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Sample records for activity oxidative stress

  1. OXIDATIVE STRESS AND PHYSICAL ACTIVITY

    Dragan Radovanović

    2012-06-01

    Full Text Available The cells continuously produce free radicals and reactive oxygen species as a part of metabolic processes. Increased aerobic metabolism during exercise is a potential source of oxidative stress. Also, anaerobic physical activity and oxidative stress are interrelated because the intense anaerobic activity leads to damage proteins, lipids and nucleic acids in muscle cells and blood. Complex system of antioxidant defense, which has the enzymatic and non-enzymatic part, has a role in protecting tissues from excessive oxidative damage. Most of the research conducted so far about the impact of various forms of physical activity on levels of oxidative stress is confirmed by changes in biomarkers that indicate lipid peroxidation and proteins modification. Untrained persons, as opposed to trained, are more susceptible to major changes in the body caused by oxidative stress during physical activity. The results of researches have shown that there are no significant differences between the genders in the level of oxidative stress during physical activity and response to antioxidant supplementation possibly applied. It is interesting that, despite of numerous studies, the exact location of oxidative stress origin during physical activity has not been reliably established. In addition, research results provide insufficient evidence on the effectiveness of using antioxidant supplementation to increase the defense against oxidative stress. It is necessary further investigation about the redox status and oxidative stress during physical activity in adolescent athletes.

  2. Multistep Phosphorelay Proteins Transmit Oxidative Stress Signals to the Fission Yeast Stress-activated Protein Kinase

    Nguyen, Aaron Ngocky; Lee, Albert; Place, Warren; Shiozaki, Kazuhiro

    2000-01-01

    In response to oxidative stress, eukaryotic cells induce transcription of genes required for detoxification of oxidants. Here we present evidence that oxidative stress stimuli are transmitted by a multistep phosphorelay system to the Spc1/Sty1 stress-activated protein kinase in the fission yeast Schizosaccharomyces pombe. The fission yeast mpr1+ gene encodes a novel protein with a histidine-containing phosphotransfer domain homologous to the budding yeast Ypd1. Spc1 activation upon oxidative ...

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

    Gurunathan S

    2012-11-01

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

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

    Anton Hermann

    2015-08-01

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

  5. Relationship between acrosin activity of human spermatozoa and oxidative stress

    AdelA.Zalata; AshrafH.Ahmed; ShyamS.R.Allamaneni; H.Comhaire; AshokAgarwal

    2004-01-01

    Aim: To study the association between seminal oxidative stress and human sperm acrosin activity.Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negativecorrelation with the acrosin activity index (r=-0.89, P<0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity. (Asian J Androl 2004 Dec; 6:313-318)

  6. Oxidative stress

    Stevanović Jelka

    2012-01-01

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

  7. Oxidative stress

    This book contains 18 chapters. Some of the chapter titles are: Oxidative Stress: Introductory Remarks; Radiolysis of DNA and Model Systems in the Presence of Oxygen; Organic Peroxy Free Radicals as Ultimate Agents in Oxygen Toxicity; Antimalarials; and the Role of Dietary Components in Oxidative Stress in Tissues

  8. Oxidative stress, activity behaviour and body mass in captive parrots

    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, Melo...

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

    Yao Zhu

    2016-08-01

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

  10. Protective Activity Against Oxidative Stress of Plants Indigenous to Korea

    We have screened the cytoprotective effect against Ha, Oa, and γ-ray radiation induced oxidative stress from 32 Korean plants. Betula ermani var, saitoana (caulis, leaves), Rosa wichuraiana (caulis), Sorbus commixta (caulis), Weigela florida (leaves), Cirsium rhinoceros (whole plant), and Viburnum erosum (caulis) were found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). As a result, extracts of six plants reduced cell death of Chinese hamster lung fibroblast (V79-4) cells induced by Ha,Oa, treatment. In addition, these extracts protected cell death of V79-4 cells damaged by γ-ray radiation. In addition, these extracts scavenged ROS generated by radiation. Taken together, the results suggest that Betula ermani var. saitoana, Rosa wichuraiana, Sorbus commixta, Weigela florida, Cirsium rhinoceros, and Viburnum erosum protect V79-4 cells against oxidative damage by radiation through scavenging ROS

  11. SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells

    Khan, Reas S.; Fonseca-Kelly, Zoe; Callinan, Catherine; Zuo, Ling; Sachdeva, Mira M.; Shindler, Kenneth S

    2012-01-01

    Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators red...

  12. Physiological responses of peanut (Arachis hypogaea L.) cultivars to water deficit stress: status of oxidative stress and antioxidant enzyme activities

    Chakraborty, Koushik; Singh, Amrit L.; Kalariya, Kuldeep A.; Goswami, Nisha

    2015-01-01

    From a field experiment, the changes in oxidative stress and antioxidant enzyme activities was studied in six Spanish peanut cultivars subjected to water deficit stress at two different stages viz. pegging and pod development stages. Imposition of water deficit stress significantly reduced relative water content, membrane stability and total carotenoid content in all the cultivars, whereas total chlorophyll content increased at initially and decreased at later stage. Chlorophyll a/b ratio inc...

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

    Jinbo Liu

    2013-01-01

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

  14. Green Tea Polyphenols Function as Prooxidants To Activate Oxidative-Stress-Responsive Transcription Factors in Yeasts▿

    Maeta, Kazuhiro; Nomura, Wataru; Takatsume, Yoshifumi; Izawa, Shingo; Inoue, Yoshiharu

    2006-01-01

    Epigallocatechin gallate (EGCG) is the most abundant polyphenolic flavonoid in green tea. Catechin and its derivatives, including EGCG, are widely believed to function as antioxidants. Here we demonstrate that both EGCG and green tea extract (GTE) cause oxidative stress-related responses in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe under weak alkaline conditions in terms of the activation of oxidative-stress-responsive transcription factors. GT...

  15. THE ASSOCIATION BETWEEN PHYSICAL ACTIVITY AND SEX-SPECIFIC OXIDATIVE STRESS IN OLDER ADULTS

    Masaki Takahashi

    2013-09-01

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

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

    Gurunathan S; Han JW; Dayem AA; Eppakayala V; Kim JH

    2012-01-01

    Sangiliyandi Gurunathan, Jae Woong Han, Ahmed Abdal Dayem, Vasuki Eppakayala, Jin-Hoi KimDepartment of Animal Biotechnology, Konkuk University, Seoul, South KoreaBackground: 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 oxid...

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

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

    2011-01-01

    AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and ...

  18. Expression of telomerase activity and oxidative stress in human hepatocellular carcinoma with cirrhosis

    Dao-Yong Liu; Zhi-Hai Peng; Guo-Qiang Qiu; Chong-Zhi Zhou

    2003-01-01

    AIM: To study the expression and significance of telomerase activity and oxidative stress in hepatocellular carcinoma (HCC) with cirrhosis.METHODS: In this study, TRAP-ELISA assay was used to determine telomerase activity in 21 cases of HCC as well as in 23 cases of hepatic cirrhosis. Malondialdehyde(MDA),glutathione S-transferase (GST) and total anti-oxidative capacity (T-AOC) were also examined in the same samples with human MDA, GST and T-AOC kits.RESULTS: Eighteen of 21 cases of HCC were found to have increased telomerase activity, whereas only three of the 23non-cancerous cirrhotic samples were found to have weak telomerase activity, and the difference was significant (P<0.001). No significant difference in telomerase activity was detected according to different tumor size, tumor stage,histological grade, HBsAg, contents of albumin, bilirubin,ALT, AFP, r-GT and platelet. There were significant differences between HCC and cirrhosis in the expression of MDA, GST and T-AOC respectively. Telomerase activity correlated positively with the content of MDA (P<0.05).CONCLUSION: Telomerase activation is the early event of carcinogenesis, which is not correlated with clinicopathological factors of HCC. The dysfunction of the anti-oxidative system is closely correlated with the progression from cirrhosis to hepatocellular carcinoma. Oxidative stress may contribute partly to telomerase activation.

  19. Anti-Oxidative Stress Activity of Stachys lavandulifolia Aqueous Extract in Human

    Naser Hosseini

    2013-01-01

    Full Text Available Medicinal plants are presumed to be natural sources of antioxidants that protect organisms from oxidative stresses. The present investigation aims to study the anti-oxidative stress activity of the Stachys lavandulifolia (S. lavandulifolia plant. This trial was conducted on 26 healthy human subjects. The study was done in a before after fashion. The included subjects were asked to consume the prepared infusion from 3 g aerial parts of S. lavandulifolia on a daily basis. Doses were administered in every morning and evening for 14 days. At the beginning and the end of the study, blood samples were acquired to determine the level of cellular lipid peroxidation and the total content of serum antioxidants. Biomarkers analyzed from samples obtained before start of treatment and 14 days post treatment, were subjected to paired t test analysis. Total blood antioxidants increased and reached from 2.3 ± 0.84 μmol/ml to 3.3 ± 0.54 μmol/ml. The lipid peroxidation reduced and reached from 8.38 ± 1.78 to 11.6 ± 2.64 nmol/ml. The results suggest that S. lavandulifolia possesses marked anti-oxidative stress activity and it can be useful as a supplement in the management of diseases related to oxidative stress (Registration Number: IRCT2013012210003N2.

  20. Response of oxidative stress and isoflavone treatment on superoxide dismutase enzyme activities and lipid peroxidation in rat’s liver

    Suarsana IN; Wresdiyati T; Suprayogi A

    2013-01-01

    Oxidative stress is defined as over-production of free radicals which lead to cells damage, pathological condition and cell death. The objective of this study was to analyze respond of oxidative stress and isoflavone treatment on superoxide dismutase (SOD) enzyme activities and lipid peroxidation in rat liver. A total of fifteen male Spraque Dawley rats were used in this study. They were sub-divided into three groups; (1) a negative control group, (2) a stress oxidative group, and (3) treatme...

  1. Oxidative Stress in Neurodegeneration

    Varsha Shukla

    2011-01-01

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

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

    Hung-Hsin Liu

    2013-01-01

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

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

    Alexis Valauri-Orton

    2015-01-01

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

  4. Oxidative stress by inorganic nanoparticles.

    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

  5. S-Glutathionylation Enhances Human Cystathionine β-Synthase Activity Under Oxidative Stress Conditions

    Niu, Wei-Ning; Yadav, Pramod Kumar; Adamec, Jiri; Banerjee, Ruma

    2015-01-01

    Aims: Cystathionine β-synthase (CBS) catalyzes the first and rate-limiting step in the two-step trans-sulfuration pathway that converts homocysteine to cysteine. It is also one of three major enzymes responsible for the biogenesis of H2S, a signaling molecule. We have previously demonstrated that CBS is activated in cells challenged by oxidative stress, but the underlying molecular mechanism of this regulation has remained unclear. Results: Here, we demonstrate that S-glutathionylation of CBS...

  6. Punica Granatum Juice Effects on Oxidative Stress in Severe Physical Activity

    Naghizadeh-Baghi, Abbas; Mazani, Mohammad; Shadman-Fard, Ali; Nemati, Ali

    2015-01-01

    Aim: The aim of this study was to investigate Punica granatum juice effects on oxidative stress in young healthy males during severe physical activity. Methods: Our subjects were selected from healthy males at 18 - 24 years. They were enrolled and randomly distributed into control and supplemented groups. 240 ml of Punica granatum juice and tap water were given to supplement and control groups daily for two weeks, respectively. Fasting blood samples were taken at the starting and the end of t...

  7. Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts.

    Keyse, S M; Applegate, L. A.; Tromvoukis, Y; Tyrrell, R M

    1990-01-01

    Treatment of cultured human skin fibroblasts with near-UV radiation, hydrogen peroxide, and sodium arsenite induces accumulation of heme oxygenase mRNA and protein. In this study, these treatments led to a dramatic increase in the rate of RNA transcription from the heme oxygenase gene but had no effect on mRNA stability. Transcriptional activation, therefore, appears to be the major mechanism of stimulation of expression of this gene by either oxidative stress or sulfydryl reagents.

  8. Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts

    Treatment of cultured human skin fibroblasts with near-UV radiation, hydrogen peroxide, and sodium arsenite induces accumulation of heme oxygenase mRNA and protein. In this study, these treatments led to a dramatic increase in the rate of RNA transcription from the heme oxygenase gene but had no effect on mRNA stability. Transcriptional activation, therefore, appears to be the major mechanism of stimulation of expression of this gene by either oxidative stress or sulfydryl reagents

  9. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis

    Lange, Matthias; Szabo, Csaba; Traber, Daniel L.; Horvath, Eszter; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D.; Cox, Robert A.; Schmalstieg, Frank C.; Herndon, David N.; Enkhbaatar, Perenlei

    2012-01-01

    The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure following acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep and were euthanized at 4, 8, 12, 18, and 24 hours p...

  10. Oxidative stress (Glutathionylation) and Na,K-ATPase activity in rat skeletal muscle

    Juel, Carsten

    2014-01-01

    Background Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation) on the Na,K-ATPase in rat skeletal muscle membranes. Results Immunoprecipitation with an anti-glutathione antibody and subsequent ...

  11. Oxidative stress (glutathionylation and Na,K-ATPase activity in rat skeletal muscle.

    Carsten Juel

    Full Text Available Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation on the Na,K-ATPase in rat skeletal muscle membranes.Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05 in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0-10 mM increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle.This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity.Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.

  12. Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide

    de Melo, Joana Barbosa; Agostinho, Paula; Oliveira, Catarina Resende

    2003-01-01

    Acetylcholinesterase (AChE) activity is increased within and around amyloid plaques, which are present in Alzheimer's disease (AD) patient's brain. In this study, using cultured retinal cells as a neuronal model, we analyzed the effect of the synthetic peptide A[beta]25-35 on the activity of AChE, the degradation enzyme of acetylcholine, as well as the involvement of oxidative stress in this process. The activity of AChE was increased when retinal cells were incubated with A[beta]25-35 (25 [m...

  13. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

  14. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Patel-Vayas, Kinal; Shen, Jianliang [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States)

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

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

    Klingelhoeffer Christoph

    2012-05-01

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

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

    Jarouliya Urmila

    2015-12-01

    Full Text Available Diabetes mellitus is a metabolic disorder characterised by hyperglycemia and oxidative stress. The aim of the present study is to explore the antioxidant effect of Spirulina maxima in rat model along with the histopathological observations. Diabetes was induced by feeding 10% fructose solution orally to Wistar rats (n = 6 for 30 days, analysed for plasma blood glucose and the markers of the oxidative stress [catalase (CAT, superoxide dismutase (SOD, reduced glutathione (GSH and thiobarbituric acid reactive substances (TBARS]. These biochemical studies were associated with histopathological examination of liver and kidney sections. The microalga Spirulina maxima being rich in proteins and other essential nutrients is widely used as a food supplement. S. maxima at a dose of 5 and 10% per kg and the metformin (500 mg/kg as reference drug were given orally for 30 days to the diabetic rats. Diabetic rats showed significant (p < 0.001 elevations in plasma blood glucose, thiobarbituric acid-reactive substances and significant reduction in catalase, superoxide dismutase and reduced glutathione activity. Oral administration of 5 and 10% aqueous extract of S. maxima for 30 days restored not only of blood glucose levels but also markers of oxidative stress. Histopathological observations of tissues manifested that the S. maxima administration had the protective and therapeutic effects against fructose-induced abnormalities in diabetic rats. It is concluded that S. maxima is effective in reinstating the antioxidant activity in addition to its antidiabetic effect in type 2 diabetic rats.

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

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

    2011-01-01

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

  18. Oxidative stress and anxiety

    Bouayed, Jaouad; Rammal, Hassan; Soulimani, Rachid

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  19. Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

    Huang, Chun-Jung; McAllister, Matthew J.; Slusher, Aaron L.; Webb, Heather E.; Mock, J. Thomas; Acevedo, Edmund O.

    2015-01-01

    Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysf...

  20. The C-ETS2-TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity.

    Ma, Shumin; Fang, Zijun; Luo, Wenwen; Yang, Yunzhi; Wang, Chenyao; Zhang, Qian; Wang, Huafei; Chen, Huaiyong; Chan, Chi Bun; Liu, Zhixue

    2016-01-01

    Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) produced as a result of ageing causes damage to macromolecules and organelles or leads to interference of cell signalling pathways, which in turn results in oxidative stress. Oxidative stress occurs in many neurodegenerative diseases (e.g., Parkinson's disease) and contributes to progressive neuronal loss. In this study, we show that cell apoptosis is induced by oxidative stress and that lysosomes play an important role in cell survival under oxidative stress. As a compensatory response to this stress, lysosomal genes were upregulated via induction of transcription factor EB (TFEB). In addition, localization of TFEB to the nucleus was increased by oxidative stress. We also confirmed that TFEB protects cells from oxidative stress both in vitro and in vivo. Finally, we found that C-ETS2 senses oxidative stress, activates TFEB transcription, and mediates the upregulation of lysosomal genes. Our results demonstrate a mechanistic pathway for inducing lysosomal activity during ageing and neurodegeneration. PMID:27195074

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

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

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

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

    2013-09-20

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

  3. Mitogen-activated protein kinase-activated protein kinase 2 mediates resistance to Hydrogen peroxide-induced oxidative stress in Human hepatobiliary Cancer cells

    Nguyen Ho-Bouldoires, Thang Huong; Clapéron, Audrey; Mergey, Martine; Wendum, Dominique; Desbois-Mouthon, Christèle; Tahraoui, Sylvana; Fartoux, Laetitia; Chettouh, Hamza; Merabtene, Fatiha; Scatton, Olivier; Gaestel, Matthias; Praz, Françoise; Housset, Chantal; Fouassier, Laura

    2015-01-01

    The development and progression of liver cancer are characterized by increased levels of reactive oxygen species (ROS). ROS-induced oxidative stress impairs cell proliferation and ultimately leads to cell death. Although liver cancer cells are especially resistant to oxidative stress, mechanisms of such resistance remain understudied. We identified the MAPK-activated protein kinase 2 (MK2)/Heat shock protein 27 (Hsp27) signaling pathway mediating defenses against oxidative stress. Besides to ...

  4. Oxidative Stress and Decrease of Paroxonase Activity in Patients whit Prostate Cancer

    Orhan N

    2015-10-01

    Full Text Available Objective: Prostate cancer is the leading cause of cancer-related deaths. Oxidative DNA damage may contribute to the prostate cancer. The paraoxonase (PON1 is an endogenous antioxidant in the human body. The aim of our study was to determine whether lipid parameters, total oxidant capacity (TOC, total antioxidant capacity (TAC, oxidative stress index (OSĠ, serum paraoxonase (PON1 and arylesterase (ARE levels and phenotypes distribution alter new diagnosis in patients with prostate cancer and to compare the values with those of healthy controls. Methods: The study was performed prospective which consist of the prostate cancer group (PC and healthy control group. Serum PON1, ARE activities, and other parameters were measured in 40 subjects in both groups. The PON1 phenotypes were defined according to the ratio of serum PON1/ARE activity. In statistical evaluation of data was performed by Student t test and Pearson’s correlation analysis. Results: TKOL and LDL-K levels were found to be lower in the patients compared to controls (p=0,044; p=0,026. OSI levels in patients was higher than the controls (p=0,029. PON1 and ARE activities were found to be lower in patients compared to the controls (p=0,040; p=0,027. PON1 enzyme activity was determined as three different phenotypes in both groups. In PC group, significant deviation of PON1 phenotype frequencies from Hardy–Weinberg equilibrium was found. Conclusion: The results of our study suggest that oxidative stress, through lipid peroxidation may play an important role for the development of prostate cancer and that PON1, and PON1 phenotyping may be predictive for prostate cancer.

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

    Julien Santi-Rocca

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

  6. Influence of chronic stress and terahertz radiation at nitric oxide frequency on functional activity of thyroid gland

    Tsymbal А.А.

    2010-12-01

    Full Text Available In the chronic stress conditions oppression of functional activity of thyroid gland is revealed. Influence of terahertz radiation at the nitric oxide frequency of 150,176-150,664 GHz on functional activity of thyroid gland in the conditions of chronic experimental stress was studied. It was shown that during 15 minutes of influence of terahertz waves at nitric oxide frequency partial restoration of studied indicators of activity of thyroid gland was observed in stressed animals. At 30 minute mode of influence of specified waves a complete recovery of broken indicators of functional condition of thyroid gland was determined

  7. Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction.

    Navarro, Elisa; Buendia, Izaskun; Parada, Esther; León, Rafael; Jansen-Duerr, Pidder; Pircher, Haymo; Egea, Javier; Lopez, Manuela G

    2015-10-15

    Subchronic oxidative stress and inflammation are being increasingly implicated in the pathogenesis of numerous diseases, such as Alzheimer's or Parkinson's disease. This study was designed to evaluate the potential protective role of α7 nicotinic receptor activation in an in vitro model of neurodegeneration based on subchronic oxidative stress. Rat organotypic hippocampal cultures (OHCs) were exposed for 4 days to low concentration of lipopolysaccharide (LPS) and the complex III mitochondrial blocker, antimycin-A. Antimycin-A (0.1μM) and lipopolysaccharide (1ng/ml) caused low neurotoxicity on their own, measured as propidium iodide fluorescence in CA1 and CA3 regions. However, their combination (LPS/AA) caused a greater detrimental effect, in addition to mitochondrial depolarization, overproduction of reactive oxygen species (ROS) and Nox4 overexpression. Antimycin-A per se increased ROS and mitochondrial depolarization, although these effects were significantly higher when combined with LPS. More interesting was the finding that exposure of OHCs to the combination of LPS/AA triggered aberrant protein aggregation, measured as thioflavin S immunofluorescence. The α7 nicotinic receptor agonist, PNU282987, prevented the neurotoxicity and the pathological hallmarks observed in the LPS/AA subchronic toxicity model (oxidative stress and protein aggregates); these effects were blocked by α-bungarotoxin and tin protoporphyrin, indicating the participation of α7 nAChRs and heme-oxygenase I induction. In conclusion, subchronic exposure of OHCs to low concentration of antimycin-A plus LPS reproduced pathological features of neurodegenerative disorders. α7 nAChR activation ameliorated these alterations by a mechanism involving heme-oxygenase I induction. PMID:26212551

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

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

    2014-12-12

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

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

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

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

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

    2014-01-24

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

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

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

  12. Is the Oxidative Stress Really a Disease?

    Fogarasi Erzsébet; Croitoru Mircea Dumitru; Fülöp Ibolya; Muntean Daniela-Lucia

    2016-01-01

    Oxidative stress is an imbalance between free radicals or other reactive species and the antioxidant activity of the organism. Oxidative stress can induce several illnesses such as cardiovascular disease, neurodegenerative disorders, diabetes, cancer, Alzheimer and Parkinson. The biomarkers of oxidative stress are used to test oxidative injury of biomolecules. The indicators of lipid peroxidation (malondialdehyde, 4-hydroxy- 2-nonenal, 2-propenal, isoprostanes), of protein oxidation (carbonyl...

  13. PPAR-pan activation induces hepatic oxidative stress and lipidomic remodelling.

    Ament, Zsuzsanna; West, James A; Stanley, Elizabeth; Ashmore, Tom; Roberts, Lee D; Wright, Jayne; Nicholls, Andrew W; Griffin, Julian L

    2016-06-01

    The peroxisome proliferator-activated receptors (PPARs) are ligand activated nuclear receptors that regulate cellular homoeostasis and metabolism. PPARs control the expression of genes involved in fatty-acid and lipid metabolism. Despite evidence showing beneficial effects of their activation in the treatment of metabolic diseases, particularly dyslipidaemias and type 2 diabetes, PPAR agonists have also been associated with a variety of side effects and adverse pathological changes. Agonists have been developed that simultaneously activate the three PPAR receptors (PPARα, γ and δ) in the hope that the beneficial effects can be harnessed while avoiding some of the negative side effects. In this study, the hepatic effects of a discontinued PPAR-pan agonist (a triple agonist of PPAR-α, -γ, and -δ), was investigated after dietary treatment of male Sprague-Dawley (SD) rats. The agonist induced liver enlargement in conjunction with metabolomic and lipidomic remodelling. Increased concentrations of several metabolites related to processes of oxidation, such as oxo-methionine, methyl-cytosine and adenosyl-methionine indicated increased stress and immune status. These changes are reflected in lipidomic changes, and increased energy demands as determined by free fatty acid (decreased 18:3 n-3, 20:5 n-3 and increased ratios of n-6/n-3 fatty acids) triacylglycerol, phospholipid (decreased and increased bulk changes respectively) and eicosanoid content (increases in PGB2 and 15-deoxy PGJ2). We conclude that the investigated PPAR agonist, GW625019, induces liver enlargement, accompanied by lipidomic remodelling, oxidative stress and increases in several pro-inflammatory eicosanoids. This suggests that such pathways should be monitored in the drug development process and also outline how PPAR agonists induce liver proliferation. PMID:26654758

  14. A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

    Ar/O2 (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

  15. Antibacterial activity of Syzygium aromaticum seed: Studies on oxidative stress biomarkers and membrane permeability.

    Ajiboye, T O; Mohammed, A O; Bello, S A; Yusuf, I I; Ibitoye, O B; Muritala, H F; Onajobi, I B

    2016-06-01

    Oxidative stress and membrane permeability as mode of antibacterial activity of aqueous extract of Syzygium aromaticum seeds against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was investigated. The concentration of phytochemical constituents of Syzygium aromaticum was determined using gas chromatography. Syzygium aromaticum seeds contain eugenol acetate > β-carophyllene > eugenin > eugenol > methyl salicylate > β-humulene > rhamnatin > fernesol > α-copeane > β-ylangene > kaempferol > cinnamic acid > oleanolic acid > benzaldehyde > α-humulene > vanillin > α-cubebene > carvicol > benzoic acid. Syzygium aromaticum showed antimicrobial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as 0.06 and 0.10 mg/mL respectively. Time kill susceptibility by Syzygium aromaticum at MBC values showed significant decrease in the optical density and colony-forming unit (CFU) of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Superoxide anion radical content of the bacterial cells increased significantly following exposure to the extract. In a similar vein, superoxide dismutase and catalase activities increased significantly, while the level of reduced glutathione reduced, malondialdehyde increased significantly in bacterial cells exposed to the extract. The extract at MBC also enhanced the leakage of 260 nm absorbing materials and outer membrane permeability. It is evident from the data generated from this study that aqueous extract of Syzygium aromaticum seeds enhanced membrane permeability and oxidative stress in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. PMID:27038843

  16. Modulated expression and enzymatic activities of Darkbarbel catfish, Pelteobagrus vachelli for oxidative stress induced by acute hypoxia and reoxygenation.

    Zhang, Guosong; Mao, Jianqiang; Liang, Fenfei; Chen, Jiawei; Zhao, Cheng; Yin, Shaowu; Wang, Li; Tang, Zhonglin; Chen, Shuqiao

    2016-05-01

    Large changes in oxygen availability in aquatic environments, ranging from anoxia through to hyperoxia, can lead to corresponding wide variation in the production of reactive oxygen species (ROS) by fish with aquatic respiration. In order to evaluate the effects of hypoxia and reoxygenation on oxidative stress in fish, the mRNA and protein expression of SODs (Cu/Zn-SOD and Mn-SOD) as well as indices (CP, LPO and MDA) and enzymatic activities (SOD, CAT, GPx, GR and GST) were analyzed in liver and brain tissues of Pelteobagrus vachelli. Predominant expression of PvSOD2 was detected in heart, brain, and liver. In contrast, PvSOD1 was highly expressed in liver. Based on the expression patterns of above parameters, we inferred that brain tissue of P. vachelli under 0.7 mg/L degree of acute hypoxia condition could experience hypometabolic states or no suffering stress, but brain tissue has effective mechanisms to minimize or prevent oxidative stress during the transition from hypoxia to reoxygenation. Our results also demonstrated an increased expression of SODs and enzymatic activities for oxidative stress in liver under hypoxic conditions, which supports the hypothesis that anticipatory preparation takes place in order to deal with the encountered oxidative stress during the recovery from hypoxia as proposed by M. Hermes-Lima. Therefore, this study will provide a clue to better understand the action mode of antioxidant genes and enzymes under oxidative stress in fish. PMID:26945243

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

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

    2010-01-01

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

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

    Tong Liu; Ru-Rong Ji

    2012-01-01

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

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

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

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

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

    2010-05-26

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

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

    Paola Massi

    2010-05-01

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

  2. Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.

    Blackburn, Anneke C; Matthaei, Klaus I; Lim, Cindy; Taylor, Matthew C; Cappello, Jean Y; Hayes, John D; Anders, M W; Board, Philip G

    2006-02-01

    Glutathione S-transferase (GST) zeta (GSTZ1-1) plays a significant role in the catabolism of phenylalanine and tyrosine, and a deficiency of GSTZ1-1 results in the accumulation of maleylacetoacetate and its derivatives maleylacetone (MA) and succinylacetone. Induction of GST subunits was detected in the liver of Gstz1(-/-) mice by Western blotting with specific antisera and high-performance liquid chromatography analysis of glutathione affinity column-purified proteins. The greatest induction was observed in members of the mu class. Induction of NAD(P)H:quinone oxidoreductase 1 and the catalytic and modifier subunits of glutamate-cysteine ligase was also observed. Many of the enzymes that are induced in Gstz1(-/-) mice are regulated by antioxidant response elements that respond to oxidative stress via the Keap1/Nrf2 pathway. It is significant that diminished glutathione concentrations were also observed in the liver of Gstz1(-/-) mice, which supports the conclusion that under normal dietary conditions, the accumulation of electrophilic intermediates such as maleylacetoacetate and MA results in a high level of oxidative stress. Elevated GST activities in the livers of Gstz1(-/-) mice suggest that GSTZ1-1 deficiency may alter the metabolism of some drugs and xenobiotics. Gstz1(-/-) mice given acetaminophen demonstrated increased hepatotoxicity compared with wild-type mice. This toxicity may be attributed to the increased GST activity or the decreased hepatic concentrations of glutathione, or both. Patients with acquired deficiency of GSTZ1-1 caused by therapeutic exposure to dichloroacetic acid for the clinical treatment of lactic acidosis may be at increased risk of drug- and chemical-induced toxicity. PMID:16278372

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

    Klingelhoeffer Christoph; Kämmerer Ulrike; Koospal Monika; Mühling Bettina; Schneider Manuela; Kapp Michaela; Kübler Alexander; Germer Christoph-Thomas; Otto Christoph

    2012-01-01

    Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. ...

  4. Response of oxidative stress and isoflavone treatment on superoxide dismutase enzyme activities and lipid peroxidation in rat’s liver

    Suarsana IN

    2013-06-01

    Full Text Available Oxidative stress is defined as over-production of free radicals which lead to cells damage, pathological condition and cell death. The objective of this study was to analyze respond of oxidative stress and isoflavone treatment on superoxide dismutase (SOD enzyme activities and lipid peroxidation in rat liver. A total of fifteen male Spraque Dawley rats were used in this study. They were sub-divided into three groups; (1 a negative control group, (2 a stress oxidative group, and (3 treatment by stress condition followed by treatment with isoflavone. Stress condition was achieved by five days fasting together with swimming for 5 mins/day and only drinking water ad libitum. Isoflavone was orally administrated on a dose of 1 mg/200g bw/day for five days. At the end of the experiment, rats were sacrificed by anesthesia. Liver was collected for analysis of SOD enzyme activities, SOD immunohistochemical analysis, and malondialdehyde (MDA level. Result showed that stress condition increase free radicals that showed by decreased SOD activity, and increased MDA level. Isoflavone treatment could get over reduction of SOD and prevented increase of MDA level in the liver of rats under stress conditions.

  5. Regulation of delta-aminolevulinate synthase activity during the development of oxidative stress.

    Kaliman, P A; Barannik, T V

    1999-06-01

    Activities of rat liver delta-aminolevulinate synthetase (delta-ALAS), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH), GSH content in the liver, and the absorption spectrum of blood serum were investigated after CoCl2, HgCl2, or beta-adrenoblocker (propranolol) injection and after CoCl2 and propranolol co-administration. Inhibition of the activity of the key heme biosynthesis enzyme delta-ALAS was most pronounced and prolonged during the first hours after CoCl2 and CoCl2 plus propranolol injections; this was associated with accumulation of Co2+--protoporphyrin-containing products of hemolysis. Inhibition of delta-ALAS after propranolol injection is not mediated by hemolysis. A decrease in GSH content precedes the induction of heme biosynthesis only in the case of HgCl2 administration, and this was associated with inhibition of GR and G6PDH. The decreased GSH content during the first hours after injection of propranolol and co-administration of CoCl2 and propranolol was not followed by increase in delta-ALAS activity 24 h after the injection. The mechanisms of the increase in the free heme content in the liver during the early stages of oxidative stress and the regulation of the key heme biosynthesis enzyme are discussed. PMID:10395986

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

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

    2015-01-01

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

  7. Effects of nonionic and ionic surfactants on survival, oxidative stress, and cholinesterase activity of planarian.

    Li, Mei-Hui

    2008-02-01

    Eight widely used surfactants (cetyltrimethylammonium bromide; CTAB, benzethonium chloride; Hyamine 1622, 4-nonylphenol; NP, octylphenol ethoxylate; Triton X-100, dodecylbenzene sulfonate; LAS, lauryl sulfate; SDS, pentadecafluorooctanoic acid; PFOA, and perfluorooctane sulfonate; PFOS) were selected to examine their acute toxicities and effects on oxidative stress and cholinesterase (ChE) activities in Dugesia japonica. The differences in acute toxicity among eight surfactants to planarians were at least in the range of three orders of magnitudes. The toxicity rank of surfactants according to estimated 48-h LC(50) was SDS>NP>LAS>Hyamine 1622>CTAB>Triton X-100>PFOS>PFOA. The toxicity rank of surfactants according to 96-h LC(50) was as follows: SDS>CTAB>NP>LAS>Hyamine 1622>Triton X-100>PFOS>PFOA. There were significant increases in catalase activities in planarians exposed to LAS at nominal concentrations of 0.5 or 1 mgl(-1) and to PFOS at nominal concentrations of 5 or 10 mgl(-1) after 48-h exposure. Inhibitions of ChE activities were found in planarians exposed to Hyamine 1622 at all concentrations tested, to PFOS at nominal concentration of 10 mgl(-1), to PFOA at nominal concentrations of 50 or 100 mgl(-1) and to NP at nominal concentration of 0.5 mgl(-1). A significant increase in ChE activities was also observed in planarian exposed to Triton X-100 at nominal concentration of 5 mgl(-1). The implication of ChE inhibition by NP, PFOS and PFOA on neurological and behavioral effects in aquatic animals requires further investigation. PMID:17905407

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

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

    2014-08-15

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

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

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

  10. Effect of Enterococcus faecium 1 (EF1 on Antioxidant Functioning Activity of Caco-2 Cells under Oxidative Stress

    H.Z. Wu

    2012-01-01

    Full Text Available The free radical scavenging systems remove most peroxide which shows antioxidantion capacity of body and lactic acid producing bacteria have capacity to support the body in the mechanism. The present study was initiated to investigate the antioxidantion functioning property of Enterococcus faecium 1 (EF1 to Caco-2 cells under oxidative stress condition. The cells were cultured and randomly divided into 4 groups, the control group (T0, the oxidative stress group (T1, Tert-Butyl Hydroquinone (TBHQ with addition of H2O2 (T2 and EF1 with combination of H2O2 (T3. The results showed that Total Antioxidation Capacity (T-AOC, Catalase (CAT, Superoxide Dismutase (SOD activities, Glutathione (GSH contents in the cultured supernatant and SOD activity of the cells lysate at 12 h increased (p3 as compared to T1. The supernatant of cells cultured at 12 h significantly improved the SOD, GSH-Px activities and GSH contents in T3. While, Anti Superoxide Anion Free Radical (ASAFR, CAT, SOD and Glutathione Peroxidase (GSH-Px activities (p3 to T2 supernatant and lysate of cells at 48 h showed significant increase in T-AOC, CAT, SOD, GSH-Px activities and GSH contents of supernatant and in lysate POD activity and GSH contents significantly increased. While, decline (p3. The findings revealed that Enterococcus faecium 1 could increase the antioxidation functioning activity of Caco-2 cells under oxidative stress condition.

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

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

    2016-04-15

    Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid β-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation. PMID:26970305

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

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

    2012-01-01

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

  13. MITOCHONDRIAL OXIDANT STRESS INCREASES PDE5 ACTIVITY IN PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN

    Farrow, Kathryn N.; Wedgwood, Stephen; Lee, Keng Jin; Czech, Lyubov; Gugino, Sylvia F.; Lakshminrusimha, Satyan; Schumacker, Paul T.; Steinhorn, Robin H.

    2010-01-01

    In the pulmonary vasculature, phosphodiesterase-5 (PDE5) degrades cGMP and inhibits nitric oxide-mediated, cGMP-dependent vasorelaxation. We previously reported that ventilation with 100% O2 increased PDE5 activity in pulmonary arteries (PA) of pulmonary hypertension lambs (PPHN) more than in control lambs. In the present study, PA smooth muscle cells (PASMC) from PPHN lambs had increased basal PDE5 activity, decreased cGMP-responsiveness to NO, and increased mitochondrial matrix oxidant stre...

  14. The synergic effect of regular exercise and resveratrol on kainate-induced oxidative stress and seizure activity in mice.

    Kim, Hee-jae; Kim, Il-Kon; Song, Wook; Lee, Jin; Park, Sok

    2013-01-01

    The synergic effect of regular exercise and resveratrol, a polyphenolic compound with potent antioxidant activity, was investigated against kainate-induced seizures and oxidative stress in mice. After 6 weeks of swimming training, the total body weight decreased and the blood concentration of lactate stabilized statistically in comparison with the sedentary mice, indicate that the training program increased the aerobic resistance of mice. Kainate (30 mg/kg) evoked seizure activity 5 min after injection, and seizure activity was measured seizure rating scores every 5 min up to 2 h. As previously well known experiments, regular exercise and resveratrol (40 mg/kg, daily supplementation for 6 weeks) have an inhibitory effect on kainate-induced seizure activity and oxidative stress. In particularly, a synergistic cooperation of regular exercise and resveratrol was observed in seizure activity, mortality and oxidative stress especially in SOD activity. These results suggest that regular exercise along with an anti-convulsant agent such as resveratrol could be a more efficient method for the prevention of seizure development than exercise alone. PMID:23054073

  15. Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles.

    Chang, Chen-Kang; Huang, Hui-Yu; Tseng, Hung-Fu; Hsuuw, Yan-Der; Tso, Tim K

    2007-01-01

    It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress. PMID:16644199

  16. Oxidative Stress in Malaria

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

  17. Oxidative Stress in Myopia

    Bosch-Morell Francisco

    2015-01-01

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

  18. Oxidative Stress in Myopia

    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

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

    Palaniswamy Radha

    2011-06-01

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

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

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

    2016-10-01

    Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. PMID:27430620

  1. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.

    Gubert, Carolina; Stertz, Laura; Pfaffenseller, Bianca; Panizzutti, Bruna Schilling; Rezin, Gislaine Tezza; Massuda, Raffael; Streck, Emilio Luiz; Gama, Clarissa Severino; Kapczinski, Flávio; Kunz, Maurício

    2013-10-01

    Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. PMID:23870796

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

    Sellamuthu S Gounder

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

  3. NITRIC OXIDE SYNTHASE ACTIVITY AND PEROXYNITRITE CONTENT IN CELLS OF RAT’S MUCOUS COAT OF STOMACH UNDER EXPERIMENTAL STRESS-INDUCED ULCER

    I. S. Maksymovych; M. V. Mylenko; O. V. Drobinska; L.I. Ostapchenko

    2009-01-01

    Nitric oxide synthase activity in gastric mucosal cells as well as peroxynitrite generation in experimental stress-induced gastric ulcer formation in rats were studied. There was made the conclusion that nitric oxide synthase activity is growing during the stress. It causes increasing of peroxynitrite’ production and ulcer formation. It was established that destructive gastric mucosal damages depend on stress’ duration. It was determined that nitric oxide is involved in complex pathogenetic m...

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

    Giovanna R. Degasperi

    2008-03-01

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

  5. Oxidative stress reduces Na+/H+ exchange (NHE) activity in a biliary epithelial cancer cell line (Mz-Cha-1).

    Elsing, Christoph; Voss, Agnieszka; Herrmann, Thomas; Kaiser, Iris; Huebner, Chrisitan A; Schlenker, Thorsten

    2011-02-01

    In cholangiocarcinogenesis, chronic inflammation and oxidative stress play a key role. The Na(+)/H(+) exchanger (NHE) forms a potential link between control of intra- and pericellular pH and tumor development. Therefore, the effects of oxidant stress were determined by the use of tert-butyl hydroperoxide (t-BOOH) on Na(+)/H(+) exchange in a biliary epithelial cancer cell line (Mz-Cha-1). The cells were exposed to the hydroperoxide and the rate of recovery from acidosis was determined by the use of the pH-sensitive fluorochrome 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF/AM). t-BOOH reduced Na(+)/H(+) exchange activity in a dose-dependent manner. At 4 mM t-BOOH, Na(+)/H(+) exchange activity was virtually absent. This was accompanied by an increase in cytotoxicity (MTT assay). Glutathione repletion and intracellular Ca(++) chelation partially restored the Na(+)/H(+) exchange activity. Hydroperoxide seemed neither to alter the intracellular signal transduction pathways (cAMP and Ca(++) oscillations) nor the membrane distribution of the exchanger (immunostaining). Decrease in Na(+)/H(+) exchange activity in this model of oxidant stress may represent an early perturbation of membrane function, and the functional integrity of Na(+)/H(+) exchange could therefore be dependent on the glutathione redox system. PMID:21378324

  6. Skin aging and oxidative stress

    Sayeeda Ahsanuddin; Minh Lam; Baron, Elma D.

    2016-01-01

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

  7. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  8. Deteriorated stress response in stationary-phase yeast: Sir2 and Yap1 are essential for Hsf1 activation by heat shock and oxidative stress, respectively.

    Inbal Nussbaum

    Full Text Available Stationary-phase cultures have been used as an important model of aging, a complex process involving multiple pathways and signaling networks. However, the molecular processes underlying stress response of non-dividing cells are poorly understood, although deteriorated stress response is one of the hallmarks of aging. The budding yeast Saccharomyces cerevisiae is a valuable model organism to study the genetics of aging, because yeast ages within days and are amenable to genetic manipulations. As a unicellular organism, yeast has evolved robust systems to respond to environmental challenges. This response is orchestrated largely by the conserved transcription factor Hsf1, which in S. cerevisiae regulates expression of multiple genes in response to diverse stresses. Here we demonstrate that Hsf1 response to heat shock and oxidative stress deteriorates during yeast transition from exponential growth to stationary-phase, whereas Hsf1 activation by glucose starvation is maintained. Overexpressing Hsf1 does not significantly improve heat shock response, indicating that Hsf1 dwindling is not the major cause for Hsf1 attenuated response in stationary-phase yeast. Rather, factors that participate in Hsf1 activation appear to be compromised. We uncover two factors, Yap1 and Sir2, which discretely function in Hsf1 activation by oxidative stress and heat shock. In Δyap1 mutant, Hsf1 does not respond to oxidative stress, while in Δsir2 mutant, Hsf1 does not respond to heat shock. Moreover, excess Sir2 mimics the heat shock response. This role of the NAD+-dependent Sir2 is supported by our finding that supplementing NAD+ precursors improves Hsf1 heat shock response in stationary-phase yeast, especially when combined with expression of excess Sir2. Finally, the combination of excess Hsf1, excess Sir2 and NAD+ precursors rejuvenates the heat shock response.

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

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

    2013-11-15

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

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

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

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

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

    2012-02-15

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

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

    Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G2/M arrest and appearance of a distinctive SubG1 peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced activities of

  13. Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness.

    Ouyang, Qiufang; Huang, Ziyang; Wang, Zhenhua; Chen, Xiaoqing; Ni, Jingqin; Lin, Ling

    2014-01-01

    We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine. PMID:25136646

  14. THERAPEUTIC ACTIVITY OF BEE-STINGS THERAPY IN RHEUMATOID ARTHRITIS CAUSES INFLAMMATION AND OXIDATIVE STRESS IN FEMALE PATIENTS

    Abdel-Rahman M.

    2013-06-01

    Full Text Available Here the present study aimed to evaluate the therapeutic activity of bee venom acupuncture in rheumatoid arthritis (RA which causes inflammation and oxidative stress in female patients. 75 female patients were divided into 5 groups as control, bee venom acupuncture, rheumatoid arthritis, treated rheumatoid arthritis and rheumatoid arthritis stung with bee venom groups. Serum rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, prostaglandins E2 and F2α, lipid peroxidation, nitric oxide, glutathione and total antioxidant capacity levels were determined in all groups. Rheumatoid arthritis in female patients was resulted in a significant elevation in serum rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, prostaglandins E2 and F2α, lipid peroxidation and nitric oxide levels (p < 0.05 compared to control group. In addition, rheumatoid arthritis caused a significant reduction in serum glutathione and total antioxidant capacity levels. On the other hand, bee venom stings alleviated rheumatoid arthritis inflammation and oxidative stress effects, where all investigated parameters were statistically significant compared to rheumatoid arthritis group. Moreover, bee venom therapy was more potent than the routine treatment of rheumatoid arthritis in patients treated group. Bee venom acupuncture in RA patient may have therapeutic, anti-inflammatory and antioxidant activities.

  15. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation.

    Han, Xiaojuan; Tai, Haoran; Wang, Xiaobo; Wang, Zhe; Zhou, Jiao; Wei, Xiawei; Ding, Yi; Gong, Hui; Mo, Chunfen; Zhang, Jie; Qin, Jianqiong; Ma, Yuanji; Huang, Ning; Xiang, Rong; Xiao, Hengyi

    2016-06-01

    AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. PMID:26890602

  16. Oxidative Stress and Psychological Disorders

    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...

  17. BRCA1 and Oxidative Stress

    Yong Weon Yi; Hyo Jin Kang; Insoo Bae

    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 tre...

  18. TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase

    Fonfria, Elena; Marshall, Ian C B; Benham, Christopher D; Boyfield, Izzy; Brown, Jason D; Hill, Kerstin; Hughes, Jane P; Skaper, Stephen D.; McNulty, Shaun

    2004-01-01

    TRPM2 (melastatin-like transient receptor potential 2 channel) is a nonselective cation channel that is activated under conditions of oxidative stress leading to an increase in intracellular free Ca2+ concentration ([Ca2+]i) and cell death. We investigated the role of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) on hydrogen peroxide (H2O2)-mediated TRPM2 activation using a tetracycline-inducible TRPM2-expressing cell line.In whole-cell patch-clamp recordings, intracellular adenine...

  19. Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways.

    Aung, Hnin Hnin; Altman, Robin; Nyunt, Tun; Kim, Jeffrey; Nuthikattu, Saivageethi; Budamagunta, Madhu; Voss, John C; Wilson, Dennis; Rutledge, John C; Villablanca, Amparo C

    2016-06-01

    Dysfunction of the cerebrovasculature plays an important role in vascular cognitive impairment (VCI). Lipotoxic injury of the systemic endothelium in response to hydrolyzed triglyceride-rich lipoproteins (TGRLs; TGRL lipolysis products) or a high-fat Western diet (WD) suggests similar mechanisms may be present in brain microvascular endothelium. We investigated the hypothesis that TGRL lipolysis products cause lipotoxic injury to brain microvascular endothelium by generating increased mitochondrial superoxide radical generation, upregulation of activating transcription factor 3 (ATF3)-dependent inflammatory pathways, and activation of cellular oxidative stress and apoptotic pathways. Human brain microvascular endothelial cells were treated with human TGRL lipolysis products that induced intracellular lipid droplet formation, mitochondrial superoxide generation, ATF3-dependent transcription of proinflammatory, stress response, and oxidative stress genes, as well as activation of proapoptotic cascades. Male apoE knockout mice were fed a high-fat/high-cholesterol WD for 2 months, and brain microvessels were isolated by laser capture microdissection. ATF3 gene transcription was elevated 8-fold in the hippocampus and cerebellar brain region of the WD-fed animals compared with chow-fed control animals. The microvascular injury phenotypes observed in vitro and in vivo were similar. ATF3 plays an important role in mediating brain microvascular responses to acute and chronic lipotoxic injury and may be an important preventative and therapeutic target for endothelial dysfunction in VCI. PMID:27087439

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

    Pedro Miramón

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

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

    Antonio Ivanildo Pinho

    2014-01-01

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

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

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

    2014-01-10

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

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

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

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

    Cisplatin has been used as a chemotherapeutic agent to treat many kinds of malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been reported. However, the underlying biochemical change in the inner ear or central vestibular nervous system is not fully understood. In this study, we attempted to examine whether cisplatin-induced vestibulotoxicity and D-methionine protection were correlated with the changes of ATPase activities and oxidative stress of ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory center of VOR system) of guinea pigs. By means of a caloric test coupled with electronystagmographic recordings, we found that cisplatin exposure caused a dose-dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of slow phase velocity (SPV). In addition, cisplatin significantly inhibited the Na+, K+-ATPase and Ca2+-ATPase activities in the ampullary tissue with a good dose-response relationship but not those of cerebellar cortex. Regression analysis indicated that a decrease of SPV was well correlated with the reduction of Na+, K+-ATPase and Ca2+-ATPase activities of the ampullary tissue. D-Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in a correlated manner. Moreover, cisplatin exposure led to a significant dose-dependent increase of lipid peroxidation and nitric oxide concentrations of the vestibules, which could be significantly suppressed by D-methionine. However, cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated cisplatin-induced vestibulotoxicity associated with ionic disturbance through its antioxidative property

  5. Is the Oxidative Stress Really a Disease?

    Fogarasi Erzsébet

    2016-03-01

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

  6. Evaluation of Antioxidant Activity and γ-radiation Induced Oxidative Stress Protection of Aquilaria crassna Leaf Extract

    In Asia Aquilaria has long been used in many traditional medicines due to its enrichment inseveral active ingredients such as flavonoids, tannins, and cardiac glycosides. The objective of this work is to investigate and evaluate antioxidant and γ-radiation induced oxidative stress protection activities of the Aquilaria leaf extract. The leaf was extracted by Soxhlet extractor in which both the upper fraction (filtrate) and the lower fraction (precipitate) were kept separately for evaluation. In terms of antioxidant activity, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) was used in a free radical scavenging assay. The precipitate of 3.13, 6.25, 12.50, 25.00, 50.00 and 100 μg/ml exhibited 17.70%, 33.52%, 45.80%, 60.49%, 76.30% and 85.71% DPPH inhibition, respectively. The filtrate at the same concentrations showed approximately 50% less inhibition than the precipitate. The extracts did not exhibit any cytotoxicity by MTT assay. However, the precipitate at 10, 20, 100 μg/ml and the filtrate at 50, 100, 200 μg/ ml could not protect human dermal fibroblast cells from irradiation damage when the cells were treated for 45 min or 24 h prior to exposure to gamma radiation at 0, 3 and 10 Gy. In conclusion, the Aquilaria leaf extract contained a potent antioxidant activity, but not μ-radiation induced oxidative stress protection activity.

  7. Aerobic exercise training improves oxidative stress and ubiquitin proteasome system activity in heart of spontaneously hypertensive rats.

    de Andrade, Luiz Henrique Soares; de Moraes, Wilson Max Almeida Monteiro; Matsuo Junior, Eduardo Hiroshi; de Orleans Carvalho de Moura, Elizabeth; Antunes, Hanna Karen Moreira; Montemor, Jairo; Antonio, Ednei Luiz; Bocalini, Danilo Sales; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Brum, Patricia Chakur; Medeiros, Alessandra

    2015-04-01

    The activity of the ubiquitin proteasome system (UPS) and the level of oxidative stress contribute to the transition from compensated cardiac hypertrophy to heart failure in hypertension. Moreover, aerobic exercise training (AET) is an important therapy for the treatment of hypertension, but its effects on the UPS are not completely known. The aim of this study was to evaluate the effect of AET on UPS's activity and oxidative stress level in heart of spontaneously hypertensive rats (SHR). A total of 53 Wistar and SHR rats were randomly divided into sedentary and trained groups. The AET protocol was 5×/week in treadmill for 13 weeks. Exercise tolerance test, non-invasive blood pressure measurement, echocardiographic analyses, and left ventricle hemodynamics were performed during experimental period. The expression of ubiquitinated proteins, 4-hydroxynonenal (4-HNE), Akt, phospho-Akt(ser473), GSK3β, and phospho-GSK3β(ser9) were analyzed by western blotting. The evaluation of lipid hydroperoxide concentration was performed using the xylenol orange method, and the proteasomal chymotrypsin-like activity was measured by fluorimetric assay. Sedentary hypertensive group presented cardiac hypertrophy, unaltered expression of total Akt, phospho-Akt, total GSK3β and phospho-GSK3β, UPS hyperactivity, increased lipid hydroperoxidation as well as elevated expression of 4-HNE but normal cardiac function. In contrast, AET significantly increased exercise tolerance, decreased resting systolic blood pressure and heart rate in hypertensive animals. In addition, the AET increased phospho-Akt expression, decreased phospho-GSK3β, and did not alter the expression of total Akt, total GSK3β, and ubiquitinated proteins, however, significantly attenuated 4-HNE levels, lipid hydroperoxidation, and UPS's activity toward normotensive group levels. Our results provide evidence for the main effect of AET on attenuating cardiac ubiquitin proteasome hyperactivity and oxidative stress in SHR

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

    Caitlin C Otto

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

  9. Quercus infectoria galls possess antioxidant activity and abrogates oxidative stress-induced functional alterations in murine macrophages.

    Kaur, Gurpreet; Athar, Mohammad; Alam, M Sarwar

    2008-02-15

    The present study reports the antioxidant activity of ethanolic extract of Quercus infectoria galls. The antioxidant potency of galls was investigated employing several established in vitro model systems. Their protective efficacy on oxidative modulation of murine macrophages was also explored. Gall extract was found to contain a large amount of polyphenols and possess a potent reducing power. HPTLC analysis of the extract suggested it to contain 19.925% tannic acid (TA) and 8.75% gallic acid (GA). The extract potently scavenged free radicals including DPPH (IC(50)~0.5 microg/ml), ABTS (IC(50)~1 microg/ml), hydrogen peroxide (H(2)O(2)) (IC(50)~2.6 microg/ml) and hydroxyl (*OH) radicals (IC(50)~6 microg/ml). Gall extract also chelated metal ions and inhibited Fe(3+) -ascorbate-induced oxidation of protein and peroxidation of lipids. Exposure of rat peritoneal macrophages to tertiary butyl hydroperoxide (tBOOH) induced oxidative stress in them and altered their phagocytic functions. These macrophages showed elevated secretion of lysosomal hydrolases, and attenuated phagocytosis and respiratory burst. Activity of macrophage mannose receptor (MR) also diminished following oxidant exposure. Pretreatment of macrophages with gall extract preserved antioxidant armory near to control values and significantly protected against all the investigated functional mutilations. MTT assay revealed gall extract to enhance percent survival of tBOOH exposed macrophages. These results indicate that Q. infectoria galls possess potent antioxidant activity, when tested both in chemical as well as biological models. PMID:18076871

  10. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 μg/gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro(α) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis.

  11. BRCA1 and Oxidative Stress

    Yi, Yong Weon; Kang, Hyo Jin [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Bae, Insoo, E-mail: ib42@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2014-04-03

    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.

  12. BRCA1 and Oxidative Stress

    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

  13. Activation of NF-{kappa}B in human skin fibroblasts by the oxidative stress generated by UVA radiation

    Vile, G.F.; Tanew-Iliitschew, Adrian; Tyrrell, R.M. [Institut Suisse de Recherches Experimentales sur le Cancer, Lausanne (Switzerland)

    1995-09-01

    We have examined the role of the nucleus and the membrane in the activation of nuclear factor (NF)-kB by oxidant stress generated via the UVA (320-380 nm) component of solar radiation. Nuclear extracts from human skin fibroblasts that had been irradiated with UVA at doses that caused little DNA damage contained activated NF-{kappa}B that bound to its recognition sequence in DNA. The UVA radiation-dependent activation of NF-{kappa}B in enucleated cells confirmed that the nucleus was not involved. On the other hand, UVA radiation-dependent activation of NF-{kappa}B appeared to be correlated with membrane damage, and activation could be prevented by {alpha}-tocopherol and butylated hydroxytoluene, agents that inhibited UVA radiation-dependent peroxidation of cell membrane lipids. The activation of NF-{kappa}B by the DNA damaging agents UVC (200-290 nm) and UVB (290-320 nm) radiation also only occurred at doses where significant membrane damage was induced, and, overall, activation was not correlated with the relative levels of DNA damage induced by UVC/UVB and UVA radiations. We conclude that the oxidative modification of membrane components may be an important factor to consider in the UV radiation-dependent activation of NF-{kappa}B over all wavelength ranges examined. (Author).

  14. Activation of NF-κB in human skin fibroblasts by the oxidative stress generated by UVA radiation

    We have examined the role of the nucleus and the membrane in the activation of nuclear factor (NF)-kB by oxidant stress generated via the UVA (320-380 nm) component of solar radiation. Nuclear extracts from human skin fibroblasts that had been irradiated with UVA at doses that caused little DNA damage contained activated NF-κB that bound to its recognition sequence in DNA. The UVA radiation-dependent activation of NF-κB in enucleated cells confirmed that the nucleus was not involved. On the other hand, UVA radiation-dependent activation of NF-κB appeared to be correlated with membrane damage, and activation could be prevented by α-tocopherol and butylated hydroxytoluene, agents that inhibited UVA radiation-dependent peroxidation of cell membrane lipids. The activation of NF-κB by the DNA damaging agents UVC (200-290 nm) and UVB (290-320 nm) radiation also only occurred at doses where significant membrane damage was induced, and, overall, activation was not correlated with the relative levels of DNA damage induced by UVC/UVB and UVA radiations. We conclude that the oxidative modification of membrane components may be an important factor to consider in the UV radiation-dependent activation of NF-κB over all wavelength ranges examined. (Author)

  15. Skin aging and oxidative stress

    Sayeeda Ahsanuddin

    2016-05-01

    Full Text Available Skin aging occurs through two main pathways, intrinsic and extrinsic. These pathways have significant interaction in contributing to the aging phenotype, which includes skin laxity, wrinkling, pigmentation irregularities, and the appearance of neoplastic skin lesions. Here, we review the critical role that oxidative stress plays in skin aging, including its effects on signaling pathways involved in skin matrix formation and degradation, proteasome activity, as well as DNA structure. Furthermore, we discuss the recent literature surrounding the prevention and treatment of skin aging. Although current research is suggestive of the role of antioxidants in anti-aging skin therapies, further research is much needed to explore its role in humans.

  16. Coal and tire burning mixtures containing ultrafine and nanoparticulate materials induce oxidative stress and inflammatory activation in macrophages.

    Gasparotto, Juciano; Somensi, Nauana; Caregnato, Fernanda F; Rabelo, Thallita K; DaBoit, Kátia; Oliveira, Marcos L S; Moreira, José C F; Gelain, Daniel P

    2013-10-01

    Ultra-fine and nano-particulate materials resulting from mixtures of coal and non-coal fuels combustion for power generation release to the air components with toxic potential. We evaluated toxicological and inflammatory effects at cellular level that could be induced by ultrafine/nanoparticles-containing ashes from burning mixtures of coal and tires from an American power plant. Coal fly ashes (CFA) samples from the combustion of high-S coal and tire-derived fuel, the latter about 2-3% of the total fuel feed, in a 100-MW cyclone utility boiler, were suspended in the cell culture medium of RAW 264.7 macrophages. Cell viability, assessed by MTT reduction, SRB incorporation and contrast-phase microscopy analysis demonstrated that CFA did not induce acute toxicity. However, CFA at 1mg/mL induced an increase of approximately 338% in intracellular TNF-α, while release of this proinflammatory cytokine was increased by 1.6-fold. The expression of the inflammatory mediator CD40 receptor was enhanced by 2-fold, the receptor for advanced glycation endproducts (RAGE) had a 5.7-fold increase and the stress response protein HSP70 was increased nearly 12-fold by CFA at 1mg/mL. Although CFA did not induce cell death, parameters of oxidative stress and reactive species production were found to be altered at several degrees, such as nitrite accumulation (22% increase), DCFH oxidation (3.5-fold increase), catalase (5-fold increase) and superoxide dismutase (35% inhibition) activities, lipoperoxidation (4.2 fold-increase) and sulfhydryl oxidation (40% decrease in free SH groups). The present results suggest that CFA containing ultra-fine and nano-particulate materials from coal and tire combustion may induce sub-chronic cell damage, as they alter inflammatory and oxidative stress parameters at the molecular and cellular levels, but do not induce acute cell death. PMID:23856402

  17. Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.

    Ben Salem, Intidhar; Boussabbeh, Manel; Kantaoui, Hiba; Bacha, Hassen; Abid-Essefi, Salwa

    2016-08-01

    The protective effects of Crocin (CRO), a carotenoid with wide spectrum of pharmacological effects, against the cytotoxicity and the apoptosis produced by exposure to Dichlorvos (DDVP) in HCT116 cells were investigated in this work. The cytotoxicity was monitored by cell viability, ROS generation, antioxidant enzymes activities, malondialdehyde (MDA) production and DNA fragmentation. The apoptosis was assessed through the measurement of the mitochondrial transmembrane potential (ΔΨm) and caspases activation. The results indicated that pretreatment of HCT116 cells with CRO, 2h prior to DDVP exposure, significantly increased the survival of cells, inhibited the ROS generation, modulated the activities of catalase (CAT) and superoxide dismutase (SOD) and reduced the MDA level. The reduction in mitochondrial membrane potential, DNA fragmentation and caspases activation were also inhibited by CRO. These findings suggest that CRO can protect HCT116 cells from DDVP-induced oxidative stress and apoptosis. PMID:27470340

  18. Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-κB activation

    Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-κB) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-κB activity. An inhibitor of NF-κB, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-κB signalling pathway by styrene is mediated via a redox-sensitive mechanism

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

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

    2016-06-01

    Streptococcus mitis from the oral cavity causes endocarditis and other systemic infections. Rising resistance against traditional antibiotics amongst oral bacteria further aggravates the problem. Therefore, antimicrobial and antibiofilm activities of zinc oxide and titanium dioxide nanoparticles (NPs) synthesized and characterized during this study against S. mitis ATCC 6249 and Ora-20 were evaluated in search of alternative antimicrobial agents. ZnO and TiO2-NPs exhibited an average size of 35 and 13 nm, respectively. The IC50 values of ZnO and TiO2-NPs against S. mitis ATCC 6249 were 37 and 77 µg ml(-1), respectively, while the IC50 values against S. mitis Ora-20 isolate were 31 and 53 µg ml(-1), respectively. Live and dead staining, biofilm formation on the surface of polystyrene plates, and extracellular polysaccharide production show the same pattern. Exposure to these nanoparticles also shows an increase (26-83 %) in super oxide dismutase (SOD) activity. Three genes, namely bapA1, sodA, and gtfB like genes from these bacteria were identified and sequenced for quantitative real-time PCR analysis. An increase in sodA gene (1.4- to 2.4-folds) levels and a decrease in gtfB gene (0.5- to 0.9-folds) levels in both bacteria following exposure to ZnO and TiO2-NPs were observed. Results presented in this study verify that ZnO-NPs and TiO2-NPs can control the growth and biofilm formation activities of these strains at very low concentration and hence can be used as alternative antimicrobial agents for oral hygiene. PMID:26837748

  20. Potential benefits of physical activity during pregnancy for the reduction of gestational diabetes prevalence and oxidative stress.

    Cid, Marcela; González, Marcelo

    2016-03-01

    Changes in quality of nutrition, habits, and physical activity in modern societies increase susceptibility to obesity, which can deleteriously affect pregnancy outcome. In particular, a sedentary lifestyle causes dysfunction in blood flow, which impacts the cardiovascular function of pregnant women. The main molecular mechanism responsible for this effect is the synthesis and bioavailability of nitric oxide, a phenomenon regulated by the antioxidant capacity of endothelial cells. These alterations affect the vascular health of the mother and vascular performance of the placenta, the key organ responsible for the healthy development of the fetus. In addition to the increases in systemic vascular resistance in the mother, placental oxidative stress also affects the feto-placental blood flow. These changes can be integrated into the proteomics and metabolomics of newborns. PMID:26833143

  1. Oxidative Stress and HPV Carcinogenesis

    Federico De Marco

    2013-02-01

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

  2. Oxidative Stress, Molecular Inflammation and Sarcopenia

    Si-Jin Meng; Long-Jiang Yu

    2010-01-01

    Sarcopenia is the decline of muscle mass and strength with age. Evidence suggests that oxidative stress and molecular inflammation play important roles in age-related muscle atrophy. The two factors may interfere with the balance between protein synthesis and breakdown, cause mitochondrial dysfunction, and induce apoptosis. The purpose of this review is to discuss some of the major signaling pathways that are activated or inactivated during the oxidative stress and molecular inflammation seen...

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

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

    2014-06-01

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

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

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

    2014-01-01

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

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

    Daniela Soares VIANA; Carvalho, Lucia Maria Jaeger de; Mirian Ribeiro Leite MOURA; Jacqueline Carvalho PEIXOTO; Carvalho, José Luiz Viana de

    2016-01-01

    Abstract The relation between oxidative stress and inflammation induced by diseases and exercise has increased the interest in the benefits of antioxidant supplements in the improvement of health and physical and mental performance. The aim of this study was to evaluate the effectiveness of açai gel in reducing oxidative stress in individuals engaged in physical activities as well as their acceptance. Sensory evaluation was performed to determine its acceptability and the biochemical paramete...

  6. Mechanisms Underlying the Delayed Activation of the Cap1 Transcription Factor in Candida albicans following Combinatorial Oxidative and Cationic Stress Important for Phagocytic Potency

    Kos, Iaroslava; Patterson, Miranda J.; Znaidi, Sadri; Kaloriti, Despoina; da Silva Dantas, Alessandra; Herrero-de-Dios, Carmen M.; d’Enfert, Christophe; Brown, Alistair J. P.

    2016-01-01

    ABSTRACT Following phagocytosis, microbes are exposed to an array of antimicrobial weapons that include reactive oxygen species (ROS) and cationic fluxes. This is significant as combinations of oxidative and cationic stresses are much more potent than the corresponding single stresses, triggering the synergistic killing of the fungal pathogen Candida albicans by “stress pathway interference.” Previously we demonstrated that combinatorial oxidative plus cationic stress triggers a dramatic increase in intracellular ROS levels compared to oxidative stress alone. Here we show that activation of Cap1, the major regulator of antioxidant gene expression in C. albicans, is significantly delayed in response to combinatorial stress treatments and to high levels of H2O2. Cap1 is normally oxidized in response to H2O2; this masks the nuclear export sequence, resulting in the rapid nuclear accumulation of Cap1 and the induction of Cap1-dependent genes. Here we demonstrate that following exposure of cells to combinatorial stress or to high levels of H2O2, Cap1 becomes trapped in a partially oxidized form, Cap1OX-1. Notably, Cap1-dependent gene expression is not induced when Cap1 is in this partially oxidized form. However, while Cap1OX-1 readily accumulates in the nucleus and binds to target genes following high-H2O2 stress, the nuclear accumulation of Cap1OX-1 following combinatorial H2O2 and NaCl stress is delayed due to a cationic stress-enhanced interaction with the Crm1 nuclear export factor. These findings define novel mechanisms that delay activation of the Cap1 transcription factor, thus preventing the rapid activation of the stress responses vital for the survival of C. albicans within the host. PMID:27025253

  7. Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2.

    Cardozo, Ludmila F M F; Pedruzzi, Liliana M; Stenvinkel, Peter; Stockler-Pinto, Milena B; Daleprane, Julio B; Leite, Maurilo; Mafra, Denise

    2013-08-01

    The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2-Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health. PMID:23643732

  8. Effect of Proline-Containing Oligopeptides PGP and RGP on Proliferative and Protein-Synthesizing Activity of Cultured Pulmonary Fibroblasts under Conditions of Oxidative Stress.

    Tolstenok, I V; Fleishman, M Yu; Sazonova, E N; Lebed'ko, O A; Maltseva, I M; Myasoedov, N F; Timoshin, S S

    2016-05-01

    We studied the effect of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly-Pro (RGP) on the primary culture of pulmonary fibroblasts from newborn albino rats under normal conditions and during oxidative stress. Under physiological conditions, the peptides had no effect on parameters of cell division. Hydrogen peroxide induced intensive oxidative stress accompanied by suppression of protein-synthesizing function. When hydrogen peroxide was added to the culture containing the test peptides, correction of the oxidative status was observed accompanied by activation of DNA-synthesizing activity and inhibition of lucigenin-dependent chemiluminescence. PMID:27265140

  9. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918530

  10. Cardiac peroxisome proliferator-activated receptor-γ expression is modulated by oxidative stress in acutely infrasound-exposed cardiomyocytes.

    Pei, Zhaohui; Meng, Rongsen; Zhuang, Zhiqiang; Zhao, Yiqiao; Liu, Fangpeng; Zhu, Miao-Zhang; Li, Ruiman

    2013-12-01

    The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ. PMID:23632742

  11. Vanillic Acid Inhibits Inflammatory Pain by Inhibiting Neutrophil Recruitment, Oxidative Stress, Cytokine Production, and NFκB Activation in Mice.

    Calixto-Campos, Cássia; Carvalho, Thacyana T; Hohmann, Miriam S N; Pinho-Ribeiro, Felipe A; Fattori, Victor; Manchope, Marília F; Zarpelon, Ana C; Baracat, Marcela M; Georgetti, Sandra R; Casagrande, Rubia; Verri, Waldiceu A

    2015-08-28

    Vanillic acid (1) is a flavoring agent found in edible plants and fruits. It is an oxidized form of vanillin. Phenolic compounds form a substantial part of plant foods used as antioxidants with beneficial biological activities. These compounds have received considerable attention because of their role in preventing human diseases. Especially, 1 presents antibacterial, antimicrobial, and chemopreventive effects. However, the mechanisms by which 1 exerts its anti-inflammatory effects in vivo are incompletely understood. Thus, the effect of 1 was evaluated in murine models of inflammatory pain. Treatment with 1 inhibited the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, the second phase of the formalin test, and complete Freund's adjuvant (CFA). Treatment with 1 also inhibited carrageenan- and CFA-induced mechanical hyperalgesia, paw edema, myeloperoxidase activity, and N-acetyl-β-D-glucosaminidase activity. The anti-inflammatory mechanisms of 1 involved the inhibition of oxidative stress, pro-inflammatory cytokine production, and NFκB activation in the carrageenan model. The present study demonstrated 1 presents analgesic and anti-inflammatory effects in a wide range of murine inflammation models, and its mechanisms of action involves antioxidant effects and NFκB-related inhibition of pro-inflammatory cytokine production. PMID:26192250

  12. Halothane induces oxidative stress and NF-κB activation in rat liver: Protective effect of propofol

    We investigated the effects of propofol on markers of oxidative stress, nuclear factor kappa B (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in liver of rats treated with halothane under hypoxic conditions. Male Wistar rats received halothane 1%/oxygen 14%, oxygen 14%/propofol 60 mg kg-1 i.p., or halothane 1%/oxygen 14%/propofol 60 mg kg-1 i.p. Morphological examination showed complete loss of architecture with massive necrosis of parenchyma in the halothane group, while only minor histological abnormalities were observed in rats receiving halothane plus propofol. The cytosolic concentration of TBARS and the hydroperoxide-initiated chemiluminescence increased significantly in the liver of animals from the halothane group (+62% and +40% versus controls, respectively), and this increase was abolished by propofol administration. Halothane induced a marked activation of NF-κB (+180%), and resulted in a significant decrease of the nonphosphorylated form of the inhibitor IκBα (-53%), while phosphorylated IκBα protein level was markedly increased (+146%). Propofol administration lowered these effects to +30% (NF-κB), -26% (nonphosphorylated IκBα), and +56% (phosphorylated IκBα). The increase of iNOS protein level (+59%) induced by halothane was significantly reduced to +22% by additional administration of propofol. Results obtained show that administration of propofol inhibits oxidative stress, NF-κB nuclear traslocation and iNOS overexpression in liver of rats receiving halothane. Propofol treatment, by inhibiting the NF-κB signal transduction pathway, might block the production of noxious mediators involved in the development of halothane-induced injury

  13. Oxidative Stress and Neurodegenerative Disorders

    Jie Li; Wuliji O; Wei Li; Zhi-Gang Jiang; 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. T...

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

    Li Jin-Lian

    2012-03-01

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

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

    Nady Braidy

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

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

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

    2014-01-15

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

  17. PPARα agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

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

  18. Oxidative Stress and Major Depression

    Bajpai, Ashutosh; 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.

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

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

    2015-12-01

    The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease. PMID:26369587

  20. Inflammation, Oxidative Stress, and Obesity

    José A. Morales-González

    2011-05-01

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

  1. Vitamin B6 Supplementation Improves Oxidative Stress and Enhances Serum Paraoxonase/Arylesterase Activities in Streptozotocin-Induced Diabetic Rats

    Sibel Taş

    2014-01-01

    Full Text Available The purpose of this study was to investigate the effects of vitamin B6 (Vit B6 on oxidant and antioxidant status in streptozotocin-induced diabetic rats. Thirty-two Wistar rats were divided into four groups: control (C, control + Vit B6 group (C + Vit B6, diabetes (D, and diabetes + Vit B6 group (D + Vit B6. Vit B6 (4 mg/kg body weight was administered in drinking water for 4 weeks after the induction of diabetes. Vitamin B6 reduced serum total cholesterol level in the C + Vit B6 (P < 0.01 and D + Vit B6 (P < 0.05 groups. Plasma and tissue malondialdehyde levels were reduced in the C + Vit B6 and D + Vit B6 groups. Whole blood glutathione peroxidase (GSH-Px and erythrocyte superoxide dismutase (SOD activities were higher in the D group (P < 0.05. GSH-Px and SOD activities were increased in C + Vit B6 group while these parameters decreased in the D + Vit B6 group. Paraoxonase and arylesterase activities were decreased in the D group while they were increased in C + Vit B6 and D + Vit B6 groups. The results of present study suggest that vitamin B6 supplementation might be a promising adjunctive agent for improving oxidative stress and metabolic disturbances and for preventing diabetic complications including atherogenesis.

  2. The Role Oxidative Stress in the Pathogenesis of Eye Diseases: Current Status and a Dual Role of Physical Activity.

    Kruk, Joanna; Kubasik-Kladna, Katarzyna; Aboul-Enein, Hassan Y

    2015-01-01

    Extensive research during the past three decades has demonstrated the mechanisms by which an imbalance in the redox status of prooxidant/antioxidant reactions in cells with advantage of prooxidant reactions (oxidative stress, OS) can cause peroxidation of nucleic acids, bases, lipids, proteins and carbohydrates, thus resulting in their damage. These actions result in stimulation of signal transduction pathways and activation of transcription factors that can lead to chronic inflammation and cause tissue dysfunction. The most important oxidants are reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by various metabolic pathways, physical, chemical and biological factors, and pathological conditions. The eye is one of the major target of the ROS/RNS attack due to exposition on several environmental factors like high pressure of oxygen, light exposure, ultraviolet rays, ionizing radiation, chemical pollutants, irritant, and pathogenic microbes, which are able to shift the redox status of a cell towards oxidizing conditions. There is increasing evidence indicating that persistent OS contributes to the development of many ocular diseases. Increases in the accumulation of hydrogen peroxide and markers of the oxidative damage to DNA, lipids, proteins observed in several eye diseases and usage of antioxidants in their treatment and prevention emphasize the involvement of OS pathways. This paper summarizes the present state of knowledge in the involvement of OS in the etiology of non-cancer ocular diseases (dry eye syndrome; corneal and conjunctive diseases; cataract; glaucoma; age-related macular degeneration; retinitis pigmentosa; diabetic retinopathy, autoimmune and inflammatory uveitis) and cancer ocular diseases (melanoma; retinoblastoma; lymphoma). The paper also discusses the potential applications of antioxidants in the prevention of eye diseases and shows a duality of physical exercise actions: protection against the ROS/RNS damage by

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

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

    2016-04-01

    Neuroblastoma is one of the most common childhood malignancies and the primary cause of death from pediatric cancer. Derivatives of 17β-estradiol, 2-methoxyestradiol, as well as selective estrogen receptor modulators, such as fulvestrant, are novel potentially active anticancer agents. In particular, 2-methoxyestradiol is effective in treatment of numerous malignancies, including breast and prostate cancer, Ewing sarcoma, and osteosarcoma. Herein, we treated neuroblastoma SH-SY5Y cells with physiologically and pharmacologically relevant concentrations of 2-methoxyestradiol. We used flow cytometry in order to determine cell viability, cell death, level of nitric oxide and mitochondrial membrane potential. We demonstrated that at pharmacologically relevant concentrations, 2-methoxyestradiol results in induction of apoptosis of neuroblastoma SH-SY5Y cells via nitric oxide generation and reduction of mitochondrial membrane potential. Based on the obtained data, we propose that 2-methoxyestradiol may be a natural modulator of cancer cell death and survival through nitro-oxidative stress-dependent mechanisms. Moreover, the results confirm the efficiency of 2-methoxyestradiol in treatment of neuroblastoma. PMID:27069147

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

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

    2012-08-15

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

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

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC50 = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

  6. SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury.

    Cheng, Yedong; Di, Shouyin; Fan, Chongxi; Cai, Liping; Gao, Chao; Jiang, Peng; Hu, Wei; Ma, Zhiqiang; Jiang, Shuai; Dong, Yushu; Li, Tian; Wu, Guiling; Lv, Jianjun; Yang, Yang

    2016-08-01

    Ischemia reperfusion (IR) injury is harmful to skeletal muscles and causes mitochondrial oxidative stress. Pterostilbene (PTE), an analogue of resveratrol, has organic protective effects against oxidative stress. However, no studies have investigated whether PTE can protect against IR-related skeletal muscular injury. In this study, we sought to evaluate the protective effect of PTE against IR-related skeletal muscle injury and to determine the mechanisms in this process. Male Sprague-Dawley rats were pretreated with PTE for a week and then underwent limb IR surgery. The IR injury induced segmental necrosis and apoptosis, myofilament disintegration, thicker interstitial spaces, and inflammatory cell infiltration. Furthermore, mitochondrial respiratory chain activity in the muscular tissue was inhibited, methane dicarboxylic aldehyde concentration and myeloperoxidase activity were up-regulated, and superoxide dismutase was down-regulated after IR. However, these effects were significantly inhibited by PTE in a dose-dependent manner. The mechanism underlying IR injury is attributed to the down-regulation of silent information regulator 1 (SIRT1)-FOXO1/p53 pathway and the increase of the Bax/Bcl2 ratio, Cleaved poly ADP-ribose polymerase 1, Cleaved Caspase 3, which can be reversed with PTE. Furthermore, EX527, an SIRT1 inhibitor, counteracted the protective effects of PTE on IR-related muscle injury. In conclusion, PTE has protective properties against IR injury of the skeletal muscles. The mechanism of this protective effect depends on the activation of the SIRT1-FOXO1/p53 signaling pathway and the decrease of the apoptotic ratio in skeletal muscle cells. PMID:27270300

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

    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. [Heme metabolism and oxidative stress].

    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

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

    Namrata eChaudhari

    2014-07-01

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

  10. Chemically induced oxidative stress increases polyamine levels by activating the transcription of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase in human hepatoma HUH7 cells.

    Smirnova, Olga A; Isaguliants, Maria G; Hyvonen, Mervi T; Keinanen, Tuomo A; Tunitskaya, Vera L; Vepsalainen, Jouko; Alhonen, Leena; Kochetkov, Sergey N; Ivanov, Alexander V

    2012-09-01

    Biogenic polyamines spermine and spermidine participate in numerous cellular processes including transcription, RNA processing and translation. Specifically, they counteract oxidative stress, an alteration of cell redox balance involved in generation and progression of various pathological states including cancer. Here, we investigated how chemically induced oxidative stress affects polyamine metabolism, specifically the expression and activities of enzymes catalyzing polyamine synthesis (ornithine decarboxylase; ODC) and degradation (spermidine/spermine-N(1)-acetyltransferase; SSAT), in human hepatoma cells. Oxidative stress induced the up-regulation of ODC and SSAT gene transcription mediated by Nrf2, and in case of SSAT, also by NF-κB transcription factors. Activation of transcription led to the elevated intracellular activities of both enzymes. The balance in antagonistic activities of ODC and SSAT in the stressed hepatoma cells was shifted towards polyamine biosynthesis, which resulted in increased intracellular levels of putrescine, spermidine, and spermine. Accumulation of putrescine is indicating for accelerated degradation of polyamines by SSAT - acetylpolyamine oxidase (APAO) pathway generating toxic products that promote carcinogenesis, whereas accelerated polyamine synthesis via activation of ODC is favorable for proliferation of cells including those sub-lethally damaged by oxidative stress. PMID:22579641

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

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

    2015-03-01

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

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

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

  13. Oxidative Stress in Placenta: Health and Diseases

    Fan Wu

    2015-01-01

    Full Text Available 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.

  14. The oxidative stress hypothesis in Alzheimer's disease.

    Padurariu, Manuela; Ciobica, Alin; Lefter, Radu; Serban, Ionela Lacramioara; Stefanescu, Cristinel; Chirita, Roxana

    2013-12-01

    Oxidative stress may be involved in many somatic and psychiatric pathological states including dementia. The hypothesis of oxidative stress involvement in dementia is supported by much scientific data through biochemical, genetic and molecular studies. Thus, there are many reports of an increased level of the markers for oxidative damage, alterations in the specific activity of the antioxidant system, mutations in specific genes, mitochondrial disturbances and also several connections between oxidative stress and amyloid plaques. Despite these evidence and clinical approaches in using antioxidant therapy in dementia treatment, studies have failed to prove a clear benefit for antioxidant treatment in dementia. Hence, there is a need for further research regarding antioxidant therapy in very early stages of dementia. PMID:24247053

  15. Evaluation of Delta-Aminolevulinic Dehydratase Activity, Oxidative Stress Biomarkers, and Vitamin D Levels in Patients with Multiple Sclerosis.

    Polachini, Carla Roberta Nunes; Spanevello, Roselia Maria; Zanini, Daniela; Baldissarelli, Jucimara; Pereira, Luciane Belmonte; Schetinger, Maria Rosa Chitolina; da Cruz, Ivana Beatrice Mânica; Assmann, Charles Elias; Bagatini, Margarete Dulce; Morsch, Vera Maria

    2016-02-01

    Multiple sclerosis (MS) is an autoimmune neurological disorder of unknown etiology. Oxidative stress and alterations in vitamin D levels have been implicated in the pathophysiology of MS. The aim of this study was to investigate δ-aminolevulinate dehydratase (δ-ALA-D) activity as well as the levels of vitamin D, lipid peroxidation levels, carbonyl protein content, DNA damage, superoxide dismutase (SOD) and catalase (CAT) activities, and the vitamin C, vitamin E, and non-protein thiol (NPSH) content in samples from patients with the relapsing-remitting form of MS (RRMS). The study population consisted of 29 RRMS patients and 29 healthy subjects. Twelve milliliters of blood was obtained from each individual and used for biochemical determinations. The results showed that δ-ALA-D and CAT activities were significantly increased, while SOD activity was decreased in the whole blood of RRMS patients compared to the control group (P vitamin C, vitamin E, NPSH, and vitamin D were significantly decreased in RRMS patients in relation to the healthy individuals (P vitamin D levels may contribute to the pathophysiology of MS. PMID:26690779

  16. Role of oxidative stress in ERK and p38 MAPK activation induced by the chemical sensitizer DNFB in a fetal skin dendritic cell line

    Matos, MT; Duarte, CB; Gonçalo, Margarida; Lopes, MC

    2005-01-01

    The intracellular mechanisms involved in the early phase of dendritic cell (DC) activation upon contact with chemical sensitizers are not well known. The strong skin sensitizer 2,4-dinitrofluorobenzene (DNFB) was shown to induce the activation of mitogen-activated protein kinases (MAPK) in DC. In the present study, we investigated a putative role for oxidative stress in DNFB-induced MAPK activation and upregulation of the costimulatory molecule CD40. In a DC line generated from fetal mouse sk...

  17. Oxidative Stress, Tumor Microenvironment, and Metabolic Reprogramming: A Diabolic Liaison

    Paola Chiarugi; Tania Fiaschi

    2012-01-01

    Conversely to normal cells, where deregulated oxidative stress drives the activation of death pathways, malignant cells exploit oxidative milieu for its advantage. Cancer cells are located in a very complex microenvironment together with stromal components that participate to enhance oxidative stress to promote tumor progression. Indeed, convincing experimental and clinical evidence underline the key role of oxidative stress in several tumor aspects thus affecting several characteristics of c...

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

    Melissa H Costell

    2012-07-01

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

  19. Effects of dietary yeast extract on turkey stress response and heterophil oxidative burst activity

    Effective nutritional approaches to counteract the negative effects of stress would both improve human health and provide food animal producers with useful alternatives to antibiotics. In this study, turkeys were fed a standard diet or the same diet supplemented with yeast extract (Alphamune™, YE), ...

  20. Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim;

    2015-01-01

    Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel...... exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were...... unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels...

  1. Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways

    Hepatic fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with accumulation of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrogenesis. Compelling evidence indicates that oxidative stress is concomitant with liver fibrosis irrespective of the underlying etiology. Natural antioxidant ligustrazine exhibits potent antifibrotic activities, but the mechanisms are poorly understood. Our studies were to investigate the ligustrazine effects on HSC activation stimulated by hydrogen peroxide (H2O2), an in vitro model mimicking the oxidative stress in liver fibrogenesis, and to elucidate the possible mechanisms. Our results demonstrated that H2O2 at 5 μM significantly stimulated HSC proliferation and expression of marker genes of HSC activation; whereas ligustrazine dose-dependently suppressed proliferation and induced apoptosis in H2O2-activated HSCs, and attenuated expression of fibrotic marker genes. Mechanistic investigations revealed that ligustrazine reduced platelet-derived growth factor-β receptor (PDGF-βR) expression and blocked the phosphorylation of extracellular regulated protein kinase (ERK) and p38 kinase, two downstream effectors of PDGF-βR. Further molecular evidence suggested that ligustrazine interruption of ERK and p38 pathways was dependent on the blockade of PDGF-βR and might be involved in ligustrazine reduction of fibrotic marker gene expression under H2O2 stimulation. Furthermore, ligustrazine modulated some proteins critical for HSC activation and ECM homeostasis in H2O2-stimulated HSCs. These data collectively indicated that ligustrazine could attenuate HSC activation caused by oxidative stress, providing novel insights into ligustrazine as a therapeutic option for hepatic fibrosis. Highlights: ► Ligustrazine inhibits oxidative stress-induced HSC activation. ► Ligustrazine reduces fibrotic marker genes in HSCs under

  2. Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity.

    Kusuma, Gina D; Abumaree, Mohamed H; Pertile, Mark D; Perkins, Anthony V; Brennecke, Shaun P; Kalionis, Bill

    2016-06-01

    The use of mesenchymal stem/stromal cells (MSC) in regenerative medicine often requires MSC to function in environments of high oxidative stress. Human pregnancy is a condition where the mother's tissues, and in particular her circulatory system, are exposed to increased levels of oxidative stress. MSC in the maternal decidua basalis (DMSC) are in a vascular niche, and thus would be exposed to oxidative stress products in the maternal circulation. Aldehyde dehydrogenases (ALDH) are a large family of enzymes which detoxify aldehydes and thereby protect stem cells against oxidative damage. A subpopulation of MSC express high levels of ALDH (ALDH(br)) and these are more potent in repairing and regenerating tissues. DMSC was compared with chorionic villous MSC (CMSC) derived from the human placenta. CMSC reside in vascular niche and are exposed to the fetal circulation, which is in lower oxidative state. We screened an ALDH isozyme cDNA array and determined that relative to CMSC, DMSC expressed high levels of ALDH1 family members, predominantly ALDH1A1. Immunocytochemistry gave qualitative confirmation at the protein level. Immunofluorescence detected ALDH1 immunoreactivity in the DMSC and CMSC vascular niche. The percentage of ALDH(br) cells was calculated by Aldefluor assay and DMSC showed a significantly higher percentage of ALDH(br) cells than CMSC. Finally, flow sorted ALDH(br) cells were functionally potent in colony forming unit assays. DMSC, which are derived from pregnancy tissues that are naturally exposed to high levels of oxidative stress, may be better candidates for regenerative therapies where MSC must function in high oxidative stress environments. PMID:26880140

  3. Hypoxia/oxidative stress alters the pharmacokinetics of CPU86017-RS through mitochondrial dysfunction and NADPH oxidase activation

    Gao, Jie; Ding, Xuan-Sheng; Zhang, Yu-mao; Dai, De-zai; Liu, Mei; Zhang, Can; Dai, Yin

    2013-01-01

    Aim: Hypoxia/oxidative stress can alter the pharmacokinetics (PK) of CPU86017-RS, a novel antiarrhythmic agent. The aim of this study was to investigate the mechanisms underlying the alteration of PK of CPU86017-RS by hypoxia/oxidative stress. Methods: Male SD rats exposed to normal or intermittent hypoxia (10% O2) were administered CPU86017-RS (20, 40 or 80 mg/kg, ig) for 8 consecutive days. The PK parameters of CPU86017-RS were examined on d 8. In a separate set of experiments, female SD ra...

  4. Ethanol and oxidative stress.

    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

  5. Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway

    Perfluoroalkyl acid (PFAA)-induced apoptosis has been reported in many cell types. However, minimal information on its mode of action is available. This study explored the possible involvement of apoptotic signaling pathways in a nine-carbon-chain length PFAA-perfluorononanoic acid (PFNA)-induced splenocyte apoptosis. After a 14-day exposure to PFNA, rat spleens showed dose-dependent levels of apoptosis. The production of pro-inflammatory and anti-inflammatory cytokines was significantly increased and decreased, respectively. However, protein levels of tumor necrosis factor receptor 1 (TNFR1), fas-associated protein with death domain (FADD), caspase 8 and caspase 3, which are involved in inflammation-related and caspase-dependent apoptosis, were discordant. Peroxisome proliferator-activated receptors alpha (PPARα) and PPARγ genes expression was up-regulated in rats treated with 3 or 5 mg/kg/day of PFNA, and the level of hydrogen peroxide (H2O2) increased concurrently in rats treated with the highest dose. Moreover, superoxide dismutase (SOD) activity and Bcl-2 protein levels were dramatically decreased in spleens after treatment with 3 and 5 mg/kg/day of PFNA. However, protein levels of Bax were unchanged. Apoptosis-inducing factor (AIF), an initiator of caspase-independent apoptosis, was significantly increased in all PFNA-dosed rats. Thus, oxidative stress and the activation of a caspase-independent apoptotic signaling pathway contributed to PFNA-induced apoptosis in rat splenocytes.

  6. Hemoglobin oxidative stress

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

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

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

    2016-08-01

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

  8. Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress

    Cheng-Chin Hsu

    2015-04-01

    Full Text Available Background: Vitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system. Objective: The purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress. Design: Four-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group, a vitamin B6-deficient diet (as a B6-deficient group, or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained. Results: Mice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented. Conclusions: Mice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

  9. HEPATOPROTECTIVE AND ANTIOXIDANT ACTIVITY OF COCCINIA GRANDIS ROOT EXTRACT AGAINST PARACETAMOL INDUCED HEPATIC OXIDATIVE STRESS IN WISTAR ALBINO RATS

    Moideen K

    2011-03-01

    Full Text Available The present study was conducted to evaluate the hepatoprotective and antioxidant activity of Coccinia grandis root extract against paracetamol induced hepatic oxidative stress in wistar albino rats. The ethanolic extracts of Coccinia grandis (200mg/kg and 400mg/kg were administered orally to the animals and hepatotoxicity induced by paracetamol (750mg/kg. The extracts were administered orally by suspending in 0.5% Carboxy methyl cellulose solution. Silymarin (25mg/kg was given as reference standard. The ethanolic extract of Coccinia grandis roots produced a significant (P<0.01 decrease in SGOT, SGPT, SALP, Total bilirubin and Direct bilirubin and it also produced a significant (P<0.01 increase in Total protein when compared to paracetamol treated group indicating hepatoprotective action. The ethanolic extract of Coccinia grandis root produced a significant (P<0.01 increase in SOD, CAT and GSH activity when compared to paracetamol treated group and it also produced significant (P<0.01 increase in activity of Px and GPx at 400mg/kg dose, indicating antioxidant activity. But it produced less significant in Px at 200mg/kg dose and it showed no significant activity in GPx at 200mg/kg dose. The histopathological study of liver section of rat treated with ethanolic extract of Coccinia grandis (200 and 400 mg/kg showed mild hepatocyte degeneration. It was concluded from the result that ethanolic extract of Coccinia grandis possesses hepatoprotective and antioxidant activity against paracetamol induced hepatotoxicity in wistar albino rats.

  10. Oxidative Stress, Molecular Inflammation and Sarcopenia

    Si-Jin Meng

    2010-04-01

    Full Text Available Sarcopenia is the decline of muscle mass and strength with age. Evidence suggests that oxidative stress and molecular inflammation play important roles in age-related muscle atrophy. The two factors may interfere with the balance between protein synthesis and breakdown, cause mitochondrial dysfunction, and induce apoptosis. The purpose of this review is to discuss some of the major signaling pathways that are activated or inactivated during the oxidative stress and molecular inflammation seen in aged skeletal muscle. Combined interventions that may be required to reverse sarcopenia, such as exercise, caloric restriction, and nutrition, will also be discussed.

  11. Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress

    Huang, Yi-Chia; Hsu, Cheng-Chin; Cheng, Chien-Hsiang; Hsu, Chin-Lin; Lee, Wan-Ju; Huang, Shih-Chien

    2015-01-01

    Background: Vitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system.Objective: The purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress.Design: Four-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group),...

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

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

    2014-03-01

    It has been documented in in vitro studies that zinc oxide nanoparticles (ZnO NPs) are capable of inducing oxidative stress, which plays a crucial role in ZnO NP-mediated apoptosis. However, the underlying molecular mechanism of apoptosis in neurocytes induced by ZnO NP exposure was not fully elucidated. In this study, we investigated the potential mechanisms of apoptosis provoked by ZnO NPs in cultured primary astrocytes by exploring the molecular signaling pathways triggered after ZnO NP exposure. ZnO NP exposure was found to reduce cell viability in MTT assays, increase lactate dehydrogenase (LDH) release, stimulate intracellular reactive oxygen species (ROS) generation, and elicit caspase-3 activation in a dose- and time-dependent manner. Apoptosis occurred after ZnO NP exposure as evidenced by nuclear condensation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. A decrease in mitochondrial membrane potential (MMP) with a concomitant increase in the expression of Bax/Bcl-2 ratio suggested that the mitochondria also mediated the pathway involved in ZnO NP-induced apoptosis. In addition, exposure of the cultured cells to ZnO NPs led to phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK). Moreover, JNK inhibitor (SP600125) significantly reduced ZnO NP-induced cleaved PARP and cleaved caspase-3 expression, but not ERK inhibitor (U0126) or p38 MAPK inhibitor (SB203580), indicating that JNK signaling pathway is involved in ZnO NP-induced apoptosis in primary astrocytes.

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

    Daniela Soares VIANA

    2016-01-01

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

  14. Oxidative Stress and Neurodegenerative Disorders

    Jie Li

    2013-12-01

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

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

    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

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

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

    2000-01-01

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

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

    Ko-Jen Li

    2012-01-01

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

  18. Potentiating Effect of Piperine on Hepatoprotective Activity of Boerhaavia diffusa to Combat Oxidative Stress

    S.K. Desai

    2008-01-01

    Full Text Available The hydro alcoholic extract of roots of Boerhaavia diffusa (HEBD was evaluated for its hepatoprotective activity against CCl4 and Rifampicin - Isoniazid combination induced hepatotoxicity at two dose levels 150 and 300 mg kg-1 . HEBD exhibited a significant protective action on the liver evident by a reduction in the elevated levels of serum lysosomal enzymes namely Serum Glutamate Pyruvate Transaminase (SGPT, Serum Glutamate Oxaloacetate Transminase (SGOT, Alkaline Phosphatase (ALP in both CCl4 and Rifampicin-Isoniazid induced hepatotoxicity. Thus HEBD showed a dose dependent hepatoprotective activity. In addition, the hepatoprotective activity of Boerhaavia diffusa was evaluated for possible potentiation in the presence of piperine based on recent research which has reported the latter enhancing bioavailability of certain drugs and nutritional compounds. Piperine was checked for potentiation, if any, at two dose levels 10 and 20 mg, respectively. Piperine was found to produce a dose dependent potentiation of the hepatoprotective activity of Boerhaavia diffusa.

  19. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    Pickering, Andrew. M.; Vojtovich, Lesya; Tower, John; Davies, Kelvin J. A.

    2012-01-01

    Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster,...

  20. Oxidative stress during aging and in Alzheimer's disease : a comparative study of oxidative damage and antioxidant enzymatic activities in mouse models and human brain tissue

    Schüssel, Katrin

    2005-01-01

    The hypothesis that oxidative stress plays a role in the pathogenesis of Alzheimer’s disease (AD) was tested by studying oxidative damage, acitvities of antioxidant enzymes and levels of reactive oxygen species (ROS) in several models. To this end, mouse models transgenic for mutant presenilin (PS1M146L) as well as mutant amyloid precursor protein (APP) and human post mortem brain tissue from sporadic AD patients and age-matched controls were studied. Aging leads to an upregulation of antioxi...

  1. Theileria induces oxidative stress and HIF1α activation that are essential for host leukocyte transformation.

    Medjkane, S; Perichon, M; Marsolier, J; Dairou, J; Weitzman, J B

    2014-04-01

    Complex links between infection and cancer suggest that we still can learn much about tumorigenesis by studying how infectious agents hijack the host cell machinery. We studied the effects of an intracellular parasite called Theileria that infects bovine leukocytes and turns them into invasive cancer-like cells. We investigated the host cells pathways that are deregulated in infected leukocytes and might link infection and lymphoproliferative disease. We show that intracellular Theileria parasites drive a Warburg-like phenotype in infected host leukocytes, characterized by increased expression of metabolic regulators, increased glucose uptake and elevated lactate production, which were lost when the parasite was eliminated. The cohabitation of the parasites within the host cells leads to disruption of the redox balance (as measured by reduced/oxidized glutathione ratio) and elevated ROS (reactive oxygen species) levels, associated with chronic stabilization of the hypoxia-inducible factor 1 alpha (HIF1α). Inhibition of HIF1α (pharmacologically or genetically), or treatment with antioxidants, led to a marked reduction in expression of aerobic glycolytic genes and inhibited the transformed phenotype. These data show that stabilization of HIF1α, following increased ROS production, modulates host glucose metabolism and is critical for parasite-induced transformation. Our study expands knowledge about the molecular strategy used by the parasite Theileria to induce the transformed phenotypes of infected cells via reprogramming of glucose metabolism and redox signaling. PMID:23665677

  2. Hypoxia, Oxidative Stress and Fat

    Nikolaus Netzer

    2015-06-01

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

  3. Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing Ocean.

    Pimentel, Marta S; Faleiro, Filipa; Diniz, Mário; Machado, Jorge; Pousão-Ferreira, Pedro; Peck, Myron A; Pörtner, Hans O; Rosa, Rui

    2015-01-01

    Until now, it is not known how the antioxidant and digestive enzymatic machinery of fish early life stages will change with the combined effects of future ocean acidification and warming. Here we show that high pCO2 (~1600 μatm) significantly decreased metabolic rates (up to 27.4 %) of flatfish larvae, Solea senegalensis, at both present (18 °C) and warmer temperatures (+4 °C). Moreover, both warming and hypercapnia increased the heat shock response and the activity of antioxidant enzymes, namely catalase (CAT) and glutathione S-transferase (GST), mainly in post-metamorphic larvae (30 dph). The lack of changes in the activity of CAT and GST of pre-metamorphic larvae (10 dph) seems to indicate that earlier stages lack a fully-developed antioxidant defense system. Nevertheless, the heat shock and antioxidant responses of post-metamorphic larvae were not enough to avoid the peroxidative damage, which was greatly increased under future environmental conditions. Digestive enzymatic activity of S. senegalensis larvae was also affected by future predictions. Hypercapnic conditions led to a decrease in the activity of digestive enzymes, both pancreatic (up to 26.1 % for trypsin and 74.5 % for amylase) and intestinal enzymes (up to 36.1 % for alkaline phosphatase) in post-metamorphic larvae. Moreover, the impact of ocean acidification and warming on some of these physiological and biochemical variables (namely, lower OCR and higher HSP and MDA levels) were translated into larvae performance, being significantly correlated with decreased larval growth and survival or increased incidence of skeletal deformities. The increased vulnerability of flatfish early life stages under future ocean conditions is expected to potentially determine recruitment and population dynamics in marine ecosystems. PMID:26221723

  4. Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing Ocean.

    Marta S Pimentel

    Full Text Available Until now, it is not known how the antioxidant and digestive enzymatic machinery of fish early life stages will change with the combined effects of future ocean acidification and warming. Here we show that high pCO2 (~1600 μatm significantly decreased metabolic rates (up to 27.4 % of flatfish larvae, Solea senegalensis, at both present (18 °C and warmer temperatures (+4 °C. Moreover, both warming and hypercapnia increased the heat shock response and the activity of antioxidant enzymes, namely catalase (CAT and glutathione S-transferase (GST, mainly in post-metamorphic larvae (30 dph. The lack of changes in the activity of CAT and GST of pre-metamorphic larvae (10 dph seems to indicate that earlier stages lack a fully-developed antioxidant defense system. Nevertheless, the heat shock and antioxidant responses of post-metamorphic larvae were not enough to avoid the peroxidative damage, which was greatly increased under future environmental conditions. Digestive enzymatic activity of S. senegalensis larvae was also affected by future predictions. Hypercapnic conditions led to a decrease in the activity of digestive enzymes, both pancreatic (up to 26.1 % for trypsin and 74.5 % for amylase and intestinal enzymes (up to 36.1 % for alkaline phosphatase in post-metamorphic larvae. Moreover, the impact of ocean acidification and warming on some of these physiological and biochemical variables (namely, lower OCR and higher HSP and MDA levels were translated into larvae performance, being significantly correlated with decreased larval growth and survival or increased incidence of skeletal deformities. The increased vulnerability of flatfish early life stages under future ocean conditions is expected to potentially determine recruitment and population dynamics in marine ecosystems.

  5. Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation

    Nardi, Geisson Marcos; Farias Januario, Adriana Graziele; Freire, Cassio Geremia; Megiolaro, Fernanda; Schneider, Kétlin; Perazzoli, Marlene Raimunda Andreola; Do Nascimento, Scheley Raap; Gon, Ana Cristina; Mariano, Luísa Nathália Bolda; Wagner, Glauber; Niero, Rivaldo; Locatelli, Claudriana

    2016-01-01

    Background: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. Objective: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Materials and Methods: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. Results: High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. Conclusion: These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. SUMMARY Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this

  6. Anti-acetylcholinesterase and Antioxidant Activities of Inhaled Juniper Oil on Amyloid Beta (1-42)-Induced Oxidative Stress in the Rat Hippocampus.

    Cioanca, Oana; Hancianu, Monica; Mihasan, Marius; Hritcu, Lucian

    2015-05-01

    Juniper volatile oil is extracted from Juniperus communis L., of the Cupressaceae family, also known as common juniper. Also, in aromatherapy the juniper volatile oil is used against anxiety, nervous tension and stress-related conditions. In the present study, we identified the effects of the juniper volatile oil on amyloid beta (1-42)-induced oxidative stress in the rat hippocampus. Rats received a single intracerebroventricular injection of amyloid beta (1-42) (400 pmol/rat) and then were exposed to juniper volatile oil (200 μl, either 1 or 3 %) for controlled 60 min period, daily, for 21 continuous days. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Additionally, the acetylcholinesterase activity in the hippocampus was assessed. The amyloid beta (1-42)-treated rats exhibited the following: increase of the acetylcholinesterase, superoxide dismutase and catalase specific activities, decrease of glutathione peroxidase specific activity and the total content of the reduced glutathione along with an elevation of malondialdehyde and protein carbonyl levels. Inhalation of the juniper volatile oil significantly decreases the acetylcholinesterase activity and exhibited antioxidant potential. These findings suggest that the juniper volatile oil may be a potential candidate for the development of therapeutic agents to manage oxidative stress associated with Alzheimer's disease through decreasing the activity of acetylcholinesterase and anti-oxidative mechanism. PMID:25743585

  7. Antioxidant Activity of Cabbage and/or Carrot Against Oxidative Stress Induced by Gamma Irradiation in Male Albino Rats

    could modulate the oxidative stress and protect against chronic diseases caused by radiation exposure and that may be due to the antioxidant activity of both cabbage and carrot

  8. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model.

    Rai, Sachchida Nand; Yadav, Satyndra Kumar; Singh, Divakar; Singh, Surya Pratap

    2016-01-01

    Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti-inflammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5 mg/kg, 25 mg/kg, and 50 mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25 mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment. PMID:26686287

  9. Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity

    Haidari, Fatemeh; Ali Keshavarz, Seid; Reza Rashidi, Mohammad; Mohammad Shahi, Majid

    2009-01-01

    Our objective was to examine the effect of orange juice and hesperetin on serum total antioxidant capacity (TAC), lipid peroxidation (MDA), uric acid and hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XDH) activity in hyperuricemic rats. Experimentally hyperuricemia in rats was induced by intraperitoneal injection of potassium oxonate (250 mg/kg). Orange juice (5 ml/kg) and hesperetin (5 mg/kg) was given by oral gavage to rats for 2 weeks and biochemical data was measured. Data sho...

  10. Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing Ocean

    Pimentel, Marta S.; Faleiro, Filipa; Diniz, Mário; Machado, Jorge; Pousão-Ferreira, Pedro; Peck, Myron A.; Pörtner, Hans O.; Rosa, Rui

    2015-01-01

    Until now, it is not known how the antioxidant and digestive enzymatic machinery of fish early life stages will change with the combined effects of future ocean acidification and warming. Here we show that high pCO2 (~1600 μatm) significantly decreased metabolic rates (up to 27.4 %) of flatfish larvae, Solea senegalensis, at both present (18 °C) and warmer temperatures (+4 °C). Moreover, both warming and hypercapnia increased the heat shock response and the activity of antioxidant enzymes, na...

  11. Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

    Yu Deng

    2012-01-01

    Full Text Available Objective. This study was to evaluate the effect of riluzole on methylmercury- (MeHg- induced oxidative stress, through promotion of glutathione (GSH synthesis by activating of glutamate transporters (GluTs in rat cerebral cortex. Methods. Eighty rats were randomly assigned to four groups, control group, riluzole alone group, MeHg alone group, and riluzole + MeHg group. The neurotoxicity of MeHg was observed by measuring mercury (Hg absorption, pathological changes, and cell apoptosis of cortex. Oxidative stress was evaluated via determining reactive oxygen species (ROS, 8-hydroxy-2-deoxyguanosine (8-OHdG, malondialdehyde (MDAs, carbonyl, sulfydryl, and GSH in cortex. Glutamate (Glu transport was studied by measuring Glu, glutamine (Gln, mRNA, and protein of glutamate/aspartate transporter (GLAST and glutamate transporter-1 (GLT-1. Result. (1 MeHg induced Hg accumulation, pathological injury, and apoptosis of cortex; (2 MeHg increased ROS, 8-OHdG, MDA, and carbonyl, and inhibited sulfydryl and GSH; (3 MeHg elevated Glu, decreased Gln, and downregulated GLAST and GLT-1 mRNA expression and protein levels; (4 riluzole antagonized MeHg-induced downregulation of GLAST and GLT-1 function and expression, GSH depletion, oxidative stress, pathological injury, and apoptosis obviously. Conclusion. Data indicate that MeHg administration induced oxidative stress in cortex and that riluzole could antagonize this situation through elevation of GSH synthesis by activating of GluTs.

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

    Jokić Aleksandar

    2010-01-01

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

  13. APOPTOSIS, OXIDATIVE STRESS AND NEUROLOGICAL DISEASE

    P. Formichi

    2012-01-01

    Full Text Available Apoptosis is a selective cell deletion process which requires the triggering of a specific cell death programme. Two main pathways determining cell death have been identified: the extrinsic or receptor-mediated pathway, activated in response to extracellular pro-apoptotic signals, and the intrinsic pathway, activated by extracellular receptor-independent stimuli or by intracellular insults, such as DNA damage and oxidative stress. All these stress signals are integrated by mitochondria which participate by releasing the main effectors of this process: a family of aspartic-specific proteases known as caspase. Today there is much evidence to suggest that deregulation of apoptosis is a key feature of many neurodegenerative disease. Our group sought cell models for the study of apoptotic pathways and for the evaluation of the role of apoptosis in specific neurodegenerative diseases. We focused on oxidative stress-induced apoptosis and activation of the intrinsic mitochondrial pathway. In our in-vitro model, lymphocytes from patients and control subjects were cultured both in basal conditions and with 2-deoxy-D-ribose (dRib, a reducing sugar which induces apoptosis through oxidative stress. In the last ten years, we evaluated the role of apoptosis in the pathogenesis of several neurodegenerative diseases: Ataxiatelangiectasia,Rett syndrome, Mitochondrial disease, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL. Here we report some of our ongoing and recently published articles.

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

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

    2010-01-01

    Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and r...

  15. Binding to WGR Domain by Salidroside Activates PARP1 and Protects Hematopoietic Stem Cells from Oxidative Stress

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

    2014-01-01

    Aims: A component of the base excision repair pathway, poly(ADP-ribose) polymerase-1 (PARP1) functions in multiple cellular processes, including DNA repair and programmed cell death. We previously showed that Salidroside, a phenylpropanoid glycoside isolated from medicinal plants, prevented the loss of hematopoietic stem cells (HSCs) in native mice and rescued HSCs repopulating in transplanted recipients under oxidative stress. The aim of this study was to investigate the mechanism by which P...

  16. Activity of myricetin and other plant-derived polyhydroxyl compounds in human LDL and human vascular endothelial cells against oxidative stress.

    Bertin, Riccardo; Chen, Zheng; Marin, Raffaella; Donati, Maddalena; Feltrinelli, Angela; Montopoli, Monica; Zambon, Sabina; Manzato, Enzo; Froldi, Guglielmina

    2016-08-01

    Studies indicate that oxidative modifications of endothelium and LDL play a preeminent role in atherogenesis; therefore, the preservation of the endothelial antioxidant capacity and the inhibition of LDL oxidation by use of plant-derived compounds are an appealing strategy against several vascular disorders. On this basis, baicalein, eupatorin, galangin, magnolol, myricetin, oleuropein, silibinin and bilobalide were studied against various oxidative conditions. The radical scavenging capacity was analysed using DPPH and ORAC assays. Furthermore, the LDL oxidation was detected by measuring the formation of thiobarbituric acid reactive substances (TBARS) and by monitoring the oxidation kinetics. Further, we used cultured HUVEC to investigate the activities of the polyhydroxyl compounds towards the oxidative stress induced by H2O2. The lowest levels of TBARS were observed in the presence of oleuropein and baicalein, while myricetin, magnolol and eupatorin inhibited these ones to a lesser extent. In addition, oleuropein and myricetin exhibited higher protection in copper-induced LDL oxidation kinetics. However, only myricetin and galangin showed significant protective effects against H2O2 oxidative injury in HUVEC cells. Taken all together the results indicate myricetin as the most active agent among the selected plant-derived polyhydroxyl compounds, with prominent capacities against ox-LDL and ROS production in HUVEC. PMID:27470387

  17. Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells.

    Chen, Kanjun; Yan, Biao; Wang, Fei; Wen, Feiting; Xing, Xingan; Tang, Xue; Shi, Yonghui; Le, Guowei

    2016-04-01

    3,3',5-triiodothyronine (T3) is largely generated from thyroxine (T4) by the catalysis of deiodinases in peripheral tissues. Emerging evidences have indicated its broad participation in regulating various metabolic process via protecting tissues from oxidative stress and improving cellular antioxidant capacity. However, the potential correlation between the oxidative stress and conversion of T4 to T3 is still unclear. In the present study, the effects of T3 and T4 on redox homeostasis in HepG2 cells pre-treated with H2O2 was investigated. It revealed that T3 significantly rescued the apoptotic cell death, consistent with an upregulation of cell antioxidant ability and reduction of ROS accumulation while T4 did not. Afterwards, we examined the enzyme activity and mRNA expression of type 1 5'-deiodianse (DIO1), T3 and rT3 level and found that H2O2 reduced both DIO1 activity and expression in a dose-dependent manner, which consequently declined T3 and rT3 generation. Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells. PMID:26947333

  18. Oxidative stress in neurodegenerative diseases

    Xueping Chen; Chunyan Guo; Jiming Kong

    2012-01-01

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

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

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

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

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

    1999-03-01

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

  1. Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways

    Zhang, Feng [Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Ni, Chunyan [Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); The First People' s Hospital of Changzhou, Changzhou 213003 (China); Kong, Desong; Zhang, Xiaoping; Zhu, Xiaojing; Chen, Li [Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Lu, Yin [Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046 (China); National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing 210046 (China); Zheng, Shizhong, E-mail: nytws@163.com [Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046 (China); National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing 210046 (China)

    2012-11-15

    Hepatic fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with accumulation of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrogenesis. Compelling evidence indicates that oxidative stress is concomitant with liver fibrosis irrespective of the underlying etiology. Natural antioxidant ligustrazine exhibits potent antifibrotic activities, but the mechanisms are poorly understood. Our studies were to investigate the ligustrazine effects on HSC activation stimulated by hydrogen peroxide (H{sub 2}O{sub 2}), an in vitro model mimicking the oxidative stress in liver fibrogenesis, and to elucidate the possible mechanisms. Our results demonstrated that H{sub 2}O{sub 2} at 5 μM significantly stimulated HSC proliferation and expression of marker genes of HSC activation; whereas ligustrazine dose-dependently suppressed proliferation and induced apoptosis in H{sub 2}O{sub 2}-activated HSCs, and attenuated expression of fibrotic marker genes. Mechanistic investigations revealed that ligustrazine reduced platelet-derived growth factor-β receptor (PDGF-βR) expression and blocked the phosphorylation of extracellular regulated protein kinase (ERK) and p38 kinase, two downstream effectors of PDGF-βR. Further molecular evidence suggested that ligustrazine interruption of ERK and p38 pathways was dependent on the blockade of PDGF-βR and might be involved in ligustrazine reduction of fibrotic marker gene expression under H{sub 2}O{sub 2} stimulation. Furthermore, ligustrazine modulated some proteins critical for HSC activation and ECM homeostasis in H{sub 2}O{sub 2}-stimulated HSCs. These data collectively indicated that ligustrazine could attenuate HSC activation caused by oxidative stress, providing novel insights into ligustrazine as a therapeutic option for hepatic fibrosis. Highlights: ► Ligustrazine inhibits oxidative stress-induced HSC activation.

  2. A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

    Derrick F. MacFabe

    2008-01-01

    Full Text Available Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD. Propionic acid (PPA is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (500ug uL-1, 4µl anima-1 or phosphate buffered saline (PBS vehicle, twice daily for 7 days. Immediately following the second daily infusion, the locomotor activity of each rat was assessed in an automated open field (Versamax for 30 min. PPA-treated rats showed significant increases in locomotor activity compared to PBS vehicle controls. Following the last treatment day, specific brain regions were assessed for neuroinflammatory or oxidative stress markers. Immunohistochemical analyses revealed reactive astrogliosis (GFAP, activated microglia (CD68, Iba1 without apoptotic cell loss (Caspase 3 and NeuN in hippocampus and white matter (external capsule of PPA treated rats. Biomarkers of protein and lipid peroxidation, total glutathione (GSH as well as the activity of the antioxidant enzymes superoxide dismutase (SOD, catalase, glutathione peroxidase (GPx, glutathione reductase (GR and glutathione S-transferase (GST were examined in brain homogenates. Some brain regions of PPA treated animals (neocortex, hippocampus, thalamus, striatum showed increased lipid and protein oxidation accompanied by decreased total GSH in neocortex. Catalase activity was decreased in most brain regions of PPA treated animals suggestive of reduced antioxidant enzymatic activity. GPx and GR activity was relatively unaffected by PPA treatment while GST was increased perhaps indicating involvement of GSH in the removal of PPA or related catabolites. Impairments in GSH and catalase levels may render CNS cells more susceptible to oxidative stress

  3. Tumor Necrosis Factor-alpha Potentiates the Cytotoxicity of Amiodarone in Hepa1c1c7 Cells: Roles of Caspase Activation and Oxidative Stress

    Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A.; Ganey, Patricia E.

    2012-01-01

    Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its t...

  4. Oxidative stress in normal and diabetic rats.

    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 (pvitaminA/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

  5. Role of oxidant stress in rheumatoid arthritis

    GS, Lekshmi; BR, Suchit Roy; K., Parvathy; K., Geetha Damodaran

    2015-01-01

    Oxygen derived free radicals have been implicated in the causation of Rheumatoid arthritis (RA) [1].In this study, evidence of free radical injury and oxidative stress in patients with RA is compared with healthy subjects by estimating superoxide dismutase (SOD) and catalase, which are anti-oxidant enzymes in RBCs, Glucose 6 Phosphate Dehydrogenase (G6PD) in RBCs and serum Malon-di-aldehyde (MDA) levels. Serum MDA levels in RA could be used as a biochemical marker of disease activity and for ...

  6. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2) anti-oxidative stress/anti-inflammatory pathways

    Wu Qing; Saw Constance; Kong Ah-Ng Tony

    2010-01-01

    Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2)-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE), a critical regulatory element in the promoter region of genes encoding cel...

  7. Elevated atherosclerosis-related gene expression, monocyte activation and microparticle-release are related to increased lipoprotein-associated oxidative stress in familial hypercholesterolemia

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

    2015-01-01

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

  8. Oxidative stress in prostate hypertrophy and carcinogenesis

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  9. Evaluation of oxidative stress in brucella infected cows

    N. Kataria

    2010-05-01

    Full Text Available Oxidative stress can influence the metabolism of cells in vital organs of the body. Oxidative stress is extremely dangerous as it does not exhibit any symptom and is recognisable with great difficulty by means of laboratory methods. It can be monitored with several biomarkers like antioxidants and pro-oxidants which can be assessed in serum. The inexorableness of exposure of cows to brucella infection makes oxidative stress associated with this infection an appropriate field of investigation. There is paucity of work to detect stress, which is essential to take timely corrective measures and to save the animal population. Therefore the investigation was carried out to evaluate oxidative stress in the cows suffering from brucellosis. For this serum iomarkers of oxidative stress viz. vitamin C, vitamin E, catalase, monoamine oxidase, glutathione reductase, superoxide dismutase, glutathione, xanthine oxidase, oxidase and peroxidase were determined. Results indicated that vitamin C, vitamin E and glutathione activity decreased significantly in affected cows as compared to healthy cows. Serum catalase, superoxide dismutase, monoamine oxidase, glutathione reductase, xanthine oxidase, oxidase and peroxidase activities increased significantly in affected cows as compared to healthy cows. Decreased activity of vitamin C, vitamin E and glutathione indicated towards their depletion which generally occurs in the oxidative stress to scavenge the free radicals. It was concluded that oxidative stress was there in the animals. This study recommends the use of antioxidants in affected cows

  10. Ionizing radiations and oxidizing stress

    The normal cell metabolism produces continuously reactive oxygenated species which sometimes are not completely transformed and can lead to a highly reactive form of oxygen: the superoxide anion (characteristic of free radicals). These aggressive molecules are normally eliminated by the enzymatic and biochemical defense systems, but some external factors, like the ionizing radiations, can accelerate their production and saturate the natural defense systems. Such a situation leads to a disorganization of the membrane structures, to the oxidation of the lipo-proteins and proteins and to a degradation and fragmentation of DNA. This oxidative stress affects all kind of tissues and metabolisms and thus participates to a large number of pathologies, in particular cancers. (J.S.)

  11. Oxidative Stress in Cardiovascular Disease

    Gábor Csányi

    2014-04-01

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

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

    Rook, Denise

    2013-01-01

    textabstractDue to immature antioxidant defenses, preterm infants are at susceptible to oxidative stress, which is associated with bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. The general aim of this thesis was to study oxidative stress in preterm infants and to explore possible options to reduce the impact of oxidative stress in neonatal care. The studies presented in this thesis concern the optimal oxygen concentration for the resuscitation at bir...

  13. Oxidative stress in inherited mitochondrial diseases.

    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

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

    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

  15. Oxidative stress in oral diseases.

    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

  16. Effects of Exogenous Nitric Oxide on Photochemical Activity of Photosystem Ⅱ in Potato Leaf Tissue Under Non-stress Condition

    YANGJia-Ding; ZHAOHa-Lin; ZHANGTong-Hui; YUNJian-Fei

    2004-01-01

    Under non-stress condition, effects of exogenous nitric oxide (NO) on chlorophyll fluorescence parameters in detached leaves and leaf discs of potato (Solanum tuberosum L.) were surveyed. Results showed that the maximal quantum efficiency (Fv/Fm) and the effective quantum efficiency (ΦPSⅡ)of photosystem Ⅱ (PSⅡ) were reduced by exogenous NO under illumination (150μmol.m-2·s-1, 25℃). This influence was related not only to the concentration of sodium nitroprusside (SNP, a NO donor) solution, but also to the active duration of NO on leaf tissue. Results with leaf discs showed that the effects of SNP on ΦPSⅡ could be prevented by bovine hemoglobin (a powerful NO scavenger), while amixture of NO2- and NO3-(the decomposition product of NO or its donor SNP) had much less influence on ΦPSⅡ than SNP, indicating that effects of exogenous SNP on PSⅡ photochemical activity was mainly due to NO generation. Under light (150μmol·m-2·s-1, 25℃) for 4h or longer period, the non-photochemical quenching (NPQ) in SNP-soaked leaves was statistically similar to that in H2O-soaked control, but ΦPSⅡ and the proportion of open reaction centers (measured as qP) were lower than control, respectively. After 25min dark-adaptation, the maximal fluorescence (Fm) in SNP treatment (8 and 12h illumination duration) was significantly lower than the control, while the initial fluorescence (Fo) in SNP and H2O-treated leaves had no significant difference. Therefore this indicated that under the present experimental condition, the NO-affected site might not be the PSⅡ reaction centers. On the donor side of PSⅡ, NO putatively influenced the light-harvesting capacity of leaves under light; on the acceptor side, NO-affected sites were some components of electron transport chain after QA, i.e.NO enhanced the reductive degree of reaction centers through blocking the electron transport after QA, thus reducing the photochemical activitv of PSⅡ.

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

    Tomoko Kawakami

    2012-01-01

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

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

    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

  19. Electroacupuncture pretreatment prevents cognitive impairment induced by limb ischemia-reperfusion via inhibition of microglial activation and attenuation of oxidative stress in rats.

    Chen, Ye; Zhou, Jun; Li, Jun; Yang, Shi-Bin; Mo, Li-Qun; Hu, Jie-Hui; Yuan, Wan-Li

    2012-01-13

    Limb ischemia-reperfusion (LI/R) is associated with high morbidity and mortality. Furthermore, critical trauma survivors can present cognitive impairment. Cognitive function, survival rate, oxidative stress and neuronal health were examined to elucidate (1) the magnitude of cognitive effects of prolonged reperfusion, (2) potential players in the mechanistic pathway mediating such effects, and (3) possible benefits of electroacupuncture (EA) pretreatment at Baihui (GV20), Yanglingquan (GB34), Taichong (LR3), Zusanli (ST36) and Xuehai (SP10) acupoints. LI/R was induced in rats by placing a rubber tourniquet on each hind limb for 3h, and the animals were evaluated periodically for 7d after LI/R. Rats subjected to LI/R had significantly lower survival rates, and displayed evidence of brain injury and cognitive dysfunction (as determined by the Morris water maze test) 1d and 3d after reperfusion compared to sham-operated controls. LI/R also resulted in higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA), microglial activation, and decreased superoxide dismutase (SOD) activity within Cornu Ammonis area 1 (CA1) of the hippocampus. Depressed survival rates, microglial activation, oxidative damage, and histological changes, as well as cognitive dysfunction were partially or fully attenuated in rats that received 14d of EA prior to LI/R. These findings indicate that LI/R can result in cognitive dysfunction related to activated microglia and elevated oxidative stress, and that EA has neuroprotective potential mediated, at least in part, by inhibition of microglial activation and attenuation of oxidative stress. PMID:22129788

  20. Biomarkers of oxidative stress and acetylcholinesterase activity in the blood of grass snake (Natrix natrix L. during prehibernation and posthibernation periods

    Jelena Gavric

    2015-06-01

    Full Text Available This work examined the enzymatic (superoxide dismutase-CuZn SOD, catalase-CAT, glutathione peroxidase-GSHPx, glutathione reductase-GR, and the biotransformation phase II enzyme glutathione-S-transferase-GST and nonenzymatic (total glutathione-GSH and lipid peroxides-TBARS concentrations biomarkers of oxidative stress and acetylcholinesterase (AChE activity in the blood of the grass snake (Natrix natrix L. during prehibernation and posthibernation. The animals were collected in October (prehibernation and April (posthibernation at the nature reserve Obedska Bara (OB and industrial region Pancevacki Rit (PR in Serbia. In posthibernation, decreased CAT activity and TBARS concentration in specimens from PR, and decreased GR and AChE activities, and TBARS concentration in specimens from OB were observed, whereas GR and GST activities and GSH concentration were significantly elevated in the specimens from PR. In prehibernation, CAT activity and GSH concentration were increased, while GSH-Px, GR, GST and AChE activities and TBARS concentration were decreased in the specimens from PR when compared to animals from OB. During the posthibernation, the activity of CuZn SOD was decreased, while GST and AChE activities were increased in the specimens from PR when compared to the specimens from OB. These differences represented an adaptive mechanism to oxidative stress induced by tissue reoxygenation during arousal from hibernation and could be modulated by environmental pollution.

  1. Actively stressed marginal networks

    Sheinman, M; MacKintosh, F C

    2012-01-01

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

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

    Sylwia Dzięgielewska-Gęsiak

    2014-01-01

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

  3. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation.

    Komirishetty, Prashanth; Areti, Aparna; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-08-01

    Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits. PMID:27084773

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

    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

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

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

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude that...... brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low......-oxygen culture conditions and in clinical specimens of both low- and high-grade tumors. The observed global checkpoint signaling, in contrast to only focal areas of overabundant p53 (indicative of p53 mutation) in grade II astrocytomas, are consistent with DDR activation being an early event in gliomagenesis...

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

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

    2005-01-01

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

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

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

    2011-01-01

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

  8. Oxidative Stress in Cystinosis Patients

    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

  9. Oxidative Stress in Cystinosis Patients

    Maria Helena Vaisbich

    2011-09-01

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

  10. Airway oxidative stress in chronic cough

    Koskela, Heikki O; Purokivi, Minna K

    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 ...

  11. Polydatin inhibits the oxidative stress-induced proliferation of vascular smooth muscle cells by activating the eNOS/SIRT1 pathway.

    Ma, Yi; Gong, Xun; Mo, Yingli; Wu, Saizhu

    2016-06-01

    Oxidative stress-mediated proliferation of vascular smooth muscle cells (VSMCs) contributes to plaque formation and the progression of atherosclerosis. Polydatin is a derivative of resveratrol, and is widely present in certain herbal medications used for the treatment of cardiovascular diseases. In the present study, we examined whether polydatin was capable of attenuating VSMC proliferation induced by oxidative stress as well as the potential involvement of the endothelial nitric oxide synthetase (eNOS)/SIRT1 pathway. Briefly, VSMCs were exposed to H2O2 for 24 h in the absence or presence of polydatin (10-100 µM) prior to performing a cell proliferation assay. In mechanistic studies, the cells were incubated with the silent information regulator 1 (SIRT1) inhibitor, EX527, or the eNOS inhibitor, L-NAME, prior to polydatin treatment. The results showed that polydatin inhibited VSMC proliferation and the level of reactive oxygen species, increased the expression of Kip1/p27, SIRT1 and eNOS, whereas the expression of cyclin B1, Cdk1 and c-myc was decreased. The number of cells in the G2/M phase was increased. Pre-treatment with L-NAME attenuated the inhibitory effects of polydatin on cell proliferation, inhibited the expression of SIRT1 and the phosphorylation of eNOS. Pre-treatment with EX527 also attenuated the inhibitory effects of polydatin on cell proliferation, but failed to reduce the activation of eNOS and the production of nitric oxide. Taken together, these findings suggest that, polydatin inhibited the oxidative stress-induced proliferation of VMSCs by activating the eNOS/SIRT1 pathway. PMID:27081912

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

    Guo C

    2015-02-01

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

  13. Squamosamide derivative FLZ protects retinal pigment epithelium cells from oxidative stress through activation of epidermal growth factor receptor (EGFR)-AKT signaling.

    Cheng, Li-Bo; Chen, Chun-Ming; Zhong, Hong; Zhu, Li-Juan

    2014-01-01

    Reactive oxygen species (ROS)-mediated retinal pigment epithelium (RPE) cell apoptosis is attributed to age-related macular degeneration (AMD) pathogenesis. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, Annona glabra, has displayed significant cyto-protective activity. In the current study, we explored the pro-survival effect of FLZ in oxidative stressed-RPE cells and studied the underlying signaling mechanisms. Our results showed that FLZ attenuated hydrogen peroxide (H2O2)-induced viability decrease and apoptosis in the RPE cell line (ARPE-19 cells) and in primary mouse RPE cells. Western blotting results showed that FLZ activated AKT signaling in RPE cells. The AKT-specific inhibitor, MK-2206, the phosphoinositide 3-kinase (PI3K)/AKT pan inhibitor, wortmannin, and AKT1-shRNA (short hairpin RNA) depletion almost abolished FLZ-mediated pro-survival/anti-apoptosis activity. We discovered that epidermal growth factor receptor (EGFR) trans-activation mediated FLZ-induced AKT activation and the pro-survival effect in RPE cells, and the anti-apoptosis effect of FLZ against H2O2 was inhibited by the EGFR inhibitor, PD153035, or by EGFR shRNA-knockdown. In conclusion, FLZ protects RPE cells from oxidative stress through activation of EGFR-AKT signaling, and our results suggest that FLZ might have therapeutic values for AMD. PMID:25329617

  14. Cu(II)-disulfide complexes with superoxide dismutase- and catalase-like activities protect mitochondria and whole cells against oxidative stress.

    Aliaga, Margarita E; Sandoval-Acuña, Cristián; López-Alarcón, Camilo; Fuentes, Jocelyn; Speisky, Hernan

    2014-10-01

    Mitochondria are a major subcellular site of superoxide (O2(-)) formation. Conditions leading to an uncontrolled production, accumulation and/or conversion of O2(-) into hydrogen peroxide result in an increment in the intramitochondrial oxidative tone which, ultimately leads to the loss of cell viability. Recently, we reported on the ability of a series of Cu(II)-disulfide complexes to act simultaneously as SOD- and catalase-like molecules. In the present study, we addressed the potential of such compounds to protect mitochondria and cells against the oxidative stress and the cytolytic damage induced by diclofenac. Exposure of Caco-2 cells to diclofenac (250µM, 20min) led to a near 80% inhibition of mitochondrial complex I activity and almost doubled the rate of mitochondrial O2(-) production (assessed by Mitosox). A comparable increment was seen in whole cells when the oxidative tone was assessed through the largely hydrogen peroxide-dependent dichlorofluorescein (DCFH) oxidation. The increment in mitochondrial O2(-) production was totally and concentration-dependently prevented by the addition of the complexes formed between Cu(II) and the disulfides of glutathione, homocysteine, or a-dehydro-lipoic acid (20µM each); comparatively, the Cu(II)-cystine complex exerted a weaker protection. A comparable protection pattern was seen at the whole cell level, as these complexes were also effective in preventing the increment in DCFH oxidation. The mitochondrial and whole cell antioxidant protection also translated into a full protection against the cytolytic effects of diclofenac (45min). Results from the present study indicate that the here-tested Cu(II)-disulfides complexes are able to effectively protect cells against the oxidative and the lytic effects of O2(-)-overproducing mitochondria, suggesting a potential for these type of compounds to act as SOD- and catalase-like molecules under oxidative-stress conditions. Supported by FONDECYT #1110018. PMID:26461399

  15. Asthmatic cough and airway oxidative stress.

    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

  16. Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans.

    Wu, J Z; Huang, J H; Khanabdali, R; Kalionis, B; Xia, S J; Cai, W J

    2016-07-01

    Pyrroloquinoline quinone (PQQ) is linked to fundamental biological processes such as mitochondrial biogenesis and lipid metabolism. PQQ may also function as an essential micronutrient during animal development. Recent studies have shown the therapeutic potential of PQQ for several age-related diseases due to its antioxidant capacity. However, whether PQQ can promote longevity is unknown. Here, we investigate the effects of PQQ on oxidative stress resistance as well as lifespan modulation in Caenorhabditis elegans. We find that PQQ enhances resistance to oxidative stress and extends the lifespan of C. elegans at optimal doses. The underlying molecular mechanism involves the increased activities of the primary lifespan extension transcriptional factors DAF-16/FOXO, the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2, and upregulation of daf-16, skn-1 downstream targets including sod-3, hsp16.2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement. PMID:27090484

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

    S. Thangapandiyan; S. Miltonprabu

    2015-01-01

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

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

    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

  19. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Xiaochun Duan

    2016-01-01

    Full Text Available 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.

  20. Treatment of 24-EBL to Brassica juncea Plants Under Cu-metal Stress Lowers Oxidative Burst by Activity of Antioxidative Enzymes

    Poonam

    2014-05-01

    Full Text Available Heavy metal contamination is becoming a major threat to plants due to increasing industrialization. Copper is one of essential element required in trace amounts for the regular development of plants. Its excessive concentration alters the metabolism of plants. Brassinosteroids are polyhydoxylated steroidal plant hormone found to alleviate the various abiotic stresses including heavy metal stress. In the present study, effect of 24-EBL was studied in Brassica juncea plants under Cu stress. The B. juncea was grown in Cu (0, 0.25mM, 0.50mM and 0.75mM treated soil. The seeds was soaked in the solution of 24-EBL (0, 10-7, 10-9 and 10-11 M for 8 hours. The plants were harvested on 45th DAS. The harvested plants were used for the protein quantification and analysis of antioxidative enzymes (CAT, SOD, POD, GR, APOX, DHAR and MDHAR. The results revealed that Cu treatment lowered the protein content, while at the same time, application of 24-EBL improved the protein content. The activity of various enzymes increased under the Cu stress. The application of 24-EBl had further enhanced the activity of enzymes indicating that it may relieve the oxidative stress caused by the copper metal.

  1. Cardiac Peroxisome Proliferator-Activated Receptor-γ Expression is Modulated by Oxidative Stress in Acutely Infrasound-Exposed Cardiomyocytes

    Pei, Zhaohui; Meng, Rongsen; Zhuang, Zhiqiang; Zhao, Yiqiao; Liu, Fangpeng; Zhu, Miao-Zhang; Li, Ruiman

    2013-01-01

    The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher le...

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

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

    2015-03-01

    Due to their aerobic lifestyle, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance for eliminating harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPClNOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II), and manganese(II) ions, which are also present in the active site of the above-noted metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed only SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50~0.4 μmol dm(-3)) and about 70-fold higher than those of iron. The manganese compound showed CAT activity higher than that of the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O2(•-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O2(•-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion dependent, in the order iron(III)>copper(II)>manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and the in vivo antioxidant activities. PMID:25511255

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

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

    2016-01-01

    This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard β of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging. PMID:27386333

  4. Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

    Hangping Yao; Xiajing Tang; Xueting Shao; Lei Feng; Nanping Wu; Ke Yao

    2007-01-01

    The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible molecular mechanisms involved. HLE cells (SRA01-04) were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide (10, 20 and 50μM). To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H2O2 for 18h, a high fraction of HLE cells underwent apoptosis, while in the presence of parthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H2O2 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation of caspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation of caspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.

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

    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

  6. Astaxanthin reduces type 2 diabetic‑associated cognitive decline in rats via activation of PI3K/Akt and attenuation of oxidative stress.

    Li, Xiaobin; Qi, Zhonghua; Zhao, Longshan; Yu, Zhan

    2016-01-01

    Astaxanthin (AST) is an oxygenated derivative of carotenoid, which possesses a strong antioxidant activity. AST can effectively remove active oxygen from the body, and is thus considered to have an important role in disease prevention and treatment. The present study aimed to determine the effects of AST on type 2 diabetic‑associated cognitive decline (DACD) in rats. Rats were intraperitoneally injected with streptozotocin (STZ), in order to establish a model of diabetes mellitus (DM). A total of 40 rats were randomly divided into five groups: The control group, the DM group, the AST (50 mg/kg) group, the AST (100 mg/kg) group, and the AST+LY294002 group (AST, 50 mg/kg and LY, 0.25 µg/100 g). Following a 14‑day treatment with AST, the body weight, blood glucose levels and cognitive function were determined. In addition, the protein expression levels of phosphatidylinositol 3‑kinase (PI3K)/Akt, glutathione peroxidase and superoxide dismutase activity, glutathione and malondialdehyde content, and inducible nitric oxide synthase (iNOS), caspase‑3 and caspase‑9 activity were detected in the rats with DM. AST clearly augmented body weight and reduced blood glucose levels in rats with DM. Furthermore, treatment with AST significantly improved the cognitive function of rats with DM. Treatment with AST activated the PI3K/Akt pathway, and suppressed oxidative stress in the DM rats. In the cerebral cortex and hippocampus of the rats with DM, the activities of iNOS, caspase‑3 and caspase‑9 were markedly reduced. Furthermore, treatment with the Akt inhibitor LY294002 reduced the effectiveness of AST on DACD in rats. In conclusion, AST may reduce type 2 DACD in rats via activation of PI3K/Akt and attenuation of oxidative stress. PMID:26648531

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

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

    2005-09-01

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

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

    Singh, Neha; Bhatla, Satish C

    2016-02-29

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

  9. Oxidative stress in primary glomerular diseases

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

    2008-01-01

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

  10. Induction of oxidative stress and inhibition of plasminogen activator inhibitor-1 production in endothelial cells following exposure to organic extracts of diesel exhaust particles and urban fine particles

    Furuyama, Akiko; Koike, Eiko [National Institute for Environmental Studies, Inhalation toxicology Team, Tsukuba (Japan); Hirano, Seishiro [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan); Kobayashi, Takahiro [National Institute for Environmental Studies, Inhalation toxicology Team, Tsukuba (Japan); National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan)

    2006-03-15

    Endothelial cells play important roles in anticoagulant and fibrinolytic systems. Recent studies suggest that increases in ambient particulate matter (PM) levels have been associated with an increase in mortality rate from cardiovascular diseases. We examined the production of heme oxygenase-1 (HO-1) and factors related to the fibrinolytic function by rat heart microvessel endothelial cells exposed to organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) to investigate the direct effects of these soluble organic fractions in these PM on the fibrinolytic function of endothelial cells. The cell monolayer exposed to 10 {mu}g/ml OE-DEP produced a larger amount of HO-1 than cells exposed to 10 {mu}g/ml OE-UFP. OE-DEP and OE-UFP exposure reduced plasminogen activator inhibitor-1 (PAI-1) production by the cells but did not affect the production of thrombomodulin, tissue-type plasminogen activator, or urokinase-type plasminogen activator. Increased PAI-1 synthesis in response to treatment with 1.0 ng/ml tumor necrosis factor-{alpha} or 0.5 ng/ml transforming growth factor-{beta}1 was reduced by OE-DEP exposure. Suppression of PAI-1 production by OE-DEP exposure was mediated through oxidative stress and was independent of HO-1 activity. These results suggest that exposure to the soluble organic fraction of PM and DEP induced oxidative stress and reduced the PAI-1 production of endothelial cells. (orig.)

  11. Oxidative stress, DNA damage and antioxidant enzyme activities in the pacific white shrimp (Litopenaeus vannamei) when exposed to hypoxia and reoxygenation.

    Li, Yuhu; Wei, Lin; Cao, Jiangrong; Qiu, Liguo; Jiang, Xiu; Li, Ping; Song, Qinqin; Zhou, Hailong; Han, Qian; Diao, Xiaoping

    2016-02-01

    To evaluate the genotoxic and physiological effects of acute hypoxia on the pacific white shrimp (L. vannamei), shrimps were treated firstly with three dissolved oxygen levels 6.5 ppm (control), 3.0 ppm and 1.5 ppm for 24 h, respectively, and then reoxygenated (6.5 ppm) for 24 h. The changes of superoxide dismutase (SOD) activity, glutathione peroxidases (GPX) activity, malondialdehyde (MDA) concentration and DNA damage in the tissues of gill, hepatopancreas and hemolymph were examined during the period of hypoxia and reoxygenation. The results indicated SOD activity, GPX activity, MDA concentration and DNA damage all increased basically compared with the control during the period of hypoxia except for MDA concentrations in the gill at 12 h and 24 h hypoxia (3.0 ppm), and these parameters were recovered to some degree during the period of reoxygenation. Moreover, the comet assays in the tissues of gill and hepatopancreas showed an obvious time- and dose-dependent response to hypoxia, which indicated comet assay in the two tissues could be used as sensitive biomarker to detect the occurrence of hypoxia. We conclude that acute hypoxia can induce oxidative stress, DNA damage and lipid peroxidation in the tissues of gill, hepatopancreas and hemolymph of L. vannamei and the DNA damage may come from hypoxia-induced oxidative stress. PMID:26363325

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

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

    2013-12-01

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

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

    Omotayo, T I; Akinyemi, G S; Omololu, P A; Ajayi, B O; Akindahunsi, A A; Rocha, J B T; Kade, I J

    2015-01-01

    The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe(2+)-mediated in vitro oxidative stress model. The results show that Fe(2+) inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe(2+) inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe(2+) may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe(2+) and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump. PMID:25618580

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

    T.I. Omotayo

    2015-04-01

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

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

    Fu-Wei Liu

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

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

    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

  17. Oxidative stress in prostate hyperplasia and carcinogenesis.

    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

  18. Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress

    Grzegorz Sawicki

    2013-01-01

    Full Text Available Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60–80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for preservation of ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again predominates as the major source of mitochondrial oxidative metabolism. Although a number of molecular mechanisms have been implicated in the development of I/R injury, their relative contributions remain to be determined. One such mechanism involves the proteolytic degradation of contractile proteins, such as troponin I (TnI, myosin heavy chain, titin, and the myosin light chains (MLC1 and MLC2 by matrix metalloproteinase-2 (MMP-2. However, very little is known about intracellular regulation of MMP-2 activity under physiological and pathological conditions. Greater understanding of the mechanisms that govern MMP-2 activity may lead to the development of new therapeutic strategies aimed at preservation of the contractile function of the heart subjected to myocardial infarction (MI or I/R. This review discusses the intracellular mechanisms controlling MMP-2 activity and highlights a new intracellular therapeutic direction for the prevention and treatment of heart injury.

  19. OXIDATIVE STRESS, INSULIN SIGNALING AND DIABETES

    Rains, Justin L.; Jain, Sushil K.

    2010-01-01

    Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can ...

  20. A STUDY OF OXIDATIVE STRESS IN DIABETES

    Babu Rao; Santhoshi; Sridhar V; Souris; Der, Margaret

    2015-01-01

    Non - enzymatic free radical mediated oxidation of biological molecules, membranes and tissues is associated with a variety of pathological events such as cancer, aging and diabetes mellitus . [1] Increased oxidative stress is seen in both types of diabetes me llitus namely type 1 and type 2, irrespective of duration, complications and treatment. In diabetes mellitus, oxidative stress seems primarily due to both an increased plasma free radical concentra...

  1. Metal-related oxidative stress in birds

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

  2. A STUDY OF OXIDATIVE STRESS IN DIABETES

    Babu Rao

    2015-06-01

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

  3. Ascorbic acid supplementation down-regulates the alcohol induced oxidative stress, hepatic stellate cell activation, cytotoxicity and mRNA levels of selected fibrotic genes in guinea pigs.

    Abhilash, P A; Harikrishnan, R; Indira, M

    2012-02-01

    Both oxidative stress and endotoxins mediated immunological reactions play a major role in the progression of alcoholic hepatic fibrosis. Ascorbic acid has been reported to reduce alcohol-induced toxicity and ascorbic acid levels are reduced in alcoholics. Hence, we investigated the hepatoprotective action of ascorbic acid in the reversal of alcohol-induced hepatic fibrosis in male guinea pigs (n = 36), and it was compared with the animals abstenting from alcohol treatment. In comparison with the alcohol abstention group, there was a reduction in the activities of toxicity markers and levels of lipid and protein peroxidation products, expression of α-SMA, caspase-3 activity and mRNA levels of CYP2E1, TGF-β(1), TNF-α and α(1)(I) collagen in liver of the ascorbic acid-supplemented group. The ascorbic acid content in liver was significantly reduced in the alcohol-treated guinea pigs. But it was reversed to normal level in the ascorbic acid-supplemented group. The anti-fibrotic action of ascorbic acid in the rapid regression of alcoholic liver fibrosis may be attributed to decrease in the oxidative stress, hepatic stellate cells activation, cytotoxicity and mRNA expression of fibrotic genes CYP2E1, TGF-β(1), TNF-α and α(1) (I) collagen in hepatic tissues. PMID:22149461

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

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

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

    Yaguchi, Takahiro; Fujikawa, Hirokazu; Nishizaki, Tomoyuki

    2010-05-01

    The present study aimed at understanding the effect of the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on oxidative stress-induced neuronal death. Sodium nitroprusside (SNP; 1 mM) reduced viability of cultured rat cerebral cortical neurons to 50% of basal levels, but DCP-LA significantly prevented the SNP effect in a concentration (1-100 nM)-dependent manner. In addition, DCP-LA (100 nM) rescued neurons from SNP-induced degradation. SNP (1 mM) activated caspase-3 and -9 in cultured rat cerebral cortical neurons, but DCP-LA (100 nM) abolished the caspase activation. For a mouse model of middle cerebral artery occlusion, oral administration with DCP-LA (1 mg/kg) significantly diminished degraded area due to cerebral infarction. The results of the present study, thus, demonstrate that DCP-LA protects neurons at least in part from oxidative stress-induced apoptosis by inhibiting activation of caspase-3/-9. PMID:20099079

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

    Santosh Singh

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

  7. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

    Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also counteracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF-κB inhibition.

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

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

    2016-07-01

    Parkinson disease (PD) is a neurodegenerative disease characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta (SNc) area. The present study was undertaken to evaluate the neuroprotective effect of β-caryophyllene (BCP) against rotenone-induced oxidative stress and neuroinflammation in a rat model of PD. In the present study, BCP was administered once daily for 4 weeks at a dose of 50 mg/kg body weight prior to a rotenone (2.5 mg/kg body weight) challenge to mimic the progressive neurodegenerative nature of PD. Rotenone administration results in oxidative stress as evidenced by decreased activities of superoxide dismutase, catalase, and depletion of glutathione with a concomitant rise in lipid peroxidation product, malondialdehyde. Rotenone also significantly increased pro-inflammatory cytokines in the midbrain region and elevated the inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Further, immunohistochemical analysis revealed loss of dopaminergic neurons in the SNc area and enhanced expression of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), indicators of microglia activation, and astrocyte hypertrophy, respectively, as an index of inflammation. However, treatment with BCP rescued dopaminergic neurons and decreased microglia and astrocyte activation evidenced by reduced Iba-1 and GFAP expression. BCP in addition to attenuation of pro-inflammatory cytokines and inflammatory mediators such as COX-2 and iNOS, also restored antioxidant enzymes and inhibited lipid peroxidation as well as glutathione depletion. The findings demonstrate that BCP provides neuroprotection against rotenone-induced PD and the neuroprotective effects can be ascribed to its potent antioxidant and anti-inflammatory activities. PMID:27316720

  9. Determination of oxidative and occupational stress in palliative care workers

    Casado Moragón, Ángela; Castellanos Asenjo, Alberto; López-Fernández, M.E.; Ruíz, R.; Imedio, E.L.; Castillo, C.; Fernández-Nieto, A.M.

    2011-01-01

    Background: In previous work, we demonstrated that some occupational workers in stressful conditions can have increases in several markers of oxidative stress when compared to other workers. We investigated two antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) concentrations, according to demographics, lifestyle and occupational parameters in palliative care unit workers, and analyzed the relationship with occupational burnout. Methods: F...

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

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

    2011-01-01

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

  11. Glucose deprivation-induced metabolic oxidative stress and cancer therapy

    Simons Andrean; Mattson David; Dornfeld Ken; Spitz Douglas

    2009-01-01

    Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (...

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

    2010-01-01

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

  13. Oxidative Stress Related Diseases in Newborns

    Yasemin Ozsurekci

    2016-01-01

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

  14. Oxidative Stress Related Diseases in Newborns.

    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

  15. Stress distributions in growing polycrystalline oxide films

    We analyze the generation of stresses in polycrystalline oxide films formed via the oxidation of a substrate using a new continuum model. The model includes a description of the polycrystalline microstructure in two dimensions. The diffusion of all independent components, the rate of the oxidation reaction and the effect of stresses on these are accounted for in a thermodynamically self-consistent manner. Grain boundaries serve both as high diffusivity paths and as sites for oxide formation. Different diffusion controlled oxidation regimes (rapid oxygen/cation diffusion, comparable oxygen/cation diffusivities) and different grain boundary/bulk diffusivity ratios are examined within this framework. Numerical solutions reveal large lateral stress gradients, with stresses concentrated around the grain boundaries. While the average in-plane stress is compressive and the stress at the film/substrate interface near the grain boundary highly so, large tensile stresses are observed near the grain boundary at the film surface. These predictions are consistent with experimental observations on polycrystalline oxide growth. We also present analytical approximations for the stress distribution in the film that capture the essential features of the numerical results

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

    Wylly Ramsés García-Niño

    2013-01-01

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

  17. [Oxidative stress, the functional activity of beta-cells, and the content of tumor necrosis factor alpha in patients with type II diabetes mellitus].

    Klebanova, E M

    2006-01-01

    The purpose of the study was to investigate the effects of dietotherapy on oxidative stress (OS) condition, the fl-cell functional activity (BCFA), insulin resistance index (IRI), and the serum tumor necrosis factor alpha (alpha-TNF) level in patients with type 2 diabetes mellitus (DM 2). The subjects, 30 patients with DM 2 (9 men, 21 women), aged 42 to 70 (mean age 58.77 +/- 8.86 years), were examined. The duration of DM 2 in the subjects was from 1 month to 5 years. OS parameters, IRI and BCFA, as well as serum alpha-TNF were measured before the study and after 3 months of observation. The tests performed after the end of the study showed that hydrocarbonate exchange remained compensated, and IRI and BCFA were moderately lowered in DM 2 patients on dietotherapy. There was an insignificant elevation of serum alpha-TNF, while the condition of hydrocarbonate exchange had bettered. Changes in OS parameters in patients on dietotherapy evidence that the reserve activity of anti-oxidative system enzymes decreases. Thus, the compensation of hydrocarbonate exchange in DM 2 patients on dietotherapy retains, which is accompanied by a decrease in IRI and BCFA, while serum alpha-TNFincreases insignificantly, and reserved anti-oxidative system enzyme activity decreases moderately. PMID:17087190

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

    Faiza Rao

    2016-01-01

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

  19. Melamine Induces Oxidative Stress in Mouse Ovary.

    Xiao-Xin Dai

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

  20. Mycotoxin-containing diet causes oxidative stress in the mouse.

    Yan-Jun Hou

    Full Text Available Mycotoxins which mainly consist of Aflatoxin (AF, Zearalenone (ZEN and Deoxynivalenol (DON are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 µg/kg, ZEN 729 µg/kg, DON 3.1 mg/kg maize was incorporated into the diet at three different doses (0, 5 and 20% to feed the mice, and blood and tissue samples were collected to examine the oxidative stress related indexes. The results showed that the indexes of liver, kidney and spleen were all increased and the liver and kidney morphologies changed in the mycotoxin-treated mice. Also, the treatment resulted in the elevated glutathione peroxidase (GPx activity and malondialdehyde (MDA level in the serum and liver, indicating the presence of the oxidative stress. Moreover, the decrease of catalase (CAT activity in the serum, liver and kidney as well as superoxide dismutase (SOD activity in the liver and kidney tissue further confirmed the occurrence of oxidative stress. In conclusion, our data indicate that the naturally contained mycotoxins are toxic in vivo and able to induce the oxidant stress in the mouse.

  1. Oxidative stress and oxidative damage in chemical carcinogenesis

    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.

  2. Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors.

    Roberts, Christian K; Won, Dean; Pruthi, Sandeep; Kurtovic, Silvia; Sindhu, Ram K; Vaziri, Nosratola D; Barnard, R James

    2006-05-01

    The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may

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

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

    2002-01-01

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

  4. Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress.

    Ogawa, R; Pacelli, R; Espey, M G; Miranda, K M; Friedman, N; Kim, S M; Cox, G; Mitchell, J B; Wink, D A; Russo, A

    2001-02-01

    The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections. PMID:11165873

  5. Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress.

    Zhenying Han

    Full Text Available Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1 and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, α-7 nAchR agonist, methyllycaconitine (MLA, nAchR antagonist, or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO. Behavior test, lesion volume, CD68(+, M1 (CD11b(+/Iba1(+ and M2 (CD206/Iba1+ microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68(+ and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in α-7 nAchR neuro-protective effect.

  6. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  7. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  8. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  9. The arbuscular mycorrhizal Rhizophagus irregularis activates storage lipid biosynthesis to cope with the benzo[a]pyrene oxidative stress.

    Calonne, Maryline; Fontaine, Joël; Debiane, Djouher; Laruelle, Frédéric; Grandmougin-Ferjani, Anne; Lounès-Hadj Sahraoui, Anissa

    2014-01-01

    The phytoremediation assisted by arbuscular mycorrhizal fungi (AMF) could constitute an ecological and economic method to restore polycyclic aromatic hydrocarbon (PAH) polluted soils. Unfortunately, little is known about the PAH impact on the beneficial symbiotic AMF. Using radiolabelling experiments, our work aims to understand how benzo[a]pyrene (B[a]P), a representative of high molecular weight PAH, acts on the AMF lipid metabolism. Our results showed decreases in the sterol precursors as well as in total phospholipid quantities, in link with the [1-(14)C]acetate incorporation decreases in these lipids. Interestingly, a concomitant increase of [1-(14)C]acetate incorporation by 29.5% into phosphatidylcholine with its content decrease in Rhizophagus irregularis extraradical mycelium was observed, suggesting a membrane regeneration. A second concomitant increase (estimated to 69%) of [1-(14)C]acetate incorporation into triacylglycerols (TAG) with the content decrease was also observed. This suggests a fungal TAG biosynthesis activation probably to offset the decrease in storage lipid content when the fungus was grown under B[a]P pollution. In addition, our findings showed that lipase activity was induced by more than 3 fold in the presence of B[a]P in comparison to the control indicating that the drop in TAG content could be a consequence of their active degradation. Taken together, our data suggest the involvement of the fungal TAG metabolism to cope B[a]P toxicity through two means: (i) by providing carbon skeletons and energy necessary for membrane regeneration and/or for B[a]P translocation and degradation as well as (ii) by activating the phosphatidic acid and hexose metabolisms which may be involved in cellular stress defence. PMID:24246754

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

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

    2012-01-01

    After oxidative stress proteins which are oxidatively modified are degraded by the 20S proteasome. However, several studies documented an enhanced ubiquitination of yet unknown proteins. Since ubiqutination is a prerequisite for degradation by the 26S proteasome in an ATP-dependent manner this...... raises the question whether these proteins are also oxidized and, if not, what proteins need to be ubiquitinated and degraded after oxidative conditions. By determination of oxidized- and ubiquitinated proteins we demonstrate here that most oxidized proteins are not preferentially ubiquitinated. However......, we were able to confirm an increase of ubiquitinated proteins 16h upon oxidative stress. Therefore, we isolated ubiquitinated proteins from hydrogen peroxide treated cells, as well as from control and lactacystin, an irreversible proteasome inhibitor, treated cells, and identified some of these...

  11. Wine and oxidative stress in inflammation

    Pavelková, Martina; Gallová, Lucie; López, D.; Mitjavila, M. T.

    Brno, 2003. s. -. [European Workshop on the Analysis of Phagocyte Functions /1./. 07.09.2003-09.09.2003, Brno] Institutional research plan: CEZ:AV0Z5004920 Keywords : wine * oxidative stress * rat Subject RIV: BO - Biophysics

  12. Oxidative stress and bivalves: a proteomic approach

    B McDonagh

    2008-09-01

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

  13. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    Lan-fang Li; Jian Li

    2007-01-01

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

  14. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Wohlenberg, Mariane; Almeida, Daniela; Bokowski, Liane; Medeiros, Niara; Agostini, Fabiana; Funchal, Cláudia; Dani, Caroline

    2014-01-01

    In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4). The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS) were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD) activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT) activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract. PMID:26784867

  15. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Mariane Wohlenberg

    2014-04-01

    Full Text Available In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4. The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract.

  16. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  17. Oxidative Stress in Patients With Acne Vulgaris

    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 wi...

  18. Ethanol-induced oxidative stress: basic knowledge

    Comporti, Mario; Signorini, Cinzia; Leoncini, Silvia; Gardi, Concetta; Ciccoli, Lucia; Giardini, Anna; Vecchio, Daniela; Arezzini, Beatrice

    2009-01-01

    After a general introduction, the main pathways of ethanol metabolism (alcohol dehydrogenase, catalase, coupling of catalase with NADPH oxidase and microsomal ethanol-oxidizing system) are shortly reviewed. The cytochrome P450 isoform (CYP2E1) specifically involved in ethanol oxidation is discussed. The acetaldehyde metabolism and the shift of the NAD/NADH ratio in the cellular environment (reductive stress) are stressed. The toxic effects of acetaldehyde are mentioned. The ethanol-induced ox...

  19. Role of Oxidative Stress in Prostate Cancer

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

    2009-01-01

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

  20. Roles of oxidative stress in stomach disorders

    Suzuki, Hidekazu; Nishizawa, Toshihiro; Tsugawa, Hitoshi; Mogami, Sachiko; Hibi, Toshifumi

    2011-01-01

    The stomach is a sensitive digestive organ that is susceptible and exposed to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, as well as functional disorders such as functional dyspepsia. In particular, the bacterium Helicobacter pylori plays a major role in eliciting and confronting oxidative stress in the stomac...

  1. Oxidative stress action in cellular aging

    Monique Cristine de Oliveira; João Paulo Ferreira Schoffen

    2010-01-01

    Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the fac...

  2. Chrononutrition against Oxidative Stress in Aging

    Garrido, M; M. P. Terrón; 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 t...

  3. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study

    Ishibashi Toru

    2012-10-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. Recently, molecular hydrogen (H2 was demonstrated to be a selective scavenger for the hydroxyl radical. Also, the method to prepare water containing extremely high concentration of H2 has been developed. We hypothesized that H2 in the water could complement conventional therapy by reducing the oxidative stress in RA. Methods Twenty patients with rheumatoid arthritis (RA drank 530 ml of water containing 4 to 5 ppm molecular hydrogen (high H2 water every day for 4 weeks. After a 4-week wash-out period, the patients drank the high H2 water for another 4 weeks. Urinary 8-hydroxydeoxyguanine (8-OHdG and disease activity (DAS28, using C-reactive protein [CRP] levels was estimated at the end of each 4-week period. Results Drinking high H2 water seems to raise the concentration of H2 more than the H2 saturated (1.6 ppm water in vivo. Urinary 8-OHdG was significantly reduced by 14.3% (p  Conclusions The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.

  4. Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis.

    Lu, Yin; Pan, Yitao; Sheng, Nan; Zhao, Allan Z; Dai, Jiayin

    2016-09-01

    Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon-fluorine bond. Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consecutively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fatty acids (FFA), and activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fatty acid (PUFA) compositions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH-Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA. These results indicate that the epididymis is a potential target of PFOA. Oxidative stress and PUFA alteration might help explain the sperm injury and male reproductive dysfunction induced by PFOA exposure. PMID:27262104

  5. Oxidative and nitrative stress in neurodegeneration.

    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

  6. Oxidative Stress and Modulatory effects of the root extract of Phlogacanthus tubiflorus on the activity of Glutathione-S-Transferase in Hydrogen Peroxide treated Lymphocyte

    Ramteke A

    2012-04-01

    Full Text Available Glutathione-S-transferase is one of the important enzyme systems that plays vital role in decomposition of lipid hydro-peroxides formed due to oxidative stress. In the present study GST activity increased in the lymphocytes treated with increasing concentration of H2O2, and decrease in the levels of GSH was observed. For similar treatment conditions LDH activity and MDA levels increased significantly leading to decrease in the cell viability. Treatment of lymphocytes with the root extract of Phlogacanthus tubiflorus (PTE resulted in dose dependent decline in the GST activity and rise in GSH levels. LDH activity and MDA levels also declined that led to the increase of cell viability. Lymphocytes pre-treated with the PTE followed by H2O2 (0.1 and 1% treatment, decline in the activity of GST and increase in GSH levels was observed. Also we have observed decline in the activity of LDH and MDA levels in the lymphocytes for both 0.1 and 1% of H2O2 though the magnitude of change was higher in the lymphocytes pre-treated with the PTE followed with 1% of H2O2 treatment. Significant increase in the cell viability for similar conditions was also observed. These findings suggest protective function of the root extracts might be through modulation of GST activity and levels of GSH and might find application in Chemomodulation in future.

  7. Exercise-induced oxidative stress and antioxidant enzyme activity in type 2 diabetic patients with and without diastolic dysfunction and hypertension

    Kostić Nada

    2009-01-01

    Full Text Available Introduction. Antioxidant systems are important factors affecting the oxidation of lipoproteins and thereby the progression of atherosclerotic disease. It has been suggested that physical activity might maintain and promote the antioxidant defence capacity against the oxidative stress. Left ventricular dysfunction (LVDD and hypertension are more common in subjects with diabetes mellitus (DM type 2. Objective. To evaluate the oxidative stress in patients with DM type 2, particularly with LVDD and hypertension and to determine the influence of acute exercise training on the investigated parameters. Methods. To assess the oxidative stress of patients, we determined the following antioxidative parameters: triglycerides (TG, total cholesterol, low density cholesterol, OxLDL cholesterol, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, plasminogen activator-type 1 (PAI-1 which were measured at rest and immediately after the acute bout of the cardiopulmonary exercise cycle ergometer test. Results. In basal conditions, diabetic patients had a significant increase of TG (3.12±1.09 vs 1.74±0.9 mmol/l; p<0.01, OxLDL cholesterol (84.73±16.9 vs 79.00±29.26 mmol/l; p<0.05 and SOD enzyme activity (913.38±120.36 vs 877.14 ±153.18; p<0.05 compared to controls. During the acute exercise test, there were significantly greater levels of OxLDL (84.73±16.90 vs 92.33±23.29 mmol/l; p<0.05 in study patients. SOD significantly increased in both groups during exercise, in diabetic patients (913.38±120.36 vs 921.50±130.03 U/g Hb; p<0.05 and in controls (877.14±153.18 vs 895.00±193.49 U/g Hb; p<0.05. GSH-Px significantly increased only in diabetic patients after acute exercise (45.04±11.19 vs 51.81±15.07 U/g Hb; p<0.01, but not in controls. PAI significantly decreased during the exercise test only in healthy subjects (2.60±0.35 vs 2.22±0.65; p<0.05. Type 2 diabetic patients with cardiovascular complications (LVDD and hypertension had a significant

  8. Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

    Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E2 modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5 g/kg i.v.) 30-min after E2 (1 μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dtmax) and systolic (SBP) and diastolic (DBP) blood pressures in E2-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E2 promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E2 for specific medical conditions. - Highlights: • Ethanol lowers blood pressure and causes LV dysfunction in E2-treated rats. • E2/ethanol aggravates cardiac oxidative state via of DAPK3/Akt/ERK activation. • E2/ethanol causes a feedback increase in cardiac HO-1, catalase and ALDH2. • Alcohol might increase risk of myocardial dysfunction in men treated with E2

  9. Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

    El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Abdel-Rahman, Abdel A., E-mail: abdelrahmana@ecu.edu

    2015-09-15

    Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E{sub 2} modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5 g/kg i.v.) 30-min after E{sub 2} (1 μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dt{sub max}) and systolic (SBP) and diastolic (DBP) blood pressures in E{sub 2}-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E{sub 2} promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E{sub 2} for specific medical conditions. - Highlights: • Ethanol lowers blood pressure and causes LV dysfunction in E{sub 2}-treated rats. • E{sub 2}/ethanol aggravates cardiac oxidative state via of DAPK3/Akt/ERK activation. • E{sub 2}/ethanol causes a feedback increase in cardiac HO-1, catalase and ALDH2. • Alcohol might increase risk of myocardial dysfunction in men treated with E{sub 2}.

  10. Oxidative stress and age-related cataract

    Zheng Selin, Jinjin

    2015-01-01

    Age-related cataract is a clouding of the lens that leads to decreased vision. It increases with age and is one of the leading causes of blindness worldwide. The only treatment currently available is surgery. Therefore, it is important to identify modifiable risk factors for cataract prevention. The cause of cataract is not fully understood and may be multifactorial, involving oxidative stress, a condition of disrupted balance between oxidants and antioxidants. Oxidative damage to lens protei...

  11. Synthetic catecholamine triggers β1-adrenergic receptor activation and stimulates cardiotoxicity via oxidative stress mediated apoptotic cell death in rats: Abrogating action of thymol.

    Meeran, M F Nagoor; Jagadeesh, G S; Selvaraj, P

    2016-05-01

    Nowadays, there are considerable interests in the studies which are more connected with the impact of natural antioxidants against the free radical mediated damage in biological systems. Cardiotoxicity is one of the lethal manifestations of cardiovascular diseases (CVDs) which have been associated with the incidence of apoptotic cell death due to oxidative stress. We evaluated the impact of thymol, a dietary monoterpene phenol on isoproterenol (ISO), a synthetic catecholamine and a β1-adrenergic receptor agonist in rats. Thymol (7.5 mg/kg body weight) was pre and co-treated into male albino Wistar rats daily for a period of 7 days. Induction of cardiotoxicity was done by the subcutaneous administration of ISO (100 mg/kg body weight) into rats on 6th and 7th day. Cardiotoxicity in rats was confirmed by the increased levels/activity of serum troponin-T and creatine kinase in the serum alongwith decreased activity of creatine kinase in the heart. ISO induced cardiotoxic rats also showed a significant increase in the concentrations of lipid peroxidation products and a significant decrease in the activities/levels of antioxidants in the myocardium whereas Reverse Transcription Polymerase Chain Reaction study revealed an increased expression of caspase-8, caspase-9 and Fas genes along with a decreased expression of Bcl-xL gene in the myocardium. Thymol pre and co-treated ISO induced cardiotoxic rats showed considerable protective effects on all the biochemical parameters studied. Histopathological and in vitro findings are found in line with our biochemical findings. Thus, the present study revealed that thymol counters ISO induced cardiotoxicity by inhibiting oxidative stress and apoptotic cell death in rats by virtue of its potent antioxidant property. PMID:26996544

  12. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.

    Estañ, María Cristina; Calviño, Eva; Calvo, Susana; Guillén-Guío, Beatriz; Boyano-Adánez, María Del Carmen; de Blas, Elena; Rial, Eduardo; Aller, Patricio

    2014-01-01

    Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic

  13. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.

    María Cristina Estañ

    Full Text Available Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox, and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin, in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content, as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the

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

    Liang-Jun Yan

    2014-01-01

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

  15. Elevated atherosclerosis-related gene expression, monocyte activation and microparticle-release are related to increased lipoprotein-associated oxidative stress in familial hypercholesterolemia.

    Morten Hjuler Nielsen

    Full Text Available Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs, as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH, in particular in the presence of Achilles tendon xanthomas (ATX.We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT and Achilles tendon (AT thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT.Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes.

  16. Activation of β1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.

    Jagadeesh, Govindan Sangaran; Nagoor Meeran, Mohamed Fizur; Selvaraj, Palanisamy

    2016-04-15

    Activation of β1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin. PMID:26930228

  17. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  18. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  19. Effect of Turmeric and its Active Principle Curcumin on T3-Induced Oxidative Stress and Hyperplasia in Rat Kidney: A Comparison

    Samanta, Luna; Panigrahi, Jogamaya; Bhanja, Shravani; Chainy, Gagan B. N.

    2010-01-01

    The present study was designed to compare the potential of turmeric and its active principle curcumin on T3-induced oxidative stress and hyperplasia. Adult male Wistar strain rats were rendered hyperthyroid by T3 treatment (10 μg · 100 g−1 · day−1 intraperitoneal for 15 days in 0.1 mM NaOH) to induce renal hyperplasia. Another two groups were treated similarly with T3 along with either turmeric or curcumin (30 mg kg−1 body weight day−1 orally for 15 days). The results indicate that T3 induces...

  20. Telomerase, mitochondria and oxidative stress

    Saretzki, Gabriele

    2009-01-01

    Abstract Telomerase plays an important role in cellular proliferation capacity and survival under conditions of stress. A large part of this protective function is due to telomere capping and maintenance. Thus it contributes to cellular immortality in stem cells and cancer. Recently, evidence has accumulated that telomerase can contribute to cell survival and stress resistance in a largely telomere-independent manner. Telomerase has been shown to shuttle dynamically between differe...

  1. Oxidative stress impairs the heat stress response and delays unfolded protein recovery.

    Masaaki Adachi

    Full Text Available BACKGROUND: Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability. PRINCIPAL FINDINGS: Pretreatment of hydrogen peroxide (H(2O(2 specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2O(2 exposure impaired the HSP40/HSP70 induction as heat shock response (HSR and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2O(2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2O(2-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2O(2-mediated enhanced heat sensitivity. CONCLUSIONS: H(2O(2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.

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

    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

  3. Rosiglitazone activation of PPARγ-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced mitochondrial dysfunction and oxidative stress.

    Chiang, Ming-Chang; Nicol, Christopher J; Cheng, Yi-Chuan; Lin, Kuan-Hung; Yen, Chia-Hui; Lin, Chien-Hung

    2016-04-01

    Neuronal cell impairment, such as that induced by amyloid-beta (Aβ) protein, is a process with limited therapeutic interventions and often leads to long-term neurodegeneration common in disorders such as Alzheimer's disease. Interestingly, peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor whose ligands control many physiological and pathologic processes, and may be neuroprotective. We hypothesized that rosiglitazone, a PPARγ agonist, would prevent Aβ-mediated effects in human neural stem cells (hNSCs). Here, we show that rosiglitazone reverses, via PPARγ-dependent downregulation of caspase 3 and 9 activity, the Aβ-mediated decreases in hNSC cell viability. In addition, Aβ decreases hNSC messenger RNA (mRNA) levels of 2 neuroprotective factors (Bcl-2 and CREB), but co-treatment with rosiglitazone significantly rescues these effects. Rosiglitazone co-treated hNSCs also showed significantly increased mitochondrial function (reflected by levels of adenosine triphosphate and Mit mass), and PPARγ-dependent mRNA upregulation of PGC1α and mitochondrial genes (nuclear respiratory factor-1 and Tfam). Furthermore, hNSCs co-treated with rosiglitazone were significantly rescued from Aβ-induced oxidative stress and correlates with reversal of the Aβ-induced mRNA decrease in oxidative defense genes (superoxide dismutase 1, superoxide dismutase 2, and glutathione peroxidase 1). Taken together, these novel findings show that rosiglitazone-induced activation of PPARγ-dependent signaling rescues Aβ-mediated toxicity in hNSCs and provide evidence supporting a neuroprotective role for PPARγ activating drugs in Aβ-related diseases such as Alzheimer's disease. PMID:26973118

  4. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation.

    Calviño, Eva; Estañ, María Cristina; Sánchez-Martín, Carlos; Brea, Rocío; de Blas, Elena; Boyano-Adánez, María del Carmen; Rial, Eduardo; Aller, Patricio

    2014-02-01

    3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of interest in antitumor therapies, although the mechanisms underlying its cytotoxicity are ill-defined. We show here that 3-BrP causes concentration-dependent cell death of HL60 and other human myeloid leukemia cells, inducing both apoptosis and necrosis at 20-30 μM and a pure necrotic response at 60 μM. Low concentrations of 3-BrP (10-20 μM) brought about a rapid inhibition of glycolysis, which at higher concentrations was followed by the inhibition of mitochondrial respiration. The combination of these effects causes concentration-dependent ATP depletion, although this cannot explain the lethality at intermediate 3-BrP concentrations (20-30 μM). The oxidative stress caused by exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen species and a concentration-dependent depletion of glutathione, which was an important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione-dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was later followed by Akt-mediated inactivation. Experiments with pharmacological inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to cooperate with antitumor agents like arsenic trioxide and curcumin in causing cell death, a response apparently mediated by both the generation of oxidative stress induced by 3-BrP and the attenuation of Akt and ERK activation by curcumin. In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy. PMID:24307199

  5. The impact of oxidative stress on hair.

    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

  6. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    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 (pdiabetic 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

  7. Oxidative stress and inflammation in liver carcinogenesis

    Natalia Olaya

    2007-02-01

    Full Text Available

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

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

  8. Clinical Relevance of Biomarkers of Oxidative Stress

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

    2015-01-01

    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...... 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...

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

    Chunyan Guo; Li Sun; Xueping Chen; Danshen Zhang

    2013-01-01

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

  10. Causes and consequences of oxidative stress in spermatozoa.

    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

  11. Biomarkers of oxidative stress in antioxidant therapy

    Wilfredo Mañon Rossi

    2016-04-01

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

  12. Battles with Iron: Manganese in Oxidative Stress Protection*

    Aguirre, J. Dafhne; Culotta, Valeria C.

    2012-01-01

    The redox-active metal manganese plays a key role in cellular adaptation to oxidative stress. As a cofactor for manganese superoxide dismutase or through formation of non-proteinaceous manganese antioxidants, this metal can combat oxidative damage without deleterious side effects of Fenton chemistry. In either case, the antioxidant properties of manganese are vulnerable to iron. Cellular pools of iron can outcompete manganese for binding to manganese superoxide dismutase, and through Fenton c...

  13. DIABETES, OXIDATIVE STRESS AND PHYSICAL EXERCISE

    Mustafa Atalay; David E. Laaksonen

    2002-01-01

    Oxidative stress, an imbalance between the generation of reactive oxygen species and antioxidant defense capacity of the body, is closely associated with aging and a number of diseases including cancer, cardiovascular diseases, diabetes and diabetic complications. Several mechanisms may cause oxidative insult in diabetes, although their exact contributions are not entirely clear. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen and nitro...

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

    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

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

    Lee Na-Young; Kang Young-Sook

    2010-01-01

    Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in vitro blood-placental barrier (BPB) model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells af...

  16. Heat shock protein 27 regulates oxidative stress-induced apoptosis in cardiomyocytes:mechanisms via reactive oxygen species generation and Akt activation

    LIU Li; ZHANG Xiao-jin; JIANG Su-rong; DING Zheng-nian; DING Guo-xian; HUANG Jun; CHENG Yun-lin

    2007-01-01

    Background Increased reactive oxygen species(ROS)formation,which in turn promotes cardiomyocytes apoptosis,is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure.Recent studies have shown that over expression of heat shock protein 27(Hsp27)confers resistance to cardiac ischemia/reperfusion injury.However,not much is known about the regulation of myocyte survival by Hsp27.Methods The rat cardiac cell line H9c2,with a stable overexpression of Hsp27,was established,with empty vector transfected H9c2 cells as controls.Following the cells challenged by Hydrogen Peroxide(H2O2),lactate dehydrogenase (LDH)release,apoptosis,intracellular ROS,cell morphology,mitochondrial transmembrane potential and the activation of serine/threonine kinase Akt were determined.Results Along with marked suppression of H2O2-induced injury by Hsp27 overexpression in H9c2 cells,ROS generation and the loss of mitochondrial membrane potential were also significantly depressed.Furthermore,augmented Akt activation was observed in Hsp27 overexpressed H9c2 cells following H2O2 exposure.Conclusions Hsp27 inhibits oxidative stress-induced H9c2 damage and inhibition of ROS generation and the augmentation of Akt activation may be involved in the protective signaling.

  17. Effect of simulated microgravity on nitric oxide synthase activity of osteocyte-like cell line MLO-Y4 in response to fluid shear stress

    Sun, Lian-Wen; Yang, Xiao; Fan, Yu-Bo

    It is well known that microgravity could induce bone loss. However, the mechanism remains poorly understood. Osteocytes are extremely sensitive to fluid shear stress, even more than osteobleasts. The effect of simulated microgravity on osteocytes in response to fluid shear was investigated in this study in order to see if the mechanosensibility of osteocytes changed under simulated microgravity. The osteocyte-like cell line, MLO-Y4, was cultured and divided into four groups, including control (CON), control and shear (CONS), rotary (RT), rotary and shear (RTS). In RT and RTS, the cells were cultured in the rotary cell culture system to simulate microgravity condition. After 5 days, the cells in RTS and CONS were subjected to flow shear for 15 min. Then nitric oxide synthase (NOS) activity in the cells was measured using assay kit. The results showed that NOS activity in respond to fluid shear decreased significantly in RTS compared with CONS. In addition, there was significant difference in NOS activity between CONS and CON while no significant difference between RTS and RT. These indicates that the mechanosensibility of osteocytes decreased under simulated microgravity and this maybe the partly causes of the poor effect of exercise to counter microgravity-induced-bone loss. However, further research need to be done to support this finding.

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

    E.V. Spiridonova; Ozolina, N. V.; I.S. Nesterkina; V.N. Nurminsky

    2016-01-01

    The investigation of the influence of gasotransmitters – a new class of signaling molecules – on the root tissues of red beet (Beta vulgaris L.) was conducted. It was found, that hydrogen sulfide (H2S) had some stabilizing effect on cellular membranes, reducing their permeability detected with the aid of conductometric technique. The reliable influence of carbon monoxide (CO) and nitrogen oxide (NO) in our experiments was not observed. A significant increase in efflux of electrolytes from bee...

  19. Enhanced oxidative stress and platelet activation combined with reduced antioxidant capacity in obese prepubertal and adolescent girls with full or partial metabolic syndrome.

    Karamouzis, I; Pervanidou, P; Berardelli, R; Iliadis, S; Papassotiriou, I; Karamouzis, M; Chrousos, G P; Kanaka-Gantenbein, C

    2011-08-01

    In adults, obesity is a main factor implicated in increased oxidative stress (OS), platelet activation (PA) and impaired antioxidant status (AS), all predisposing factors for cardiovascular disease leading to increased morbidity and mortality. Furthermore, the metabolic syndrome (MetS) is an important cardiovascular risk factor, which progressively develops and may already be present during late childhood or adolescence. However, scarce data exist on oxidative-antioxidant balance and PA in childhood and adolescence in the presence of partial (PMetS) or full MetS. The aim of the study was to evaluate OS, PA, and AS in prepubertal and adolescent obese girls with partial or full MetS. 96 girls with a clinical and metabolic evaluation for obesity and 44 healthy normal-weight sex- and age-matched girls were studied. IDF-adopted criteria were used to define full and partial MetS and the patient population was divided into 4 groups: the first comprised 31 pre-pubertal girls with PMetS (PR-PMetS), the second 37 adolescents with PMetS (AD-PMetS), the third 10 prepubertal girls with full MetS (PR-MetS), and the fourth 18 adolescents with full MetS (AD-MetS). The OS was evaluated by measuring plasma 15-F(2t)-Isoprostane levels (15-F(2t)-IsoP) and protein carbonyls, PA by thromboxane B(2) levels (TXB(2)), and AS by serum vitamin E and plasma total antioxidant capacity (TAC) levels. 15-F(2t)-IsoP, protein carbonyls, and TXB(2) levels were significantly gradually amplified, and vitamin E and TAC reduced, and significantly correlated with obesity from childhood to adolescence and from partial to full MetS. This study demonstrates the loss of the normal homeostatic balance between oxidant-antioxidant state in obese children and adolescents with manifestations of partial and full MetS. PMID:21823055

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

    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 th...

  1. Evaluation of the Antioxidant and Anti-glication Effects of the Hexane Extract from Piper auritum Leaves in Vitro and Beneficial Activity on Oxidative Stress and Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Treated Diabetic Rats

    Adriana Maria Neira Gonzalez

    2012-10-01

    Full Text Available The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS. Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

  2. Oxidative stress parameters and erythrocyte membrane adenosine triphosphatase activities in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe Pinnata leaves

    Nikhil Menon

    2016-01-01

    Full Text Available Background: Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. Objective: To evaluate red blood cell (RBC membrane adenosine triphosphatase (ATPase activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Materials and Methods: Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg. Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. Results: We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05 increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05 increase in Mg2+ ATPase activity and a nonsignificant increase in Na+/K+ ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. Conclusion: The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism

  3. Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

    Tomoko Kurita-Ochiai

    2015-09-01

    Full Text Available 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.

  4. Peroxisomes,oxidative stress,and inflammation

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

    2012-01-01

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

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

    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

  6. Vitamin B6 Supplementation Improves Oxidative Stress and Enhances Serum Paraoxonase/Arylesterase Activities in Streptozotocin-Induced Diabetic Rats

    Sibel Taş; Emre Sarandöl; Melahat Dirican

    2014-01-01

    The purpose of this study was to investigate the effects of vitamin B6 (Vit B6) on oxidant and antioxidant status in streptozotocin-induced diabetic rats. Thirty-two Wistar rats were divided into four groups: control (C), control + Vit B6 group (C + Vit B6), diabetes (D), and diabetes + Vit B6 group (D + Vit B6). Vit B6 (4 mg/kg body weight) was administered in drinking water for 4 weeks after the induction of diabetes. Vitamin B6 reduced serum total cholesterol level in the C + Vit B6 (P < 0...

  7. Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress

    Daniele Martarelli

    2011-01-01

    Full Text Available 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.

  8. Diaphragmatic breathing reduces exercise-induced oxidative stress.

    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

  9. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    Jinhua Tang

    2012-01-01

    Full Text Available Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and subsequent deregulation of cell function in renal glomeruli that leads to pathological changes. Oxidative stress is also associated with obesity-related renal diseases and may trigger the initiation or progression of renal damage in obesity. In this paper, we focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity.

  10. Evaluation of Oxidative Stress in Colorectal Cancer Patients

    DONG CHANG; FAN WANG; YA-SHUANG ZHAO; HONG-ZHI PAN

    2008-01-01

    To evaluate the oxidative stress in patients with colorectal cancer and to investigate the relationship between oxidative stress and colorectal cancer. Methods Seventy-six subjects were divided into two groups (36 colorectal cancerpatients as the study group and 40 normal healthy individuals as the control group). Their protein oxidation, DNA damage, lipid peroxidation and antioxidants, vitamin C, vitamin E, glutathione (GSH), and antioxidative enzymes in serum were detected. Results The levels of protein carbonyl and advanced oxidation protein products (AOPP) were significantly higher in the study group than in the control group (P<0.01). Serum 8-OHdG was significantly increased in the study group compared to the control group (P<0.01). However, the mean serum level of MDA and conjugated diene was lower in the study group than in the control group (P<0.01). The activity of antioxidative enzymes was significantly decreased in the study group compared to the control group (P<0.01). Serum vitamins C and E concentrations were significantly reduced in the study group compared to the control group (P<0.01). Conclusion Colorectal cancer is associated with oxidative stress, and assessment of oxidative stress and given antioxidants is important for the treatment and prevention of colorectal cancer.

  11. Oxidative stress in patients with regular hemodialysis

    Kubala, Lukáš; Číž, Milan; Čížová, Hana; Soška, V.; Studeník, P.; Černý, J.; Lojek, Antonín

    Budapest, 2000. s. 12. [International Workshop on Oxidative Stress in Ischemia/Reperfusion Injury /2./. 29.09.2000-01.10.2000, Sümeg] R&D Projects: GA MZd NA4796 Institutional research plan: CEZ:AV0Z5004920 Subject RIV: BO - Biophysics

  12. Neuro-oxidative-nitrosative stress in sepsis

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

    2011-01-01

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

  13. Genetics of Oxidative Stress in Obesity

    Azahara I. Rupérez

    2014-02-01

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

  14. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Simon Melov

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

  15. Oxidative stress, NADPH oxidases, and arteries.

    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

  16. Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NFκ-B activation and proinflammatory cytokine production

    Oxidative stress and inflammation are two major etiological factors that are suggested to play key roles in the development of ethanol induced liver injury. Release of proinflammatory cytokine like tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa-B (NFκ-B) may strongly intensify inflammation and cell damage. Additionally, reactive oxygen species (ROS) also exerts significant effect in this whole cell signaling machinery. The present study was designed to investigate the protective effects of perillyl alcohol (POH) on ethanol-induced acute liver injury in Wistar rats and its probable mechanism. We have successfully demonstrated that pre-treatment with POH, besides exerting antioxidant activity might be able to modulate TNF-α release and NFκ-B activation. Rats were divided into five groups and treated with ethanol or POH via an intragastric tube for one week. Control group was treated with vehicle, and ethanol treated group was given ethanol (5 g/kg body wt). Animal of treatment groups were pretreated with POH (50 and 100 mg/kg body wt) and have been given ethanol. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase and hepatic malondialdehyde were increased significantly by ethanol treatment. Ethanol administration decreased hepatic reduced glutathione content and various antioxidant enzymes activity. TNF-α production and NFκ-B activation was also found to be increased after ethanol administration. POH pre-treatment significantly ameliorates ethanol induced acute liver injury possibly by inhibition of lipid peroxidation, replenishment of endogenous enzymatic and non-enzymatic defense system, downregulation of TNF-α as well as NFκ-B.

  17. Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord.

    Kenji W Ruiz-Miyazawa

    Full Text Available Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH levels, superoxide anion, tumor necrosis factor alpha (TNF-α and interleukin 1 beta (IL-1β levels, as well as nuclear factor kappa B (NF-κB activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases, as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

  18. Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

    Ruiz-Miyazawa, Kenji W.; Zarpelon, Ana C.; Pinho-Ribeiro, Felipe A.; Pavão-de-Souza, Gabriela F.; Casagrande, Rubia; Verri, Waldiceu A.

    2015-01-01

    Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels. PMID:25822523

  19. Effects of tributyltin (TBT) on enzyme activity and oxidative stress in hepatopancreas and hemolymph of small abalone, Haliotis diversicolor supertexta

    Jia Xiwei; Zhang Ziping; Wang Shuhong; Lin Peng; Zou Zhihua; Huang Bangqin; Wang Yilei

    2009-01-01

    We investigated the effect of tributyltin (TBT) exposure on the concentration of malondialdehyde (MDA) and the activity levels of the superoxide dismutase (SOD), catalase (CAT), and acid and alkaline phosphatase (ACP and AKP) enzymes in the small abalone, Haliotis diversicolor supertexta. We collected samples of the hepatopancreas and hemolymph 2, 6, 24, 48, 96, and 192 h after exposure to 0.35μg (Sn)/L TBT. In the hepatopancreas, ACP activity was significantly higher in animals exposed to TBT 2, 24, and 96 h post-exposure compared with the control animals. AKP activity was also higher after 2 h, but SOD and CAT activity was unchanged. The concentration of MDA in the hemolymph was significantly higher than the control animals 2 and 6 h post-exposure. In the hemolymph of animals exposed to TBT, ACP activity was significantly lower than in the control animals 192 h post-exposure, whereas AKP activity was significantly lower 2 and 192 h post-exposure. Hemolymph SOD activity and levels of MDA were significantly lower than in the control animals 24 h after exposure but significantly higher after 96 h. Our results demonstrate that exposure to TBT cause rapid changes in ACP and AKP activity as well as altering the concentration of MDA in the hepatopancreas and hemolymph. SOD and CAT do not appear to be involved in the detoxification of TBT in the hepatopancreas of small abalone.

  20. Anticholinesterase Toxicity and Oxidative Stress

    Dejan Milatovic

    2006-01-01

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

  1. OXIDATIVE STRESS AND ANTI OXIDANTS STATUS IN PELLAGRA

    Desireddy Neelima, Bandi Hari Krishna, Masthan Saheb, Natham Mallikarjuna Reddy.

    2015-10-01

    Full Text Available Background and objectives: Pellagra was vanished from most parts of the world where it was formerly present due to its dietary modification. However, it is still encountered among the jowar eating populations of India. The information about the role of oxidative stress in pellagra was not established. Therefore, in this study we assessed the oxidative stress status by using malondialdehyde (MDA, total anti oxidant status (TAOS and redox ratio (RER in clinically diagnosed pellagra patients. Materials and methods: Clinically diagnosed pellagra patients aged between 18 to 40 years, both male and females were recruited (n=78 from department of Dermatology. Age and gender matched controls (n=78 were recruited from the student and residents of the hospital. Malondialdehyde (MDA is a marker of lipid peroxidation, Total Anti Oxidant Status (TAOS and Redox Ratio (RER markers were assessed by using commercially available kits. Results: There were no significant differences in the anthropometric parameters. However, the oxidative stress markers MDA (p<0.05, RER (p<0.001 were significantly high and TAOS was low (P<0.001 in pellagra patients in comparison with age and gender matched controls. Conclusion: The results of this study showed the increased MDA, RER levels and decreased TAOS levels. Estimation of these markers at early stage will help to take measures to prevent the progression of disease and develop antioxidant strategies.

  2. Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

    Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

    2015-03-01

    Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent. PMID:25730806

  3. Cation transport in oxidant-stressed human erythrocytes: heightened N-ethylmaleimide activation of passive K+ influx after mild peroxidation.

    Sheerin, H E; Snyder, L M; Fairbanks, G

    1989-07-24

    Normal and chronically dehydrated (hereditary xerocytosis) human red cells were subjected to mild peroxidative treatment (315 microM hydrogen peroxide (H2O2), 15 min) in the presence of azide. The subsequent expression of passive (ouabain-resistant) K+ transport activities was analyzed by measurement of 86Rb+ influx. Peroxidation of normal red cells did not affect basal K+ transport activity, but the increment in K+ influx elicited by 0.5 mM N-ethylmaleimide (NEM) was increased 3-fold. The enhanced K+ influx was chloride-dependent, but only partially inhibited by 0.1 mM furosemide. Stimulated activity declined progressively after NEM activation, but could be restored by a second NEM treatment. Prior conversion of hemoglobin to the carbonmonoxy form abolished the response to peroxide, while 200 microM butylated hydroxytoluene (BHT) exerted only partial inhibition, suggesting that the effect of H2O2 requires interaction of activated, unstable hemoglobin species with the membrane, but that lipid peroxidation is not sufficient. Peroxidation following NEM treatment also enhanced NEM activation, indicating that enhancement does not require altered NEM reactions with stimulatory or inhibitory sites. Passive K+ transport in hereditary xerocytosis red cells was not activated by NEM, with or without H2O2 pretreatment. The results demonstrate that modest peroxidative damage to red cells can heighten the activation of a transport system that is thought to be capable of mediating net K+ efflux and volume reduction in cells that express it. Models are proposed in which the effects of NEM, H2O2, cell swelling and other factors are mediated by conformational changes in a postulated subpopulation of anion channel (Band 3) molecules that bind the K+ transporter. PMID:2758051

  4. Antioxidative protection of dietary rosehips and polyphenol active lactobacilli in mice subjected to intestinal oxidative stress by ischemia-reperfusion

    Jakesevic, Maja; Håkansson, Åsa; Adawi, Diya; Jeppsson, Bengt; Rumpunen, Kimmo; Ekholm, Anders; Ahrné, Siv; Molin, Göran

    2011-01-01

    Background and aim: Ischemia-reperfusion (I/R) in the intestines activates leukocytes and reactive oxygen species (ROS) and leads to lipid peroxidation and DNA damage. Rosehips have a high content of polyphenols and might prevent lipid peroxidation. Some Lactobacillus species are capable of degrading polyphenols to simpler and non-toxic constituents, sometimes with enhanced antioxidative capacity. Methods: A mixture of eight polyphenol active Lactobacillus strains (LAB) were administered in f...

  5. Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats

    Ch. Naga Kavitha

    2011-01-01

    Conclusions: This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.

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

    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.

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

    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

    predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other. PMID:26811750

  8. Ethanol toxicity and oxidative stress

    Bondy, SC

    1992-01-01

    The mechanisms underlying the toxicity of ethanol have been the subject of much study, but are not well understood. Unlike many selective pharmacological agents, ethanol clearly has several major loci of action. One deleterious factor in ethanol metabolism is the potential for generation of excess amounts of free radicals. The extent to which this activity accounts for the overall toxicity of ethanol is unknown. This review outlines the enzymic steps that have the capacity to generate reactiv...

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

    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

  10. Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation

    Nardi, Geisson Marcos; Farias Januario, Adriana Graziele; Freire, Cassio Geremia; Megiolaro, Fernanda; Schneider, Kétlin; Perazzoli, Marlene Raimunda Andreola; Do Nascimento, Scheley Raap; Gon, Ana Cristina; Mariano, Luísa Nathália Bolda; Wagner, Glauber; Niero, Rivaldo; Locatelli, Claudriana

    2016-01-01

    Background: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. Objective: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Materials and Methods: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by hi...

  11. Regulation of heme oxygenase activity in rat liver during oxidative stress induced by cobalt chloride and mercury chloride.

    Kaliman, P A; Nikitchenko, I V; Sokol, O A; Strel'chenko, E V

    2001-01-01

    Activities of heme oxygenase and tryptophan-2,3-dioxygenase and cytochrome P450 content in liver as well as absorption of the Soret band and optical density at 280 nm in serum were determined 2 and 24 h after administration of HgCl(2) and CoCl(2) and after co-administration of the metal salts with alpha-tocopherol. Administration of HgCl(2) and CoCl(2) increased the contents of hemolysis products in the serum, induced heme oxygenase, and decreased cytochrome P450 content in the liver. Injection of HgCl(2) increased the activity of tryptophan-2,3-dioxygenase holoenzyme and enzyme saturation with the heme, but administration of CoCl(2) decreased these parameters. Pretreatment with alpha-tocopherol completely blocked the changes induced by HgCl(2) after 24 h. Induction of heme oxygenase induced by CoCl(2) was not blocked by alpha-tocopherol, but this antioxidant normalized the increase in the level of hemolysis products in the serum and decrease in tryptophan-2,3-dioxygenase holoenzyme activity and cytochrome P450 content. Mechanisms of regulation of heme oxygenase by mercury and cobalt ions are discussed. PMID:11240397

  12. The Effects of Quinacrine, Proglumide, and Pentoxifylline on Seizure Activity, Cognitive Deficit, and Oxidative Stress in Rat Lithium-Pilocarpine Model of Status Epilepticus

    Mohammad Ahmad

    2014-01-01

    Full Text Available The present data indicate that status epilepticus (SE induced in adult rats is associated with cognitive dysfunctions and cerebral oxidative stress (OS. This has been demonstrated using lithium-pilocarpine (Li-Pc model of SE. OS occurring in hippocampus and striatum of mature brain following SE is apparently due to both the increased free radicals production and the limited antioxidant defense. Pronounced alterations were noticed in the enzymatic, glutathione-S transferase (GST, catalase (CAT, and superoxide dismutase (SOD, as well as in the nonenzymatic; thiobarbituric acid (TBARS and reduced glutathione (GST, indices of OS in the hippocampus and striatum of SE induced animals. Quinacrine (Qcn, proglumide (Pgm, and pentoxifylline (Ptx administered to animals before inducing SE, were significantly effective in ameliorating the seizure activities, cognitive dysfunctions, and cerebral OS. The findings suggest that all the drugs were effective in the order of Ptx < Pgm < Qcn indicating that these drugs are potentially antiepileptic as well as antioxidant; however, further studies are needed to establish this fact. It can be assumed that these antiepileptic substances with antioxidant properties combined with conventional therapies might provide a beneficial effect in treatment of epilepsy through ameliorating the cerebral OS.

  13. Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1α activation in hepatic ischemia/reperfusion injury.

    Bellanti, Francesco; Mirabella, Lucia; Mitarotonda, Domenica; Blonda, Maria; Tamborra, Rosanna; Cinnella, Gilda; Fersini, Alberto; Ambrosi, Antonio; Dambrosio, Michele; Vendemiale, Gianluigi; Serviddio, Gaetano

    2016-07-01

    Mitochondrial dysfunction, reactive oxygen species (ROS) production and oxidative stress during reperfusion are determinant in hepatic ischemia/reperfusion (I/R) injury but may be impacted by different anesthetic agents. Thus, we aimed at comparing the effects of inhaled sevoflurane or intravenous propofol anesthesia on liver mitochondria in a rodent model of hepatic I/R injury. To this, male Wistar rats underwent I/R surgery using sevoflurane or propofol. In the I/R model, propofol limited the raise in serum aminotransferase levels as compared to sevoflurane. Mitochondrial oxygen uptake, respiratory activity, membrane potential and proton leak were altered in I/R; however, this impairment was significantly prevented by propofol but not sevoflurane. In addition, differently from sevoflurane, propofol limited hepatic I/R-induced mitochondria H2O2 production rate, free radical leak and hydroxynonenal-protein adducts levels. The I/R group anesthetized with propofol also showed a better recovery of hepatic ATP homeostasis and conserved integrity of mitochondrial PTP. Moreover, hypoxia-inducible factor 1 alpha (HIF-1α) expression was limited in such group. By using a cell model of desferoxamine-dependent HIF activation, we demonstrated that propofol was able to inhibit apoptosis and mitochondrial depolarization associated to HIF-1α action. In conclusion, hepatic I/R injury induces mitochondrial dysfunction that is not prevented by inhaled sevoflurane. On the contrary, propofol reduces liver damage and mitochondrial dysfunction by preserving respiratory activity, membrane potential and energy homeostasis, and limiting free radicals production as well as PTP opening. These hepatoprotective effects may involve the inhibition of HIF-1α. PMID:27154980

  14. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  15. Effects of metals on blood oxidative stress biomarkers and acetylcholinesterase activity in dice snakes (Natrix tessellata from Serbia

    Gavrić Jelena P.

    2015-01-01

    Full Text Available The effects of waterborne metals in water on the activities of blood copper-zinc superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase (GSH-Px, glutathione reductase (GR, glutathione-S-transferase (GST, and acetylcholinesterase (AChE, and on the concentrations of total glutathione (GSH and lipid peroxides (TBARS in the blood of dice snakes (Natrix tessellata caught in Obedska Bara, Sebia (control area, with snakes caught in Pančevački Rit, a contaminated area in Serbia were examined. The activities of CAT, GSH-Px, GR and AChE, and the concentration of TBARS were significantly decreased, while GST activity and GSH concentration were significantly increased in snakes from the contaminated area compared to specimens from the control area. Significantly increased concentrations of Al, As, B, Ba, Ca, Cu, Fe, K, Li, Mn, Na, Ni and Zn in the water at the contaminated area as compared to control area were detected. The metals Ag, Bi, Cd, Co, Hg, In and Tl were not observed in any of the localities. Cr, Mo and Pb were not detected at the control area but were observed at the contaminated area. The concentrations of Sr were similar at both sites. The concentration of Mg was 2-fold higher at the control site than at the contaminated area. The obtained results show that most of the investigated blood biomarkers correlate with concentrations of metals present in the environment. These findings suggest that dice snakes are sensitive bioindicator species for monitoring the effects of increased metal concentrations in the environment. [Projekat Ministarstva nauke Republike Srbije, br. 173041 i br. 173043

  16. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Sobinoff, A.P.; Pye, V. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); Nixon, B.; Roman, S.D. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia)

    2012-04-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  17. Vascular oxidative stress upregulates angiotensin II type I receptors via mechanisms involving nuclear factor kappa B

    Bhatt, Siddhartha R.; Lokhandwala, Mustafa F.; Banday, Anees Ahmad

    2014-01-01

    The association of oxidative stress with hypertension is well known. However, a causal role of oxidative stress in hypertension is unclear. Vascular angiotensin II type 1 receptor (AT1R) upregulation is a prominent contributor to pathogenesis of hypertension. However, the mechanisms causing this upregulation are unknown. Oxidative stress is an important regulator of protein expression via activation of transcription factors such as nuclear factor kappa B (NFκB). The present study was carried ...

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

    Namrata eChaudhari; Priti eTalwar; Avinash eParimisetty; Christian eLefebvre d'Hellencourt; Palaniyandi eRavanan

    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 b...

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

    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 b...

  20. Oxidative stress in songbirds exposed to dietary methylmercury.

    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

  1. Fiber networks amplify active stress

    Ronceray, Pierre; Broedersz, Chase; Lenz, Martin

    2015-01-01

    Large-scale force generation is essential for biological functions such as cell motility, embryonic development, and muscle contraction. In these processes, forces generated at the molecular level by motor proteins are transmitted by disordered fiber networks, resulting in large-scale active stresses. While these fiber networks are well characterized macroscopically, this stress generation by microscopic active units is not well understood. Here we theoretically study force transmission in th...

  2. Effect of Excess Iodine on Oxidative Stress Markers, Steroidogenic-Enzyme Activities, Testicular Morphology, and Functions in Adult Male Rats.

    Chakraborty, Arijit; Mandal, Jagadis; Mondal, Chiranjit; Sinha, Sabyasachi; Chandra, Amar K

    2016-08-01

    Improper iodine intake is a major concern in public health. Chronic intake of low iodine affects gonadal functions of man and animals; however, such effects of excess iodine in male reproduction, specially on testicular morphology, testicular steroidogenic enzyme activities, sperm morphology, sperm viability, and sperm count including male hormonal profiles in reference to iodine status and thyroid hormone profiles are yet to be explored. With this background, adult male rats of 120 ± 10 gm Bw of 90 ± 5 days were divided broadly in two groups depending on the duration of the treatment for 30 and 60 days, respectively. Both the groups consisted of control animals. Excess iodine (100EI), i.e., 100 times more than its recommended level but within its tolerable ranges, was administered through gavage regularly to the first group of experimental animals for 30 and 60 days, respectively, and excessive iodine (500EI), i.e., 500 times more than its recommended level and above tolerable range in the same way and for the same durations, was administered to the other group of experimental animals. Overall results revealed that regular consumption of iodine in excess impairs reproductive functions in adult male rats depending on the dose and duration of its exposure through different mechanisms. Excess iodine accumulates in the testis which results in generation of reactive oxygen species (ROS) as evidenced by higher lipid peroxidation level as well as an imbalance in the pro-/antioxidant status inhibiting the activity of ∆(5) 3β- hydroxysteroid dehydrogenase (HSD) and 17β-HSD resulting to reduced synthesis of testosterone that causes structural and functional changes of the testis. Secondly, persistent generation of ROS in testis as a result of prolonged excess iodine exposure affects hypothalamo-pituitary-adrenal axis that stimulates synthesis and secretion of corticosterone which inhibits LH release that downregulates testosterone synthesis causing further

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

    Ficarra, Silvana; Russo, Annamaria; Barreca, Davide; Giunta, Elena; Galtieri, Antonio; Tellone, Ester

    2016-01-01

    The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism. PMID:27579150

  4. Endocrine control of oxidative stress in Insects

    Krishnan, N.; Kodrík, Dalibor

    New Jersey: Wiley-Blackwell, 2012 - (Farooqui, T.; Farooqui, A.), s. 261-270 ISBN 978-1-118-14814-3 R&D Projects: GA ČR GAP501/10/1215 Institutional research plan: CEZ:AV0Z50070508 Keywords : oxidative stress Subject RIV: ED - Physiology http://eu.wiley.com/WileyCDA/WileyTitle/productCd-111800194X.html

  5. Computer diagnosis in cardiology: Oxidative stress hypothesis

    Ezekiel Uba Nwose; Graham Wilfred Ewing

    2009-01-01

    Background : Virtual scanning is one of the emerging technologies in complementary medicine practice. The diagnostic principle is hinged on perception and ultra weak light emission, while the treatment options associated with it includes diet, flash light, exercise and relaxation. However, a mechanism that links the diagnostic and treatment principles has yet to be elucidated. Aims: The objective here is to further explanation of oxidative stress concept as the biochemical basis of the techno...

  6. Postoperative atrial fibrillation, oxidative stress, and inflammation

    ÖZAYDIN, Mehmet

    2011-01-01

    Postoperative atrial fibrillation is the most common complication of cardiac surgery. It is associated with increased complication rates. Recent trials have suggested that inflammation and oxidative stress have key roles in the pathophysiology of atrial fibrillation. Current evidence evaluating the use of antiinflammatory and antioxidant agents, including statins, corticosteroids, N-acetylcysteine, vitamin C, and fish oil, to prevent postoperative atrial fibrillation is promising. However, la...

  7. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio; Hill, Joseph A.

    2014-01-01

    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 tra...

  8. A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

    Derrick F. MacFabe; Karina Rodríguez-Capote; Jennifer E.  Franklin; Martin Kavaliers; Fred Possmayer; Klaus-Peter Ossenkopp; Andrew E. Franklin

    2008-01-01

    Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (500ug uL-1, 4µl anima-1) or phosphate buffered saline (PBS) ...

  9. Oxidative stress-dependent activation of collagen synthesis is induced in human pulmonary smooth muscle cells by sera from patients with scleroderma-associated pulmonary hypertension

    Boin, Francesco; Erre, Gian Luca; Posadino, Anna Maria; Cossu, Annalisa; Giordo, Roberta; Spinetti, Gaia; Passiu, Giuseppe; Emanueli, Costanza; PINTUS, GIANFRANCO

    2014-01-01

    Pulmonary arterial hypertension is a major complication of systemic sclerosis. Although oxidative stress, intima hyperplasia and a progressive vessel occlusion appear to be clearly involved, the fine molecular mechanisms underpinning the onset and progression of systemic sclerosis-associated pulmonary arterial hypertension remain largely unknown. Here we shows for the first time that an increase of NADPH-derived reactive oxygen species production induced by sera from systemic sclerosis patien...

  10. Oxidant Stress in Renal Inflammation: Mechanisms and Remedies

    Ishola, D.A.

    2006-01-01

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

  11. Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway.

    Yang, Wencheng; Yang, Yan; Yang, Jian-Yi; Liang, Ming; Song, Jiangtao

    2016-04-01

    The aim of the present study was to investigate the protective effect exerted by bone marrow mesenchymal stem cells (BMSCs) in combination with plumbagin on spinal cord injury (SCI) and explore the mechanism behind this protective effect. Firstly, BMSCs were extracted from male Sprague-Dawley rats, cultured in vitro, and identified by hematoxylin. Sprague-Dawley rats were then randomly divided into a control group, SCI model group, BMSC-treated group, a plumbagin-treated group, and a BMSC and plumbagin-treated group. After treatment with BMSCs combined with plumbagin, a Basso, Beattie and Bresnahan (BBB) test was carried out and the spinal cord water content was examined in order to analyze the effect of BMSCs combined with plumbagin on SCI. The myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor-κB (NF-κB) p65 unit, tumor necrosis factor-α (TNF-α) levels were also detected. Moreover, nuclear factor erythroid 2‑related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)Akt, p-p38 mitogen-activated protein kinase (MAPK), and p-extracellular-signal-regulated kinase (ERK) protein expression levels were measured using western blot analysis. Treatment with BMSCs combined with plumbagin significantly improved locomotor recovery and reduced the spinal cord water content after SCI. The increased MPO, MDA, NF-κB p65 and TNF-α levels were significantly suppressed and the decreased SOD was significantly increased in SCI rats. The suppression of Nrf2, p-Akt and p-ERK, as well as the promotion of p-p38 MAPK, were reversed by treatment with BMSCs combined with plumbagin. These effects suggest that treatment with BMSCs combined with plumbagin alleviates SCI through its effects on oxidative stress, inflammation, apoptotis and activation of the Nrf2 pathway. PMID:26936518

  12. The effect of squalane-dissolved fullerene-C60 on adipogenesis-accompanied oxidative stress and macrophage activation in a preadipocyte-monocyte co-culture system.

    Xiao, Li; Aoshima, Hisae; Saitoh, Yasukazu; Miwa, Nobuhiko

    2010-08-01

    Effects of squalane-dissolved fullerene-C60 (Sql-fullerene) on macrophage activation and adipose conversion with oxidative stress were studied using an inflammatory adipose-tissue equivalent (ATE) and OP9 mouse stromal preadipocyte-U937 lymphoma cell co-culture systems. Differentiation of OP9 cells was initiated by insulin-rich serum replacement (SR) as an adipogenic stimulant, and then followed by accumulation of intracellular lipid droplets and reactive oxygen species (ROS), both of which were significantly inhibited by Sql-fullerene. In the OP9-U937 cell co-culture system, U937 cells rapidly differentiated to macrophage-like cells during SR-induced adipogenesis in OP9 cells. The ROS accumulation was in the co-culture more marked than in OP9 cells alone, suggesting that the interaction between adipocytes and monocytes/macrophages promotes inflammatory responses. Sql-fullerene significantly inhibited macrophage activation and low-grade adipogenesis in the OP9-U937 co-culture system. We developed a three-dimensional inflammatory adipose-tissue model "ATE" consisting of, characteristically, U937 cells in the culture-wells, and, in addition, mounted a culture insert containing OP9 cells-populated collagen gel. ATE is enabled with suitable stimulation to represent the pathology of inflammatory disorders, such as macrophage infiltration in adipose tissue. Five-day culturing of ATE in SR medium occurred U937 macrophage migration and intracellular oil-droplet accumulation that were significantly inhibited by Sql-fullerene. Our results suggest that Sql-fullerene might be explored as a potential medicine for the treatment of metabolic syndrome or other obesity-related disorders. PMID:20488530

  13. Oxidative stress and male reproductive health

    Robert J Aitken

    2014-02-01

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

  14. Lamins as mediators of oxidative stress

    Highlights: ► The nuclear lamina defines structural and functional properties of the cell nucleus. ► Lamina dysfunction leads to a broad spectrum of laminopathies. ► Recent data is reviewed connecting laminopathies to oxidative stress. ► 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.

  15. Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers

    Yankai Araya

    2010-05-01

    Full Text Available Abstract Purpose The aim of this study was to evaluate the effects of Vernonia cinerea Less. (VC supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking. Methods Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly. Before and after a two month period, exhaled carbon monoxide (CO, blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC], beta-endorphin and smoking rate were measured, and statistically analyzed. Results In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p 0.05. In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p 0.05. All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%, 1(59.52%, 3 (53.57% and 4(14.04%, whereas in self-rolled cigarettes it decreased in group 1 (54.47%, 3 (42.30%, 2 (40% and 4 (9.2%. Conclusion Supplementation with Vernonia cinerea Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels.

  16. Iron, Oxidative Stress and Gestational Diabetes

    Taifeng Zhuang

    2014-09-01

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

  17. Oxidative stress and DNA damages induced by cadmium accumulation

    LIN Ai-jun; ZHANG Xu-hong; CHEN Mei-mei; CAO Qing

    2007-01-01

    Experimental evidence shows that cadmium (Cd) could induce oxidative stress and then causes DNA damage in animal cells, however, whether such effect exists in plants is still unclear. In the present study, Vicia faba plants was exposed to 5 and 10 mg/L Cd for 4 d to investigate the distribution of Cd in plant, the metal effects on the cell lipids, antioxidative enzymes and DNA damages in leaves. Cd induced an increase in Cd concentrations in plants. An enhanced level of lipid peroxidation in leaves and an enhanced concentration of H2O2 in root tissues suggested that Cd caused oxidative stress in Vicia faba. Compared with control, Cd-induced enhancement in superoxide dismutase activity was significant at 5 mg/L than at 10 mg/kg in leaves, by contrast, catalase and peroxidaseactivities were significantly suppressed by Cd addition. DNA damage was detected by neutral/neutral, alkaline/neutral and alkaline/alkaline Comet assay. Increased levels of DNA damages induced by Cd occurred with reference to oxidative stress in leaves, therefore, oxidative stress induced by Cd accumulation in plants contributed to DNA damages and was possibly an important mechanism of Cd-phytotoxicity in Vicia faba plants.

  18. Thoracic radiography and oxidative stress indices in heartworm affected dogs

    P. K. Rath

    2014-09-01

    Full Text Available Aim: The aim was to study the pathomorphological changes through thoracic radiography and status of oxidative stress parameters in heartworm affected dogs in Odisha. Materials and Methods: A total of 16 dogs with clinically established diagnosis of dirofilariasis by wet blood smear and modified Knott’s test and equal numbers of dogs as control were included in this study. The present study was conducted in heartworm affected dogs to see the pathomorphological changes through thoracic radiography. Similarly, the evaluation was undertaken for observing any alterations in oxidative stress status in affected as well as non-affected, but healthy control dogs by adopting standard procedure. Results: Thoracic radiography revealed cardiac enlargement, round heart appearance suggestive of right ventricular hypertrophy, tortuous pulmonary artery and darkening of lungs. Alterations in oxidative stress indices showed a significant rise of lipid peroxidase activity, non-significant rise of superoxide dismutase and a significant although reverse trend for catalase levels in affected dogs in comparison to Dirofilaria negative control but apparently healthy dogs. Conclusions: Radiographic changes, as well as alterations in oxidative stress parameters, may not be diagnostic for heartworm infection, but useful for detecting heartworm disease, assessing severity and evaluating cardiopulmonary parenchyma changes and gives a fair idea about the degree of severity of the disease. It aids as contributing factors in disease pathogenesis.

  19. Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

    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

  20. Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

    Kuo, Lih; Hein, Travis W.

    2013-01-01

    Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO) during oxidative stress and inflammation related to the activation of L-...

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

    Laura Bravo

    2013-07-01

    Full Text Available 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.

  2. Activation of constitutive nitric oxide synthases by oxidized calmodulin mutants.

    Montgomery, Heather J; Bartlett, Ryan; Perdicakis, Basil; Jervis, Eric; Squier, Thomas C; Guillemette, J Guy

    2003-07-01

    Several calmodulin (CaM) mutants were engineered in an effort to identify the functional implications of the oxidation of individual methionines in CaM on the activity of the constitutive isoforms of nitric oxide synthase (NOS). Site-directed mutagenesis was used to substitute the majority of methionines with leucines. Substitution of all nine methionine residues in CaM with leucines had minimal effects on the binding affinity or maximal enzyme activation for either the neuronal (nNOS) or endothelial (eNOS) isoform. Selective substitution permitted determination of the functional consequences of the site-specific oxidation of Met(144) and Met(145) on the regulation of electron transfer within nNOS and eNOS. Site-specific oxidation of Met(144) and Met(145) resulted in changes in the CaM concentration necessary for half-maximal activation of nNOS and eNOS, suggesting that these side chains are involved in stabilizing the productive association between CaM and NOS. However, the site-specific oxidation of Met(144) and Met(145) had essentially no effect on the maximal extent of eNOS activation in the presence of saturating concentrations of CaM. In contrast, the site-specific oxidation of Met(144) (but not Met(145)) resulted in a reduction in the level of nNOS activation that was associated with decreased rates of electron transfer within the reductase domain. Thus, nNOS and eNOS exhibit different functional sensitivities to conditions of oxidative stress that are expected to oxidize CaM. This may underlie some aspects of the observed differences in the sensitivities of proteins in vasculature and neuronal tissues to nitration that are linked to NOS activation and the associated generation of peroxynitrite. PMID:12820885

  3. Assessment of Free Radical Scavenging Activity of Dimethylglycine Sodium Salt and Its Role in Providing Protection against Lipopolysaccharide-Induced Oxidative Stress in Mice.

    Bai, Kaiwen; Xu, Wen; Zhang, Jingfei; Kou, Tao; Niu, Yu; Wan, Xiaoli; Zhang, Lili; Wang, Chao; Wang, Tian

    2016-01-01

    the LPS-induced oxidative stress by enhancing the free radical scavenging capacity, and increasing the activity of antioxidant defense system. PMID:27171376

  4. Role of oxidative stress in female reproduction

    Sharma Rakesh K

    2005-07-01

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

  5. Stress hormones and physical activity

    Editorial Office

    1991-01-01

    Hormone secretion during physical activity of specific duration and intensity is part of the stress response. In a study to investigate the secretion of ß-endorphin, leucine enkephalin and other recognised stress hormones during physical exercise, blood samples were taken from fourteen (14) healthy, male athletes who competed in a 21 km roadrace. Blood samples were collected before and after completion of the race. This study shows that ß-endorphin/ß-lipotropin, leucine enkephalin, prolact...

  6. Protective Effects of Carvacrol against Oxidative Stress Induced by Chronic Stress in Rat's Brain, Liver, and Kidney

    Samarghandian, Saeed; Farkhondeh, Tahereh; Samini, Fariborz; Borji, Abasalt

    2016-01-01

    Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P < 0.001) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals (P < 0.001). CAR ameliorated the changes in the stressed animals as compared with the control group (P < 0.001). This study indicates that CAR can prevent restraint stress induced oxidative damage. PMID:26904286

  7. Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats.

    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

  8. D-Serine exposure resulted in gene expression changes indicative of activation of fibrogenic pathways and down-regulation of energy metabolism and oxidative stress response

    , metabolism and transport, inflammatory response, proteasome-mediated degradation of oxidatively damaged cytosolic proteins, Ras protein signal transduction, TGF-beta signaling pathway and mRNA transcription, processing, splicing and transport. On the other hand, major metabolic pathways, which include carbohydrate metabolism, TCA cycle, oxidative phosphorylation, ATP synthesis coupled electron transport, amino acid metabolism and transport, lipid metabolism, nucleotide metabolism, and vitamin metabolism, and oxidative stress response including induction of antioxidant genes and glutathione metabolism are down-regulated. As tubular epithelia have strong energy demand for normal functions, down-regulation of energy metabolism after D-serine treatment may be related to the mechanism of its nephrotoxicity. In addition, hydrogen peroxide, a reactive oxygen species, is produced as a byproduct of the metabolism of D-serine by D-amino acid oxidase in the peroxisomes of the tubular epithelia. Down-regulation of pathways for antioxidant genes induction and glutathione metabolism will likely exacerbate the cytotoxicity of this reactive oxygen species. The observation that the genes involved in apoptosis, DNA repair, proteasome pathway for the degradation of oxidatively damaged cytosolic proteins were up-regulated lends some supports to this premise. Up-regulation of pathways of cell proliferation cycle, DNA replication and gene expression process, including mRNA transcription, processing, splicing, transport, translation initiation, and protein transport along with protein complex assembly, suggests ongoing tissue repair and regeneration. Consistent with the fibrogenic function of the TGF-beta signaling pathway in various experimental renal diseases, genes encoding major extracellular matrix components such as collagens, laminins, fibronectin 1 and tenascins are also strongly up-regulated. Taken together, the results of this study provide important insights into the molecular mechanism

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

    2007-01-01

    Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.

  10. Oxidative stress in kidney transplantation: causes, consequences, and potential treatment.

    2011-01-01

    Oxidative stress is a major mediator of adverse outcomes throughout the course of transplantation. Transplanted kidneys are prone to oxidative stress-mediated injury by pre-transplant and post-transplant conditions that cause reperfusion injury or imbalance between oxidants and antioxidants. Besides adversely affecting the allograft, oxidative stress and its constant companion, inflammation, cause cardiovascular disease, cancer, metabolic syndrome, and other disorders in transplant recipients...

  11. Boolean modeling and fault diagnosis in oxidative stress response

    Sridharan Sriram; Layek Ritwik; Datta Aniruddha; Venkatraj Jijayanagaram

    2012-01-01

    Abstract 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 ...

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

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

    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...

  13. Oxidative stress associated with exercise, psychological stress and life-style factors

    Møller, P; Wallin, H; Knudsen, Lisbeth E.

    1996-01-01

    generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress. Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress....... Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property....

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

    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

  15. Effect of sodium salicylate on oxidative stress andinsulinresistanceinducedbyfreefattyacids

    Bing He; Sheng Zhao; Wei Zhang; Yan Li; Ping Han

    2010-01-01

    BACKGROUND: It has been reported that high-dose salicy-lates improve free fatty acids (FFAs)-induced insulin resistance andβ-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was performed with [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inlfammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-β and NF-κB provide potential pathogenic links to oxidative stress.

  16. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  17. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  18. Protein Thiols as an Indication of Oxidative Stress

    Yousef Rezaei Chianeh; Krishnananda Prabhu

    2014-01-01

    Thiol is an organic compound that contain sulphhydryl group that have a critical role in preventing any involvement of oxidative stress in the cell. These defensive functions are generally considered to be carried out by the low molecular weight thiol glutathione and by cysteine residues in the active sites of proteins such as thioredoxin and peroxiredoxin. In addition, there are thiols exposed on protein surfaces that are not directly involved with protein function, although they can intera...

  19. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    Jinhua Tang; Haidong Yan; Shougang Zhuang

    2012-01-01

    Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and ...

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

    Shu-Ju Chen

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

  1. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    V. D. Prokopieva

    2016-01-01

    Full Text Available 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.

  2. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies.

    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. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    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.

  4. Oxidative stress in haemodialysis--intradialytic changes.

    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

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

    Xi-Feng Zhang

    2016-06-01

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

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

    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

  7. Nitric oxide triggers a concentration-dependent differential modulation of superoxide dismutase (FeSOD and Cu/ZnSOD) activity in sunflower seedling roots and cotyledons as an early and long distance signaling response to NaCl stress.

    Arora, Dhara; Bhatla, Satish C

    2015-01-01

    Dark-grown sunflower (Helianthus annuus L.) seedlings exhibit modulation of total superoxide dismutase (SOD;EC 1.15.1.1) activity in roots and cotyledons (10,000g supernatant) in response to salt stress (NaCl; 120 mM) through a differential, zymographically detectable, whole tissue activity of FeSOD and Cu/ZnSOD. Confocal laser scanning microscopic imaging (CLSM) has further shown that NaCl stress significantly influences differential spatial distribution of Cu/ZnSOD and MnSOD isoforms in an inverse manner. Dual action of nitric oxide (NO) is evident in its crosstalk with FeSOD and Cu/ZnSOD in seedling roots and cotyledons in control and NaCl(-) stress conditions. Cu/ZnSOD activity in the roots of 2 d old NaCl(-) stressed seedlings is enhanced in the presence of 125-1000 µM of NO donor (sodium nitroprusside; SNP) indicating salt sensitivity of the enzyme activity. Quenching of endogenous NO by cPTIO treatment (500, 1000 µM) lowers FeSOD activity in roots (-NaCl). Cotyledons from control seedlings show an upregulation of FeSOD activity with increasing availability of SNP (125-1000 µM) in the Hoagland irrigation medium. Quenching of NO by cPTIO provides evidence for an inverse correlation between NO availability and FeSOD activity in seedling cotyledons irrespective of NaCl stress. Variable response due to NO on SOD isoforms in sunflower seedlings reflects its concentration-dependent biphasic (pro- and antioxidant) nature of action. Differential induction of SOD isoforms by NO indicates separate intracellular signaling pathways (associated with their respective functional separation) operative in seedling roots as an early salt stress mechanism and in cotyledons as an early long-distance NaCl stress sensing mechanism. PMID:26339977

  8. Assessment of the degree of oxidative stress injury, renin-angiotensin system activity and podocyte loss after combined treatment of keto acid with low protein diet for patients with diabetic nephropathy

    Yuan-Hua Xu; Mei Wang

    2016-01-01

    Objective:To analyze the degree of oxidative stress injury, RAS activity and podocyte loss after patients with diabetic nephropathy received keto acid combined with low protein diet. Methods:A total of 106 cases of patients with diabetic nephropathy who received hospital treatment in our hospital from September 2012 to July 2015 were selected as research subjects and randomly divided into observation group and control group according to different treatment, each group with 53 cases. Control group received low protein diet treatment alone, observation group received keto acid combined with low protein diet treatment, and then the degree of oxidative stress injury, RAS activity and podocyte loss of two groups were compared. Results:Serum MDA and AOPP levels of observation group after treatment were lower than those of control group, and levels of SOD and T-AOC were higher than those of control group;PRA, AngⅡand Aldosterone levels of observation group after treatment were lower than those of control group;mRNA expression levels of podocin and synaptopodin in urine sediment of observation group after treatment were lower than those of control group. Conclusion:Keto acid combined with low protein diet treatment for patients with diabetic nephropathy can reduce the degree of oxidative stress injury and RAS activity, decrease podocyte loss and optimize patients’ condition.

  9. Oxidative stress induced expression of monodehydroascorbate reductase gene in Eleusine coracana.

    Sudan, Jebi; Negi, Bhawana; Arora, Sandeep

    2015-10-01

    Abiotic stresses constitute a serious threats to the world food security as they cause significant economic losses in terms of reduction in crop productivity and also greatly limit the geographical locations where crops can be grown. Exposure to abiotic stress causes over-production of reactive oxygen species, leading to oxidative stress in plants. Induction of oxidative stress is primarily responsible for a variety of detrimental changes in the cellular physiology. However, plants have evolved intricate anti-oxidative defence machinery, for their survival under stress. Plant defence strategies for stress tolerance rely on the expression of anti-oxidative genes required for scavenging the toxic reactive oxygen species. Monodehydroascorbate reductase is one of the key anti-oxidant enzyme responsible for scavenging reactive oxygen species. In the present study, efforts have been made to understand the role of monodehydroascorbate reductase in finger millet under different abiotic stresses (drought, salt and UV radiation). The study establishes a differential link between mdar gene expression and enzyme activity under oxidative stress that is validated under different types of imposed stresses. Alteration in correlation between gene expression and enzyme activities under varying magnitude of oxidative stress is elucidated. PMID:26600681

  10. Oxidative stress and antioxidant vitamins in leprosy

    Sangeeta B. Trimbake

    2013-06-01

    Full Text Available Background: Leprosy is a disease of great antiquity and it still continues to be a significant public health problem in few countries including India .Of the various mechanisms that influence the pathogenesis of leprosy, oxidative stress is important which occurs due to derangement in the balance between ROS and natural antioxidants. Hence this study attempted to assess the oxidative stress and antioxidant status in terms of MDA and vitamin E, vitamin C respectively in leprosy. Methods: Hundred untreated leprosy patients (50 PB and 50 MB were studied and compared with 50 healthy controls. Serum Malondialdehyde (MDA and vitamin E, vitamin C was measured by spectrophotometric method. Serum malondialdehyde (MDA was measured as an indicator of lipid peroxidation and antioxidant status was assessed by estimating serum vitamin E and vitamin C levels. Results: Significant rise in serum MDA (P <0.001 in both PB and MB leprosy was seen when compared with controls. The vitamin E level was significantly decreased in both PB and MB leprosy patients as compared to controls. The vitamin C level was significantly decrease (P<0.001 in MB leprosy patients as compared to controls. Conclusions: Elevated MDA levels indicate oxidative stress in leprosy patients, denoting its crucial involvement in the pathogenesis and tissue damage in leprosy. Hence MDA levels can be used to monitor prognosis, treatment and control of leprosy. Decreased vitamin E, C levels in leprosy can be improved by oral vitamin E, C supplementation. [Int J Res Med Sci 2013; 1(3.000: 226-229

  11. Assessment of Eccentric Exercise-Induced Oxidative Stress Using Oxidation-Reduction Potential Markers

    Dimitrios Stagos

    2015-01-01

    Full Text Available The aim of the present study was to investigate the use of static (sORP and capacity ORP (cORP oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress.

  12. Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation

    exposure to Nano-Co, but not to Nano-TiO2. However, neither Nano-Co nor Nano-TiO2 exposure led to any transcriptional change of TIMP-1. The decrease of TIMP-2 after exposure to Nano-Co was also inhibited by pre-treatment with ROS scavengers or inhibitors. Our results also showed that pre-treatment of U937 cells with AP-1 inhibitor, curcumin, or the PTK specific inhibitor, herbimycin A or genistein, prior to exposure to Nano-Co, significantly abolished Nano-Co-induced pro-MMP-2 and-9 activity. Our results suggest that Nano-Co causes an imbalance between the expression and activity of MMPs and their inhibitors which is mediated by the AP-1 and tyrosine kinase pathways due to oxidative stress

  13. The Role of Metallothionein in Oxidative Stress

    Rene Kizek

    2013-03-01

    Full Text Available Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.

  14. Antiviral activity of oxidized polyamines.

    Bachrach, U

    2007-08-01

    Polyamines, oxidized by serum amine oxidase, yield aminoaldehydes and hydrogen peroxide. Acrolein may be formed from the aminoaldehydes by a spontaneous beta-elimination process. These oxidation products "oxidized polyamines" inhibit bacterial growth and exhibit anticancer activity. The antimicrobial activity of oxidized polyamines is not limited to bacteria; and the inactivation of bacterial viruses, plant viruses and animal viruses, was also reported. Bacteriophages of the T-odd series are permeable and were inactivated by oxidized polyamines. The inactive phages absorb to their bacterial host and injected their DNA, which formed a stable inactive complex with the aminoaldehydes. Aminoaldehydes, synthesized chemically, also inactivated viruses. The growth of the plant viruses: Tobacco mosaic virus, Potato virus X and Alfalfa mosaic virus was also inhibited by oxidized polyamines. The animal viruses, which were inactivated by oxidized polyamines included Myxoviruses (influenza and Newcastle disease viruses), West Nile, vaccinia and Sindbis viruses. These findings may have practical implications. PMID:17429570

  15. Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study

    Ali Akal; Turgay Ulas; Tugba Goncu; Mehmet Fatih Adibelli; Sezen Kocarslan; Muhammet Emin Guldur; Muslum Guler; Ufuk Ozkan; Mehmet Dusunur; Tuncer Demir

    2014-01-01

    Purpose: The present experimental study aimed to investigate the effects of intracameral trypan blue (TB) on oxidative stress parameters and apoptosis in corneal tissue. Methods: Thirty rats were randomly assigned to three groups of 10 rats each: the sham group (Group 1); control group (Group 2); and treatment group (Group 3). The control group was administered 0.01 cc of balanced salt solution. The treatment group was administered 0.006 mg/0.01 cc of TB. The total antioxidant status (TAS) an...

  16. L-cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, oxidative stress and inhibits NFkB activation in the livers of Zucker diabetic rats

    Jain, Sushil K.; Velusamy, Thirunavukkarasu; Croad, Jennifer L.; Rains, Justin L.; Bull, Rebeca

    2009-01-01

    This study examined the hypothesis that L-cysteine supplementation can lower insulin resistance, glycemia, oxidative stress and markers of vascular inflammation in type 2 diabetes using zucker diabetic rats (ZDF) rats as a model. Starting at age of 6 wks, ZDF rats were supplemented orally (daily gavage, 8 wks) with saline-placebo (D) or L-cysteine (LC, 1mg/KgBW) and fed a high calorie diet. 6 weeks age rats without any supplementation were considered baseline (BL) rats. D rats showed elevated...

  17. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Alessandra da Silva Dantas

    2015-02-01

    Full Text Available 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.

  18. Oxidative Stress in Children with Chronic Spontaneous Urticaria

    Fatih Dilek

    2016-01-01

    Full Text Available 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.

  19. The response of Paracoccus sp. SKG to acetonitrile-induced oxidative stress.

    Kirankumar, B; Guruprasad, B Kulkarni; Santoshkumar, M; Anand, S Nayak; Karegoudar, T B

    2013-11-01

    Organic solvents enhance intracellular oxidative stress and induce various physiological responses in bacteria. The study shows the morphological changes in Paracoccus sp. SKG when exposed to higher concentrations of acetonitrile, which alter the composition of the membrane fatty acid that accompanies the increase in K(+) efflux. This enhances the oxidative stress with greater activities of catalase and super oxide dismutase (SOD). The increased oxidative stress results in the generation of free radicals, which was confirmed by electron paramagnetic resonance (EPR) studies. The free radical scavenging activities were measured by ABTS and DPPH to understand the non-enzymatic defensive system during oxidative stress. The studies demonstrate the increase in free radicals in association with enzymatic and non-enzymatic defense systems under solvent stress. PMID:24092001

  20. Stress hormones and physical activity

    Editorial Office

    1991-07-01

    Full Text Available Hormone secretion during physical activity of specific duration and intensity is part of the stress response. In a study to investigate the secretion of ß-endorphin, leucine enkephalin and other recognised stress hormones during physical exercise, blood samples were taken from fourteen (14 healthy, male athletes who competed in a 21 km roadrace. Blood samples were collected before and after completion of the race. This study shows that ß-endorphin/ß-lipotropin, leucine enkephalin, prolactin, and melatonin may be classified as stress hormones in physical activity of duration 80 to 120 minutes and intensity exceeding 75%-V0₂max. Widespread intra-individual variation in serum cortisol concentrations prevent definite conclusion. The un­expected increase in serum testosterone levels warrants further research.

  1. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress

    BernardGENY; MichelKINDO; LaurentMONASSIER; FabriceFAVRET

    2012-01-01

    Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced left ventricular hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure...

  2. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

    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

  3. Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation.

    Mossakowski, Agata A; Pohlan, Julian; Bremer, Daniel; Lindquist, Randall; Millward, Jason M; Bock, Markus; Pollok, Karolin; Mothes, Ronja; Viohl, Leonard; Radbruch, Moritz; Gerhard, Jenny; Bellmann-Strobl, Judith; Behrens, Janina; Infante-Duarte, Carmen; Mähler, Anja; Boschmann, Michael; Rinnenthal, Jan Leo; Füchtemeier, Martina; Herz, Josephine; Pache, Florence C; Bardua, Markus; Priller, Josef; Hauser, Anja E; Paul, Friedemann; Niesner, Raluca; Radbruch, Helena

    2015-12-01

    The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation. PMID:26521072

  4. Salt stress induced lipid accumulation in heterotrophic culture cells of Chlorella protothecoides: Mechanisms based on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration.

    Wang, Tao; Ge, Haiyan; Liu, Tingting; Tian, Xiwei; Wang, Zejian; Guo, Meijin; Chu, Ju; Zhuang, Yingping

    2016-06-20

    Salt stress as an effective stress factor that could improve the lipid content and lipid yield of glucose in the heterotrophic culture cells of Chlorella protothecoides was demonstrated in this study. The highest lipid content of 41.2% and lipid yield of 185.8mg/g were obtained when C. protothecoides was stressed under 30g/L NaCl condition at its late logarithmic growth phase. Moreover, the effects of salt and osmotic stress on lipid accumulation were comparatively analyzed, and it was found that the effects of NaCl and KCl stress had no significant differences at the same osmolarity level of 1150mOsm/kg with lipid contents of 41.7 and 40.8% as well as lipid yields of 192.9 and 186.8mg/g, respectively, whereas these results were obviously higher than those obtained under the iso-osmotic glycerol and sorbitol stresses. Furthermore, basing on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration, the superior performance of salt stress driving lipid over-synthesis was probably ascribed to the more ROS production as a result of additional ion effect besides the osmotic effect, subsequently mediating the alteration from carbohydrate storage to lipid accumulation in signal transduction process of C. protothecoides. PMID:27085889

  5. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis.

    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

  6. Oxidative Stress after Surgery on the Immature Heart

    Daniel Fudulu

    2016-01-01

    Full Text Available 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.

  7. Excessive Selenium Supplementation Induced Oxidative Stress and Endoplasmic Reticulum Stress in Chicken Spleen.

    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

  8. Inducible nitric oxide synthase inhibition attenuates physical stress-induced lung hyper-responsiveness and oxidative stress in animals with lung inflammation.

    Marques, Ricardo Henrique; Reis, Fabiana G; Starling, Claudia M; Cabido, Claudia; de Almeida-Reis, Rafael; Dohlnikoff, Marisa; Prado, Carla M; Leick, Edna A; Martins, Mílton A; Tibério, Iolanda F L C

    2012-01-01

    Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2α density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2α density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. PMID:22262048

  9. Oxidative stress and mechanisms of ochronosis in alkaptonuria.

    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

  10. Exogenous Nitric Oxide Enhances Root Activity, Decreases H2O2 Accumulation by Increasing Activities of CAT and GR in Root of Potato cv. Desiree under Water-stress

    Xue-Qin He

    2013-02-01

    Full Text Available We studied water content, H2O2 content, antioxidant enzymes activities of different organs and root activity in potato cv. Desiree pretreated with NO under water-stress. It was found that the bound water content in root and root activity was significantly increased by treating NO before water-stress. Pretreatment with NO decreased the H2O2 content and raised activities of CAT and GR significantly in roots under water-stress. The results suggested that NO might enhance the resistance to water-stress in potato.

  11. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    Gulay Hacioglu

    2016-04-01

    Full Text Available Objective(s: Exposing to stress may be associated with increased production of reactive oxygen species (ROS. Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT and superoxide dismutase (SOD enzymes, and the amount of malondialdehyde (MDA were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

  12. Biomarkers of oxidant stress, insulin sensitivity and endothelial activation in rheumatoid arthritis: a cross-sectional study of their association with accelerated atherosclerosis

    Walker Michael G

    2009-05-01

    Full Text Available Abstract Background Women with rheumatoid arthritis (RA have increased morbidity and mortality due to coronary heart disease. Chronic systemic inflammation is known to accelerate atherosclerosis and increase arterial stiffness in patients, but other mechanisms may also be involved. Biomarkers of oxidant stress, inflammation, insulinaemia and endothelial dysfunction were measured in blood and urine from 46 RA patients and 48 age-matched controls. Plaque formation and intima-medial thickness (IMT were measured using B-mode carotid Doppler scan. Findings The prevalence of plaque was increased (p = 0.042 in RA patients between 50–59 years old compared to the same age group in controls. 8-isoprostane (p = 0.004, C-reactive protein (p Conclusion The burden of atherosclerosis is particularly increased in middle-aged women with RA. Patients with RA have increased levels of oxidant stress, inflammation, insulin and soluble adhesion molecules. As the association between classical risk factors was much weaker in RA patients compared to controls, these additional factors may be more important in the accelerated development of atheroma in RA.

  13. Effects of Physalis peruviana fruit extract on stress oxidative parameters in streptozotocin-diabetic rats

    Mora, Ángela C.; Aragón, Diana M.; Ospina, Luis F.

    2010-01-01

    Diabetes mellitus is a metabolic disease associated to oxidative stress. In this work, the hypoglycaemic and antioxidant effect of an extract of Physalis peruviana fruits in an experimental diabetes model was evaluated. The diabetes was induced in Wistar rats by a single administration of streptozotocin. The oxidative stress markers evaluated were lipid peroxidation, protein oxidation, ferric reducing ability of plasma (FRAP) and the superoxide dismutase and catalase activities in pancreas, l...

  14. Oxidative stress action in cellular aging

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  15. Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer

    Brown, Nicholas S; Bicknell, Roy

    2001-01-01

    Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the possible impact of oxidative stress on the clinical outcome of breast carcinoma.

  16. Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer

    Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the possible impact of oxidative stress on the clinical outcome of breast carcinoma

  17. Oxidative Stress Tolerance by Calcium and Histidine in Two Tomato Cultivars Under Nickel Stress

    Mozafari H.

    2014-05-01

    Full Text Available We investigated calcium (Ca and L-histidine (His interaction on nickel (Ni-induced oxidative stress tolerance in two tomato (Solanum lycopersicum Mill. cultivars including Cal-J N3 and Petoearly CH. CaCl2 (0 and 300 µM and L-histidine (0 and 300 µM effects on the oxidative responses in these cultivars cultured were compared in the hydroponic media under Ni stress (NiSO4; 0,150 and 300 µM. The activities of antioxidative enzymes including catalase (CAT, guaiacol peroxidase (GPX, ascorbate peroxidase (APX, superoxide dismutase (SOD and total content of proteins, malondialdehyde (MDA, other aldehydes, H2O2, Ca2+, Ni2+, ascorbate (ASC, dehydroascorbate (DHA and electrolytes leakage (EL were determined. The obtained results indicated that the application of Ca and His generally reduced oxidative markers such as the contents of EL, H2O2, MDA and activity of CAT as well as the Ni2+content of root and shoot organs under nickel toxicity, while application of Ni treatment without Ca+His increased these oxidative parameters and accumulation of Ni2+, compared to the control. Applying Ni without Ca and His has resulted in reduction of GPX, APX and SOD activities as well as concentrations of root and shoot Ca2+and ASC in the two mentioned cultivars. Application of Ca and His lead to the elevated contents of Ca2+ and ASC, increased activities of GPX, APX and SOD as well as inhibition of Ni2+ accumulation differently in both cultivars. Ca and His also alleviated the adverse effects of Ni stress on the selected investigated parameters especially in Petoearly CH cultivar. Thus, interaction of Ca and His appeared to improve adaptive responses to Ni stress leading to decreasing Ni-induced oxidative stress in the tomato plants. Therefore, our results suggest that Ca+His alleviated nickel-induced oxidative stress by uptake and inhibition of translocation of Ni2+ plus Ni chelating mechanism improvement in the tomato cultivars.

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

    María Muriach

    2014-01-01

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

  19. EFFECTS OF PROLONGED EXERCISE ON OXIDATIVE STRESS AND ANTIOXIDANT DEFENSE IN ENDURANCE HORSE

    Susanna Kinnunen

    2005-12-01

    Full Text Available Increased oxidative stress during prolonged endurance exercise may end up with muscle damage, fatigue and decreased physical performance. We have recently shown that acute exercise at moderate intensity induced lipid peroxidation, protein oxidation and oxygen radical absorbance capacity (ORAC in trained trotters. The aim of this study was to measure the changes in oxidative stress and antioxidant defense following an 80-km ride in the blood of endurance horses. Blood samples were collected before and immediately after the ride. Unlike to our previous studies performed on trotters, in endurance horses there were no measurable changes in antioxidants or oxidative stress marker lipid hydroperoxides (LPO after prolonged exercise. ORAC, vitamin E and lipid hydroperoxide (LPO concentration or glutathione related enzyme activities were not altered due to the 80-km ride. However, the base line levels of oxidative stress marker were higher in endurance horses compared to trotters. A positive correlation between the pre-ride LPO concentration and erythrocyte glutathione peroxidase (GPx activity after the ride was observed, which may indicate a protective response of glutathione peroxidase against exercise-induced oxidative stress. Our results suggest that endurance horses have higher oxidative stress levels compared to trotters and a single 80-km ride probably did not suffice to induce oxidative stress and to activate antioxidant defense mechanisms.

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

    Zimmer, C; Spencer, K A

    2015-01-01

    This study was funded by a BBSRC David Phillips Research Fellowship to K.A. Spencer. 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 underly...

  1. Nitric Oxide Reduces Hydrogen Peroxide Accumulation Involved in Water Stress-induced Subcellular Anti-oxidant Defense in Maize Plants

    Jianrong Sang; Mingyi Jiang; Fan Lin; Shucheng Xu; Aying Zhang; Mingpu Tan

    2008-01-01

    Nitric oxide (NO) Is a bioactive molecule involved in many biological events, and has been reported as pro-oxidant as well as anti-oxidant in plants. In the present study, the sources of NO production under water stress, the role of NO in water stress-induced hydrogen peroxide (H2O2) accumulation and subcellular activities of anti-oxidant enzymes in leaves of maize (Zea mays L.) plants were investigated. Water stress Induced defense increases in the generation of NO In maize mesphyll cells and the activity of nitric oxide synthase (NOS) in the cytosolic and microsomal fractions of maize leaves. Water stress-induced defense increases in the production of NO were blocked by pretreatments with Inhibitors of NOS and nitrate reductase (NR), suggesting that NO is produced from NOS and NR in leaves of maize plants exposed to water stress. Water stress also induced increases in the activities of the chloroplastic and cytosolic anti-oxidant enzymes superoxide dismutase (SOD), ascorbate peroxidass (APX), and glutathione reductase (GR), and the increases in the activities of anti-oxidant enzymes were reduced by pretreatments with inhibitors of NOS and NR. Exogenous NO increases the activities of water stress-induced subcellular anti-oxidant enzymes, which decreases accumulation of H2O2. Our results suggest that NOS and NR are involved in water strese-induced NO production and NOS is the major source of NO. The potential ability of NO to scavenge H2O2 is, at least in part, due to the induction of a subcellular anti-oxidant defense.

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

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

    2015-06-01

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

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

    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

  4. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  5. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  6. Dietary grape poliphenols modulate oxidative stress in ageing rabbits

    R. Della Loggia; G. Altimer; S. Sgorlon; Stefanon, B.; G. Stradaioli

    2010-01-01

    The imbalance between reactive oxygen species (ROS) and antioxidant capacity of the organism leads to a condition of oxidative stress (Urso and Clarkson, 2003). Studies in humans and laboratory animals have reported that oxidative stress is related to some common degenerative diseases, such as cancer and cardiovascular pathologies (Pellegrini et al., 2003). Oxidative stress has also been identified as causative agent for diseases, such as decline of immune function and atherosclerosis (Meydan...

  7. Oxidative Stress in Diabetes: Implications for Vascular and Other Complications

    Dario Pitocco; Manfredi Tesauro; Rizzi Alessandro; Giovanni Ghirlanda; Carmine Cardillo

    2013-01-01

    In recent decades, oxidative stress has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence shows that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on these studies, an emerging concept is that oxidative stress is the “final common pathway” through which the risk factor...

  8. Fatty acids and oxidative stress in psychiatric disorders

    Tonello Lucio; Cocchi Massimo; Tsaluchidu Sofia; Puri Basant K

    2008-01-01

    Abstract Background The aim of this study was to determine whether there is published evidence for increased oxidative stress in neuropsychiatric disorders. Methods A PubMed search was carried out using the MeSH search term 'oxidative stress' in conjunction with each of the DSM-IV-TR diagnostic categories of the American Psychiatric Association in order to identify potential studies. Results There was published evidence of increased oxidative stress in the following DSM-IV-TR diagnostic categ...

  9. The Role of Flavonoids on Oxidative Stress in Epilepsy

    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 epil...

  10. Oxidative stress modulates PPAR gamma in vascular endothelial cells.

    Blanquicett, Carmelo; Kang, Bum-Yong; Ritzenthaler, Jeffrey D; Jones, Dean P; Hart, C Michael

    2010-06-15

    The peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in vascular regulation. However, the impact of oxidative stress on PPAR gamma expression and activity has not been clearly defined. Human umbilical vein endothelial cells (HUVECs) were exposed to graded concentrations of H(2)O(2) for 0.5-72h, or bovine aortic endothelial cells (BAECs) were exposed to alterations in extracellular thiol/disulfide redox potential (E(h)) of the cysteine/cystine couple. Within 2h, H(2)O(2) reduced HUVEC PPAR gamma mRNA and activity and reduced the expression of two PPAR gamma-regulated genes without altering PPAR gamma protein levels. After 4h H(2)O(2) exposure, mRNA levels remained reduced, whereas PPAR gamma activity returned to control levels. PPAR gamma mRNA levels remained depressed for up to 72 h after exposure to H(2)O(2), without any change in PPAR gamma activity. Catalase prevented H(2)O(2)-induced reductions in PPAR gamma mRNA and activity. H(2)O(2) (1) reduced luciferase expression in HUVECs transiently transfected with a human PPAR gamma promoter reporter, (2) failed to alter PPAR gamma mRNA half-life, and (3) transiently increased expression and activity of c-Fos and phospho-c-Jun. Treatment with the AP1 inhibitor curcumin prevented H(2)O(2)-mediated reductions in PPAR gamma expression. In addition, medium having an oxidized E(h) reduced BAEC PPAR gamma mRNA and activity. These findings demonstrate that oxidative stress, potentially through activation of inhibitory redox-regulated transcription factors, attenuates PPAR gamma expression and activity in vascular endothelial cells through suppression of PPAR gamma transcription. PMID:20302927

  11. Oxidative stress and antibacterial properties of a graphene oxide-cystamine nanohybrid

    Nanda SS

    2015-01-01

    Full Text Available Sitansu Sekhar Nanda,1 Seong Soo A An,1 Dong Kee Yi2,3 1Department of Bionanotechnology, Gachon University, Seongnam, South Korea; 2Department of Chemistry, 3Department of Environmental Engineering, Myongji University, Yongin, South Korea Abstract: Oxidative stress can damage proteins, DNA, and lipids, and is involved in the progression of many diseases. Damage to infected cells caused by oxidative stress is related to increased levels of reactive oxygen species, including hydrogen peroxide. During oxidative stress, hydrogen peroxide levels are often increased and catalase level decreased inside cells. This can lead to the death of skin and other cells. Hydrophobic low molecular weight compounds are useful in treating hemorrhagic conditions of the skin. To this end, cystamine has been successfully conjugated with graphene oxide (GO as a drug carrier. The current study used the microdilution method to determine the minimum inhibitory concentrations of cystamine-conjugated GO against four types of pathogenic bacteria. Minimum inhibitory concentrations values were 1 µg/mL against Escherichia coli and Salmonella typhimurium, 6 µg/mL against Enterococcus faecalis, and 4 µg/mL against Bacillus subtilis. Toxicity of the conjugate against squamous cell carcinoma 7 cells was minimal at low concentrations, but increased in a dose-dependent manner. These results demonstrated that our protocol produced a cystamine-conjugated GO with low cytotoxicity, but strong reactive oxygen species effects and high antibacterial activity. This nanohybrid may be useful in the treatment of dermatological disorders. Moreover, this class of nanohybrid may have other biomedical applications due to their low cytotoxicity and high antibacterial activity. Keywords: graphene, oxide, cystamine conjugate, reactive oxygen species, antibacterial, oxidative stress

  12. Postprandial Oxidative Stress in Exercise Trained and Sedentary Cigarette Smokers

    2009-02-01

    Full Text Available Cigarette smokers experience an exaggerated triglyceride (TAG and oxidative stress response to high fat feeding. Exercise training may serve to attenuate the rise in these variables, by improving TAG clearance and antioxidant defense. We compared blood TAG, antioxidant capacity, and oxidative stress biomarkers in exercise trained (>2 hrs per wk and untrained smokers matched for age, in response to a high fat test meal. We report here that low volume exercise training can attenuate postprandial lipid peroxidation, but has little impact on blood TAG and other markers of oxidative stress. Higher volumes of exercise may be needed to allow for clinically meaningful adaptations in postprandial lipemia and oxidative stress.

  13. Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice

    Highlights: ► 1,2-Dimethylhydrazine (DMH) toxicity was driven by oxidative stress. ► Arginase activity correlated to aberrant crypt foci (ACF). ► Curcumin diet restored redox status and induced apoptosis of dysplastic ACF. ► Curcumin reduced arginase activity and up regulated TGF-β1 and HES-1 transcripts. -- Abstract: This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin.

  14. Influence of Turmeric Rhizome Powder diets on decreasing oxidative stress caused by heat stress inbroiler model

    Seyyed Javad Hosseini-Vashan

    2012-08-01

    Full Text Available Background and Aim: Production of reactive oxygen species (ROS increases during oxidative stress conditions, which stimulates diabetes, inflammatory reactions, rheumatism and anemia. Some antioxidant properties of turmeric rhizome powder (TRP were revealed by previous researchers. The present study was conducted to evaluate the influence of TRP on decreasing effects of oxidative stress resulted from heat stress in broiler chickens.   Materials and Methods: In this experimental study, two-hundred-sixty-four 1-day-old broilers were divided into 3 dietary treatments. The dietary treatments involved 0(control, 0.4 and 0.8% turmeric rhizome powder (cases. In order to create oxidative stress, the ambient temperature was daily raised from 21 to 33oc for 5 hours (11a.m-4p.m throughout the 28th-42nd days. Blood lipids, Glutathione peroxidase (GPx ,superoxide dismutase (SOD, and Tiobarbituric acid reaction score (TBARS were determined at the end of the experiment.   Results: The results revealed that total cholesterol and triglyceride were not affected. The 0.4 TRP diet decreased blood LDL (46.7±3.01 compared to basal group (52.0±2.17. HDL increased in broilers fed 0.8% TRP (74.0 ± 3.87 compared to chickens with basal diet (63.7± 2.98. Enzyme activity of GPx improved in broilers fed TRP diets (225.9± 11.52 as compared to chickens with basal diet(183.1± 8.52 however, the TRP diet did not affect enzyme activity of SOD (P > 0.05. The TBARS index decreased in broilers fed TRP (0.76 ± 0.0052 in basal vs.0.49 ± 0.0032 in 0.8% TRP.   Conclusion: The major bioactive component of TRP is Curcumin that can improve the antioxidant properties under oxidative stress and high ambient temperature.

  15. Aldehyde Dehydrogenases in Cellular Responses to Oxidative/electrophilic Stress

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

    2012-01-01

    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/electrophili...

  16. Melanocytes as Instigators and Victims of Oxidative Stress

    Denat, L.; Kadekaro, A.L.; Marrot, L; Leachman, S; Abdel-Malek, Z.A.

    2014-01-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress due to the pro-oxidant state generated during melanin synthesis, and to intrinsic antioxidant defences 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 countera...

  17. Oxidative Stress and Anxiety: Relationship and Cellular Pathways

    Jaouad Bouayed; Hassan Rammal; Rachid Soulimani

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  18. Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes.

    Kerns, Michelle L; Hakim, Jill M C; Lu, Rosemary G; Guo, Yajuan; Berroth, Andreas; Kaspar, Roger L; Coulombe, Pierre A

    2016-06-01

    Palmoplantar keratoderma (PPK) are debilitating lesions that arise in individuals with pachyonychia congenita (PC) and feature upregulation of danger-associated molecular patterns and skin barrier regulators. The defining features of PC-associated PPK are reproduced in mice null for keratin 16 (Krt16), which is commonly mutated in PC patients. Here, we have shown that PPK onset is preceded by oxidative stress in footpad skin of Krt16-/- mice and correlates with an inability of keratinocytes to sustain nuclear factor erythroid-derived 2 related factor 2-dependent (NRF2-dependent) synthesis of the cellular antioxidant glutathione (GSH). Additionally, examination of plantar skin biopsies from individuals with PC confirmed the presence of high levels of hypophosphorylated NRF2 in lesional tissue. In Krt16-/- mice, genetic ablation of Nrf2 worsened spontaneous skin lesions and accelerated PPK development in footpad skin. Hypoactivity of NRF2 in Krt16-/- footpad skin correlated with decreased levels or activity of upstream NRF2 activators, including PKCδ, receptor for activated C kinase 1 (RACK1), and p21. Topical application of the NRF2 activator sulforaphane to the footpad of Krt16-/- mice prevented the development of PPK and normalized redox balance via regeneration of GSH from existing cellular pools. Together, these findings point to oxidative stress and dysfunctional NRF2 as contributors to PPK pathogenesis, identify K16 as a regulator of NRF2 activation, and suggest that pharmacological activation of NRF2 should be further explored for PC treatment. PMID:27183391

  19. Oxidative stress and signal transduction pathways in alcoholic liver disease.

    Zima, Tomás; Kalousová, Marta

    2005-11-01

    Ethanol is linked to several pathologies like alcohol liver injury, neurotoxicity, cardiomyopathy, fetal alcoholic syndrome or cancer. It is generally accepted that oxidative stress plays a central role in their pathogenesis. After chronic and excessive consumption, alcohol may accelerate oxidative mechanisms both directly via increased production of reactive oxygen species and indirectly by impairing protective mechanisms against them. Ethanol, its metabolites arising during its metabolic degradation as well as novel compounds formed via ethanol induced oxidative stress, especially during the action of the ethanol inducible microsomal cytochrome CYP2E1, may apart from direct damage to biological structures affect signal transduction pathways thus modulating and potentiating damage. Alteration of the redox status of cells following chronic ethanol misuse may have profound effects on cellular function and viability and lead to cell death and tissue damage. These changes linked to pathologic processes in the organism, are related to alteration of intracellular signaling pathways associated with protein kinases and transcription factor activation. Mainly mitogen activated protein kinase (MAPK) family, transcription factors-nuclear factor kappaB (NF-kappaB) and activating protein 1 (AP-1) are involved in the deterioration of cells and organs. The response is cell-type specific and depends on the dose of ethanol. Oxido-reduction balance, regulatory disturbances and signal transduction cascades responsible for alcoholic damage have been partially described, nevertheless, further studies are required to allow future novel diagnostic and therapeutical strategies. We are only at the beginning ... PMID:16344594

  20. Reproduction is not costly in terms of oxidative stress.

    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

  1. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress

    Kindo, Michel; Gerelli, Sébastien; Bouitbir, Jamal; Charles, Anne-Laure; Zoll, Joffrey; Hoang Minh, Tam; Monassier, Laurent; Favret, Fabrice; Piquard, François; Geny, Bernard

    2012-01-01

    Objective: Increased mechanical stress and contractility characterizes normal left ventricular (LV) subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced LV hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function...

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

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

    2009-01-01

    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 devel...

  3. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development.

    Aviram, Michael; Rosenblat, Mira

    2004-11-01

    Paraoxonases PON1 and PON3, which are both associated in serum with HDL, protect the serum lipids from