial cells demonstrated the presence of dense permeable microcapillaries in the tumor periphery and in intratumoral regions that surrounded necrotic loci. The high leakage from the intratumoral permeable capillaries indicated an induction of a specific angiogenic process associated with stress conditions that cause necrosis. This induction was augmented in tumors responding to tamoxifen treatment. Determination of the distribution and extent of this stress-induced angiogenic activity by contrast-enhanced MRI might be of diagnostic and of prognostic value.

  18. Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors.

    PubMed

    Furman-Haran, E; Margalit, R; Grobgeld, D; Degani, H

    1996-06-25

    The mechanism of contrast enhancement of tumors using magnetic resonance imaging was investigated in MCF7 human breast cancer implanted in nude mice. Dynamic contrast-enhanced images recorded at high spatial resolution were analyzed by an image analysis method based on a physiological model, which included the blood circulation, the tumor, the remaining tissues, and clearance via the kidneys. This analysis enabled us to map in rapidly enhancing regions within the tumor, the capillary permeability factor (capillary permeability times surface area per voxel volume) and the fraction of leakage space. Correlation of these maps with T2-weighted spin echo images, with histopathology, and with immunohistochemical staining of endothelial cells demonstrated the presence of dense permeable microcapillaries in the tumor periphery and in intratumoral regions that surrounded necrotic loci. The high leakage from the intratumoral permeable capillaries indicated an induction of a specific angiogenic process associated with stress conditions that cause necrosis. This induction was augmented in tumors responding to tamoxifen treatment. Determination of the distribution and extent of this stress-induced angiogenic activity by contrast-enhanced MRI might be of diagnostic and of prognostic value. PMID:8692800

  19. Influence of Endodontic Treatment on Systemic Oxidative Stress

    PubMed Central

    Inchingolo, Francesco; Marrelli, Massimo; Annibali, Susanna; Cristalli, Maria Paola; Dipalma, Gianna; Inchingolo, Alessio Danilo; Palladino, Antonio; Inchingolo, Angelo Michele; Gargari, Marco; Tatullo, Marco

    2014-01-01

    Introduction: An increased production of oxidizing species related to reactive oral diseases, such as chronic apical periodontitis, could have systemic implications such as an increase in cardiovascular morbidity. Based on this consideration, we conducted a prospective study to assess whether subjects affected by chronic periodontitis presented with higher values of oxidative stress than reference values before endodontic treatment, and whether endodontic treatment can reduce the oxidative imbalance and bring it back to normal in these subjects. Materials and methods: The authors recruited 2 groups of patients from private studies and dental clinics: these patients were recruited randomly. The oxidative balance in both patients with chronic apical periodontitis (CAP) and healthy control patients was determined by measuring the oxidant status, using an identification of the reactive oxygen metabolites (d-ROMs) test, while the antioxidant status in these patients was determined using a biological antioxidant potential (BAP) test. Both these tests were carried on plasma samples taken from enrolled patients. Values were measured both before the endodontic treatment of the patients with chronic apical periodontitis, and 30 and 90 days after treatment, and compared to those obtained from healthy control patients. Results: It was found that, on recruitment, the patients with chronic apical periodontitis exhibited significantly higher levels of oxidative stress than control patients, as determined by the d-ROMs and BAP tests. Furthermore, the d-ROMs test values were shown to decrease and the BAP test values to increase over time in patients with chronic apical periodontitis following endodontic therapy. As the levels of oxidative stress in these patients tended to reduce and return to normal by 90 days following treatment. Conclusions: This study has demonstrated a positive association between chronic apical periodontitis and oxidative stress. Subjects affected by chronic

  20. Early onset Alzheimer's disease and oxidative stress.

    PubMed

    Meraz-Ríos, Marco Antonio; Franco-Bocanegra, Diana; Toral Rios, Danira; Campos-Peña, Victoria

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in elderly adults. It is estimated that 10% of the world's population aged more than 60-65 years could currently be affected by AD, and that in the next 20 years, there could be more than 30 million people affected by this pathology. One of the great challenges in this regard is that AD is not just a scientific problem; it is associated with major psychosocial and ethical dilemmas and has a negative impact on national economies. The neurodegenerative process that occurs in AD involves a specific nervous cell dysfunction, which leads to neuronal death. Mutations in APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have demonstrated that alterations in these proteins are able to induce oxidative damage, which in turn favors the development of AD. This paper provides a review of many, although not all, of the mutations present in patients with familial Alzheimer's disease and the association between some of these mutations with both oxidative damage and the development of the pathology. PMID:24669286

  1. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

    PubMed

    Tomlinson, Ryan E; Shoghi, Kooresh I; Silva, Matthew J

    2014-02-15

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected. PMID:24356518

  2. Adrenaline and noradrenaline: protectors against oxidative stress or molecular targets?

    PubMed

    Álvarez-Diduk, Ruslán; Galano, Annia

    2015-02-26

    Density functional theory was used to investigate the potential role of neurotransmitters adrenaline and noradrenaline regarding oxidative stress. It is predicted that they can be efficient as free radical scavengers both in lipid and aqueous media, with the main reaction mechanism being the hydrogen transfer and the sequential proton loss electron transfer, respectively. Despite the polarity of the environment, adrenaline and noradrenaline react with (•)OOH faster than Trolox, which suggests that they are better peroxyl radical scavengers than the reference compound. Both catecholamines are also proposed to be capable of efficiently inhibiting the oxidative stress induced by copper(II)-ascorbate mixtures, and the (•)OH production via Haber-Weiss reaction, albeit the effects on the later are only partial. They exert such beneficial effects by sequestering Cu(II) ions. In summary, these catecholamines can be capable of reducing oxidative stress, by scavenging free radicals and by sequestering metal ions. However, at the same time they might lose their functions in the process due to the associated structural modifications. Consequently, adrenaline and noradrenaline can be considered as both protectors and molecular targets of oxidative stress. Fortunately, under the proper conditions, both catecholamines can be regenerated to their original form so their functions are restored. PMID:25646569

  3. Study of Oxidative Stress in Different Forms of Leprosy

    PubMed Central

    Swathi, Manchala; Tagore, Ravirala

    2015-01-01

    Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. India records the highest number of new leprosy cases in the world. Oxidative stress may play a significant role in leprosy. Aim: The aim of the study was to evaluate oxidative stress in various forms of leprosy and compared to healthy controls. Materials and Methods: Seventy newly diagnosed, untreated leprosy patients were selected as cases and sixty healthy controls. Oxidative stress was evaluated by measuring serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. Student's unpaired t-test and Anova (Analysis of Variance) test were used for analysis of data. P < 0.05 was considered as significant. Results: There was a statistically significant increase in the mean values of serum MDA level, MDA/SOD and a decrease in serum SOD activity in cases when compared to controls and the values were significantly associated with increased duration, bacterial load and multibacillary type in leprosy. Conclusion: Our study suggests that there was oxidative stress in leprosy. This warrants antioxidant supplementation to prevent tissue injury. PMID:26120177

  4. Power of Proteomics in Linking Oxidative Stress and Female Infertility

    PubMed Central

    Gupta, Sajal; Sharma, Rakesh; Agarwal, Ashok

    2014-01-01

    Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions. PMID:24900998

  5. Effect of antioxidants on the oxidative stress in cataract patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the relationship between oxidative stress and eye disease, and the impact of antioxidant supplementation, forty subjects (50-70 y, F25, M15) were enrolled in a double blinded randomized study. Subjects were randomized to receive either 1) lutein (12 mg) or 2) lutein (12 mg) + green tea...

  6. Obesity and Oxidative Stress Predict AKI after Cardiac Surgery

    PubMed Central

    Pretorius, Mias; Schildcrout, Jonathan S.; Mercaldo, Nathaniel D.; Byrne, John G.; Ikizler, T. Alp; Brown, Nancy J.

    2012-01-01

    Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F2-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m2 [95% confidence interval, 4.3%–53.4%]; P=0.02). Baseline F2-isoprostane (P=0.04), intraoperative F2-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F2-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F2-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association. PMID:22626819

  7. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity

    PubMed Central

    Wang, Liying

    2013-01-01

    The rapidly emerging field of nanotechnology has offered innovative discoveries in the medical, industrial, and consumer sectors. The unique physicochemical and electrical properties of engineered nanoparticles (NP) make them highly desirable in a variety of applications. However, these novel properties of NP are fraught with concerns for environmental and occupational exposure. Changes in structural and physicochemical properties of NP can lead to changes in biological activities including ROS generation, one of the most frequently reported NP-associated toxicities. Oxidative stress induced by engineered NP is due to acellular factors such as particle surface, size, composition, and presence of metals, while cellular responses such as mitochondrial respiration, NP-cell interaction, and immune cell activation are responsible for ROS-mediated damage. NP-induced oxidative stress responses are torch bearers for further pathophysiological effects including genotoxicity, inflammation, and fibrosis as demonstrated by activation of associated cell signaling pathways. Since oxidative stress is a key determinant of NP-induced injury, it is necessary to characterize the ROS response resulting from NP. Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed. PMID:24027766

  8. Inducing mitophagy in diabetic platelets protects against severe oxidative stress.

    PubMed

    Lee, Seung Hee; Du, Jing; Stitham, Jeremiah; Atteya, Gourg; Lee, Suho; Xiang, Yaozu; Wang, Dandan; Jin, Yu; Leslie, Kristen L; Spollett, Geralyn; Srivastava, Anup; Mannam, Praveen; Ostriker, Allison; Martin, Kathleen A; Tang, Wai Ho; Hwa, John

    2016-01-01

    Diabetes mellitus (DM) is a growing international concern. Considerable mortality and morbidity associated with diabetes mellitus arise predominantly from thrombotic cardiovascular events. Oxidative stress-mediated mitochondrial damage contributes significantly to enhanced thrombosis in DM A basal autophagy process has recently been described as playing an important role in normal platelet activation. We now report a substantial mitophagy induction (above basal autophagy levels) in diabetic platelets, suggesting alternative roles for autophagy in platelet pathology. Using a combination of molecular, biochemical, and imaging studies on human DM platelets, we report that platelet mitophagy induction serves as a platelet protective mechanism that responds to oxidative stress through JNK activation. By removing damaged mitochondria (mitophagy), phosphorylated p53 is reduced, preventing progression to apoptosis, and preserving platelet function. The absence of mitophagy in DM platelets results in failure to protect against oxidative stress, leading to increased thrombosis. Surprisingly, this removal of damaged mitochondria does not require contributions from transcription, as platelets lack a nucleus. The considerable energy and resources expended in "prepackaging" the complex mitophagy machinery in a short-lived normal platelet support a critical role, in anticipation of exposure to oxidative stress. PMID:27221050

  9. Propofol and in vivo oxidative stress: effects of preservative.

    PubMed

    Brown, Robert H; Wagner, Elizabeth M; Cope, Keary A; Risby, Terence H

    2009-03-01

    Reactive oxygen species are associated with tissue inflammation and injury. Our laboratory has demonstrated that ethane, a stable product of lipid peroxidation, in exhaled breath can be used to measure total body oxidative stress. An ischemia-reperfusion model of lung injury in sheep has been studied in which pulmonary and bronchial lung perfusion could be interrupted and restored. The goal of this study was to investigate whether two commercial formulations of propofol and the individual components of the commercial formulations attenuated the oxidative stress produced in this model. Breath ethane and breath carbon monoxide were measured as biomarkers of oxidative stress that occur at reperfusion of ischemic tissue. Data were analyzed by a standard least-squares-fit model. One of the formulations for propofol, which contained the preservative ethylenediaminetetraacetic acid (EDTA), was found to decrease the overall level of oxidative stress in sheep. Furthermore, while several models of severe lung injury demonstrate additional production of reactive oxygen species, our model of ischemia/reperfusion of lung tissue did not. PMID:21383451

  10. NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions

    PubMed Central

    Murata, Hitoshi; Takamatsu, Hitoshi; Liu, Sulai; Kataoka, Ken; Huh, Nam-ho; Sakaguchi, Masakiyo

    2015-01-01

    Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson’s disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival. PMID:26555609

  11. Cocoa Phenolic Extract Protects Pancreatic Beta Cells against Oxidative Stress

    PubMed Central

    Martín, María Ángeles; Ramos, Sonia; Cordero-Herrero, Isabel; Bravo, Laura; Goya, Luis

    2013-01-01

    Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5–20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult. PMID:23912326

  12. Oxidative stress in songbirds exposed to dietary methylmercury.

    PubMed

    Henry, Katie A; Cristol, Daniel A; Varian-Ramos, Claire W; Bradley, Eric L

    2015-04-01

    Long-term, sublethal methylmercury exposure can cause reproductive depression, immune suppression, endocrine disruption and other problems in birds. We used two biomarkers to detect oxidative stress in livers of zebra finches (Taeniopygia guttata) developmentally exposed to sublethal levels of dietary methylmercury (0.0, 0.3, 0.6, 1.2, or 2.4 μg/g wet weight in diet). Our findings indicate that young adult finches exposed to environmentally relevant concentrations of mercury in ovo and through their diets, exhibited oxidative stress in their livers. We measured the ratio of the antioxidant glutathione in its reduced form (GSH) versus its oxidized form (GSSG) and the activity of the superoxide dismutase (SOD) enzyme suite. Blood total mercury served as a proxy for liver mercury concentration, and was on average 8.4 times the dietary dose (e.g., birds consuming 0.6 μg/g had blood mercury levels of ~5 μg/g on a wet weight basis). Consistent with what is known from large, aquatic bird species, there was a significant, negative relationship between GSH/GSSG ratios and tissue mercury concentrations, which is indicative of oxidative stress. This relationship was driven by a significant increase in the oxidized glutathione in the livers of birds with higher blood mercury levels. SOD activity was also found to have a significant, negative relationship with blood mercury. PMID:25519780

  13. Caffeic Acid, a Phenol Found in White Wine, Modulates Endothelial Nitric Oxide Production and Protects from Oxidative Stress-Associated Endothelial Cell Injury

    PubMed Central

    Mannari, Claudio; Bertelli, Alberto A. E.; Medica, Davide; Quercia, Alessandro Domenico; Navarro, Victor; Scatena, Alessia; Giovannini, Luca; Biancone, Luigi; Panichi, Vincenzo

    2015-01-01

    Introduction Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities. Aim of the study The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury. Results CAF increased basal as well as acetylcholine—induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration. Conclusion The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury. PMID:25853700

  14. Non-thermal Plasma and Oxidative Stress

    NASA Astrophysics Data System (ADS)

    Toyokuni, Shinya

    2015-09-01

    Thermal plasmas and lasers have been used in medicine to cut and ablate tissues and for coagulation. Non-equilibrium atmospheric pressure plasma (NEAPP; non-thermal plasma) is a recently developed, non-thermal technique with possible biomedical applications. Although NEAPP reportedly generates reactive oxygen/nitrogen species, electrons, positive ions, and ultraviolet radiation, few research projects have been conducted to merge this technique with conventional free radical biology. Recently, Prof. Masaru Hori's group (Plasma Nanotechnology Research Center, Nagoya University) developed a NEAPP device with high electron density. Here electron spin resonance revealed hydroxyl radicals as a major product. To merge non-thermal plasma biology with the preexisting free radical biology, we evaluated lipid peroxidation and DNA modifications in various in vitro and ex vivo experiments. Conjugated dienes increased after exposure to linoleic and alfa-linolenic acids. An increase in 2-thiobarbituric acid-reactive substances was also increased after exposure to phosphatidylcholine, liposomes or liver homogenate. Direct exposure to rat liver in medium produced immunohistochemical evidence of 4-hydroxy-2-nonenal- and acrolein-modified proteins. Exposure to plasmid DNA induced dose-dependent single/double strand breaks and increased the amounts of 8-hydroxy-2'-deoxyguanosine and cyclobutane pyrimidine dimers. These results indicate that oxidative biomolecular damage by NEAPP is dose-dependent and thus can be controlled in a site-specific manner. Simultaneous oxidative and UV-specific DNA damage may be useful in cancer treatment. Other recent advancements in the related studies of non-thermal plasma in Nagoya University Graduate School of Medicine will also be discussed.

  15. The effects of anesthetic agents on oxidative stress

    NASA Astrophysics Data System (ADS)

    Yakan, Selvinaz; Düzgüner, Vesile

    2016-04-01

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

  16. ER Protein Processing Under Oxidative Stress: Implications and Prevention.

    PubMed

    Khalil, Mahmoud F; Valenzuela, Carlos; Sisniega, Daniella; Skouta, Rachid; Narayan, Mahesh

    2016-06-01

    Elevated levels of mitochondrial nitrosative stress have been associated with the pathogenesis of both Parkinson's and Alzheimer's diseases. The mechanism involves catalytic poisoning of the endoplasmic reticulum (ER)-resident oxidoreductase chaperone, protein disulfide isomerase (PDI), and the subsequent accumulation of ER-processed substrate proteins. Using a model system to mimic mitochondrial oxidative and nitrosative stress, we demonstrate a PDI-independent mechanism whereby reactive oxygen species (ROS) compromise regeneration rates of disulfide bond-containing ER-processed proteins. Under ROS-duress, the secretion-destined traffic adopts disulfide-exposed structures making the protein flux retrotranslocation biased. We also demonstrate that ROS-compromised protein maturation rates can be rescued by the polyphenol ellagic acid (EA). Our results are significant in that they reveal an additional mechanism which could promote neurodegenerative disorders. Furthermore, our data reveal that EA possesses therapeutic potential as a lead prophylactic agent against oxidative/nitrosative stress-related neurodegenerative diseases. PMID:26983927

  17. Proinflammatory and Oxidative Stress Markers in Patients with Periodontal Disease

    PubMed Central

    Borges Jr., Ivan; Moreira, Emília Addison Machado; Filho, Danilo Wilhem; de Oliveira, Tiago Bittencourt; da Silva, Marcelo Barreto Spirelle; Fröde, Tânia Silvia

    2007-01-01

    Objective. To evaluate the involvement of proinflammatory and oxidative stress markers in gingival tissue in individuals with chronic periodontitis. Subject and methods. Eighteen subjects were divided in two groups: experimental (age 52.9±5.0) and control (age 51.1±9.6). The activities of enzymatic antioxidants such as catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase, nonenzymatic antioxidants: total glutathione and reduced glutathione, oxidized glutathione (GSSG), thiobarbituric acid reactive substances (TBARS), and myeloperoxidase activity (MPO) were evaluated in gingival tissues from interproximal sites. Statistical differences between groups were determined by independent Student t test and P<.05. Results. Individuals with periodontal disease exhibited a significant increase in the activities of MPO, GPx, GST, and also in TBARS and GSSG levels in gingival tissue compared to the control group (P<.05). Conclusion. The results of the present work showed an important correlation between oxidative stress biomarkers and periodontal disease. PMID:18288271

  18. [Neuroprotection strategies: effect of vinpocetine in vitro oxidative stress models].

    PubMed

    Pereira, Cláudia; Agostinho, Paula; Moreira, Paula I; Duarte, Ana I; Santos, Maria S; Oliveira, Catarina R

    2003-01-01

    Reactive oxygen species (ROS) play an important role in neuronal damage and death that occurs in several neurodegenerative disorders, namely in Alzheimer's disease (AD). The observation that ROS neutralization may slow or reduce the neurodegenerative process associated with those pathologies stimulates the development of new drugs, more efficient and well tolerated, with antioxidant properties. Vinpocetine [14-etoxicarbonyl-3alpha,16alpha-ethyl)-14,15-eburnamine], a vincamine derivative, efficiently protects cells from ROS attack. Recently, the protective effect of vinpocetine was demonstrated using in vitro models of oxidative stress induced by the oxidant pair ascorbate/Fe2+ and by synthetic peptides of the AD-associated b-amyloid protein (Abeta). Results obtained from these in vitro experiences support that additional clinical trials should be carried out using vinpocetine, or vinpocetine derivatives, in order to test its therapeutical or preventive effects in diseases where oxidative stress plays a crucial role. PMID:15631851

  19. Targeting Oxidative Stress in Central Nervous System Disorders.

    PubMed

    Patel, Manisha

    2016-09-01

    There is widespread recognition that reactive oxygen species (ROS) play key roles in normal brain function and pathology in the context of neurological disease. Oxidative stress continues to be a key therapeutic target for neurological diseases. In developing antioxidant therapies for neurological disease, special attention should be given to the brain's unique vulnerability to oxidative insults and its architecture. Consideration of antioxidant therapy should be guided by a strong rationale for oxidative stress in a given neurological disease. This review provides an overview of processes that can guide the development of antioxidant therapies in neurological diseases, such as knowledge of basic redox mechanisms, unique features of brain pathophysiology, mechanisms and classes of antioxidants, and desirable properties of drug candidates. PMID:27491897

  20. Exercise-induced oxidative stress and hypoxic exercise recovery.

    PubMed

    Ballmann, Christopher; McGinnis, Graham; Peters, Bridget; Slivka, Dustin; Cuddy, John; Hailes, Walter; Dumke, Charles; Ruby, Brent; Quindry, John

    2014-04-01

    Hypoxia due to altitude diminishes performance and alters exercise oxidative stress responses. While oxidative stress and exercise are well studied, the independent impact of hypoxia on exercise recovery remains unknown. Accordingly, we investigated hypoxic recovery effects on post-exercise oxidative stress. Physically active males (n = 12) performed normoxic cycle ergometer exercise consisting of ten high:low intensity intervals, 20 min at moderate intensity, and 6 h recovery at 975 m (normoxic) or simulated 5,000 m (hypoxic chamber) in a randomized counter-balanced cross-over design. Oxygen saturation was monitored via finger pulse oximetry. Blood plasma obtained pre- (Pre), post- (Post), 2 h post- (2Hr), 4 h post- (4Hr), and 6 h (6Hr) post-exercise was assayed for Ferric Reducing Ability of Plasma (FRAP), Trolox Equivalent Antioxidant Capacity (TEAC), Lipid Hydroperoxides (LOOH), and Protein Carbonyls (PC). Biopsies from the vastus lateralis obtained Pre and 6Hr were analyzed by real-time PCR quantify expression of Heme oxygenase 1 (HMOX1), Superoxide Dismutase 2 (SOD2), and Nuclear factor (euthyroid-derived2)-like factor (NFE2L2). PCs were not altered between trials, but a time effect (13 % Post-2Hr increase, p = 0.044) indicated exercise-induced blood oxidative stress. Plasma LOOH revealed only a time effect (p = 0.041), including a 120 % Post-4Hr increase. TEAC values were elevated in normoxic recovery versus hypoxic recovery. FRAP values were higher 6Hr (p = 0.045) in normoxic versus hypoxic recovery. Exercise elevated gene expression of NFE2L2 (20 % increase, p = 0.001) and SOD2 (42 % increase, p = 0.003), but hypoxic recovery abolished this response. Data indicate that recovery in a hypoxic environment, independent of exercise, may alter exercise adaptations to oxidative stress and metabolism. PMID:24384982

  1. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

    PubMed Central

    Li, Ning; Sioutas, Constantinos; Cho, Arthur; Schmitz, Debra; Misra, Chandan; Sempf, Joan; Wang, Meiying; Oberley, Terry; Froines, John; Nel, Andre

    2003-01-01

    The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria. PMID:12676598

  2. Myocardial Oxidative Stress in Infants Undergoing Cardiac Surgery.

    PubMed

    Sznycer-Taub, Nathaniel; Mackie, Stewart; Peng, Yun-Wen; Donohue, Janet; Yu, Sunkyung; Aiyagari, Ranjit; Charpie, John

    2016-04-01

    Cardiac surgery for congenital heart disease often necessitates a period of myocardial ischemia during cardiopulmonary bypass and cardioplegic arrest, followed by reperfusion after aortic cross-clamp removal. In experimental models, myocardial ischemia-reperfusion is associated with significant oxidative stress and ventricular dysfunction. A prospective observational study was conducted in infants (<1 year) who underwent elective surgical repair of a ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Blood samples were drawn following anesthetic induction (baseline) and directly from the coronary sinus at 1, 3, 5, and 10 min following aortic cross-clamp removal. Samples were analyzed for oxidant stress using assays for thiobarbituric acid-reactive substances, protein carbonyl, 8-isoprostane, and total antioxidant capacity. For each subject, raw assay data were normalized to individual baseline samples and expressed as fold-change from baseline. Results were compared using a one-sample t test with Bonferroni correction for multiple comparisons. Sixteen patients (ten with TOF and six with VSD) were enrolled in the study, and there were no major postoperative complications observed. For the entire cohort, there was an immediate, rapid increase in myocardial oxidative stress that was sustained for 10 min following aortic cross-clamp removal in all biomarker assays (all P < 0.01), except total antioxidant capacity. Infant cardiac surgery is associated with a rapid, robust, and time-dependent increase in myocardial oxidant stress as measured from the coronary sinus in vivo. Future studies with larger enrollment are necessary to assess any association between myocardial oxidative stress and early postoperative outcomes. PMID:26843460

  3. Linking phosphorus availability with photo-oxidative stress in plants.

    PubMed

    Hernández, Iker; Munné-Bosch, Sergi

    2015-05-01

    Plants have evolved a plethora of mechanisms to circumvent the potential damaging effects of living under low phosphorus availability in the soil. These mechanisms include different levels of organization, from root-shoot signalling at the whole-plant level to specific biochemical responses at the subcellular level, such as reductions in photosynthesis and the consequent activation of photo- and antioxidant mechanisms in chloroplasts. Some recent studies clearly indicate that severe phosphorus deficiency can lead to alterations in the photosynthetic apparatus, including reductions in CO2 assimilation rates, a down-regulation of photosynthesis-related genes and photoinhibition at the photosystem II level, thus causing potential photo-oxidative stress. Photo-oxidative stress is characterized by an increased production of reactive oxygen species in chloroplasts, which at low concentrations can serve a signalling, protective role, but when present at high concentrations can cause damage to lipids, proteins and nucleic acids, thus leading to irreversible injuries. We discuss here the mechanisms that phosphate-starved plants have evolved to withstand photo-oxidative stress, including changes at the subcellular level (e.g. activation of photo- and antioxidant protection mechanisms in chloroplasts), cellular and tissular levels (e.g. activation of photorespiration and anthocyanin accumulation) and whole-plant level (alterations in source-sink relationships modulated by hormones). Of particular importance is the current evidence demonstrating that phosphate-starved plants activate simultaneous responses at multiple levels, from transcriptional changes to root-shoot signalling, to prevent oxidative damage. In this review, we summarize current knowledge about the occurrence of photo-oxidative stress in phosphate-starved plants and highlight the mechanisms these plants have evolved to prevent oxidative damage under phosphorus limitation at the subcellular, cellular and whole

  4. Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways

    PubMed Central

    El Hasasna, Hussain; Saleh, Alaaeldin; Samri, Halima Al; Athamneh, Khawlah; Attoub, Samir; Arafat, Kholoud; Benhalilou, Nehla; Alyan, Sofyan; Viallet, Jean; Dhaheri, Yusra Al; Eid, Ali; Iratni, Rabah

    2016-01-01

    Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-α-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-α, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFκB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis. PMID:26888313

  5. A theoretical framework for predicting the oxidative stress potential of oxide nanoparticles.

    PubMed

    Burello, Enrico; Worth, Andrew P

    2011-06-01

    In this paper we propose a theoretical model that predicts the oxidative stress potential of oxide nanoparticles by looking at the ability of these materials to perturb the intracellular redox state. The model uses reactivity descriptors to build the energy band structure of oxide nanoparticles, assuming a particle diameter larger than 20-30 nm and no surface states in the band gap, and predicts their ability to induce an oxidative stress by comparing the redox potentials of relevant intracellular reactions with the oxides' energy structure. Nanoparticles displaying band energy values comparable with redox potentials of antioxidants or radical formation reactions have the ability to cause an oxidative stress and a cytotoxic response in vitro. We discuss the model's predictions for six relevant oxide nanoparticles (TiO(2), CuO, ZnO, FeO, Fe(2)O(3), Fe(3)O(4)) with literature in vitro studies and calculate the energy structure for 64 additional oxide nanomaterials. Such a framework would guide the development of more rational and efficient screening strategies avoiding random or exhaustive testing of new nanomaterials. PMID:21609138

  6. Oxidative Stress to the Cornea, Changes in Corneal Optical Properties, and Advances in Treatment of Corneal Oxidative Injuries

    PubMed Central

    Cejka, Cestmir; Cejkova, Jitka

    2015-01-01

    Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown. PMID:25861412

  7. Oxidative stress to the cornea, changes in corneal optical properties, and advances in treatment of corneal oxidative injuries.

    PubMed

    Cejka, Cestmir; Cejkova, Jitka

    2015-01-01

    Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown. PMID:25861412

  8. Endoplasmic reticulum stress and oxidative stress are involved in ZnO nanoparticle-induced hepatotoxicity

    PubMed Central

    Yang, Xia; Shao, Huali; Liu, Weirong; Gu, Weizhong; Shu, Xiaoli; Mo, Yiqun; Chen, Xuejun; Zhang, Qunwei; Jiang, Mizu

    2015-01-01

    Zinc oxide nanoparticles (Nano-ZnO) are widely used in sunscreens, clothes, medicine and electronic devices. However, the potential risks of human exposure and the potential for adverse health impacts are not well understood. Previous studies have demonstrated that exposure to Nano-ZnO caused liver damage and hepatocyte apoptosis through oxidative stress, but the molecular mechanisms that are involved in Nano-ZnO-induced hepatotoxicity are still unclear. Endoplasmic reticulum (ER) is sensitive to oxidative stress, and also plays a crucial role in oxidative stress-induced damage. Previous studies showed that ER stress was involved in many chemical-induced liver injuries. We hypothesized that exposure to Nano-ZnO caused oxidative stress and ER stress that were involved in Nano-ZnO-induced liver injury. To test our hypothesis, mice were gavaged with 200 mg/kg or 400 mg/kg of Nano-ZnO once a day for a period of 90 days, and blood and liver tissues were obtained for study. Our results showed that exposure to Nano-ZnO caused liver injury that was reflected by focal hepatocellular necrosis, congestive dilation of central veins, and significantly increased alanine transaminase (ALT) and aspartate transaminase (AST) levels. Exposure to Nano-ZnO also caused depletion of glutathione (GSH) the liver tissues. In addition, our electron microscope results showed that ER swelling and ribosomal degranulation were observed in the liver tissues from mice treated with Nano-ZnO. The mRNA expression levels of ER stress-associated genes (grp78, grp94, pdi-3, xbp-1) were also up-regulated in Nano-ZnO-treated mice. Nano-ZnO caused increased phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and eukaryotic initiation factor 2α (eIF2α). Finally, we found that exposure to Nano-ZnO caused increased ER stress-associated apoptotic protein levels, such as caspase-3, caspase-9, caspase-12, phosphorylation of JNK, and CHOP/GADD153, and up-regulation of pro-apoptotic genes (chop

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

    PubMed Central

    Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

    2012-01-01

    Background Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. Methods The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Results Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of 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

  10. Angiogenesis and liver fibrosis

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis. PMID:25848465

  11. Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function.

    EPA Science Inventory

    OBJECTIVE: Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and i...

  12. Protein Carbonyl Formation in Response to Propiconazole-Induced Oxidative Stress.

    EPA Science Inventory

    Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propico...

  13. An update on oxidative stress-mediated organ pathophysiology.

    PubMed

    Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

    2013-12-01

    Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. PMID:24084033

  14. Oxidative stress responses in the human fungal pathogen, Candida albicans.

    PubMed

    Dantas, Alessandra da Silva; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  15. Oxidative stress inhibits distant metastasis by human melanoma cells

    PubMed Central

    Piskounova, Elena; Agathocleous, Michalis; Murphy, Malea M.; Hu, Zeping; Huddlestun, Sara E.; Zhao, Zhiyu; Leitch, A. Marilyn; Johnson, Timothy M.; DeBerardinis, Ralph J.; Morrison, Sean J.

    2015-01-01

    Solid cancer cells commonly enter the blood and disseminate systemically but are highly inefficient at forming distant metastases for poorly understood reasons. We studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NSG mice. All melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficient metastasizers. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence upon NADPH-generating enzymes in the folate pathway. Anti-oxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumors in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo. PMID:26466563

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

    SciTech Connect

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    2013-12-15

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

  17. Measurement of Isoprostanes as Markers of Oxidative Stress

    PubMed Central

    Milatovic, Dejan; Montine, Thomas J.; Aschner, Michael

    2012-01-01

    Oxidative stress results from an imbalance between production of reactive oxygen and nitrogen species (ROS and RNS, respectively) and endogenous antioxidant defense mechanisms. Increased generation of ROS/RNS is implicated in the pathogenesis of a variety of human diseases, including neurodegenerative disease, atherosclerosis, cancer and aging. However, measuring oxidative stress in biological systems is complex and requires accurate quantification of either free radicals or damaged biomolecules. One method to quantify oxidative injury is to measure lipid peroxidation. Lipids are readily attacked by free radicals, resulting in the formation of a number of peroxidation products. F2-isoprostanes (F2-IsoPs) are one group of these compounds and they are derived by the free radical peroxidation of arachidonic acid (AA). The F2-IsoPs, prostaglandine F2-like compounds, provide an accurate measure of oxidative stress both in vitro and in vivo. This protocol details current methodology used to quantify these molecules using gas chromatography-mass spectrometry (GC-MS). PMID:21815067

  18. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

    PubMed Central

    Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

  19. Oxidative Stress in Children with Chronic Spontaneous Urticaria

    PubMed Central

    Dilek, Fatih; Ozceker, Deniz; Ozkaya, Emin; Guler, Nermin; Tamay, Zeynep; Kesgin, Siddika; Yazici, Mebrure; Kocyigit, Abdurrahim

    2016-01-01

    The pathogenesis of chronic spontaneous urticaria (CSU) has not been fully understood; nevertheless, significant progress has been achieved in recent years. The aim of this study was to investigate the possible role of reactive oxygen species (ROS) in the pathogenesis of CSU. Sixty-two children with CSU and 41 healthy control subjects were enrolled in the study. An extensive evaluation of demographic and clinical features was done, and serum oxidative stress was evaluated by plasma total oxidant status (TOS) and total antioxidant status (TAS) measurements. The median value of plasma TOS was found to be 10.49 μmol H2O2 equiv./L (interquartile range, 7.29–17.65) in CSU patients and 7.68 μmol H2O2 equiv./L (5.95–10.39) in the control group. The difference between the groups was statistically significant (p = 0.003). Likewise, the median plasma TAS level in the CSU group was decreased significantly compared to that of the control group (2.64 [2.30–2.74] versus 2.76 [2.65–2.86] mmol Trolox equiv./L, resp., p = 0,001). Our results indicated that plasma oxidative stress is increased in children with CSU when compared to healthy subjects, and plasma oxidative stress markers are positively correlated with disease activity. PMID:27127547

  20. Prevention of oxidative stress in porcine islet isolation.

    PubMed

    Stiegler, Philipp; Stadlbauer, Vanessa; Hackl, Florian; Schaffellner, Silvia; Iberer, Florian; Greilberger, Joachim; Strunk, Dirk; Zelzer, Sieglinde; Lackner, Carolin; Tscheliessnigg, Karlheinz

    2010-04-01

    High yields of pure and viable porcine islet cells (PICs) to be used for microencapsulation are crucial for successful xenotransplantation. Mechanical disruption of the pancreas, enzymes used for digestion, digestion temperature and time are among the factors known to cause oxidative stress and to impact on the yield, purity and viability of PICs. The aim of our study was to optimize conventional procedures in order to minimize the oxidative stress that occurs during the isolation and purification of PICs. Porcine pancreatic tissue was harvested at a local slaughterhouse, and 15 consecutive isolations of PICs were performed with a modified automated Ricordi method (Graz method) using a shorter digestion time, a lower digestion temperature and minimal mechanical stress. PICs were purified with the Lymphoprep density gradient medium. Purity and viability were assessed immediately after the isolation process and after overnight culture. PIC function was tested in glucose stimulation experiments and insulin concentration was determined by ELISA. Oxidative stress was assessed by measuring isoprostanes (IP), malondialdehyde (MDA) and lipase levels using a HPLC-based, colorimetric liquid assay or ELISA, respectively. The mean yield of PICs was 3479 +/- 542 IEQs/g pancreas, with 96.4% viability and 97.7% purity. There was no significant loss in PIC viability after overnight culture. Insulin secretion in response to glucose was not impaired after isolation and purification. IP, MDA and lipase levels did not change significantly during the isolation procedure. With our new Graz method we seem to have succeeded in preventing oxidative stress and achieving high yields of pure and viable PICs. PMID:20204442

  1. Differential oxidative stress responses in castor semilooper, Achaea janata.

    PubMed

    Pavani, Ayinampudi; Chaitanya, R K; Chauhan, Vinod K; Dasgupta, Anwesha; Dutta-Gupta, Aparna

    2015-11-01

    Balance between reactive oxygen species (ROS) and the antioxidant (AO) defense mechanisms is vital for organism survival. Insects serve as an ideal model to elucidate oxidative stress responses as they are prone to different kinds of stress during their life cycle. The present study demonstrates the modulation of AO enzyme gene expression in the insect pest, Achaea janata (castor semilooper), when subjected to different oxidative stress stimuli. Antioxidant enzymes' (catalase (Cat), superoxide dismutase (Sod), glutathione-S-transferase (GST) and glutathione peroxidase (Gpx)) partial coding sequences were cloned and characterized from larval whole body. Tissue expression studies reveal a unique pattern of AO genes in the larval tissues with maximum expression in the gut and fat body. Ontogeny profile depicts differential expression pattern through the larval developmental stages for each AO gene studied. Using quantitative RT-PCR, the expression pattern of these genes was monitored during sugar-induced (d-galactose feeding), infection-induced (Gram positive, Gram negative and non-pathogenic bacteria) and pesticide-induced oxidative stress (Bt Cry toxin). d-Galactose feeding differentially modulates the expression of AO genes in the larval gut and fat body. Immune challenge with Escherichia coli induces robust upregulation of AO genes when compared to Bacillus coagulans and Bacillus cereus in the larval fat body and gut. Cry toxin feeding predominantly induced GST upregulation in the gut. The current study suggests that though there are multiple ways of generation of oxidative stress in the insect, the organism tailors its response by insult- and tissue-specific recruitment of the antioxidant players and their differential regulation for each inducer. PMID:26455997

  2. Heat stress causes oxidative stress but not inflammatory signaling in porcine skeletal muscle

    PubMed Central

    Montilla, Sandra I Rosado; Johnson, Theresa P; Pearce, Sarah C; Gardan-Salmon, Delphine; Gabler, Nicholas K; Ross, Jason W; Rhoads, Robert P; Baumgard, Lance H; Lonergan, Steven M; Selsby, Joshua T

    2014-01-01

    Heat stress is associated with death and other maladaptions including muscle dysfunction and impaired growth across species. Despite this common observation, the molecular effects leading to these pathologic changes remain unclear. The purpose of this study was to determine the extent to which heat stress disrupted redox balance and initiated an inflammatory response in oxidative and glycolytic skeletal muscle. Female pigs (5–6/group) were subjected to thermoneutral (20 °C) or heat stress (35 °C) conditions for 1 or 3 days and the semitendinosus removed and dissected into red (STR) and white (STW) portions. After 1 day of heat stress, relative abundance of proteins modified by malondialdehyde, a measure of oxidative damage, was increased 2.5-fold (P < 0.05) compared with thermoneutral in the STR but not the STW, before returning to thermoneutral conditions following 3 days of heat stress. This corresponded with increased catalase and superoxide dismutase-1 gene expression (P < 0.05) and superoxide dismutase-1 protein abundance (P < 0.05) in the STR but not the STW. In the STR catalase and total superoxide dismutase activity were increased by ~30% and ~130%, respectively (P < 0.05), after 1 day of heat stress and returned to thermoneutral levels by day 3. One or 3 days of heat stress did not increase inflammatory signaling through the NF-κB pathway in the STR or STW. These data suggest that oxidative muscle is more susceptible to heat stress-mediated changes in redox balance than glycolytic muscle during chronic heat stress.

  3. Copper Oxide Nanoparticles Induce Oxidative Stress and Cytotoxicity in Airway Epithelial Cells

    PubMed Central

    Fahmy, Baher; Cormier, Stephania A.

    2009-01-01

    Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO2), ferric oxide (Fe2O3) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose dependent manner; while even high doses (400 µg/cm2) of SiO2 and Fe2O3 were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling. PMID:19699289

  4. β2-Glycoprotein I Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis by Suppressing the Phosphorylation of Extracellular Signal-Regulated Kinase 1/2, Akt, and Endothelial Nitric Oxide Synthase.

    PubMed

    Chiu, Wen-Chin; Chiou, Tzeon-Jye; Chung, Meng-Ju; Chiang, An-Na

    2016-01-01

    Angiogenesis is the process of new blood vessel formation, and it plays a key role in various physiological and pathological conditions. The β2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple biological functions, some of which remain to be elucidated. This study aimed to identify the contribution of 2-GPI on the angiogenesis induced by vascular endothelial growth factor (VEGF), a pro-angiogenic factor that may regulate endothelial remodeling, and its underlying mechanism. Our results revealed that β2-GPI dose-dependently decreased the VEGF-induced increase in endothelial cell proliferation, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the bromodeoxyuridine (BrdU) incorporation assays. Furthermore, incubation with both β2-GPI and deglycosylated β2-GPI inhibited the VEGF-induced tube formation. Our results suggest that the carbohydrate residues of β2-GPI do not participate in the function of anti-angiogenesis. Using in vivo Matrigel plug and angioreactor assays, we show that β2-GPI remarkably inhibited the VEGF-induced angiogenesis at a physiological concentration. Moreover, β2-GPI inhibited the VEGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, and endothelial nitric oxide synthase (eNOS). In summary, our in vitro and in vivo data reveal for the first time that β2-GPI inhibits the VEGF-induced angiogenesis and highlights the potential for β2-GPI in anti-angiogenic therapy. PMID:27579889

  5. Energy intake, oxidative stress and antioxidant in mice during lactation

    PubMed Central

    ZHENG, Guo-Xiao; LIN, Jiang-Tao; ZHENG, Wei-Hong; CAO, Jing; ZHAO, Zhi-Jun

    2015-01-01

    Reproduction is the highest energy demand period for small mammals, during which both energy intake and expenditure are increased to cope with elevated energy requirements of offspring growth and somatic protection. Oxidative stress life history theory proposed that reactive oxygen species (ROS) were produced in direct proportion to metabolic rate, resulting in oxidative stress and damage to macromolecules. In the present study, several markers of oxidative stress and antioxidants activities were examined in brain, liver, kidneys, skeletal muscle and small intestine in non-lactating (Non-Lac) and lactating (Lac) KM mice. Uncoupling protein (ucps) gene expression was examined in brain, liver and muscle. During peak lactation, gross energy intake was 254% higher in Lac mice than in Non-Lac mice. Levels of H2O2 of Lac mice were 17.7% higher in brain (P<0.05), but 21.1% (P<0.01) and 14.5% (P<0.05) lower in liver and small intestine than that of Non-Lac mice. Malonadialdehyde (MDA) levels of Lac mice were significantly higher in brain, but lower in liver, kidneys, muscle and small intestine than that of Non-Lac mice. Activity of glutathione peroxidase (GSH-PX) was significantly decreased in brain and liver in the Lac group compared with that in the Non-Lac group. Total antioxidant capacity (T-AOC) activity of Lac mice was significantly higher in muscle, but lower in kidneys than Non-Lac mice. Ucp4 and ucp5 gene expression of brain was 394% and 577% higher in Lac mice than in Non-Lac mice. These findings suggest that KM mice show tissue-dependent changes in both oxidative stress and antioxidants. Activities of antioxidants may be regulated physiologically in response to the elevated ROS production in several tissues during peak lactation. Regulations of brain ucp4 and ucp5 gene expression may be involved in the prevention of oxidative damage to the tissue. PMID:25855228

  6. Cellular mechanisms underlying oxidative stress in human exercise.

    PubMed

    Jackson, Malcolm J; Vasilaki, Aphrodite; McArdle, Anne

    2016-09-01

    A relative increase in oxidation of lipids, proteins and DNA has been recognised to occur in the circulation and tissues of exercising humans and animals since the late 1970s and throughout the ensuing 40 years a great deal of work has been undertaken to elucidate the potential source(s) of this exercise-induced "oxidative stress". Specific aspects of physical exercise (e.g. contractile activity, relative hypoxia, hyperaemia) may theoretically induce increased generation of reactive oxygen species in a number of potential tissues, but data strongly indicate that contractile activity of skeletal muscle predominates as the source of oxidants and contributes to local oxidation and that of extracellular biomaterials. Taken together with the relatively large mass of muscle compared with other tissues and cells it appears that muscle fibres are the major contributor to the relative increase in whole body "oxidative stress" during some forms of exercise. The sub-cellular sources of this increased oxidation have also been the subject of considerable research with early studies predominantly indicating that muscle mitochondria were the likely increased source of oxidants, such as hydrogen peroxide, but assessments of the relative concentrations of hydrogen peroxide in skeletal muscle fibres at rest and during contractile activity do not support this possibility. In contrast, several recent studies have identified NADPH oxidase enzymes in skeletal muscle that appear to play a signalling role in physiological responses exercise and together with xanthine oxidase enzymes may contribute to the relative increase in whole body oxidation. A fuller understanding of the relative roles of these sources and the function(s) of the species generated appears increasingly important in attempts to harness the beneficial effects of exercise for maintenance of health in aging and a variety of chronic conditions. PMID:26912036

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

    PubMed

    Zhang, Xi-Feng; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

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

  8. Oxidative stress and mechanisms of ochronosis in alkaptonuria.

    PubMed

    Braconi, Daniela; Millucci, Lia; Bernardini, Giulia; Santucci, Annalisa

    2015-11-01

    Alkaptonuria (AKU) is a rare metabolic disease due to a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD), involved in Phe and Tyr catabolism. Due to such a deficiency, AKU patients undergo accumulation of the metabolite homogentisic acid (HGA), which is prone to oxidation/polymerization reactions causing the production of a melanin-like pigment. Once the pigment is deposited onto connective tissues (mainly in joints, spine, and cardiac valves), a classical bluish-brown discoloration is imparted, leading to a phenomenon known as "ochronosis", the hallmark of AKU. A clarification of the molecular mechanisms for the production and deposition of the ochronotic pigment in AKU started only recently with a range of in vitro and ex vivo human models used for the study of HGA-induced effects. Thanks to redox-proteomic analyses, it was found that HGA could induce significant oxidation of a number of serum and chondrocyte proteins. Further investigations allowed highlighting how HGA-induced proteome alteration, lipid peroxidation, thiol depletion, and amyloid production could contribute to oxidative stress generation and protein oxidation in AKU. This review briefly summarizes the most recent findings on HGA-induced oxidative stress in AKU, helping in the clarification of the molecular mechanisms of ochronosis and potentially providing the basis for its pharmacological treatment. Future work should be undertaken in order to validate in vivo the results so far obtained in in vitro AKU models. PMID:25733348

  9. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    PubMed

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging. PMID:25834301

  10. A mitochondrial superoxide theory for oxidative stress diseases and aging

    PubMed Central

    Indo, Hiroko P.; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K. St.; Majima, Hideyuki J.

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging. PMID:25834301

  11. Embryonic exposure to corticosterone modifies the juvenile stress response, oxidative stress and telomere length

    PubMed Central

    Haussmann, Mark F.; Longenecker, Andrew S.; Marchetto, Nicole M.; Juliano, Steven A.; Bowden, Rachel M.

    2012-01-01

    Early embryonic exposure to maternal glucocorticoids can broadly impact physiology and behaviour across phylogenetically diverse taxa. The transfer of maternal glucocorticoids to offspring may be an inevitable cost associated with poor environmental conditions, or serve as a maternal effect that alters offspring phenotype in preparation for a stressful environment. Regardless, maternal glucocorticoids are likely to have both costs and benefits that are paid and collected over different developmental time periods. We manipulated yolk corticosterone (cort) in domestic chickens (Gallus domesticus) to examine the potential impacts of embryonic exposure to maternal stress on the juvenile stress response and cellular ageing. Here, we report that juveniles exposed to experimentally increased cort in ovo had a protracted decline in cort during the recovery phase of the stress response. All birds, regardless of treatment group, shifted to oxidative stress during an acute stress response. In addition, embryonic exposure to cort resulted in higher levels of reactive oxygen metabolites and an over-representation of short telomeres compared with the control birds. In many species, individuals with higher levels of oxidative stress and shorter telomeres have the poorest survival prospects. Given this, long-term costs of glucocorticoid-induced phenotypes may include accelerated ageing and increased mortality. PMID:22072607

  12. Circadian rhythms, oxidative stress, and antioxidative defense mechanisms.

    PubMed

    Hardeland, Rüdiger; Coto-Montes, Ana; Poeggeler, Burkhard

    2003-11-01

    Endogenous circadian and exogenously driven daily rhythms of antioxidative enzyme activities and of low molecular weight antioxidants (LMWAs) are described in various phylogenetically distant organisms. Substantial amplitudes are detected in several cases, suggesting the significance of rhythmicity in avoiding excessive oxidative stress. Mammalian and/or avian glutathione peroxidase and, as a consequence, glutathione reductase activities follow the rhythm of melatonin. Another hint for an involvement of melatonin in the control of redox processes is seen in its high-affinity binding to cytosolic quinone reductase 2, previously believed to be a melatonin receptor. Although antioxidative protection by pharmacological doses of melatonin is repeatedly reported, explanations of these findings are still insufficient and their physiological and chronobiological relevance is not yet settled. Recent data indicate a role of melatonin in the avoidance of mitochondrial radical formation, a function which may prevail over direct scavenging. Rhythmic changes in oxidative damage of protein and lipid molecules are also reported. Enhanced oxidative protein modification accompanied by a marked increase in the circadian amplitude of this parameter is detected in the Drosophila mutant rosy, which is deficient in the LMWA urate. Preliminary evidence for the significance of circadian rhythmicity in diminishing oxidative stress comes from clock mutants. In Drosophila, moderately enhanced protein damage is described for the arrhythmic and melatonin null mutant per0, but even more elevated, periodic damage is found in the short-period mutant per(s), synchronized to LD 12:12. Remarkably large increases in oxidative protein damage, along with impairment of tissue integrity and--obviously insufficient--compensatory elevations in protective enzymes are observed in a particularly vulnerable organ, the Harderian gland, of another short-period mutant tau, in the Syrian hamster. Mice deficient in

  13. In situ stress observation in oxide films and how tensile stress influences oxygen ion conduction

    PubMed Central

    Fluri, Aline; Pergolesi, Daniele; Roddatis, Vladimir; Wokaun, Alexander; Lippert, Thomas

    2016-01-01

    Many properties of materials can be changed by varying the interatomic distances in the crystal lattice by applying stress. Ideal model systems for investigations are heteroepitaxial thin films where lattice distortions can be induced by the crystallographic mismatch with the substrate. Here we describe an in situ simultaneous diagnostic of growth mode and stress during pulsed laser deposition of oxide thin films. The stress state and evolution up to the relaxation onset are monitored during the growth of oxygen ion conducting Ce0.85Sm0.15O2-δ thin films via optical wafer curvature measurements. Increasing tensile stress lowers the activation energy for charge transport and a thorough characterization of stress and morphology allows quantifying this effect using samples with the conductive properties of single crystals. The combined in situ application of optical deflectometry and electron diffraction provides an invaluable tool for strain engineering in Materials Science to fabricate novel devices with intriguing functionalities. PMID:26912416

  14. In situ stress observation in oxide films and how tensile stress influences oxygen ion conduction

    NASA Astrophysics Data System (ADS)

    Fluri, Aline; Pergolesi, Daniele; Roddatis, Vladimir; Wokaun, Alexander; Lippert, Thomas

    2016-02-01

    Many properties of materials can be changed by varying the interatomic distances in the crystal lattice by applying stress. Ideal model systems for investigations are heteroepitaxial thin films where lattice distortions can be induced by the crystallographic mismatch with the substrate. Here we describe an in situ simultaneous diagnostic of growth mode and stress during pulsed laser deposition of oxide thin films. The stress state and evolution up to the relaxation onset are monitored during the growth of oxygen ion conducting Ce0.85Sm0.15O2-δ thin films via optical wafer curvature measurements. Increasing tensile stress lowers the activation energy for charge transport and a thorough characterization of stress and morphology allows quantifying this effect using samples with the conductive properties of single crystals. The combined in situ application of optical deflectometry and electron diffraction provides an invaluable tool for strain engineering in Materials Science to fabricate novel devices with intriguing functionalities.

  15. In situ stress observation in oxide films and how tensile stress influences oxygen ion conduction.

    PubMed

    Fluri, Aline; Pergolesi, Daniele; Roddatis, Vladimir; Wokaun, Alexander; Lippert, Thomas

    2016-01-01

    Many properties of materials can be changed by varying the interatomic distances in the crystal lattice by applying stress. Ideal model systems for investigations are heteroepitaxial thin films where lattice distortions can be induced by the crystallographic mismatch with the substrate. Here we describe an in situ simultaneous diagnostic of growth mode and stress during pulsed laser deposition of oxide thin films. The stress state and evolution up to the relaxation onset are monitored during the growth of oxygen ion conducting Ce0.85Sm0.15O2-δ thin films via optical wafer curvature measurements. Increasing tensile stress lowers the activation energy for charge transport and a thorough characterization of stress and morphology allows quantifying this effect using samples with the conductive properties of single crystals. The combined in situ application of optical deflectometry and electron diffraction provides an invaluable tool for strain engineering in Materials Science to fabricate novel devices with intriguing functionalities. PMID:26912416

  16. Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

    PubMed Central

    Hu, Xin; Tao, Chuanyuan; Gan, Qi; Zheng, Jun; Li, Hao; You, Chao

    2016-01-01

    Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH. PMID:26843907

  17. Nitric oxide and biopterin in depression and stress.

    PubMed

    van Amsterdam, J G; Opperhuizen, A

    1999-01-18

    Depression has been hypothesized to be related to the reduced biosynthesis of neurotransmitters such as serotonin, noradrenalin and dopamine. Much past research has also been devoted to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression. The present article reviews the evidence linking tetrahydrobiopterin, a co-factor in the biosynthesis of neurotransmitters, and nitric oxide, an apparent neuroendocrine modulator of the HPA axis, to the immune system and to neuronal control within affective disorder and stress. On the basis of this review, it is suggested that future psychoneuroimmunological research should more fully explore the possible role of tetrahydrobiopterin and nitric oxide in depressive disorders. PMID:10195314

  18. Genotoxicity and oxidative stress in gasoline station attendants.

    PubMed

    Moro, Angela M; Charão, Mariele F; Brucker, Natália; Durgante, Juliano; Baierle, Marília; Bubols, Guilherme; Goethel, Gabriela; Fracasso, Rafael; Nascimento, Sabrina; Bulcão, Rachel; Gauer, Bruna; Barth, Anelise; Bochi, Guilherme; Moresco, Rafael; Gioda, Adriana; Salvador, Mirian; Farsky, Sandra; Garcia, Solange C

    2013-06-14

    We evaluated genotoxic effects of exposure to low levels of benzene, a class I human carcinogen, among gasoline station attendants (GSA). Oxidative stress and the protective effects of antioxidants on DNA damage were also analyzed. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, the GSA group presented higher DNA damage indices and micronucleus frequencies, increased oxidative protein damage, and decreased antioxidant capacity relative to the control group. Duration of benzene exposure was correlated with DNA and protein damage. The biomarkers evaluated in this work may provide early signals of damage in subjects occupationally exposed to benzene. PMID:23628435

  19. A novel approach in psoriasis: first usage of known protein oxidation markers to prove oxidative stress.

    PubMed

    Yazici, Cevat; Köse, Kader; Utaş, Serap; Tanrikulu, Esen; Taşlidere, Nazan

    2016-04-01

    Oxidative stress may play a pivotal role in the pathogenesis of psoriasis, an inflammatory/hyperproliferative skin disease characterized by the cutaneous accumulation of neutrophils releasing reactive oxygen species, as revealed in a number of studies. This study was performed to demonstrate the presence of oxidative stress in psoriasis, as measured by protein oxidation markers. Twenty-nine psoriasis patients were selected based on disease severity assessment using body surface area as well as the psoriasis area severity index (PASI), and were grouped as mild (PASI ≤ 10) and moderate-to-severe (PASI > 10). The measured parameters in psoriatic patients and fourteen healthy volunteers were as follows: erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (CRP), myeloperoxidase (MPO) activity, neopterin, total lipid hydroperoxides (LHP), pyrrolized protein (PP), protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP), thiol levels, along with complete blood count. Except lower thiols, all parameters were found to be higher in total patients as well as in subgroups, compared to controls. There was no significant difference among the subgroups. In conclusion, protein oxidation in psoriatics, not only in moderate-to-severe, but also in mild patients, may be explained by the findings of inflammation, phagocytic cell oxidation, and MPO-hypochlorous acid-oxidation reactions; as reflected by increased total/differential leucocytes counts, CRP, ESR as well as MPO, neopterin, AOPP, PCC, PP, LHP, and decreased thiol levels. Demonstrating the AOPP and PP formation for the first time, oxidants from active neutrophils/monocytes may play an important role in the pathogenesis of psoriasis, leading to oxidative stress, especially by protein oxidation. PMID:26842230

  20. Mediators of ocular angiogenesis

    PubMed Central

    Qazi, Yureeda; Maddula, Surekha; Ambati, Balamurali K.

    2011-01-01

    Angiogenesis is the formation of new blood vessels from pre-existing vasculature. Pathologic angiogenesis in the eye can lead to severe visual impairment. In our review, we discuss the roles of both pro-angiogenic and anti-angiogenic molecular players in corneal angiogenesis, proliferative diabetic retinopathy, exudative macular degeneration and retinopathy of prematurity, highlighting novel targets that have emerged over the past decade. PMID:20090210

  1. Excessive Selenium Supplementation Induced Oxidative Stress and Endoplasmic Reticulum Stress in Chicken Spleen.

    PubMed

    Wang, Yachao; Jiang, Li; Li, Yuanfeng; Luo, Xuegang; He, Jian

    2016-08-01

    Excessive selenium (Se) intake is harmful for animals and humans. The aim of the present study was to examine the effect of long-term excessive Se supplementation on oxidative stress and endoplasmic reticulum (ER) stress-related injuries in chicken spleen. A total of 180 1-day-old chickens were randomly divided into four groups with different Se dietary contents (0.2 mg/kg Se, 5 mg/kg Se, 10 mg/kg Se, or 15 mg/kg Se) for 45 days. Then, the levels of antioxidative enzymes, GPx, SOD, and MDA as well as the expression levels of GRP78, ARF6, caspase 3, caspase 12, and Bcl 2 in the spleen were determined at days 15, 30, and 45, respectively. The results showed that excessive Se treatment decreased the activities of GPx and SOD (P < 0.05) but increased the levels of MDA (P < 0.05) in a dose- and time-dependent manner. In addition, the ER stress genes GRP78 and ATF6 were highly expressed (P < 0.05), and the apoptosis genes caspase 3 and caspase 12 were increased, but Bcl 2 was decreased by Se treatment (P < 0.05). Correlation analysis showed that there was a high correlation between these biomarkers, which indicated that ER stress and ER stress-related apoptosis were correlated with oxidative stress. These results showed the important role of oxidative stress and ER stress in Se-related immune injuries in chicken. PMID:26740217

  2. Reproduction is not costly in terms of oxidative stress.

    PubMed

    Ołdakowski, Łukasz; Wasiluk, Aleksandra; Sadowska, Edyta T; Koteja, Paweł; Taylor, Jan R E

    2015-12-01

    One of the core assumptions of life-history theory is the negative trade-off between current and future reproduction. Investment in current reproduction is expected to decrease future reproductive success or survival, but the physiological mechanisms underlying these costs are still obscure. To test for a role of oxidative stress, we measured oxidative damage to lipids and proteins in liver, heart, kidneys and muscles, as well as the level of antioxidants (total glutathione and catalase), in breeding and non-breeding bank voles. We used females from lines selected for high aerobic metabolism and non-selected control lines and manipulated their reproductive investment by decreasing or increasing litter size. Unlike in most previous studies, the females reared four consecutive litters (the maximum possible during a breeding season). Contrary to predictions, oxidative damage in reproducing females was decreased or not changed, and did not differ between the selected and control lines. Oxidative damage to lipids and proteins in the liver was lower in females that weaned enlarged litters than in non-breeding ones, and was intermediate in those with reduced litters. Oxidative damage to proteins in the heart also tended to be lower in breeding females than in non-breeding ones. A negative relationship between the level of oxidative damage and activity of catalase in kidneys indicated a protective action of antioxidants. In conclusion, our study falsified the hypothesis that oxidative stress is a part of the proximate physiological mechanism underlying the fundamental life-history trade-off between current and future reproduction. PMID:26519508

  3. Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

    PubMed Central

    Kupsco, Allison; Schlenk, Daniel

    2016-01-01

    Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems. PMID:26008783

  4. Preclinical Alzheimer Disease: Brain Oxidative Stress, Aβ Peptide & Proteomics

    PubMed Central

    Aluise, Christopher D.; Robinson, Renã A. Sowell; Beckett, Tina L.; Murphy, M. Paul; Cai, Jian; Pierce, William M.; Markesbery, William R.; Butterfield, D. Allan

    2010-01-01

    Alzheimer disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory loss and subsequent dementia and neuropathologically by senile plaques, neurofibrillary tangles, and synapse loss. Interestingly, a small percentage of individuals with normal antemortem psychometric scores meet the neuropathological criteria for AD (termed `preclinical' AD (PCAD)). In this study, inferior parietal lobule (IPL) from PCAD and control subjects were compared for oxidative stress markers by immunochemistry, amyloid beta-peptide by ELISA, and identification of protein expression differences by proteomics. We observed a significant increase in highly insoluble monomeric Aβ42, but no significant differences in oligomeric Aβ nor in oxidative stress measurements between controls and PCAD subjects. Expression proteomics identified proteins whose trends in PCAD are indicative of cellular protection, possibly correlating with previous studies showing no cell loss in PCAD. Our analyses may reveal processes involved in a period of protection from neurodegeneration that mimic the clinical phenotype of PCAD. PMID:20399861

  5. Cardiovascular Complications in CKD Patients: Role of Oxidative Stress

    PubMed Central

    Gosmanova, Elvira O.; Le, Ngoc-Anh

    2011-01-01

    Starting with the early stages, patients with chronic kidney disease (CKD) experience higher burden of cardiovascular disease (CVD). Moreover, CVD complications are the major cause of mortality in CKD patients as compared with complications from chronic kidney failure. While traditional CVD risk factors, including diabetes, hypertension, hyperlipidemia, obesity, physical inactivity, may be more prevalent among CKD patients, these factors seem to underestimate the accelerated cardiovascular disease in the CKD population. Search for additional biomarkers that could explain the enhanced CVD risk in CKD patients has gained increasing importance. Although it is unlikely that any single nontraditional risk factor would fully account for the increased CVD risk in individuals with CKD, oxidative stress appears to play a central role in the development and progression of CVD and its complications. We will review the data that support the contribution of oxidative stress in the pathogenesis of CVD in patients with chronic kidney failure. PMID:21253517

  6. Oxidative Stress after Surgery on the Immature Heart

    PubMed Central

    Fudulu, Daniel; Angelini, Gianni

    2016-01-01

    Paediatric heart surgery is associated with increased inflammation and the production of reactive oxygen species. Use of the extracorporeal cardiopulmonary bypass during correction of congenital heart defects generates reactive oxygen species by various mechanisms: haemolysis, neutrophil activation, ischaemia reperfusion injury, reoxygenation injury, or depletion of the endogenous antioxidants. The immature myocardium is more vulnerable to reactive oxygen species because of developmental differences compared to the adult heart but also because of associated congenital heart diseases that can deplete its antioxidant reserve. Oxidative stress can be manipulated by various interventions: exogenous antioxidants, use of steroids, cardioplegia, blood prime strategies, or miniaturisation of the cardiopulmonary bypass circuit. However, it is unclear if modulation of the redox pathways can alter clinical outcomes. Further studies powered to look at clinical outcomes are needed to define the role of oxidative stress in paediatric patients. PMID:27123154

  7. Endothelial dysfunction and preeclampsia: role of oxidative stress

    PubMed Central

    Sánchez-Aranguren, Lissette C.; Prada, Carlos E.; Riaño-Medina, Carlos E.; Lopez, Marcos

    2014-01-01

    Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5–10% of the pregnancies. The problem is particularly important in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries. Risk factors for the development of PE include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED). However, how all these clinical manifestations concur to develop PE is still not very well understood. The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED. Here we aim to review current literature from research showing the interplay between oxidative stress, ED and PE to the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation. PMID:25346691

  8. [Oxidative stress and antioxitant therapy of chronic periodontitis].

    PubMed

    Shen, Y X; Guo, S J; Wu, Y F

    2016-07-01

    Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis. PMID:27480437

  9. Oxidative Stress and Programmed Cell Death in Yeast

    PubMed Central

    Farrugia, Gianluca; Balzan, Rena

    2012-01-01

    Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed. PMID:22737670

  10. Relationship between Oxidative Stress, Circadian Rhythms, and AMD

    PubMed Central

    Fanjul-Moles, María Luisa; López-Riquelme, Germán Octavio

    2016-01-01

    This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed. PMID:26885250

  11. Oxidative stress does not influence carotenoid mobilization and plumage pigmentation

    PubMed Central

    Isaksson, Caroline; Andersson, Staffan

    2007-01-01

    Summary Oxidative stress has been suggested to create a link between ‘good genes’ and carotenoid coloration via an allocation conflict between external pigmentation and internal antioxidant functions. However, although carotenoid displays have been extensively investigated, there are no experimental tests of the antioxidant efficiency of carotenoids in vivo. We induced oxidative stress in a small passerine (the great tit, Parus major) under both carotenoid deprivation and supplementation, and investigated the effect on carotenoid mobilization (i.e. plasma) and allocation (i.e. deposition in feather incorporation and liver storage). We found no effects of the stressor on either mobilization or allocation of carotenoids. These results reject the previously suggested superior role of carotenoid's function as antioxidant in vivo with important implications for signal content and honesty. PMID:18029305

  12. Oxidative stress and species of genus Ganoderma (higher Basidiomycetes).

    PubMed

    Cilerdzic, Jasmina; Stajic, Mirjana; Vukojevic, Jelena; Duletic-Lausevic, Sonja

    2013-01-01

    Oxidative stress, which is a factor in the aging process and in a series of serious disorders, arises when the reactive oxygen or nitrogen species are produced in excess and the capacity of cellular antioxidant defense is insufficient to detoxify and remove them. An internal antioxidant system is not always active enough to protect the human body from oxidative stress and, therefore, it needs the help of either synthetic or natural antioxidants. Nowadays, there is a growing interest in the substitution of synthetic antioxidants, which could have toxic and mutagen effects, with natural antioxidants. Recent studies revealed that besides their high nutritional value, mushrooms have great potential as antioxidant agents. Species of the genus Ganoderma, especially G. lucidum, are well-known medicinal mushrooms that traditionally are used in the prevention and treatment of many diseases and possess appreciable antioxidant potential. PMID:23510281

  13. Nitric Oxide, Oxidative Stress, and p66Shc Interplay in Diabetic Endothelial Dysfunction

    PubMed Central

    Greco, Simona; Capogrossi, Maurizio C.; Gaetano, Carlo

    2014-01-01

    Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, p66Shc protein. PMID:24734227

  14. Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

    PubMed

    Vaanholt, L M; Milne, A; Zheng, Y; Hambly, C; Mitchell, S E; Valencak, T G; Allison, D B; Speakman, J R

    2016-02-01

    Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis. PMID:26569452

  15. Oxidative stress and plasma lipoproteins in cancer patients

    PubMed Central

    Maia, Fernanda Maria Machado; Santos, Emanuelly Barbosa; Reis, Germana Elias

    2014-01-01

    Objective To evaluate the relation between oxidative stress and lipid profile in patients with different types of cancer. Methods This was an observational cross-sectional. A total of 58 subjects were evaluated, 33 males, divided into two groups of 29 patients each: Group 1, patients with cancer of the digestive tract and accessory organs; Group 2 patients with other types of cancers, all admitted to a public hospital. The plasma levels (lipoproteins and total cholesterol, HDL, and triglycerides, for example) were analyzed by enzymatic kits, and oxidative stress based on thiobarbituric acid-reactive substances, by assessing the formation of malondialdehyde. Results In general the levels of malondialdehyde of patients were high (5.00μM) as compared to 3.31μM for healthy individuals. The median values of lipids exhibited normal triacylglycerol (138.78±89.88mg/dL), desirable total cholesterol values (163.04±172.38mg/dL), borderline high LDL (151.30±178.25mg/dL) and low HDL (31.70±22.74mg/dL). Median HDL levels in Group 1 were lower (31.32mg/dL) than the cancer patients in Group 2 (43.67mg/dL) (p=0.038). Group 1 also showed higher levels of oxidative stress (p=0.027). Conclusion The lipid profile of patients with cancer was not favorable, which seems to have contributed to higher lipid peroxidation rate, generating a significant oxidative stress. PMID:25628201

  16. Oxidative stress and intracellular infections: more iron to the fire.

    PubMed

    Andrews, Norma W

    2012-07-01

    The immune system's battle against pathogens includes the "respiratory burst," a rapid release of ROS from leukocytes, thought to play a role in destroying the invading species. In this issue of the JCI, Paiva et al. demonstrate that oxidative stress actually enhances infection with the protozoan Trypanosoma cruzi, by a mechanism that may involve facilitating parasite access to iron. Their findings suggest a novel direction for the development of drugs against intracellular parasites. PMID:22728929

  17. The influence of homocysteine and oxidative stress on pregnancy outcome.

    PubMed

    Micle, O; Muresan, M; Antal, L; Bodog, F; Bodog, A

    2012-02-22

    Oxidative stress in utero-placental tissues plays an important role in the development of placental-related diseases. Maternal hiperhomocysteinemia is associated with placental mediated diseases, such as preeclampsia, spontaneous abortion and placental abruption. The aim of our study is to appreciate the clinical usefulness of the dosage serum homocysteine and malondialdehyde, as an oxidative stress marker, in the pregnancies complicated with risk of abortion or preterm birth. The study was performed at the Obstetric Gynecology Clinical Hospital Oradea from December 2009 until April 2010. It included 18 patients with risk of abortion (group 1), 22 with preterm birth (group 2). The results were compared with a control group composed by 14 healthy pregnant women. Serum homocysteine level was measured by an enzymatic method, on the instrument Hitachi 912, Roche, reagent: Axis-Shield Enzymatic. For proving the oxidative stress we established the level of malondialdehyde using a method with thiobarbituric acid TBA (Kei Satoh 1978) and the level of ceruloplasmin with the Ravin method .Also AST, ALT,CRP, iron, uric acid, urea were assessed.High level of homocysteine in both groups of study in comparison with the control group was found. The concentration of MDA was significantly higher in pregnancies complicated with risk of abortion and preterm birth compared to the control group (p=0.040, p=0.031). Considerable differences of ceruloplasmin concentration between group 1 and group 2 (p=0.045), and between group 2 and control group (p=0.034), was noticed but not any important differences between group 1 and control group (p=0.683). In women with risk of abortion or with preterm birth an oxidative stress and a hyperhomocysteinemia are present. PMID:22574089

  18. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    PubMed Central

    Prokopieva, V. D.; Yarygina, E. G.; Bokhan, N. A.; Ivanova, S. A.

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress. PMID:26904160

  19. Procedural Pain and Oxidative Stress in Premature Neonates

    PubMed Central

    Slater, Laurel; Asmerom, Yayesh; Boskovic, Danilo S.; Bahjri, Khaled; Plank, Megan S; Angeles, Katherine R.; Phillips, Raylene; Deming, Douglas; Ashwal, Stephen; Hougland, Kristen; Fayard, Elba; Angeles, Danilyn M.

    2012-01-01

    Preterm neonates exposed to painful NICU procedures exhibit increased pain scores and alterations in oxygenation and heart rate. It is unclear whether these physiologic responses increase the risk of oxidative stress. Using a prospective study design, we examined the relationship between a tissue-damaging procedure (TDP, tape removal during discontinuation of an indwelling central arterial or venous catheter) and oxidative stress in 80 preterm neonates. Oxidative stress was quantified by measuring uric acid (UA) and malondialdehyde (MDA) concentration in plasma before and after neonates experienced a TDP (n=38) compared to those not experiencing any TDP (control group, n=42). Pain was measured before and during the TDP using the Premature Infant Pain Profile(PIPP). We found that pain scores were higher in the TDP group compared to the control group (median scores:11 and 5, respectively, P<0.001). UA significantly decreased over time in control neonates but remained stable in TDP neonates (132.76μM to 123.23μM vs.140.50μM to 138.9μM, P=0.002). MDA levels decreased over time in control neonates but increased in TDP neonates (2.07μM to 1.81μM vs. 2.07μM to 2.21μM, P=0.01). We found significant positive correlations between PIPP scores and MDA. Our data suggest a significant relationship between procedural pain and oxidative stress in preterm neonates. PMID:22543043

  20. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

    SciTech Connect

    Fleckenstein, Katharina; Zgonjanin, Larisa; Chen Liguang; Rabbani, Zahid; Jackson, Isabel L.; Thrasher, Bradley; Kirkpatrick, John; Foster, W. Michael; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2007-05-01

    Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-{beta} [TGF-{beta}]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-{beta} expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.

  1. Increased oxidative stress following acute and chronic high altitude exposure.

    PubMed

    Jefferson, J Ashley; Simoni, Jan; Escudero, Elizabeth; Hurtado, Maria-Elena; Swenson, Erik R; Wesson, Donald E; Schreiner, George F; Schoene, Robert B; Johnson, Richard J; Hurtado, Abdias

    2004-01-01

    The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude. PMID:15072717

  2. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies.

    PubMed

    Prokopieva, V D; Yarygina, E G; Bokhan, N A; Ivanova, S A

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress. PMID:26904160

  3. Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress

    PubMed Central

    Park, Ji Young; Han, Xia; Piao, Mei Jing; Oh, Min Chang; Fernando, Pattage Madushan Dilhara Jayatissa; Kang, Kyoung Ah; Ryu, Yea Seong; Jung, Uhee; Kim, In Gyu; Hyun, Jin Won

    2016-01-01

    Background: Hyperoside, a flavonoid which is mainly found in Hypericum perforatum L., has many biological effects. One of the most important effects is to prevent the oxidative stress induced by reactive oxygen species. However, the molecular mechanisms underlying its effect are not fully understood. Oxidative stress is implicated in the occurrence of various physical diseases. A wide array of enzymatic antioxidant defense systems include NADH: quinone oxidoreductase 1, superoxide dismutase, and heme oxygenase-1 (HO-1). In the present study, the protective effects of hyperoside against hydrogen peroxide-induced oxidative stress in human lens epithelial cells, HLE-B3, were investigated in terms of HO-1 induction. Methods: The protein and mRNA expressions of HO-1 were examined by Western blotting and reverse transcriptase-PCR assays, respectively. To evaluate the ability of hyperoside to activate nuclear factor erythroid 2-related factor 2 (Nrf2), Western blotting and electrophoretic mobility shift assay were performed with nuclear extracts prepared from HLE-B3 cells treated with hyperoside. The activation of extracellular signal-regulated kinase (ERK), the upstream kinase of Nrf2 signaling, was monitored by Western blot analysis. The protective effect of hyperoside in HLE-B3 cells against hydrogen peroxide was performed by MTT assay. Results: Hyperoside increased both the mRNA and protein expression of HO-1 in a time- and dose-dependent manner. In addition, hyperoside elevated the level of of Nrf2 and its antioxidant response element-binding activity, which was modulated by upstream of ERK. Moreover, it activated ERK and restored cell viability which was decreased by hydrogen peroxide. Conclusions: Hyperoside is an effective compound to protect cells against oxidative stress via HO-1 induction. PMID:27051648

  4. Oxidative stress and lung pathology following geogenic dust exposure.

    PubMed

    Leetham, M; DeWitt, J; Buck, B; Goossens, D; Teng, Y; Pollard, J; McLaurin, B; Gerads, R; Keil, D

    2016-10-01

    This study was designed to evaluate markers of systemic oxidative stress and lung histopathology following subacute exposure to geogenic dust with varying heavy metal content collected from a natural setting prone to wind erosion and used heavily for off-road vehicle recreation. Adult female B6C3F1 mice were exposed to several concentrations of dust collected from seven different types of surfaces at the Nellis Dunes Recreation Area in Clark County, Nevada, designated here as CBN 1-7. Dust representing each of the seven surface types, with an average median diameter of 4.2 μm, was selected and administered via oropharyngeal aspiration to mice at concentrations from 0.01 to 100 mg of dust kg(-1) of body weight. Exposures were given four times spaced a week apart over a 28 day period to mimic a month of weekend exposures. Lung pathology was evaluated while plasma markers of oxidative stress included levels of reactive oxygen and nitrogen species, superoxide dismutase, total antioxidant capacity and total glutathione. Overall, results of these assays to evaluate markers of oxidative stress indicate that no single CBN surface type was able to consistently induce markers of systemic oxidative stress at a particular dose or in a dose-response manner. All surface types were able to induce some level of lung inflammation, typically at the highest exposure levels. These data suggest that dust from the Nellis Dunes Recreation Area may present a potential health risk, but additional studies are necessary to characterize the full extent of health risks to humans. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26922875

  5. Role of Glyoxylate Shunt in Oxidative Stress Response.

    PubMed

    Ahn, Sungeun; Jung, Jaejoon; Jang, In-Ae; Madsen, Eugene L; Park, Woojun

    2016-05-27

    The glyoxylate shunt (GS) is a two-step metabolic pathway (isocitrate lyase, aceA; and malate synthase, glcB) that serves as an alternative to the tricarboxylic acid cycle. The GS bypasses the carbon dioxide-producing steps of the tricarboxylic acid cycle and is essential for acetate and fatty acid metabolism in bacteria. GS can be up-regulated under conditions of oxidative stress, antibiotic stress, and host infection, which implies that it plays important but poorly explored roles in stress defense and pathogenesis. In many bacterial species, including Pseudomonas aeruginosa, aceA and glcB are not in an operon, unlike in Escherichia coli In P. aeruginosa, we explored relationships between GS genes and growth, transcription profiles, and biofilm formation. Contrary to our expectations, deletion of aceA in P. aeruginosa improved cell growth under conditions of oxidative and antibiotic stress. Transcriptome data suggested that aceA mutants underwent a metabolic shift toward aerobic denitrification; this was supported by additional evidence, including up-regulation of denitrification-related genes, decreased oxygen consumption without lowering ATP yield, increased production of denitrification intermediates (NO and N2O), and increased cyanide resistance. The aceA mutants also produced a thicker exopolysaccharide layer; that is, a phenotype consistent with aerobic denitrification. A bioinformatic survey across known bacterial genomes showed that only microorganisms capable of aerobic metabolism possess the glyoxylate shunt. This trend is consistent with the hypothesis that the GS plays a previously unrecognized role in allowing bacteria to tolerate oxidative stress. PMID:27036942

  6. Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats.

    PubMed

    Akhtar, Muhammad Furqan; Ashraf, Muhammad; Anjum, Aftab Ahmad; Javeed, Aqeel; Sharif, Ali; Saleem, Ammara; Akhtar, Bushra

    2016-01-01

    Exposure to complex mixtures like textile effluent poses risks to animal and human health such as mutations, genotoxicity and oxidative damage. Aim of the present study was to quantify metals in industrial effluent and to determine its mutagenic, genotoxic and cytotoxic potential and effects on oxidative stress biomarkers in effluent exposed rats. Metal analysis revealed presence of high amounts of zinc, copper, chromium, iron, arsenic and mercury in industrial effluent. Ames test with/without enzyme activation and MTT assay showed strong association of industrial effluent with mutagenicity and cytotoxicity respectively. In-vitro comet assay revealed evidence of high oxidative DNA damage. When Wistar rats were exposed to industrial effluent in different dilutions for 60 days, then activities of total superoxide dismutase and catalase and hydrogen peroxide concentration were found to be significantly lower in kidney, liver and blood/plasma of effluent exposed rats than control. Vitamin C in a dose of 50 mg/kg/day significantly reduced oxidative effects of effluent in rats. On the basis of this study it is concluded that industrial effluent may cause mutagenicity, in-vitro oxidative stress-related DNA damage and cytotoxicity and may be associated with oxidative stress in rats. Vitamin C may have ameliorating effect when exposed to effluent. PMID:26710178

  7. Oxidative stress and anti-oxidant defense system in Iranian women with polycystic ovary syndrome

    PubMed Central

    Moti, Mahtab; Amini, Leila; Mirhoseini Ardakani, Soheila Sadat; Kamalzadeh, Sara; Masoomikarimi, Masoomeh; jafarisani, Moslem

    2015-01-01

    Background: Polycystic ovary syndrome (PCOS) is a common disorder of infertility which affects more than 100 million women. It is characterized by chronic anovulation, hyper androgenism and obesity. PCOS is also associated with oxidative stress changes. Objective: Here, we aimed to investigate the level of antioxidants and oxidative stress in Iranian women with PCOS as a predictive factor for cardiovascular disease for the first time in Iran. Materials and Methods: In this cross sectional study 30 women with PCOS and 30 healthy women were included. C-reactive protein, serum insulin, advanced oxidation protein products, and level of total antioxidants status were measured from blood samples. Results: The levels of serum insulin, C-reactive protein, advanced oxidation protein productswere significantly increased in women with PCOS compared with healthy women but there was a decrease in level of total antioxidants status in PCOS women. Conclusion: These changes show that oxidative stress contributes to PCOS and the decrease of antioxidants leads to increase of oxidation products contributing to PCOS. PMID:26330853

  8. Antioxidant supplementation overcomes the deleterious effects of maternal restraint stress-induced oxidative stress on mouse oocytes.

    PubMed

    Lian, Hua-Yu; Gao, Yan; Jiao, Guang-Zhong; Sun, Ming-Ju; Wu, Xiu-Fen; Wang, Tian-Yang; Li, Hong; Tan, Jing-He

    2013-12-01

    In this study, using a mouse model, we tested the hypothesis that restraint stress would impair the developmental potential of oocytes by causing oxidative stress and that antioxidant supplementation could overcome the adverse effect of stress-induced oxidative stress. Female mice were subjected to restraint stress for 24 h starting 24 h after equine chorionic gonadotropin injection. At the end of stress exposure, mice were either killed to recover oocytes for in vitro maturation (IVM) or injected with human chorionic gonadotropin and caged with male mice to observe in vivo development. The effect of antioxidants was tested in vitro by adding them to IVM medium or in vivo by maternal injection immediately before restraint stress exposure. Assays carried out to determine total oxidant and antioxidant status, oxidative stress index, and reactive oxygen species (ROS) and glutathione levels indicated that restraint stress increased oxidative stress in mouse serum, ovaries, and oocytes. Whereas the percentage of blastocysts and number of cells per blastocyst decreased significantly in oocytes from restraint-stressed mice, addition of antioxidants to IVM medium significantly improved their blastocyst development. Supplementation of cystine and cysteamine to IVM medium reduced ROS levels and aneuploidy while increasing glutathione synthesis and improving pre- and postimplantation development of oocytes from restraint-stressed mice. Furthermore, injection of the antioxidant epigallocatechin gallate into restraint-stressed mice significantly improved the blastocyst formation and postimplantation development of their oocytes. In conclusion, restraint stress at the oocyte prematuration stage impaired the developmental potential of oocytes by increasing oxidative stress and addition of antioxidants to IVM medium or maternal antioxidant injection overcame the detrimental effect of stress-induced oxidative stress. The data reported herein are helpful when making attempts to

  9. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis

    PubMed Central

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-01-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2) induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  10. Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites.

    PubMed

    Ozer, Ufuk; Barbour, Karen W; Clinton, Sarah A; Berger, Franklin G

    2015-12-01

    Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of fluoropyrimidine and folate analogs have been developed that lead to inhibition of the enzyme, resulting in dTMP deficiency and cell death. In the current study, we have examined the role of oxidative stress in response to TYMS inhibitors. We observed that intracellular reactive oxygen species (ROS) concentrations are induced by these inhibitors and promote apoptosis. Activation of the enzyme NADPH oxidase (NOX), which catalyzes one-electron reduction of O2 to generate superoxide (O2 (●-)), is a significant source of increased ROS levels in drug-treated cells. However, gene expression profiling revealed a number of other redox-related genes that may contribute to ROS generation. TYMS inhibitors also induce a protective response, including activation of the transcription factor nuclear factor E2-related factor 2 (NRF2), a critical mediator of defense against oxidative and electrophilic stress. Our results show that exposure to TYMS inhibitors induces oxidative stress that leads to cell death, while simultaneously generating a protective response that may underlie resistance against such death. PMID:26443810

  11. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis.

    PubMed

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-11-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2)-induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  12. Oxytocin induced oxidative stress in lactating Bubalis bubalis (Nili Ravi)

    PubMed Central

    2013-01-01

    Background Oxytocin has been reported for a wide range of adverse effects in different species of lactating animals. The present study was aimed to evaluate the adverse effects of oxytocin on biomarkers of oxidative stress in buffaloes. Lactating buffaloes (n = 40) were randomly selected from a commercial dairy farm located in the peri-urban area of district Faisalabad, Pakistan and divided into two equal groups viz. treatment and control groups, each containing 20 buffaloes. Buffaloes in treatment group were injected with oxytocin before each milking (morning and evening) for milk let down; whereas, animals in control group were milked naturally without oxytocin injection. Both the groups were assessed for oxidative stress biomarkers. Results Results showed significantly higher levels (P ≤ 0.05) of TOS, tHcy and ceruloplasmin oxidase activity in lactating buffaloes injected with oxytocin as compared to those of control group. On the other hand, serum levels of TAS, PON1 and arylesterase were significantly lower (P ≤ 0.05) in the buffaloes of treatment group. Conclusions Oxytocin injection in lactating buffaloes resulted in elevated oxidative stress by increasing the total homocysteine and ceruloplasmin oxidase activity and decreasing enzymatic activities of antioxidant enzymes including paraoxonase-1 and arylesterase; that might render the animals to poor productive and reproductive potential. PMID:23981231

  13. Inflammation, oxidative stress and metabolic syndrome: dietary modulation.

    PubMed

    Fernández-García, José C; Cardona, Fernando; Tinahones, Francisco J

    2013-11-01

    The metabolic syndrome (MetS) is a cluster of risk factors for the development of cardiovascular disease and type 2 diabetes mellitus. These risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. MetS has become a serious public health and clinical problem whose prevalence and incidence are increasing along with the worldwide rise in rates of obesity and sedentary lifestyles. A number of studies have shown that MetS is associated with a state of low-grade inflammation, characterized by abnormal pro-inflammatory cytokine production, increased acute-phase reactants, and activation of a network of inflammatory signalling pathways. Moreover, MetS has also been linked to oxidative stress, a consequence of a reduction in the antioxidant systems and an increase in the production of reactive oxygen species. Nevertheless, agreement exists that dietary intervention may modulate the pro-inflammatory state and lessen oxidative stress related to MetS, thereby decreasing the cardiovascular risk. In this review we address the current available evidence regarding dietary modulation of inflammation and oxidative stress associated with MetS. PMID:24168441

  14. Oxidative stress parameters in bitches with mammary gland tumours.

    PubMed

    Szczubiał, M; Kankofer, M; Łopuszyński, W; Dabrowski, R; Lipko, J

    2004-01-01

    The aim of the present study was to describe some of the oxidative stress parameters in bitches suffering from spontaneously occurring mammary gland tumours. The experiment involved 28 bitches which had mammary gland tumours removed surgically (15 bitches with malignant tumour and 13 with benign tumour) as well as 10 clinically healthy bitches. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in haemolysates of erythrocytes derived from the animals. The concentrations of thiobarbituric acid reactive substances (TBARS), as well as -SH groups, were determined in blood plasma. GSH-Px activity was significantly higher in the malignant tumour group than in healthy animals. SOD activity was significantly higher in animals with tumours compared with the control group. Activities of both enzymes were higher in animals with malignant tumours than in benign groups, but the differences were not statistically significant. The concentrations of TBARS and -SH groups were similar in all examined groups. The increase of antioxidative enzyme activities in these animals may suggest the activation of antioxidative defence mechanisms in mammary gland carcinogenesis. Moreover, it might indicate the participation of oxidative stress in malignancies. Further experiments involving more animals, with more frequent sample collection and the use of other oxidative stress markers are necessary. PMID:15533114

  15. Oxidative stress and proteasome inhibitors in multiple myeloma.

    PubMed

    Lipchick, Brittany C; Fink, Emily E; Nikiforov, Mikhail A

    2016-03-01

    Multiple myeloma is a form of plasma cell neoplasm that accounts for approximately 10% of all hematological malignancies. Recently, several novel drugs have been discovered that almost doubled the overall survival of multiple myeloma patients. One of these drugs, the first-in-class proteasome inhibitor bortezomib (Velcade) has demonstrated remarkable response rates in multiple myeloma patients, and yet, currently this disease remains incurable. The major factor undermining the success of multiple myeloma treatment is a rapidly emerging resistance to the available therapy. Thus, the development of stand-alone or adjuvant anti-myeloma agents becomes of paramount importance. Overproduction of intracellular reactive oxygen species (ROS) often accompanies malignant transformation due to oncogene activation and/or enhanced metabolism in tumor cells. As a result, these cells possess higher levels of ROS and lower levels of antioxidant molecules compared to their normal counterparts. Unbalanced production of ROS leads to oxidative stress which, if left unchecked, could be toxic for the cell. In multiple myeloma cells where high rates of immunoglobulin synthesis is an additional factor contributing to overproduction of ROS, further induction of oxidative stress can be an effective strategy to cope with this disease. Here we will review the available data on the role of oxidative stress in the cytotoxicity of proteasome inhibitors and the use of ROS-inducing compounds as anti-myeloma agents. PMID:26827824

  16. Markers of Oxidative Stress in Pregnant Women with Sleep Disturbances

    PubMed Central

    Rajendiran, Soundravally; Nimesh, Archana; Ananthanarayanan, P. H.; Dhiman, Pooja

    2015-01-01

    Objective The quality and duration of sleep is impaired during pregnancy. Our study aimed to determine whether maternal sleep deprivation occurring during the second and third trimester of pregnancy could alter fetal well-being with respect to birth weight and APGAR score by altering the inflammatory status and oxidative stress in the mothers.  Methods Sleep adequacy was assessed using the Pittsburgh Sleep Quality Index (PSQI). We investigated the inflammatory status and oxidative stress at term in the blood of pregnant subjects with and without sleep deprivation by measuring the levels of protein-bound sialic acid (PBSA), high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA) and protein carbonyl (PCO). Homocysteine (Hcy) and its vitamin determinants were also measured. Fetal outcome with respect to birth weight and APGAR score were compared between study subjects.  Results A significant increase was observed in the levels of hsCRP, PBSA, Hcy, MDA, and PCO, in the sleep-deprived group when compared to the control group. Fetal outcome at birth showed a significant difference between the cases with high sleep deprivation and those with low sleep deprivation.  Conclusion Sleep deprivation in pregnancy leads to an increase in the inflammatory parameters, oxidative stress, and Hcy levels. Fetal outcome at birth was affected more in mothers with high sleep deprivation than those with low sleep deprivation. Follow-up in these babies are needed to reveal any differences in their growth and development. PMID:26366260

  17. Induction of oxidative stress in paraquat formulating workers.

    PubMed

    Ranjbar, Akram; Pasalar, Parvin; Sedighi, Alireza; Abdollahi, Mohammad

    2002-05-28

    Paraquat as a bipyridyl compound is widely used as an effective herbicide worldwide. In this study, oxidative stress was investigated in blood samples of workers in a pesticide factory, formulating paraquat products for use in agriculture. Controls were age-matched workers with no history of pesticide exposure. They were measured for lipid peroxidation (LPO), antioxidant power and total thiol (SH) groups in blood. The results expressed as mean+/-SD show induction of oxidative stress in workers as revealed by increased plasma LPO (11.46+/-0.99 vs 10.11+/-0.69, P<0.001), decreased plasma antioxidant capacity (1.35+/-0.03 vs 1.54+/-0.05, P<0.001) and plasma SH groups (0.16+/-0.01 vs 0.21+/-0.01, P<0.001) in comparison to those of controls. It is concluded that paraquat-formulating factory workers have elevated LPO and decreased antioxidant power, which may put them in further consequences of oxidative stress. PMID:11992738

  18. Oxidative Stress Levels in Aqueous Humor from High Myopic Patients

    PubMed Central

    Kim, Eun Bi; Kim, Ha Kyoung; Hyon, Joon Young; Wee, Won Ryang

    2016-01-01

    Purpose To compare oxidative stress status in the aqueous humor of highly myopic eyes and control eyes. Methods Aqueous humor samples were collected from 15 highly myopic eyes (high myopia group) and 23 cataractous eyes (control group) during cataract surgery. Central corneal thickness, corneal endothelial cell density, hexagonality of corneal endothelial cells, and cell area of corneal endothelial cells were measured using specular microscopy. Axial length was measured using ultrasound biometry. 8-Hydroxydeoxyguanosine (8-OHdG) and malondialdehyde levels were measured using enzyme-linked immunosorbent assay. Results 8-OHdG level was lower in the aqueous humor of myopic patients than in that of control group (p = 0.014) and was positively correlated with central corneal thickness and negatively correlated with axial length (r = 0.511, p = 0.02; r = -0.382, p < 0.001). There was no correlation between 8-OHdG level and corneal endothelial cell density, hexagonality, or cell area. Malondialdehyde level did not show any correlation with any parameters evaluated. Conclusions 8-OHdG might be a sensitive biomarker for evaluating oxidative stress status in the eye. Oxidative stress level was lower in the aqueous humor of highly myopic eyes compared to that in control eyes, which indicates lower metabolic activity in these eyes. PMID:27247516

  19. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    PubMed Central

    Naderi, Roya; Mohaddes, Gisou; Mohammadi, Mustafa; Ghaznavi, Rana; Ghyasi, Rafigheh; Vatankhah, Amir Mansour

    2015-01-01

    Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Results: Exercise significantly reduced MDA levels both in the heart tissue (p<0.01) and blood samples (p<0.05). In addition, exercise significantly increased SOD (p<0.05), GPX (p<0.001) and CAT (p<0.05) in the heart tissue. Voluntary exercise also significantly increased SOD (p<0.01), GPX (p<0.05) and CAT (p<0.001) in the blood. Conclusion: Voluntary exercise diminishes the MDA level in blood and heart tissue of diabetic rats. It also accentuates activities of SOD, GPX and CAT. Therefore, it may be considered a useful tool for the reduction of oxidative stress in diabetes. PMID:26236662

  20. PML nuclear bodies: assembly and oxidative stress-sensitive sumoylation.

    PubMed

    Sahin, Umut; de Thé, Hugues; Lallemand-Breitenbach, Valérie

    2014-01-01

    PML Nuclear Bodies (NBs) have fascinated cell biologists due to their exquisitely dynamic nature and their involvement in human diseases, notably acute promyelocytic leukemia. NBs, as well as their master organizer--the PML protein--exhibit multiple connections with stress responses. Initially viewed as a tumor suppressor, PML recently re-emerged as a multifaceted protein, capable of controlling numerous aspects of cellular homeostasis. NBs recruit many functionally diverse proteins and function as stress-regulated sumoylation factories. SUMO-initiated partner retention can subsequently facilitate a variety of other post-translational modifications, as well as partner degradation. With this newly elucidated central role of stress-enhanced sumoylation, it should now be possible to build a working model for the different NB-regulated cellular activities. Moreover, pharmacological manipulation of NB formation by interferons or oxidants holds the promise of clearing many undesirable proteins for clinical management of malignant, viral or neurodegenerative diseases. PMID:25482067

  1. Stress and phase transformation phenomena in oxide films

    SciTech Connect

    Exarhos, G.J.; Hess, N.J.

    1992-04-01

    In situ optical methods are reviewed for characterization of phase transformation processes and evaluation of residual stress in solution- deposited metastable oxide films. Such low density films most often are deposited as disordered phases making them prone to crystallization and attendant densification when subjected to increased temperature and/or applied pressure. Inherent stress imparted during film deposition and its evolution during the transformation are evaluated from phonon frequency shifts seen in Raman spectra (TiO{sub 2}) or from changes in the laser-induced fluorescence emission spectra for films containing rare earth (Sm{sup +3}:Y{sub 3}Al{sub 5}O{sub 12}) or transition metal (Cr{sup +3}:Al{sub 2}O{sub 3}) dopants. The data in combination with measured increases in line intensities intrinsic to the evolving phase are used to follow crystallization processes in thin films. In general, film deposition parameters are found to influence the crystallite ingrowth kinetics and the magnitude of stress and stress relaxation in the film during the transformation. The utility of these methods to probe crystallization phenomena in oxide films will be addressed.

  2. Nrf2 protects mitochondrial decay by oxidative stress.

    PubMed

    Strom, Joshua; Xu, Beibei; Tian, Xiuqing; Chen, Qin M

    2016-01-01

    Sublethal levels of oxidative stress are commonly associated with various pathophysiological conditions. Cardiomyocytes have the highest content of mitochondria among all cell types, allowing the study of mitochondria in cells surviving oxidative stress and address whether nuclear factor-erythroid-derived 2-related factor 2 (Nrf2) can reverse these changes. Mitochondria normally exist in elaborated networks, which were replaced by predominately individual punctuate mitochondria 24 h after exposure to a nonlethal dose of H2O2. Electron microscopy revealed that cells surviving H2O2 show swelling of mitochondria with disorganized cristae and areas of condensation. Measurements of functional mitochondria showed a H2O2 dose-dependent decrease over a course of 5 d. At the protein and mRNA levels, cells surviving H2O2 treatment show a reduction of mitochondrial components, cytochrome c, and cytochrome b. Nrf2 overexpression prevented H2O2 from inducing mitochondria morphologic changes and reduction of cytochrome b/c. Although Nrf2 is known as a transcription factor regulating antioxidant and detoxification genes, Nrf2 overexpression did not significantly reduce the level of protein oxidation. Instead, Nrf2 was found to associate with the outer mitochondrial membrane. Mitochondria prepared from the myocardium of Nrf2 knockout mice are more sensitive to permeability transition. Our data suggest that Nrf2 protects mitochondria from oxidant injury likely through direct interaction with mitochondria. PMID:26340923

  3. Neuroprotective role of melatonin in oxidative stress vulnerable brain.

    PubMed

    Gupta, Y K; Gupta, Madhur; Kohli, K

    2003-10-01

    The brain is deficient in oxidative defense mechanisms and hence is at greater risk of damage mediated by reactive oxygen species (ROS) resulting in molecular and cellular dysfunction. Emerging evidence suggesting the activation of glutamate gated cation channels, may be another source of oxidative stress, leading to neuronal degeneration. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinsonism, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, epileptic seizures, and stroke. Melatonin, the pineal hormone, acts as a direct free radical scavenger and indirect antioxidant. It is suggested that the increase in neurodegenerative diseases is attributable to a decrease in the levels of melatonin with age. Melatonin has been shown to either stimulate gene expression for the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) or to increase their activity. Additionally, it neutralizes hydoxyl radical, superoxide radical, peroxyl radical, peroxynitrite anion, singlet oxygen, hydrogen peroxide, nitric oxide, and hypochlorous acid. Unlike other antioxidants, melatonin can easily cross all morphophysiological barriers, e.g., the blood brain barrier, and enters cells and subcellular compartments. Though evidence are accumulating to suggest the potential of melatonin in neurodegenerative conditions, much information needs to be generated before the drug can find place in neurology clinics. PMID:15266948

  4. Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice

    PubMed Central

    Gamez-Mendez, Ana María; Vargas-Robles, Hilda; Ríos, Amelia; Escalante, Bruno

    2015-01-01

    Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model. Coronary perfusion pressure in response to acetylcholine in isolated hearts from obese mice showed increased vasoconstriction and reduced vasodilation responses compared with control mice. Vascular nitric oxide assessed in situ with DAF-2 DA showed diminished levels in coronary arteries from obese mice in both basal and acetylcholine-stimulated conditions. Also, released prostacyclin was decreased in heart perfusates from obese mice, along with plasma tetrahydrobiopterin level and endothelium nitric oxide synthase dimer/monomer ratio. Obesity increased thromboxane A2 synthesis and oxidative stress evaluated by superoxide and peroxynitrite levels, compared with control mice. Obese mice treated with apocynin, a NADPH oxidase inhibitor, reversed all parameters to normal levels. These results suggest that after 8 weeks on a high-fat diet, the increase in oxidative stress lead to imbalance in vasoactive substances and consequently to endothelial dysfunction in coronary arteries. PMID:26381906

  5. Statins and oxidative stress in chronic heart failure.

    PubMed

    Costa, Sónia; Reina-Couto, Marta; Albino-Teixeira, António; Sousa, Teresa

    2016-01-01

    Statins are the most commonly prescribed drugs for the treatment of dyslipidemia. They are also recommended in primary and secondary prevention of cardiovascular disease. In addition to decreasing cholesterol synthesis, statins interfere with the synthesis of isoprenoid intermediates, which may explain many of their pleiotropic properties, including their antioxidant effects. Oxidative stress is defined as an imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems, with a prevailing pro-oxidant status that results in macromolecular damage and disruption of cellular redox signaling. Reactive oxygen species interfere with various processes that affect cardiac structure and function, contributing to the contractile dysfunction, myocardial hypertrophy and fibrosis observed in the pathophysiology of heart failure. By regulating several molecular pathways that control nicotinamide adenine dinucleotide phosphate oxidase and endothelial nitric oxide synthase activity, statins help restore redox homeostasis. These drugs also contribute to the control of inflammation and appear to have a protective role in various diseases. The results of observational studies and clinical trials with statins in heart failure have not been consensual. This review aims to analyze the role of oxidative stress in heart failure and the molecular mechanisms underlying statins' antioxidant properties. It also examines current scientific evidence on the use of these drugs as a specific treatment for heart failure. PMID:26763895

  6. Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability.

    PubMed

    Ravera, S; Bartolucci, M; Cuccarolo, P; Litamè, E; Illarcio, M; Calzia, D; Degan, P; Morelli, A; Panfoli, I

    2015-01-01

    Oxidative phosphorylation (OXPHOS) is not only the main source of ATP for the cell, but also a major source of reactive oxygen species (ROS), which lead to oxidative stress. At present, mitochondria are considered the organelles responsible for the OXPHOS, but in the last years we have demonstrated that it can also occur outside the mitochondrion. Myelin sheath is able to conduct an aerobic metabolism, producing ATP that we have hypothesized is transferred to the axon, to support its energetic demand. In this work, spectrophotometric, cytofluorimetric, and luminometric analyses were employed to investigate the oxidative stress production in isolated myelin, as far as its respiratory activity is concerned. We have evaluated the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), markers of lipid peroxidation, as well as of hydrogen peroxide (H2O2), marker of ROS production. To assess the presence of endogenous antioxidant systems, superoxide dismutase, catalase, and glutathione peroxidase activities were assayed. The effect of certain uncoupling or antioxidant molecules on oxidative stress in myelin was also investigated. We report that isolated myelin produces high levels of MDA, 4-HNE, and H2O2, likely through the pathway composed by Complex I-III-IV, but it also contains active superoxide dismutase, catalase, and glutathione peroxidase, as antioxidant defense. Uncoupling compounds or Complex I inhibitors increase oxidative stress, while antioxidant compounds limit ROS generation. Data may shed new light on the role of myelin sheath in physiology and pathology. In particular, it can be presumed that the axonal degeneration associated with myelin loss in demyelinating diseases is related to oxidative stress caused by impaired OXPHOS. PMID:25971447

  7. Oxidative Stress and the Homeodynamics of Iron Metabolism

    PubMed Central

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

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

  8. Oxidative Stress and Therapeutic Development in Lung Diseases

    PubMed Central

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2016-01-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies. PMID:27019769

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

    PubMed Central

    Hermann, Anton; Sitdikova, Guzel F.; Weiger, Thomas M.

    2015-01-01

    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. PMID:26287261

  10. Modeling Oxidation Induced Stresses in Thermal Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Ferguson, B. L.; Freborg, A. M.; Petrus, G. J.; Brindley, William J.

    1998-01-01

    The use of thermal barrier coatings (TBC's) in gas turbines has increased dramatically in recent years, due mainly to the need for component protection from ever increasing service temperatures. Oxidation of the bond coat has been identified as an important contributing factor to spallation of the ceramic top coat during service. Additional variables found to influence TBC thermal cycle life include bond coat coefficient of thermal expansion, creep behavior of both the ceramic and bond coat layers, and modulus of elasticity. The purpose of this work was to characterize the effects of oxidation on the stress states within the TBC system, as well as to examine the interaction of oxidation with other factors affecting TBC life.

  11. Adrenergic signaling and oxidative stress: a role for sirtuins?

    PubMed Central

    Corbi, Graziamaria; Conti, Valeria; Russomanno, Giusy; Longobardi, Giancarlo; Furgi, Giuseppe; Filippelli, Amelia; Ferrara, Nicola

    2013-01-01

    The adrenergic system plays a central role in stress signaling and stress is often associated with increased production of ROS. However, ROS overproduction generates oxidative stress, that occurs in response to several stressors. β-adrenergic signaling is markedly attenuated in conditions such as heart failure, with downregulation and desensitization of the receptors and their uncoupling from adenylyl cyclase. Transgenic activation of β2-adrenoceptor leads to elevation of NADPH oxidase activity, with greater ROS production and p38MAPK phosphorylation. Inhibition of NADPH oxidase or ROS significantly reduced the p38MAPK signaling cascade. Chronic β2-adrenoceptor activation is associated with greater cardiac dilatation and dysfunction, augmented pro-inflammatory and profibrotic signaling, while antioxidant treatment protected hearts against these abnormalities, indicating ROS production to be central to the detrimental signaling of β2-adrenoceptors. It has been demonstrated that sirtuins are involved in modulating the cellular stress response directly by deacetylation of some factors. Sirt1 increases cellular stress resistance, by an increased insulin sensitivity, a decreased circulating free fatty acids and insulin-like growth factor (IGF-1), an increased activity of AMPK, increased activity of PGC-1a, and increased mitochondrial number. Sirt1 acts by involving signaling molecules such P-I-3-kinase-Akt, MAPK and p38-MAPK-β. βAR stimulation antagonizes the protective effect of the AKT pathway through inhibiting induction of Hif-1α and Sirt1 genes, key elements in cell survival. More studies are needed to better clarify the involvement of sirtuins in the β-adrenergic response and, overall, to better define the mechanisms by which tools such as exercise training are able to counteract the oxidative stress, by both activation of sirtuins and inhibition of GRK2 in many cardiovascular conditions and can be used to prevent or treat diseases such as heart failure

  12. A Novel Role for Connexin Hemichannel in Oxidative Stress and Smoking-Induced Cell Injury

    PubMed Central

    Ramachandran, Srinivasan; Xie, Lai-Hua; John, Scott A.; Subramaniam, Shankar; Lal, Ratnesh

    2007-01-01

    Oxidative stress is linked to many pathological conditions, including ischemia, atherosclerosis and neurodegenerative disorders. The molecular mechanisms of oxidative stress induced pathophysiology and cell death are currently poorly understood. Our present work demonstrates that oxidative stress induced by reactive oxygen species and cigarette smoke extract depolarize the cell membrane and open connexin hemichannels. Under oxidative stress, connexin expression and connexin silencing resulted in increased and reduced cell deaths, respectively. Morphological and live/dead assays indicate that cell death is likely through apoptosis. Our studies provide new insights into the mechanistic role of hemichannels in oxidative stress induced cell injury. PMID:17684558

  13. Oxidative stress, activity behaviour and body mass in captive parrots.

    PubMed

    Larcombe, S D; Tregaskes, C A; Coffey, J; Stevenson, A E; Alexander, L G; Arnold, K E

    2015-01-01

    Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally 'active' individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes. PMID:27293729

  14. Oxidative stress, activity behaviour and body mass in captive parrots

    PubMed Central

    Larcombe, S. D.; Tregaskes, C. A.; Coffey, J.; Stevenson, A. E.; Alexander, L. G.; Arnold, K. E.

    2015-01-01

    Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally ‘active’ individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes. PMID

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

    SciTech Connect

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada; Quaroni, Andrea; Autore, Giuseppina; Severino, Lorella; Marzocco, Stefania

    2015-06-01

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

  16. Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs

    PubMed Central

    2014-01-01

    Background The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Results Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Conclusions Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory. PMID:25056725

  17. ADP Protects Cardiac Mitochondria under Severe Oxidative Stress

    PubMed Central

    Sokolova, Niina; Pan, Shi; Provazza, Sarah; Beutner, Gisela; Vendelin, Marko; Birkedal, Rikke; Sheu, Shey-Shing

    2013-01-01

    ADP is not only a key substrate for ATP generation, but also a potent inhibitor of mitochondrial permeability transition pore (mPTP). In this study, we assessed how oxidative stress affects the potency of ADP as an mPTP inhibitor and whether its reduction of reactive oxygen species (ROS) production might be involved. We determined quantitatively the effects of ADP on mitochondrial Ca2+ retention capacity (CRC) until the induction of mPTP in normal and stressed isolated cardiac mitochondria. We used two models of chronic oxidative stress (old and diabetic mice) and two models of acute oxidative stress (ischemia reperfusion (IR) and tert-butyl hydroperoxide (t-BH)). In control mitochondria, the CRC was 344 ± 32 nmol/mg protein. 500 μmol/L ADP increased CRC to 774 ± 65 nmol/mg protein. This effect of ADP seemed to relate to its concentration as 50 μmol/L had a significantly smaller effect. Also, oligomycin, which inhibits the conversion of ADP to ATP by F0F1ATPase, significantly increased the effect of 50 μmol/L ADP. Chronic oxidative stress did not affect CRC or the effect of 500 μmol/L ADP. After IR or t-BH exposure, CRC was drastically reduced to 1 ± 0.2 and 32 ± 4 nmol/mg protein, respectively. Surprisingly, ADP increased the CRC to 447 ± 105 and 514 ± 103 nmol/mg protein in IR and t-BH, respectively. Thus, it increased CRC by the same amount as in control. In control mitochondria, ADP decreased both substrate and Ca2+-induced increase of ROS. However, in t-BH mitochondria the effect of ADP on ROS was relatively small. We conclude that ADP potently restores CRC capacity in severely stressed mitochondria. This effect is most likely not related to a reduction in ROS production. As the effect of ADP relates to its concentration, increased ADP as occurs in the pathophysiological situation may protect mitochondrial integrity and function. PMID:24349464

  18. Oxidative stress profiling: part II. Theory, technology, and practice.

    PubMed

    Cutler, Richard G; Plummer, John; Chowdhury, Kajal; Heward, Christopher

    2005-12-01

    Many of the most serious human diseases have a strong association with the steady-state level of oxidative damage in tissues. On an individual level this damage is defined as the patient's oxidative stress status (OSS). OSS is associated with many of the major age-related diseases such as cancer, heart disease, diabetes, and Alzheimer's disease, as well as with the aging process itself. In general, the greater the OSS of the individual, the higher the risk for disease development. To further understand the role that OSS has as a causative or an associated factor for these diseases, and to develop more effective personalized therapy to minimize OSS, requires a reliable means to measure the many different components contributing to an individual's OSS. This procedure is called oxidative stress profiling (OSP) and represents a new strategy to simultaneously assess an individual's OSS as well as to identify key physiological parameters, such as the hormone, lipid, antioxidant, or iron profile, that may be responsible for that individual's OSS. The OSP strategy provides physicians with information that enable them to make a more accurate diagnosis of the patient's condition and to recommend specific types of therapy based on better scientific data. Follow-up studies of the patient would then be conducted using these same tests until the OSS of the patient has been minimized. The OSP strategy is particularly well suited for a personalized health optimization program. The procedure is based on measuring both the steady-state levels of oxidative damage in nucleic acids, proteins, and lipids and the protective and defense processes of these components using blood, urine, and breath samples. Testing individuals before and after a controlled amount of exercise (70% VO2) may also help to obtain greater sensitivity and reproducibility. Evaluation of test results to obtain an integrated calculated OSS result for a patient represents a major challenge. One approach is to present

  19. Sea buckthorn seed oil protects against the oxidative stress produced by thermally oxidized lipids.

    PubMed

    Zeb, Alam; Ullah, Sana

    2015-11-01

    Thermally oxidized vegetable ghee was fed to the rabbits for 14 days with specific doses of sea buckthorn seed oil (SO). The ghee and SO were characterized for quality parameters and fatty acid composition using GC-MS. Rabbits serum lipid profile, hematology and histology were investigated. Major fatty acids were palmitic acid (44%) and oleic acid (46%) in ghee, while SO contains oleic acid (56.4%) and linoleic acid (18.7%). Results showed that oxidized vegetable ghee increases the serum total cholesterol, LDL-cholesterols, triglycerides and decrease the serum glucose. Oxidized ghee produced toxic effects in the liver and hematological parameters. Sea buckthorn oil supplementation significantly lowered the serum LDL-cholesterols, triglycerides and increased serum glucose and body weight of the animals. Sea buckthorn oil was found to reduce the toxic effects and degenerative changes in the liver and thus provides protection against the thermally oxidized lipids induced oxidative stress. PMID:25976784

  20. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

    PubMed

    López-López, Ana Laura; Jaime, Herlinda Bonilla; Escobar Villanueva, María Del Carmen; Padilla, Malinalli Brianza; Palacios, Gonzalo Vázquez; Aguilar, Francisco Javier Alarcón

    2016-07-01

    Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic