Sample records for gamma-radiation-induced oxidative stress

  1. The combined effect of uranium and gamma radiation on biological responses and oxidative stress induced in Arabidopsis thaliana.

    PubMed

    Vanhoudt, Nathalie; Vandenhove, Hildegarde; Horemans, Nele; Wannijn, Jean; Van Hees, May; Vangronsveld, Jaco; Cuypers, Ann

    2010-11-01

    Uranium never occurs as a single pollutant in the environment, but always in combination with other stressors such as ionizing radiation. As effects induced by multiple contaminants can differ markedly from the effects induced by the individual stressors, this multiple pollution context should not be neglected. In this study, effects on growth, nutrient uptake and oxidative stress induced by the single stressors uranium and gamma radiation are compared with the effects induced by the combination of both stressors. By doing this, we aim to better understand the effects induced by the combined stressors but also to get more insight in stressor-specific response mechanisms. Eighteen-day-old Arabidopsis thaliana seedlings were exposed for 3 days to 10 muM uranium and 3.5 Gy gamma radiation. Gamma radiation interfered with uranium uptake, resulting in decreased uranium concentrations in the roots, but with higher transport to the leaves. This resulted in a better root growth but increased leaf lipid peroxidation. For the other endpoints studied, effects under combined exposure were mostly determined by uranium presence and only limited influenced by gamma presence. Furthermore, an important role is suggested for CAT1/2/3 gene expression under uranium and mixed stressor conditions in the leaves.

  2. Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

    PubMed

    Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

    2015-12-01

    The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions

  3. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong

    2006-04-01

    Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, {alpha}-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, {gamma}-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treatingmore » the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects.« less

  4. ER stress and genomic instability induced by gamma radiation in mice primary cultured glial cells.

    PubMed

    Chatterjee, Jit; Nairy, Rajesha K; Langhnoja, Jaldeep; Tripathi, Ashutosh; Patil, Rajashekhar K; Pillai, Prakash P; Mustak, Mohammed S

    2018-06-01

    Ionizing radiation induces various pathophysiological conditions by altering central nervous system (CNS) homeostasis, leading to neurodegenerative diseases. However, the potential effect of ionizing radiation response on cellular physiology in glial cells is unclear. In the present study, micronucleus test, comet assay, and RT-PCR were performed to investigate the potential effect of gamma radiation in cultured oligodendrocytes and astrocytes with respect to genomic instability, Endoplasmic Reticulum (ER) stress, and inflammation. Further, we studied the effect of alteration in ER stress specific gene expression in cortex post whole body radiation in mice. Results showed that exposure of gamma radiation of 2Gy in-vitro cultured astrocytes and oligodendrocytes and 7Gy in-vivo induced ER stress and Inflammation along with profuse DNA damage and Chromosomal abnormality. Additionally, we observed downregulation of myelin basic protein levels in cultured oligodendrocytes exposed to radiation. The present data suggests that ER stress and pro inflammatory cytokines serve as the major players in inducing glial cell dysfunction post gamma irradiation along with induction of genomic instability. Taken together, these results indicate that ER stress, DNA damage, and inflammatory pathways may be critical events leading to glial cell dysfunction and subsequent cell death following exposure to ionizing radiation.

  5. Exposure to Heavy Ion Radiation Induces Persistent Oxidative Stress in Mouse Intestine

    PubMed Central

    Datta, Kamal; Suman, Shubhankar; Kallakury, Bhaskar V. S.; Fornace, Albert J.

    2012-01-01

    Ionizing radiation-induced oxidative stress is attributed to generation of reactive oxygen species (ROS) due to radiolysis of water molecules and is short lived. Persistent oxidative stress has also been observed after radiation exposure and is implicated in the late effects of radiation. The goal of this study was to determine if long-term oxidative stress in freshly isolated mouse intestinal epithelial cells (IEC) is dependent on radiation quality at a dose relevant to fractionated radiotherapy. Mice (C57BL/6J; 6 to 8 weeks; female) were irradiated with 2 Gy of γ-rays, a low-linear energy transfer (LET) radiation, and intestinal tissues and IEC were collected 1 year after radiation exposure. Intracellular ROS, mitochondrial function, and antioxidant activity in IEC were studied by flow cytometry and biochemical assays. Oxidative DNA damage, cell death, and mitogenic activity in IEC were assessed by immunohistochemistry. Effects of γ radiation were compared to 56Fe radiation (iso-toxic dose: 1.6 Gy; energy: 1000 MeV/nucleon; LET: 148 keV/µm), we used as representative of high-LET radiation, since it's one of the important sources of high Z and high energy (HZE) radiation in cosmic rays. Radiation quality affected the level of persistent oxidative stress with higher elevation of intracellular ROS and mitochondrial superoxide in high-LET 56Fe radiation compared to unirradiated controls and γ radiation. NADPH oxidase activity, mitochondrial membrane damage, and loss of mitochondrial membrane potential were greater in 56Fe-irradiated mice. Compared to γ radiation oxidative DNA damage was higher, cell death ratio was unchanged, and mitotic activity was increased after 56Fe radiation. Taken together our results indicate that long-term functional dysregulation of mitochondria and increased NADPH oxidase activity are major contributing factors towards heavy ion radiation-induced persistent oxidative stress in IEC with potential for neoplastic transformation. PMID

  6. Role of oxidative stress in a rat model of radiation-induced erectile dysfunction.

    PubMed

    Kimura, Masaki; Rabbani, Zahid N; Zodda, Andrew R; Yan, Hui; Jackson, Isabel L; Polascik, Thomas J; Donatucci, Craig F; Moul, Judd W; Vujaskovic, Zeljko; Koontz, Bridget F

    2012-06-01

    Chronic oxidative stress is one of the major factors playing an important role in radiation-induced normal tissue injury. However, the role of oxidative stress in radiation-induced erectile dysfunction (ED) has not been fully investigated. Aims.  To investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED. Fifty-four young adult male rats (10-12 weeks of age) were divided into age-matched sham radiotherapy (RT) and RT groups. Irradiated animals received prostate-confined radiation in a single 20 Gy fraction. Intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation were conducted at 2, 4, and 9 weeks following RT. The protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox4 and gp91(phox)), markers of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), lipid peroxidation (4-hydroxynonenal [4HNE]), and inflammatory response including inducible nitric oxide synthase, macrophage activation (ED-1), and nitrotyrosine, and endogenous antioxidant defense by nuclear factor erythroid 2-related factor (Nrf2) were evaluated in irradiated prostate tissue and corpora cavernosa (CC). In addition, we investigated the relationships between results of ICP/mean arterial pressure (MAP) ratios and expression level of oxidative stress markers. In the RT group, hemodynamic functional studies demonstrated a significant time-dependent decrease in ICP. Increased expression of Nox4, gp91(phox), 8-OHdG, and 4HNE were observed in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased. There was a trend for increased Nrf2 after 4 weeks. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers. NADPH oxidase activation and chronic oxidative stress were observed in irradiated prostate tissue and CC, which correlated with lower ICP/MAP ratio. Persistent inflammatory responses were also

  7. Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

    PubMed

    Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

    2017-01-01

    The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

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

    PubMed Central

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

    2013-01-01

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

  9. Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.

    PubMed

    Martinez, R M; Fattori, V; Saito, P; Melo, C B P; Borghi, S M; Pinto, I C; Bussmann, A J C; Baracat, M M; Georgetti, S R; Verri, W A; Casagrande, R

    2018-04-27

    Lipoxin A4 (LXA 4 ) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA 4 has effect on ultraviolet (UV) radiation-induced skin inflammation. To investigate the effects of systemic administration with LXA 4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm 2 ). Pretreatment with LXA 4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA 4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA 4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP + cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA 4 increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA 4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA 4 also reduced UV radiation-induced gp91 phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. LXA 4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2. Copyright © 2018. Published by Elsevier B.V.

  10. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

    PubMed

    Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hasan, Hesham F

    2016-09-01

    Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

    PubMed Central

    Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

    2012-01-01

    Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

  12. Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.

    PubMed

    Adaramoye, O A; Popoola, Bosede O; Farombi, E O

    2010-09-01

    Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.

  13. Secondary metabolite perturbations in Phaseolus vulgaris leaves due to gamma radiation.

    PubMed

    Ramabulana, T; Mavunda, R D; Steenkamp, P A; Piater, L A; Dubery, I A; Madala, N E

    2015-12-01

    Oxidative stress is a condition in which the balance between the production and elimination of reactive oxygen species (ROS) is disturbed. However, plants have developed a very sophisticated mechanism to mitigate the effect of ROS by constantly adjusting the concentration thereof to acceptable levels. Electromagnetic radiation is one of the factors which results in oxidative stress. In the current study, ionizing gamma radiation generated from a Cobalt-60 source was used to induce oxidative stress in Phaseolus vulgaris seedlings. Plants were irradiated with several radiation doses, with 2 kGy found to be the optimal, non-lethal dose. Metabolite distribution patterns from irradiated and non-irradiated plants were analyzed using UHPLC-qTOF-MS and multivariate data models such as principal component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA). Metabolites such as hydroxycinnamic phenolic acids, flavonoids, terpenes, and a novel chalcone were found to be perturbed in P. vulgaris seedlings treated with the aforementioned conditions. The results suggest that there is a compensatory link between constitutive protectants and inducible responses to injury as well as defense against oxidative stress induced by ionizing radiation. The current study is also the first to illustrate the power of a metabolomics approach to decipher the effect of gamma radiation on crop plants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte.

    PubMed

    Singha, Indrani; Das, Subir Kumar

    2015-11-01

    Ionizing radiation (IR) causes oxidative stress through overwhelming generation of reactive oxygen species (ROS) in the living cells leading the oxidative damage further to biomolecules. Grapevine (Vitis vinifera L.) posses several bioactive phytochemicals and is the richest source of antioxidants. In this study, we investigated V. vinifera for its phytochemical content, enzymes profile and, ROS- and oxidant-scavenging activities. We have also studied the fruit extract of four different grapevine viz., Thompson seedless, Flame seedless, Kishmish chorni and Red globe for their radioprotective actions in human lymphocytes. The activities of ascorbic acid oxidase and catalase significantly (P < 0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. Pretreatment with grape extracts attenuated the oxidative stress induced by 4 Gy γ-radiation in human lymphocytes in vitro. Further, γ-radiation-induced increase in caspase 3/7 activity was significantly attenuated by grape extracts. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars.

  15. Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats.

    PubMed

    Aziz, Maha M; Eid, Nihad I; Nada, Ahmed S; Amin, Nour El-Din; Ain-Shoka, Afaf A

    2018-03-01

    The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and glucose while decreasing albumin and protein levels. There was a noticeable increase in kidney content of GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was observed. Treatment with Sp significantly reversed the changes induced by CSA and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while increasing SOD activity. Histopathological examination further confirmed Sp protective efficacy. Moreover, kidney caspase-3 expression that was triggered by CSA and/or gamma radiation was decreased. In conclusion, spirulina can be regarded as a promising renoprotective natural agent against renal injury induced by CSA and/or gamma radiation.

  16. Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus.

    PubMed

    Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Leung, Kenneth Mei Yee; Lee, Yong Sung; Lee, Jae-Seong

    2014-07-01

    Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase

  17. Protective effect of rare earth against oxidative stress under ultraviolet-B radiation.

    PubMed

    Wang, Lihong; Huang, Xiaohua; Zhou, Qing

    2009-04-01

    The effects of lanthanum (III) (La(III)) in protecting soybean leaves against oxidative stress induced by ultraviolet-B (UV-B) radiation were investigated. The increase in contents of hydrogen peroxide (H(2)O(2)) and superoxide (O2*-) due to UV-B radiation suggested oxidative stress. The increase in the content of malondialdehyde (MDA) and the decrease in the index of unsaturated fatty acid (IUFA) indicated oxidative damage on cell membrane induced by UV-B radiation. La(III) partially reversed UV-B-radiation-induced damage of plant growth. The reduction in the contents of H(2)O(2), O2*-, and MDA and increase in the content of IUFA, compared with UV-B treatment, also indicated that La(III) alleviated the oxidative damage induced by UV-B radiation. The increase in the activities of superoxide dismutase and peroxidase and the contents of ascorbate, carotenoids, and flavonoids were observed in soybean leaves with La(III) + UV-B treatment, compared with UV-B treatment. Our data suggested that La(III) could protect soybean plants from UV-B-radiation-induced oxidative stress by reacting with reactive oxygen species directly or by improving the defense system of plants.

  18. Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight.

    PubMed

    Schoenfeld, Michael P; Ansari, Rafat R; Zakrajsek, June F; Billiar, Timothy R; Toyoda, Yoshiya; Wink, David A; Nakao, Atsunori

    2011-01-01

    Cosmic radiation is known to induce DNA and lipid damage associated with increased oxidative stress and remains a major concern in space travel. Hydrogen, recently discovered as a novel therapeutic medical gas in a variety of biomedical fields, has potent antioxidant and anti-inflammatory activities. It is expected that space mission activities will increase in coming years both in numbers and duration. It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Gamma radiation induced oxidation and tocopherols decrease in in-shell, peeled and blanched peanuts.

    PubMed

    de Camargo, Adriano Costa; de Souza Vieira, Thais Maria Ferreira; Regitano-D'Arce, Marisa Aparecida Bismara; de Alencar, Severino Matias; Calori-Domingues, Maria Antonia; Canniatti-Brazaca, Solange Guidolin

    2012-01-01

    In-shell, peeled and blanched peanut samples were characterized in relation to proximate composition and fatty acid profile. No difference was found in relation to its proximate composition. The three major fatty acids were palmitic acid, oleic acid, and linoleic acid. In order to investigate irradiation and storage effects, peanut samples were submitted to doses of 0.0, 5.0, 7.5 or 10.0 kGy, stored for six months at room temperature and monitored every three months. Peanuts responded differently to irradiation, particularly with regards to tocopherol contents, primary and secondary oxidation products and oil stability index. Induction periods and tocopherol contents were negatively correlated with irradiation doses and decreased moderately during storage. α-Tocopherol was the most gamma radiation sensitive and peeled samples were the most affected. A positive correlation was found among tocopherol contents and the induction period of the oils extracted from irradiated samples. Gamma radiation and storage time increased oxidation compounds production. If gamma radiation is considered an alternative for industrial scale peanut conservation, in-shell samples are the best feedstock. For the best of our knowledge this is the first article with such results; this way it may be helpful as basis for future studies on gamma radiation of in-shell crops.

  20. Gamma Radiation Induced Oxidation and Tocopherols Decrease in In-Shell, Peeled and Blanched Peanuts

    PubMed Central

    de Camargo, Adriano Costa; de Souza Vieira, Thais Maria Ferreira; Regitano-D’Arce, Marisa Aparecida Bismara; de Alencar, Severino Matias; Calori-Domingues, Maria Antonia; Canniatti-Brazaca, Solange Guidolin

    2012-01-01

    In-shell, peeled and blanched peanut samples were characterized in relation to proximate composition and fatty acid profile. No difference was found in relation to its proximate composition. The three major fatty acids were palmitic acid, oleic acid, and linoleic acid. In order to investigate irradiation and storage effects, peanut samples were submitted to doses of 0.0, 5.0, 7.5 or 10.0 kGy, stored for six months at room temperature and monitored every three months. Peanuts responded differently to irradiation, particularly with regards to tocopherol contents, primary and secondary oxidation products and oil stability index. Induction periods and tocopherol contents were negatively correlated with irradiation doses and decreased moderately during storage. α-Tocopherol was the most gamma radiation sensitive and peeled samples were the most affected. A positive correlation was found among tocopherol contents and the induction period of the oils extracted from irradiated samples. Gamma radiation and storage time increased oxidation compounds production. If gamma radiation is considered an alternative for industrial scale peanut conservation, in-shell samples are the best feedstock. For the best of our knowledge this is the first article with such results; this way it may be helpful as basis for future studies on gamma radiation of in-shell crops. PMID:22489128

  1. Eckol protects V79-4 lung fibroblast cells against gamma-ray radiation-induced apoptosis via the scavenging of reactive oxygen species and inhibiting of the c-Jun NH(2)-terminal kinase pathway.

    PubMed

    Zhang, Rui; Kang, Kyoung Ah; Piao, Mei Jing; Ko, Dong Ok; Wang, Zhi Hong; Lee, In Kyung; Kim, Bum Joon; Jeong, Il Yun; Shin, Taekyun; Park, Jae Woo; Lee, Nam Ho; Hyun, Jin Won

    2008-09-04

    The radioprotective effect of eckol against gamma-ray radiation-induced oxidative stress and its possible protective mechanisms were investigated. Eckol was found to reduce the intracellular reactive oxygen species generated by gamma-ray radiation. Moreover, eckol also protected against radiation-induced cellular DNA damage and membrane lipid peroxidation, which are the main targets of radiation-induced damage. In addition, eckol recovered the cell viability damaged by radiation via the inhibition of apoptosis. Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase 9 and caspase 3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation. In summary, the results suggest that eckol protects cells against the oxidative stress induced by radiation via the reduction of reactive oxygen species and the attenuation of activation in SEK1-JNK-AP-1 pathway.

  2. Royal jelly modulates oxidative stress and tissue injury in gamma irradiated male Wister Albino rats.

    PubMed

    Azab, Khaled Shaaban; Bashandy, Mohamed; Salem, Mahmoud; Ahmed, Osama; Tawfik, Zaki; Helal, Hamed

    2011-06-01

    Royal jelly is a nutritive secretion produced by the worker bees, rich in proteins, carbohydrates, vitamins and minerals. The present study was designed to determine the possible protective effects of royal jelly against radiation induced oxidative stress, hematological, biochemical and histological alterations in male Wister albino rats. Male Wister albino rats were exposed to a fractionated dose of gamma radiation (2 Gy every 3 days up to 8 Gy total doses). Royal jelly was administrated (g/Kg/day) by gavages 14 days before exposure to the 1(st) radiation fraction and the treatment was continued for 15 days after the 1(st) irradiation fraction till the end of the experiment. The rats were sacrificed 3(rd), equivalent to 3rd post 2nd irradiation fraction, and equivalent to 3rd day post last irradiation fraction. In the present study, gamma- irradiation induced hematological, biochemical and histological effects in male Wister albino rats. In royal jelly treated irradiated group, there was a noticeable decrease recorded in thiobarbituric reactive substances concentration when compared to γ-irradiated group. Also, the serum nitric oxide concentration was significantly improved. The administration of royal jelly to irradiated rats according to the current experimental design significantly ameliorates the changes induced in serum lipid profile. Moreover, in royal jelly treated irradiated group, there was a noticeable amelioration recorded in all hematological parameters along the three experimental intervals. The microscopic examination of cardiac muscle of royal jelly treated irradiated rats demonstrated structural amelioration, improved nuclei and normal features of capillaries and veins in endomysium when compared to gamma-irradiated rats. It was suggested that the biochemical, hematological and histological amelioration observed in royal jelly (g/Kg/day) treated irradiated rats might be due to the antioxidant capacity of royal jelly active constituents.

  3. A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

    PubMed Central

    Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

    2017-01-01

    Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

  4. The effects of chronic radiation of gamma ray on protein expression and oxidative stress in Brachypodium distachyon.

    PubMed

    Kim, Dae Yeon; Hong, Min Jeong; Park, Cheong-Sool; Seo, Yong Weon

    2015-05-01

    To compare the effects of gamma-irradiation on biochemical responses and growth, six-week-old Brachypodium plants were chronically exposed to gamma-irradiation for 30 days at various dosages. Growth surveys of Brachypodium plants in response to different dosages of gamma-irradiation were conducted to compare physiological changes between irradiated and non-irradiated plants. Photosynthetic pigments, soluble sugar content, activities of antioxidant enzymes, and malonaldehyde (MDA) induced by reactive oxygen species (ROS) production were also measured. Gamma-irradiation had a negative influence on the average plant height, leaf length, leaf width, and fresh weight. Photosynthetic pigment levels decreased with increasing dosages of gamma-irradiation, while soluble sugar content slightly increased. Gamma-irradiation responsive proteins were detected and identified by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). The proteins had a role in photosynthetic carbon fixation, anabolic pathway glycolysis, mitochondrial ATP production, and oxidative stress response regulation. MDA levels and activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD) increased with the increase in gamma-irradiation dosage level. This study provides some basic information regarding responses to gamma-irradiation, and provides valuable physiological and biological data on the effects of different gamma-irradiation dosages on Triticeae species.

  5. Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis.

    PubMed

    Shaban, Nadia Z; Ahmed Zahran, Ahmed M; El-Rashidy, Fatma H; Abdo Kodous, Ahmad S

    2017-12-01

    Gamma (γ) ray, an electromagnetic radiation, is occasionally accompanying the emission of an alpha or beta particle. Exposure to such radiation can cause cellular changes such as mutations, chromosome aberration and cellular damage which depend upon the total amount of energy, duration of exposure and the dose. Ionizing radiation can impair spermatogenesis and can cause mutations in germ cells. In general, type B spermatogonia are sensitive to this type of radiation. The current study was carried out to evaluate the protective role of hesperidin (H), as a polyphenolic compound, on rat testis injury induced by γ-radiation. Rats were divided into groups including C group (control rats), R (irradiated) group (rats irradiated with γ-radiation), Vehicle (V) group (rats administered with dimethylsulfoxide "DMSO"), H group (rats administered with H only), HR and RH groups (rats treated with H before and after exposure to γ-radiation, respectively). Malondialdehyde (MDA: the end product of lipid peroxidation "LPO") and xanthine oxidase (XO: it generates reactive oxygen species "ROS") in testes homogenate as well as nitric oxide (NO: as ROS) in mitochondrial matrix were determined. The apoptotic markers including DNA-fragmentation (DNAF) in testes homogenate and calcium ions (Ca 2+ ) in mitochondrial matrix were determined. Superoxide dismutase (SOD) and catalase (CAT) activities in testes homogenate, while reduced glutathione "GSH" in nuclear matrix were determined. Also histopathological examination for testes tissues through electron microscope was studied. Exposure of rats to γ-radiation (R group) increased the levels of MDA, NO, DNAF, Ca 2+ and XO activity, while it decreased GSH level, SOD and CAT activities as compared to the C groups; γ-radiation increased oxidative stress (OS), LPO, apoptosis and induced testes injuries. These results are in agreement with the histopathological examination. In contrast, treatment with H before or after exposure to γ-radiation

  6. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

    PubMed

    Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

    2015-12-01

    Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p<0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p<0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p<0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p<0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect

  7. Cardioprotective effect of zingerone against oxidative stress, inflammation, and apoptosis induced by cisplatin or gamma radiation in rats.

    PubMed

    Soliman, Ahmed F; Anees, Lobna M; Ibrahim, Doaa M

    2018-05-07

    Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.

  8. Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model.

    PubMed

    Zolali, Elmira; Asgharian, Parina; Hamishehkar, Hamed; Kouhsoltani, Maryam; Khodaii, Hajhir; Hamishehkar, Hadi

    2015-12-01

    There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO) is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. To induce sepsis, cecal ligation and puncture (CLP) method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase), TAC (total antioxidant capacity), MDA (Malondialdehyde), MPO (Myeloperoxidase) and PAI-1 (Plasminogen Activator Inhibitor-1). Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P <0.05 was considered as statistical significance. TAC level increased in GO- treated CLP groups (P<0.05). Inflammation score of lung tissue and MPO activity were significantly lower in GO treated CLP group (P<0.05). It seems that GO has a protective effect on lung inflammation and improves the body redox capacity during sepsis.

  9. Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

    PubMed

    Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

    2017-10-01

    Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (<100 mGy) and oxidative stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

  10. Gamma-oryzanol rich fraction regulates the expression of antioxidant and oxidative stress related genes in stressed rat's liver.

    PubMed

    Ismail, Maznah; Al-Naqeeb, Ghanya; Mamat, Wan Abd Aziz Bin; Ahmad, Zalinah

    2010-03-24

    Gamma-oryzanol (OR), a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities in particular, it has antioxidant properties. The regulatory effect of gamma-oryzanol rich fraction (ORF) extracted and fractionated from rice bran using supercritical fluid extraction (SFE) in comparison with commercially available OR on 14 antioxidant and oxidative stress related genes was determined in rat liver. Rats were subjected to a swimming exercise program for 10 weeks to induce stress and were further treated with either ORF at 125, 250 and 500 mg/kg or OR at 100 mg/kg in emulsion forms for the last 5 weeks of the swimming program being carried out. The GenomeLab Genetic Analysis System (GeXPS) was used to study the multiplex gene expression of the selected genes. Upon comparison of RNA expression levels between the stressed and untreated group (PC) and the unstressed and untreated group (NC), seven genes were found to be down-regulated, while seven genes were up-regulated in PC group compared to NC group. Further treatment of stressed rats with ORF at different doses and OR resulted in up-regulation of 10 genes and down regulation of four genes compared to the PC group. Gamma-oryzanol rich fraction showed potential antioxidant activity greater than OR in the regulation of antioxidants and oxidative stress gene markers.

  11. Gamma-oryzanol rich fraction regulates the expression of antioxidant and oxidative stress related genes in stressed rat's liver

    PubMed Central

    2010-01-01

    Background Gamma-oryzanol (OR), a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities in particular, it has antioxidant properties. Methods The regulatory effect of gamma-oryzanol rich fraction (ORF) extracted and fractionated from rice bran using supercritical fluid extraction (SFE) in comparison with commercially available OR on 14 antioxidant and oxidative stress related genes was determined in rat liver. Rats were subjected to a swimming exercise program for 10 weeks to induce stress and were further treated with either ORF at 125, 250 and 500 mg/kg or OR at 100 mg/kg in emulsion forms for the last 5 weeks of the swimming program being carried out. The GenomeLab Genetic Analysis System (GeXPS) was used to study the multiplex gene expression of the selected genes. Results Upon comparison of RNA expression levels between the stressed and untreated group (PC) and the unstressed and untreated group (NC), seven genes were found to be down-regulated, while seven genes were up-regulated in PC group compared to NC group. Further treatment of stressed rats with ORF at different doses and OR resulted in up-regulation of 10 genes and down regulation of four genes compared to the PC group. Conclusions Gamma-oryzanol rich fraction showed potential antioxidant activity greater than OR in the regulation of antioxidants and oxidative stress gene markers. PMID:20331906

  12. Influence of UV and Gamma radiations on the induced birefringence of stretched poly(vinyl) alcohol foils

    NASA Astrophysics Data System (ADS)

    Nechifor, Cristina-Delia; Zelinschi, Carmen Beatrice; Dorohoi, Dana-Ortansa

    2014-03-01

    The aim of our paper is to evidence the influence of Gamma and UV radiations on the induced birefringence of poly(vinyl alcohol) stretched foils. Thin foils of PVA were prepared and dried without modifying their surfaces. The polymeric foils were irradiated from 15 min to 6 h using UV and Gamma radiations. The induced by stretching under heating birefringence of PVA films was measured at λ = 589.3 nm with a Babinet Compensator. Physico-chemical processes (photo stabilization, photo degradation, oxidation) induced by irradiation of polymer matrix influence both the stretching degree and the anisotropy of etired foils. An increase of birefringence versus the stretching ratio of the PVA foils was evidenced for all studied samples. The dependence of the birefringence on the exposure time, stretching ratio and nature of radiation was also confirmed.

  13. Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model

    PubMed Central

    Zolali, Elmira; Asgharian, Parina; Hamishehkar, Hamed; Kouhsoltani, Maryam; Khodaii, Hajhir; Hamishehkar, Hadi

    2015-01-01

    Objective (s): There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO) is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. Materials and Methods: To induce sepsis, cecal ligation and puncture (CLP) method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase), TAC (total antioxidant capacity), MDA (Malondialdehyde), MPO (Myeloperoxidase) and PAI-1 (Plasminogen Activator Inhibitor-1). Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P <0.05 was considered as statistical significance. Results: TAC level increased in GO- treated CLP groups (P<0.05). Inflammation score of lung tissue and MPO activity were significantly lower in GO treated CLP group (P<0.05). Conclusion: It seems that GO has a protective effect on lung inflammation and improves the body redox capacity during sepsis. PMID:26877858

  14. Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

    PubMed Central

    Singh, Abhinav; Yashavarddhan, M. H.; Kalita, Bhargab; Ranjan, Rajiv; Bajaj, Sania; Prakash, Hridayesh; Gupta, Manju Lata

    2017-01-01

    The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (−1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury. PMID:28289414

  15. Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Globus, Ruth; Schreurs, Ann-Sofie; Tahimic, Candice; Shirazi-Fard, Yasaman; Alwood, Joshua; Shahnazari, Mohammed; Halloran, Bernard

    2015-01-01

    Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

  16. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    PubMed Central

    2009-01-01

    Background Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. Results TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment. PMID:19943946

  17. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

    PubMed

    Gharib, Ola Ali

    2009-11-27

    Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  18. High dietary iron increases oxidative stress and radiosensitivity in the rat retina and vasculature after exposure to fractionated gamma radiation

    PubMed Central

    Theriot, Corey A; Westby, Christian M; Morgan, Jennifer L L; Zwart, Sara R; Zanello, Susana B

    2016-01-01

    Radiation exposure in combination with other space environmental factors including microgravity, nutritional status, and deconditioning is a concern for long-duration space exploration missions. Astronauts experience altered iron homeostasis due to adaptations to microgravity and an iron-rich food system. Iron intake reaches three to six times the recommended daily allowance due to the use of fortified foods on the International Space Station. Iron is associated with certain optic neuropathies and can potentiate oxidative stress. This study examined the response of eye and vascular tissue to gamma radiation exposure (3 Gy fractionated at 37.5 cGy per day every other day for 8 fractions) in rats fed an adequate-iron diet or a high-iron diet. Twelve-week-old Sprague-Dawley rats were assigned to one of four experimental groups: adequate-iron diet/no radiation (CON), high-iron diet/no radiation (IRON), adequate-iron diet/radiation (RAD), and high-iron diet/radiation (IRON+RAD). Animals were maintained on the corresponding iron diet for 2 weeks before radiation exposure. As previously published, the high-iron diet resulted in elevated blood and liver iron levels. Dietary iron overload altered the radiation response observed in serum analytes, as evidenced by a significant increase in catalase levels and smaller decrease in glutathione peroxidase and total antioxidant capacity levels. 8-OHdG immunostaining, showed increased intensity in the retina after radiation exposure. Gene expression profiles of retinal and aortic vascular samples suggested an interaction between the response to radiation and high dietary iron. This study suggests that the combination of gamma radiation and high dietary iron has deleterious effects on retinal and vascular health and physiology. PMID:28725729

  19. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury

    PubMed Central

    Banerjee, Sudip; Shah, Sumit K.; Melnyk, Stepan B.; Hauer-Jensen, Martin

    2018-01-01

    Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta (Cebpd−/−) display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that Cebpd protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether Cebpd mediates the radio protective functions of GT3. We found that GT3-treated Cebpd−/− mice showed partial recovery of white blood cells compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd−/− mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both Cebpd+/+ and Cebpd−/− mice. These results identify a novel role for Cebpd in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF. PMID:29642403

  20. Ionizing radiation potentiates the induction of nitric oxide synthase by interferon-gamma (Ifn-gamma) or Ifn-gamma and lipopolysaccharide in bnl cl.2 murine embryonic liver cells: role of hydrogen peroxide.

    PubMed

    Yoo, J C; Pae, H O; Choi, B M; Kim, W I; Kim, J D; Kim, Y M; Chung, H T

    2000-02-01

    The effects of ionizing irradiation on the nitric oxide (NO) production in murine embryonic liver cell line, BNL CL.2 cells, were investigated. Various doses (5-40 Gy) of radiation made BNL CL.2 cells responsive to interferon-gamma alone for the production of NO in a dose-dependent manner. Small amounts of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) synergized with IFN-gamma in the production of NO from irradiated BNL CL.2 cells, even though LPS or TNF-alpha alone did not induce NO production from the same cells. Immunoblots showed parallel induction of inducible nitric oxide synthase (iNOS). NO production in irradiated BNL CL.2 cells by IFN-gamma or IFN-gamma plus LPS was decreased by the addition of catalase, suggesting that H(2)O(2) produced by ionizing irradiation primed the cells to trigger NO production in response to IFN-gamma or IFN-gamma plus LPS. Furthermore, the treatment of nongamma-irradiated BNL CL.2 cells with H(2)O(2) made the cells responsive to IFN-gamma or IFN-gamma plus LPS for the production of NO. This study shows that ionizing irradiation has the ability to induce iNOS gene expression in responsive to IFN-gamma via the formation of H(2)O(2) in BNL CL.2 murine embryonic liver cells.

  1. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    PubMed Central

    Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

    2013-01-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

  2. [Chlorophyll mutations induced by gamma radiation in Phaseolus vulgaris L].

    PubMed

    Meoño, M E

    1975-07-01

    In a study of chlorophyll mutants of Phaseolus vulgaris L. through Co60 gamma radiation, five types of mutants, classified as albino, cream, yellow, yellow-green and light green were obtained; all were lethal; their segregation was always proportionally lower than the Mendelian. Gamma radiation-induced mutations in black beans do not depart significantly from those obtained elsewhere in barley and wheat.

  3. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

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

  4. Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

    NASA Technical Reports Server (NTRS)

    Globus, Ruth

    2015-01-01

    Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of

  5. The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells.

    PubMed

    Yao, Ke; Zhang, Li; Zhang, Yidong; Ye, PanPan; Zhu, Ning

    2008-01-01

    Ultraviolet (UV) radiation-induced oxidative stress plays a significant role in the progression of cataracts. This study investigated the photoprotective effect of fisetin on UV radiation-induced oxidative stress in human lens epithelial cells and the possible molecular mechanism involved. SRA01/04 cells exposed to different doses of ultraviolet B (UVB) were cultured with various concentrations of fisetin and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of fisetin on the generation of reactive oxygen species (ROS) of SRA01/04 cells was determined by flow cytometry. Translocation of nuclear factor kappa-B (NF-kappaB) was examined by immunocytochemistry. Expression of NF-kappaB/P65, inhibiter kappa B (IkappaB), and mitogen activated protein kinase (MAPK) proteins were measured by western blot. Treatment of SRA01/04 cells with fisetin inhibited UVB-induced cell death and the generation of ROS. Fisetin inhibited UVB-induced activation and translocation of NF-kappaB/p65, which was mediated through an inhibition of the degradation and activation of IkappaB. Fisetin also inhibited UVB-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied. The flavonoid, fisetin, could be useful in attenuation of UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells, which suggests that fisetin has a potential protective effect against cataractogenesis.

  6. Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

    PubMed

    Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

    2017-03-01

    Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

  7. Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

    PubMed Central

    Das, Ujjal; Manna, Krishnendu; Sinha, Mahuya; Datta, Sanjukta; Das, Dipesh Kr; Chakraborty, Anindita; Ghosh, Mahua; Saha, Krishna Das; Dey, Sanjit

    2014-01-01

    Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation. PMID:24854039

  8. Oxidative Stress and Autophagy Responses of Osteocytes Exposed to Spaceflight-like Radiation.

    NASA Technical Reports Server (NTRS)

    Tahimic, Candice; Rael, Victoria E.; Globus, Ruth K.

    2015-01-01

    Weightlessness and radiation, two of the unique elements of the space environment, causes a profound decrement in bone mass that mimics aging. This bone loss is thought to result from increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our current understanding of the signaling factors and mechanisms underlying bone loss is incomplete. However, it is known that oxidative stress, characterized by the excess production of free radicals, is elevated during radiation exposure. The goals of this study is to examine the response of osteocytes to spaceflight-like radiation and to identify signaling processes that may be targeted to mitigate bone loss in scenarios of space exploration, earth-based radiotherapy and accidental radiation exposure. We hypothesize that (1) oxidative stress, as induced by radiation, decreases osteocyte survival and increases pro-osteoclastogenic signals and that (2) autophagy is one of the key cellular defenses against oxidative stress. Autophagy is the process by which cellular components including organelles and proteins are broken down and recycled. To test our hypothesis, we exposed the osteocyte-like cell line, MLO-Y4, to 0.5, 1, and 2 Gy of simulated space radiation (Iron-56 radiation at 600 MeV/n) and assessed cell numbers, cell growth-associated molecules as well as markers of autophagy and oxidative stress at various time points post-irradiation. We observed a reduction in cell numbers in the groups exposed to 1 and 2 Gy of Iron-56 radiation. Collectively, flow cytometry and gene expression analysis revealed that radiation caused a shift in cell cycle distribution consistent with growth arrest. Compared to sham-treatment, 2 Gy of Iron-56 increased FoxO3, SOD1, and RANKL gene expression yet unexpectedly decreased LC3B-II protein levels at 4 and 24 hours post-IR. Taken together, these findings suggest that simulated space radiation invoke

  9. Extract of Xylopia aethiopica (Annonaceae) protects against gamma-radiation induced testicular damage in Wistar rats.

    PubMed

    Adaramoye, Oluwatosin Adekunle; Adedara, Isaac Adegboyega; Popoola, Bosede; Farombi, Ebenezer Olatunde

    2010-01-01

    Ionizing radiation is an important environmental risk factor and, a major therapeutic agent for cancer treatment. This study was designed to evaluate the protective effect of extract of Xylopia aethiopica (XA) on gamma-radiation-induced testicular damage in rats. Vitamin C (VC) served as the reference antioxidant during the study. The study consists of 4 groups of 11 rats each. Group I received corn oil (vehicle), groups II and IV were pretreated with XA (250 mg/kg) and VC (250mg/kg) for 6 weeks before and 8 weeks after exposure to gamma-radiation; group III was exposed to a single dose of gamma-radiation (5 Gy). Biochemical analysis revealed that gamma-irradiation caused a significant increase (p < .05) in serum and testicular lipid peroxidation (LPO) levels by 217% and 221%, respectively. Irradiated rats had markedly decreased testicular catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and reduced glutathione (GSH) levels. Irradiation resulted in 59% and 40% decreases in spermatozoa motility and live/dead sperm count, respectively, and a 161% increase in total sperm abnormalities. Histologically, testes of the irradiated rats showed extensive degenerative changes in the seminiferous tubules and defoliation of spermatocytes. Supplementation of XA and VC reversed the adverse effects of gamma-radiation on biochemical and histological indices of the rats. These findings demonstrated that Xylopia aethiopica has a protective effect by inhibiting oxidative damage in testes of irradiated rats.

  10. Mobile phone radiation inhibits Vigna radiata (mung bean) root growth by inducing oxidative stress.

    PubMed

    Sharma, Ved Parkash; Singh, Harminder Pal; Kohli, Ravinder Kumar; Batish, Daizy Rani

    2009-10-15

    During the last couple of decades, there has been a tremendous increase in the use of cell phones. It has significantly added to the rapidly increasing EMF smog, an unprecedented type of pollution consisting of radiation in the environment, thereby prompting the scientists to study the effects on humans. However, not many studies have been conducted to explore the effects of cell phone EMFr on growth and biochemical changes in plants. We investigated whether EMFr from cell phones inhibit growth of Vigna radiata (mung bean) through induction of conventional stress responses. Effects of cell phone EMFr (power density: 8.55 microW cm(-2); 900 MHz band width; for 1/2, 1, 2, and 4 h) were determined by measuring the generation of reactive oxygen species (ROS) in terms of malondialdehyde and hydrogen peroxide (H(2)O(2)) content, root oxidizability and changes in levels of antioxidant enzymes. Our results showed that cell phone EMFr significantly inhibited the germination (at > or =2 h), and radicle and plumule growths (> or =1 h) in mung bean in a time-dependent manner. Further, cell phone EMFr enhanced MDA content (indicating lipid peroxidation), and increased H(2)O(2) accumulation and root oxidizability in mung bean roots, thereby inducing oxidative stress and cellular damage. In response to EMFr, there was a significant upregulation in the activities of scavenging enzymes, such as superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases, catalases and glutathione reductases, in mung bean roots. The study concluded that cell phone EMFr inhibit root growth of mung bean by inducing ROS-generated oxidative stress despite increased activities of antioxidant enzymes.

  11. Consequences of Lethal-Whole-Body Gamma Radiation and Possible Ameliorative Role of Melatonin

    PubMed Central

    Mihandoost, Ehsan; Shirazi, Alireza; Mahdavi, Seied Rabie; Aliasgharzadeh, Akbar

    2014-01-01

    Gamma radiation induces the generation of free radicals, leading to serious cellular damages in biological systems. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the deleterious effects of radiation. Melatonin synergistically acts as an immune-stimulator and antioxidant. We investigated the possible radioprotective role of melatonin (100 mg/kg i.p.) against lethal-whole-body radiation- (10 Gy) induced sickness, body weight loss, and mortality in rats. Results of the present study suggest that exposure to lethal-whole-body radiation incurred mortality, body weight loss, and apoptosis and it also depleted the immunity and the antioxidant status of the rats. Our results show that melatonin pretreatment provides protection against radiation induced mortality, oxidative stress, and immune-suppression. The melatonin pretreated irradiated rats showed less change in body weight as compared to radiation only group. On the other hand, melatonin appeared to have another radioprotective role, suggesting that melatonin may reduce apoptosis through a caspase-3-mediated pathway by blocking caspase-3 activity. PMID:25431791

  12. Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress.

    PubMed

    Spencer, Jennifer; Phister, Trevor G; Smart, Katherine A; Greetham, Darren

    2014-03-17

    Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress.

  13. Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress

    PubMed Central

    2014-01-01

    Background Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Results Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Conclusions Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress. PMID:24636079

  14. Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: protective effect of alpha-lipoic acid.

    PubMed

    Manda, Kailash; Ueno, Megumi; Moritake, Takashi; Anzai, Kazunori

    2007-02-12

    Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant.

  15. Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

    PubMed Central

    McAdam, Elizabeth; Brem, Reto; Karran, Peter

    2016-01-01

    The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

  16. Oxidative stress in MeHg-induced neurotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Farina, Marcelo, E-mail: farina@ccb.ufsc.br; Aschner, Michael; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN

    2011-11-15

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

  17. Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

    PubMed Central

    Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

    2014-01-01

    Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance

  18. Role of melatonin on electromagnetic radiation-induced oxidative stress and Ca2+ signaling molecular pathways in breast cancer.

    PubMed

    Naziroğlu, Mustafa; Tokat, Sümeyye; Demirci, Seda

    2012-12-01

    Exposure to electromagnetic radiation (EMR) may increase breast cancer risk by inducing oxidative stress and suppressing the production of melatonin. Aim of the present review is to discuss the mechanisms and risk factors of EMR and oxidative stress-induced breast cancer, to summarize the controlled studies evaluating measures for prevention, and to conclude with evidence-based strategies for prevention. Review of the relevant literature and results from our recent basic studies, as well as critical analyses of published systematic reviews were obtained from the Pubmed and the Science Citation Index. It has been proposed that chronic exposure to EMR may increase the risk of breast cancer by suppressing the production of melatonin; this suppression may affect the development of breast cancer either by increasing levels of circulation of estrogen or through over production of free oxygen radicals. Most epidemiological studies have also indicated overall effect of EMR exposure in premenopausal women, particularly for estrogen receptor positive breast tumors. Enhanced voltage-dependent Ca(2+) current and impaired inhibitory G-protein function, and derangement of intracellular organelles with a Ca(2+) buffering effect, such as endoplasmic reticulum and mitochondria have been also shown to contribute to disturbed Ca(2+) signaling in breast cancer. Melatonin may modulate breast cancer through modulation of enhanced oxidative stress and Ca(2+) influx in cell lines. However, there is not enough evidence on increased risk of breast cancer related to EMR exposure.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu

    2014-03-01

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

  20. Radiation hardness of β-Ga2O3 metal-oxide-semiconductor field-effect transistors against gamma-ray irradiation

    NASA Astrophysics Data System (ADS)

    Wong, Man Hoi; Takeyama, Akinori; Makino, Takahiro; Ohshima, Takeshi; Sasaki, Kohei; Kuramata, Akito; Yamakoshi, Shigenobu; Higashiwaki, Masataka

    2018-01-01

    The effects of ionizing radiation on β-Ga2O3 metal-oxide-semiconductor field-effect transistors (MOSFETs) were investigated. A gamma-ray tolerance as high as 1.6 MGy(SiO2) was demonstrated for the bulk Ga2O3 channel by virtue of weak radiation effects on the MOSFETs' output current and threshold voltage. The MOSFETs remained functional with insignificant hysteresis in their transfer characteristics after exposure to the maximum cumulative dose. Despite the intrinsic radiation hardness of Ga2O3, radiation-induced gate leakage and drain current dispersion ascribed respectively to dielectric damage and interface charge trapping were found to limit the overall radiation hardness of these devices.

  1. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A.

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stemmore » cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

  2. Cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats.

    PubMed

    Azab, Khaled Sh; Mostafa, Abdel-Halem A; Ali, Ehab M M; Abdel-Aziz, Mohamed A S

    2011-11-01

    The present study aimed to investigate the protective role of cinnamon extract against inflammatory and oxidative injuries in gamma irradiated rats. Rats were subjected to fractionated doses of gamma radiation. Cinnamon extract were daily administrated before starting irradiation and continued after radiation exposure. The results obtained revealed that the administration of cinnamon extract to irradiated rats significantly ameliorated the changes induced in liver antioxidant system; catalase, superoxide dismutase and glutathione peroxidase activities as well as reduced glutathione concentration. The liver's lipid peroxidation and protein oxidation indices were significantly decreased when compared with their equivalent values in irradiated rats. Furthermore, the changes induces in xanthine oxidoreductase system were significantly diminished. In addition, the changes in liver nitric oxide contents, serum tumor necrosis factor alpha and C-reactive protein levels were markedly improved. In conclusion, the administration of cinnamon extract might provide substantial protection against radiation-induced oxidative and inflammatory damages. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis.

    PubMed

    Köse, O; Arabaci, T; Kizildag, A; Erdemci, B; Özkal Eminoğlu, D; Gedikli, S; Özkanlar, S; Zihni, M; Albayrak, M; Kara, A; Kermen, E

    2017-06-01

    The aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis. Sixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped-Rt); radiotherapy and protective melatonin administration (Rt-Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped-Rt-Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups. The oxidative stress index and the levels of 8-hydroxy-2'-deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen were found to be significantly higher in the Ped-Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). It was found that radiotherapy increased oxidative stress, the periodontal attachment level and alveolar bone loss, and protective melatonin administration significantly reduced the oxidative parameters and prevented periodontal damage in irradiated rats with experimental periodontitis. Further research is needed regarding the use of systemic melatonin administration before radiation therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

  6. Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

    PubMed

    Yang, Lin; Yu, Ming-wei; Wang, Xiao-min; Zhang, Yi; Yang, Guo-wang; Luo, Xiao-qin; Peng, Rui-yun; Gao, Ya-bing; Zhao, Li; Wang, Li-feng

    2016-02-01

    To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor β1 (TGF-β1) were analyzed by western blot. Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-β1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-β1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-β1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up

  7. UV-B radiation-induced oxidative stress and p38 signaling pathway involvement in the benthic copepod Tigriopus japonicus.

    PubMed

    Kim, Bo-Mi; Rhee, Jae-Sung; Lee, Kyun-Woo; Kim, Min-Jung; Shin, Kyung-Hoon; Lee, Su-Jae; Lee, Young-Mi; Lee, Jae-Seong

    2015-01-01

    Ultraviolet B (UV-B) radiation presents an environmental hazard to aquatic organisms. To understand the molecular responses of the intertidal copepod Tigriopus japonicus to UV-B radiation, we measured the acute toxicity response to 96 h of UV-B radiation, and we also assessed the intracellular reactive oxygen species (ROS) levels, glutathione (GSH) content, and antioxidant enzyme (GST, GR, GPx, and SOD) activities after 24 h of exposure to UV-B with LD50 and half LD50 values. Also, expression patterns of p53 and hsp gene families with phosphorylation of p38 MAPK were investigated in UV-B-exposed copepods. We found that the ROS level, GSH content, and antioxidant enzyme activity levels were increased with the transcriptional upregulation of antioxidant-related genes, indicating that UV-B induces oxidative stress by generating ROS and stimulating antioxidant enzymatic activity as a defense mechanism. Additionally, we found that p53 expression was significantly increased after UV-B irradiation due to increases in the phosphorylation of the stress-responsive p38 MAPK, indicating that UV-B may be responsible for inducing DNA damage in T. japonicus. Of the hsp family genes, transcriptional levels of hsp20, hsp20.7, hsp70, and hsp90 were elevated in response to a low dose of UV-B radiation (9 kJ m(-2)), suggesting that these hsp genes may be involved in cellular protection against UV-B radiation. In this paper, we performed a pathway-oriented mechanistic analysis in response to UV-B radiation, and this analysis provides a better understanding of the effects of UV-B in the intertidal benthic copepod T. japonicus. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Nitric oxide alleviates oxidative damage induced by enhanced ultraviolet-B radiation in cyanobacterium.

    PubMed

    Xue, Lingui; Li, Shiweng; Sheng, Hongmei; Feng, Huyuan; Xu, Shijian; An, Lizhe

    2007-10-01

    To study the role of nitric oxide (NO) on enhanced ultraviolet-B (UV-B) radiation (280-320 nm)-induced damage of Cyanobacterium, the growth, pigment content, and antioxidative activity of Spirulina platensis-794 cells were investigated under enhanced UV-B radiation and under different chemical treatments with or without UV-B radiation for 6 h. The changes in chlorophyll-a, malondialdehyde content, and biomass confirmed that 0.5 mM: sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the damage caused by enhanced UV-B. Specifically, the biomass and the chlorophyll-a content in S. platensis-794 cells decreased 40% and 42%, respectively under enhanced UV-B stress alone, but they only decreased 10% and 18% in the cells treated with UV-B irradiation and 0.5 mM: SNP. Further experiments suggested that NO treatment significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the accumulation of O (2)(-) in enhanced UV-B-irradiated cells. SOD and CAT activity increased 0.95- and 6.73-fold, respectively. The accumulation of reduced glutathione (GSH) increased during treatment with 0.5 mM: SNP in normal S. platensis cells, but SNP treatment could inhibit the increase of GSH in enhanced UV-B-stressed S. platensis cells. Thus, these results suggest that NO can strongly alleviate oxidative damage caused by UV-B stress by increasing the activities of SOD, peroxidase, CAT, and the accumulation of GSH, and by eliminating O (2)(-) in S. platensis-794 cells. In addition, the difference of NO origin between plants and cyanobacteria are discussed.

  9. Oxidative Stress Resistance in Deinococcus radiodurans†

    PubMed Central

    Slade, Dea; Radman, Miroslav

    2011-01-01

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

  10. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)

    PubMed Central

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-01-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  11. Radioprotective Efficacy of Lutein in Ameliorating Electron Beam Radiation-induced Oxidative Injury in Swiss Albino Mice

    PubMed Central

    Vasudeva, Vidya; Tenkanidiyoor, Yogish Somayaji; Peter, Alex John; Shetty, Jayaram; Lakshman, Srikant Patil; Fernandes, Ronald; Patali, Krishna Ananthapura

    2018-01-01

    Background: Lutein, a carotenoid compound, has previously been studied for its antioxidant and medicinal properties as well as the moderate protection it confers against gamma radiation. This study aimed at evaluating the effects of lutein against radiation-induced hematological and biochemical changes in mice. Methods: The optimized dose of the compound was orally administered for 15 days, and the mice were irradiated (6 Gy) on day 15 after the administration of the compound. The groups were divided (6 mice in each group) into normal control, radiation control, gallic acid control, 10% DMSO control, lutein control, and irradiated groups pretreated with gallic acid, 10% DMSO, and lutein. Gallic acid was used to maintain a standard since it is a proven radioprotector. Within 24 hours post irradiation, the animals were anesthetized and sacrificed. The hematological, biochemical, and antioxidant changes were determined using suitable methods. Data were analyzed by the Kaplan–Meier curve (log-rank test) and ANOVA (the Tukey test). The independent t test was used to compare the independent groups. SPSS (ver. 16) was employed. Results: Maximum survival was observed with a dose of 250 mg/kg b.wt lutein. The total leukocyte count and the percentage lymphocyte count exhibited a significant decline in the irradiated groups pretreated with gallic acid and lutein in comparison to their controls, whereas the percentage granulocyte count showed a significant rise. Antioxidant activity had markedly declined in the irradiated groups, indicating oxidative stress. Lutein pretreatment reduced the damage and maintained the antioxidant system. Conclusion: The present study suggests a protective role for lutein in palliating radiation-induced oxidative changes and maintaining the antioxidant system in vivo. PMID:29398751

  12. Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of: (1) peripheral leukocyte distribution, (2) plasma cytokine levels and (3) cytokine production profiles following whole blood mitogenic stimulation

  13. Photo-protection by 3-bromo-4, 5-dihydroxybenzaldehyde against ultraviolet B-induced oxidative stress in human keratinocytes.

    PubMed

    Hyun, Yu Jae; Piao, Mei Jing; Zhang, Rui; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

    2012-09-01

    Exposure of the skin to ultraviolet B (UVB) radiation leads to epidermal damage and the generation of reactive oxygen species (ROS) in skin cells, including keratinocytes. Therefore, the photo-protective effect of 3-bromo-4, 5-dihydroxybenzaldehyde (BDB) against UVB was assessed in human HaCaT keratinocytes exposed to UVB radiation in vitro. BDB restored cell viability, which decreased upon exposure to UVB radiation. BDB exhibited scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl radicals, intracellular ROS induced by hydrogen peroxide (H(2)O(2)) or UVB radiation, the superoxide anion generated by the xanthine/xanthine oxidase system, and the hydroxyl radical generated by the Fenton reaction (FeSO(4)+H(2)O(2)). Moreover, BDB absorbed UVB and decreased injury resulting from UVB-induced oxidative stress to lipids, proteins and DNA. Finally, BDB reduced UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and a reduction in DNA fragmentation. Taken together, these results suggest that BDB protects human keratinocytes against UVB-induced oxidative stress by scavenging ROS and absorbing UVB rays, thereby reducing injury to cellular components. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats.

    PubMed

    Ahmed, Nawal A; Radwan, Nasr M; Aboul Ezz, Heba S; Salama, Noha A

    2017-01-01

    Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm 2 , SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain.

  15. Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.

    PubMed

    Mahmoud, Ayman M

    2014-09-01

    The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

  16. Hepatoprotective Role of Wheatgrass on Alcohol and ΔPUFA-Induced Oxidative Stress in Rats.

    PubMed

    Durairaj, Varalakshmi; Shakya, Garima; Rajagopalan, Rukkumani

    2015-06-01

    Alcohol abuse is recognized as the most common cause for the development of various abnormalities including liver disease. Excessive free radicals are generated during the metabolism of ethanol. The ingestion of alcohol along with polyunsaturated fatty acid (PUFA) aggravates the production of free radicals and enhances the oxidative stress. Medicinal plants contain active phytocomponents, which are the principal healthcare resources. We aimed to analyze the effect of wheatgrass extract on alcohol and thermally oxidized PUFA (ΔPUFA) induced oxidative stress in male albino Wistar rats. The levels of marker enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lipid peroxidative markers; thiobarbutric acid reactive substances (TBARS) and lipid hydroperoxides (LH), the levels of enzymatic (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]) and nonenzymatic (reduced glutathione [GSH], vitamin E, vitamin C) antioxidants were analyzed in liver to evaluate the effects of wheatgrass. The levels of TBARS and LH were significantly (p ≤ .05) increased in alcohol + ΔPUFA group, which were found to be reduced on treatment with wheatgrass. The levels of both enzymatic and nonenzymatic antioxidants were significantly (p ≤ .05) decreased in alcohol + ΔPUFA group, which were found to be restored on treatment with wheatgrass. From the results obtained, we conclude that wheatgrass protects the liver against alcohol and ΔPUFA induced oxidative stress.

  17. American Ginseng Modifies 137Cs-Induced DNA Damage and Oxidative Stress in Human Lymphocytes

    PubMed Central

    Lee, Tung-Kwang; O’Brien, Kevin F.; Wang, Weidong; Sheng, Chao; Wang, Tao; Johnke, Roberta M.; Allison, Ron R.

    2009-01-01

    The multifold bioactive medicinal properties of ginseng have been closely linked to its antioxidative ability, which is related to its ginsenoside content. Since the key mechanism of radiation-induced cell death and tissue damage is the generation of reactive oxygen species (ROS) that attack cellular DNA, this study focuses on the impact of a standardized North American ginseng extract (NAGE) on 137Cs-induced oxidative stress in human peripheral lymphocytes (PBL) obtained from 10 healthy individuals (6M/4F), 42.7 ± 4.6 years of age. At two different time points (0 h and 24 h before irradiation), we applied NAGE (250 – 1000 µg ml−1) to mononuclear cell cultures for cytokinesis-block micronuclei (MN) assay and determination of the state of oxidative stress in PBL. We found that at both time points, NAGE significantly reduced the MN yields in PBL after irradiation (1 and 2 Gy) in a concentration-dependent manner (P<0.001). Compared with radiation alone, the maximum reduction rate of MN yield were 51.1% and 49.1% after 1 Gy and 2 Gy exposures, respectively. We also found that before irradiation the presence of NAGE in the culture medium resulted in a significant increased intracellular total antioxidant capacity (TAC) in PBL. At both time points, the increment of 137Cs-induced MN yields in PBL was positively correlated with the increment of intracellular ROS production (R = 0.6 – 0.7, P = 0.002), but negatively correlated with the reduction of TAC levels (R = −0.4 −0.5, P = 0.02 – 0.004). However, the presence of NAGE in the culture medium significantly increased the TAC levels, while concomitantly decreasing both ROS production and MN yields in PBL (P<0.001). Our findings that NAGE is effective in protecting human PBL against radiation-induced oxidative stress should encourage further in vivo study of dietary supplementation with NAGE as an effective natural radiation countermeasure. PMID:19946576

  18. Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gan, Xueqi; Huang, Shengbin; Yu, Qing

    Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activitymore » and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.« less

  19. Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

    PubMed Central

    Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

    2016-01-01

    Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

  20. Menadione reduction by pharmacological doses of ascorbate induces an oxidative stress that kills breast cancer cells.

    PubMed

    Beck, Raphaël; Verrax, Julien; Dejeans, Nicolas; Taper, Henryk; Calderon, Pedro Buc

    2009-01-01

    Oxidative stress generated by ascorbate-driven menadione redox cycling kills MCF7 cells by a concerted mechanism including glycolysis inhibition, loss of calcium homeostasis, DNA damage and changes in mitogen activated protein kinases (MAPK) activities. Cell death is mediated by necrosis rather than apoptosis or macroautophagy. Neither 3-methyladenine nor Z-VAD affects cytotoxicity by ascorbate/menadione (Asc/Men). BAPTA-AM, by restoring cellular capacity to reduce MTT, underlines the role of calcium in the necrotic process. Oxidative stress-mediated cell death is shown by the opposite effects of N-acetylcysteine and 3-aminotriazole. Moreover, oxidative stress induces DNA damage (protein poly-ADP-ribosylation and gamma-H2AX phosphorylation) and inhibits glycolysis. Asc/Men deactivates extracellular signal-regulated kinase (ERK) while activating p38, suggesting an additional mechanism to kill MCF7 cells. Since ascorbate is taken up by cancer cells and, due to their antioxidant enzyme deficiency, oxidative stress should affect cancer cells to a greater extent than normal cells. This differential sensitivity may have clinical applications.

  1. Effects of carotenoids on damage of biological lipids induced by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Saito, Takeshi; Fujii, Noriko

    2014-05-01

    Carotenoids are considered to be involved in the radioresistant mechanisms of radioresistant bacteria. In these bacterial cells, carotenoids are present in biological lipids, and therefore may be related to the radiation-induced damage of lipids. However, only limited data are available for the role of carotenoids in such damage. In this study, we irradiated an α-linolenic acid-benzene solution with gamma rays and analyzed the resulting oxidative degradation and peroxidation damage in the presence or absence of two typical carotenoids: β-carotene and astaxanthin. The analyses revealed that oxidative degradation and peroxidation of α-linolenic acid, as evaluated by the amount of malondialdehyde and conjugated diene formed, respectively, increased in a dose-dependent manner. Moreover, 8.5×10-3 M β-carotene inhibited gamma radiation-induced oxidative degradation of α-linolenic acid, whereas 5.0×10-5 and 5.0×10-6 M β-carotene, and 5.0×10-7 and 5.0×10-8 M astaxanthin promoted degradation. In contrast, neither β-carotene nor astaxanthin affected peroxidation of α-linolenic acid. These results suggest that an optimum concentration of carotenoids in radioresistant bacteria protects biological lipid structures from radiation-induced damage.

  2. Exercise-Induced Oxidative Stress Responses in the Pediatric Population

    PubMed Central

    Avloniti, Alexandra; Chatzinikolaou, Athanasios; Deli, Chariklia K.; Vlachopoulos, Dimitris; Gracia-Marco, Luis; Leontsini, Diamanda; Draganidis, Dimitrios; Jamurtas, Athanasios Z.; Mastorakos, George; Fatouros, Ioannis G.

    2017-01-01

    Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty. PMID:28106721

  3. Investigation of gamma radiation induced changes in local structure of borosilicate glass by TDPAC and EXAFS

    NASA Astrophysics Data System (ADS)

    Kumar, Ashwani; Nayak, C.; Rajput, P.; Mishra, R. K.; Bhattacharyya, D.; Kaushik, C. P.; Tomar, B. S.

    2016-12-01

    Gamma radiation induced changes in local structure around the probe atom (Hafnium) were investigated in sodium barium borosilicate (NBS) glass, used for immobilization of high level liquid waste generated from the reprocessing plant at Trombay, Mumbai. The (NBS) glass was doped with 181Hf as a probe for time differential perturbed angular correlation (TDPAC) spectroscopy studies, while for studies using extended X-ray absorption fine structure (EXAFS) spectroscopy, the same was doped with 0.5 and 2 % (mole %) hafnium oxide. The irradiated as well as un-irradiated glass samples were studied by TDPAC and EXAFS techniques to obtain information about the changes (if any) around the probe atom due to gamma irradiation. TDPAC spectra of unirradiated and irradiated glasses were similar and reminescent of amorphous materials, indicating negligible effect of gamma radiation on the microstructure around Hafnium probe atom, though the quaqdrupole interaction frequency ( ω Q) and asymmetry parameter ( η) did show a marginal decrease in the irradiated glass compared to that in the unirradiated glass. EXAFS measurements showed a slight decrease in the Hf-O bond distance upon gamma irradiation of Hf doped NBS glass indicating densification of the glass matrix, while the cordination number around hafnium remains unchanged.

  4. (abstract) Effects of Radiation and Oxidative Stress on Development and Morphology of Intestinal Cells

    NASA Technical Reports Server (NTRS)

    Honda, Shuji; Nelson, Gregory; Schubert, Wayne

    1993-01-01

    Intestinal cells when subjected to oxidative stress or radiation exhibit abnormal nuclear divisions observed as: 1) supernumerary cell divisions in anterior intestinal cells or 2) incomplete nuclear division and the persistence of anaphase bridges between daughter nuclei. Two oxygen sensitive mutants, mev-1 and rad-8 were observed to exhibit spontaneous supernumerary nuclear divisions at low frequency. N2 can be induced to undergo these divisions by treatment with the superoxide dismutase (SOD) inhibitor diethyl dithicarbamate or with the free radical generator methyl viologen. By contrast, the free radical generator bleomycin produces anaphase bridges in N2 intestinal nuclei at high frequency. Intestinal anaphase bridges can be induced by ionizing radiation and their formation is dependent on dose and radiation type.

  5. Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

    PubMed Central

    Milton Prabu, S.; Muthumani, M.; Shagirtha, K.

    2012-01-01

    The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats. PMID:23961183

  6. Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats.

    PubMed

    Milton Prabu, S; Muthumani, M; Shagirtha, K

    2012-04-01

    The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.

  7. Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress and reproductive signaling pathways in females and males.

    PubMed

    Nazıroğlu, Mustafa; Yüksel, Murat; Köse, Seyit Ali; Özkaya, Mehmet Okan

    2013-12-01

    Environmental exposure to electromagnetic radiation (EMR) has been increasing with the increasing demand for communication devices. The aim of the study was to discuss the mechanisms and risk factors of EMR changes on reproductive functions and membrane oxidative biology in females and males. It was reported that even chronic exposure to EMR did not increase the risk of reproductive functions such as increased levels of neoantigens abort. However, the results of some studies indicate that EMR induced endometriosis and inflammation and decreased the number of follicles in the ovarium or uterus of rats. In studies with male rats, exposure caused degeneration in the seminiferous tubules, reduction in the number of Leydig cells and testosterone production as well as increases in luteinizing hormone levels and apoptotic cells. In some cases of male and female infertility, increased levels of oxidative stress and lipid peroxidation and decreased values of antioxidants such as melatonin, vitamin E and glutathione peroxidase were reported in animals exposed to EMR. In conclusion, the results of current studies indicate that oxidative stress from exposure to Wi-Fi and mobile phone-induced EMR is a significant mechanism affecting female and male reproductive systems. However, there is no evidence to this date to support an increased risk of female and male infertility related to EMR exposure.

  8. Spectral analysis of paramagnetic centers induced in human tooth enamel by x-rays and gamma radiation

    NASA Astrophysics Data System (ADS)

    Kirillov, V. A.; Kuchuro, I. I.

    2010-03-01

    Based on study of spectral and relaxation characteristics, we have established that paramagnetic centers induced in tooth enamel by x-rays and gamma radiation are identical in nature. We show that for the same exposure dose, the intensity of the electron paramagnetic resonance (EPR) signal induced by x-radiation with effective energy 34 keV is about an order of magnitude higher than the amplitude of the signal induced by gamma radiation. We have identified a three-fold attenuation of the EPR signal along the path of the x-radiation from the buccal to the lingual side of a tooth, which is evidence that the individual had undergone diagnostic x-ray examination of the dentition or skull. We have shown that the x-ray exposure doses reconstructed from the EPR spectra are an order of magnitude higher than the applied doses, while the dose loads due to gamma radiation are equal to the applied doses. The data obtained indicate that for adequate reconstruction of individual absorbed doses from EPR spectra of tooth enamel in the population subjected to the combined effect of x-radiation and accidental external gamma radiation as a result of the disaster at the Chernobyl nuclear power plant, we need to take into account the contribution to the dose load from diagnostic x-rays in examination of the teeth, jaw, or skull.

  9. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    PubMed

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  10. Selenium reduces mobile phone (900 MHz)-induced oxidative stress, mitochondrial function, and apoptosis in breast cancer cells.

    PubMed

    Kahya, Mehmet Cemal; Nazıroğlu, Mustafa; Çiğ, Bilal

    2014-08-01

    Exposure to mobile phone-induced electromagnetic radiation (EMR) may affect biological systems by increasing free oxygen radicals, apoptosis, and mitochondrial depolarization levels although selenium may modulate the values in cancer. The present study was designed to investigate the effects of 900 MHz radiation on the antioxidant redox system, apoptosis, and mitochondrial depolarization levels in MDA-MB-231 breast cancer cell line. Cultures of the cancer cells were divided into four main groups as controls, selenium, EMR, and EMR + selenium. In EMR groups, the cells were exposed to 900 MHz EMR for 1 h (SAR value of the EMR was 0.36 ± 0.02 W/kg). In selenium groups, the cells were also incubated with sodium selenite for 1 h before EMR exposure. Then, the following values were analyzed: (a) cell viability, (b) intracellular ROS production, (c) mitochondrial membrane depolarization, (d) cell apoptosis, and (e) caspase-3 and caspase-9 values. Selenium suppressed EMR-induced oxidative cell damage and cell viability (MTT) through a reduction of oxidative stress and restoring mitochondrial membrane potential. Additionally, selenium indicated anti-apoptotic effects, as demonstrated by plate reader analyses of apoptosis levels and caspase-3 and caspase-9 values. In conclusion, 900 MHz EMR appears to induce apoptosis effects through oxidative stress and mitochondrial depolarization although incubation of selenium seems to counteract the effects on apoptosis and oxidative stress.

  11. N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of UV-induced melanoma in mice

    PubMed Central

    Cotter, Murray A.; Thomas, Joshua; Cassidy, Pamela; Robinette, Kyle; Jenkins, Noah; Scott, R. Florell; Leachman, Sancy; Samlowski, Wolfram E.; Grossman, Douglas

    2008-01-01

    UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In melan-a cells, a mouse melanocyte line, NAC (1–10 mM) conferred protection from several UV-induced oxidative sequelae including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine (8-OG), and depletion of free reduced thiols (primarily glutathione). Mice transgenic for hepatocyte growth factor and Survivin, previously shown to develop melanoma following a single neonatal dose of UV irradiation, were administered NAC (7 mg/ml, mother’s drinking water) transplacentally and through nursing until two weeks after birth. Delivery of NAC in this manner reduced thiol depletion and blocked formation of 8-OG in skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared to control mice (21 vs. 14 weeks, p=0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma, and suggest that NAC may be useful as a chemopreventive agent. PMID:17908992

  12. Stress pre-conditioning with temperature, UV and gamma radiation induces tolerance against phosphine toxicity.

    PubMed

    Alzahrani, Saad M; Ebert, Paul R

    2018-01-01

    Phosphine is the only general use fumigant for the protection of stored grain, though its long-term utility is threatened by the emergence of highly phosphine-resistant pests. Given this precarious situation, it is essential to identify factors, such as stress preconditioning, that interfere with the efficacy of phosphine fumigation. We used Caenorhabditis elegans as a model organism to test the effect of pre-exposure to heat and cold shock, UV and gamma irradiation on phosphine potency. Heat shock significantly increased tolerance to phosphine by 3-fold in wild-type nematodes, a process that was dependent on the master regulator of the heat shock response, HSF-1. Heat shock did not, however, increase the resistance of a strain carrying the phosphine resistance mutation, dld-1(wr4), and cold shock did not alter the response to phosphine of either strain. Pretreatment with the LD50 of UV (18 J cm-2) did not alter phosphine tolerance in wild-type nematodes, but the LD50 (33 J cm-2) of the phosphine resistant strain (dld-1(wr4)) doubled the level of resistance. In addition, exposure to a mild dose of gamma radiation (200 Gy) elevated the phosphine tolerance by ~2-fold in both strains.

  13. Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha-lipoic acid.

    PubMed

    Manda, Kailash; Ueno, Megumi; Anzai, Kazunori

    2008-03-05

    Exposure to high-energy particle radiation (HZE) may cause oxidative stress and cognitive impairment in the same manner that seen in aged mice. This phenomenon has raised the concerns about the safety of an extended manned mission into deep space where a significant portion of the radiation burden would come from HZE particle radiation. The present study aimed at investigating the role of alpha-lipoic acid against space radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body irradiation of mice with high-LET (56)Fe beams (500 MeV/nucleon, 1.5 Gy) substantially impaired the reference memory at 30 day post-irradiation; however, no significant effect was observed on motor activities of mice. Acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such memory dysfunction. Radiation-induced apoptotic damage in cerebellum was examined using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labeling method (NeuroTACS). Radiation-induced apoptotic and necrotic cell death of granule cells and Purkinje cells were inhibited significantly by alpha-lipoic acid pretreatment. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of DNA damage (comet tail movement and serum 8-OHdG), lipid proxidation products (MDA+HAE) and protein carbonyls in mice cerebellum. Further, radiation-induced decline of non-protein sulfhydryl (NP-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Results clearly indicate that alpha-lipoic acid is a potent neuroprotective antioxidant. Moreover, present finding also support the idea suggesting the cerebellar

  14. Nano-silymarin provides protection against γ-radiation-induced oxidative stress in cultured human embryonic kidney cells.

    PubMed

    Adhikari, Manish; Arora, Rajesh

    2015-10-01

    Radiation can produce biological damage, mainly oxidative stress, via production of free radicals, including reactive oxygen species (ROS). Nanoparticles are of interest as radioprotective agents, particularly due to their high solubility and bioavailability. Silymarin is a hepatoprotective agent but has poor oral bioavailability. Silymarin was formulated as a nanoemulsion with the aim of improving its bioavailability and therapeutic efficacy. In the present study, we evaluated self-nanoemulsifying drug delivery systems (SNEDDS) formulated with surfactants and co-surfactants. Nano-silymarin was characterized by estimating % transmittance, globule size, and polydispersity index, and by transmission electron microscopy (TEM). The nano-silymarin obtained was in the range of 3-8nm diameter. With regard to DNA damage, measured by a plasmid relaxation assay, maximum protection was obtained at 10μg/mL. Cytotoxicity of nano-silymarin to human embryonic kidney (HEK) cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Protective efficacy against γ-radiation was assessed by reduction in micronucleus frequency and ROS generation, using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. Radiation-induced apoptosis was estimated by microscopic analysis and cell-cycle estimation. Nano-silymarin was radioprotective, supporting the possibility of developing new approaches to radiation protection via nanotechnology. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Phoenix dactylifera protects against oxidative stress and hepatic injury induced by paracetamol intoxication in rats.

    PubMed

    Salem, Gamal A; Shaban, Ahmed; Diab, Hussain A; Elsaghayer, Wesam A; Mjedib, Manal D; Hnesh, Aomassad M; Sahu, Ravi P

    2018-05-16

    The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group. These PCM-induced effects were associated with oxidative stress as demonstrated by increased levels of malondialdehyde (MDA) and reduced levels of hepatic antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Pretreatment of PLME decreased ALT and AST by 78.2% and tissue MDA by 54.1%, and increased hepatic GPx (3.5 folds), CAT (7 folds) and SOD (2.5 folds) compared to PCM group. These PLME-mediated effects were comparable to NAC pretreatment. Histological analysis demonstrates that PLME conserved hepatic tissues against lesions such as inflammation, centrilobular necrosis, and hemorrhages induced by PCM. In contrast, PLAE-mediated effects were less effective in reducing levels of liver function enzymes, oxidative stress, and liver histopathological profiles, and restoring antioxidant defenses against PCM-induced intoxication. These findings indicate that PLME exerts protective effects against PCM-induced hepatotoxicity via scavenging free radicals and restoring hepatic antioxidant enzymes. Thus, PLME and its bioactive components could further be evaluated for their pharmacological properties against drug-induced deleterious effects. Copyright © 2018. Published by Elsevier Masson SAS.

  16. Visualization of Oxidative Stress Induced by Experimental Periodontitis in Keap1-Dependent Oxidative Stress Detector-Luciferase Mice.

    PubMed

    Kataoka, Kota; Ekuni, Daisuke; Tomofuji, Takaaki; Irie, Koichiro; Kunitomo, Muneyoshi; Uchida, Yoko; Fukuhara, Daiki; Morita, Manabu

    2016-11-16

    The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days. The expressions of heme oxygenase-1 (HO-1) and malondialdehyde in periodontal tissue were significantly higher in the periodontitis group than in the control group. Immunofluorescent analysis confirmed that the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) occurred more frequently in the periodontitis group than in the control group. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the OKD-LUC model. Thus, the OKD-LUC mouse model may be useful for exploring the mechanism underlying the relationship between the Nrf2/antioxidant defense pathway and periodontitis by enabling the visualization of oxidative stress over time.

  17. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

    2017-03-01

    Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Protective effects of tea polyphenols and β-carotene against γ-radiation induced mutation and oxidative stress in Drosophila melanogaster.

    PubMed

    Nagpal, Isha; Abraham, Suresh K

    2017-01-01

    The commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster . Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae. Different stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed. β-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila . This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products.

  19. Malvidin and cyanidin derivatives from açai fruit (Euterpe oleracea Mart.) counteract UV-A-induced oxidative stress in immortalized fibroblasts.

    PubMed

    Petruk, Ganna; Illiano, Anna; Del Giudice, Rita; Raiola, Assunta; Amoresano, Angela; Rigano, Maria Manuela; Piccoli, Renata; Monti, Daria Maria

    2017-07-01

    UV-A radiations are known to induce cellular oxidative stress, leading to premature skin aging. Consumption of açai fruit (Euterpe oleracea Martius) is known to have many health benefits due to its high level of antioxidants. Herein, we analyzed the ability of phenolic compounds extracted from this fruit to attenuate UV-A-induced oxidative stress in immortalized fibroblast. A methanol/water açai extract was fractionated by HPLC and each fraction tested for anti-oxidant stress activity. Immortalized fibroblasts were pre-incubated with açai fractions and then exposed to UV-A radiations. Açai extract was found to be able to strongly protect cells from oxidative stress. In particular, reactive oxygen species (ROS) production, GSH depletion, lipid peroxidation and no increase in the phosphorylation levels of proteins involved in the oxidative stress pathway was observed in cells pre-incubated with the extract and then irradiated by UV-A. Mass spectrometry analyses of HPLC fractionated extract led us to the identification of malvidin and cyanidin derivatives as the most active molecules able to counteract the negative effects induced by UV-A irradiation. Our results indicate, for the first time, that açai fruit is a valuable natural source for malvidin and cyanidin to be used as anti-stress molecules and represent good candidates for dietary intervention in the prevention of age related skin damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

    PubMed

    Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

    2017-04-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. PMID:24398106

  2. Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

    PubMed

    Rajagopalan, Rema; Wani, Khalida; Huilgol, Nagaraj G; Kagiya, Tsutomu V; Nair, Cherupally K Krishnan

    2002-06-01

    Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.

  3. Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

    PubMed

    Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

    2016-11-01

    In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

  4. A review: oxidative stress in fish induced by pesticides.

    PubMed

    Slaninova, Andrea; Smutna, Miriam; Modra, Helena; Svobodova, Zdenka

    2009-01-01

    The knowledge in oxidative stress in fish has a great importance for environmental and aquatic toxicology. Because oxidative stress is evoked by many chemicals including some pesticides, pro-oxidant factors' action in fish organism can be used to assess specific area pollution or world sea pollution. Hepatotoxic effect of DDT may be related with lipid peroxidation. Releasing of reactive oxygen species (ROS) after HCB exposure can be realized via two ways: via the uncoupling of the electron transport chain from monooxygenase activity and via metabolism of HCB major metabolite pentachlorophenol. Chlorothalonil disrupts mitochondrial metabolism due to the impairment of NADPH oxidase function. Activation of spleen macrophages and a decrease of catalase (CAT) activity have been observed after endosulfan exposure. Excessive release of superoxide radicals after etoxazole exposure can cause a decrease of CAT activity and increase phagocytic activity of splenocytes. Anticholinergic activity of organophosphates leads to the accumulation of ROS and resulting lipid peroxidation. Carbaryl induces changes in the content of glutathione and antioxidant enzymes activities. The antioxidant enzymes changes have been observed after actuation of pesticides deltamethrin and cypermethrin. Bipyridyl herbicides are able to form redox cycles and thereby cause oxidative stress. Low concentrations of simazine do not cause oxidative stress in carps during sub-chronic tests while sublethal concentrations of atrazin can induce oxidative stress in bluegill sunfish. Butachlor causes increased activity of superoxide dismutase -catalase system in the kidney. Rotenon can inhibit the electron transport in mitochondria and thereby increase ROS production. Dichloroaniline, the metabolite of diuron, has oxidative effects. Oxidative damage from fenpyroximate actuation is related to the disruption of mitochondrial redox respiratory chain. Low concentration of glyphosate can cause mild oxidative stress.

  5. Blue light-induced oxidative stress in live skin.

    PubMed

    Nakashima, Yuya; Ohta, Shigeo; Wolf, Alexander M

    2017-07-01

    Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing redox-sensitive GFP to detect ROS, blue light could produce oxidative stress in live skin. Blue light induced oxidative stress preferentially in mitochondria, but green, red, far red or infrared light did not. Blue light-induced oxidative stress was also detected in cultured human keratinocytes, but the per photon efficacy was only 25% of UVA in human keratinocyte mitochondria, compared to 68% of UVA in mouse skin. Skin autofluorescence was reduced by blue light, suggesting flavins are the photosensitizer. Exposing human skin to the blue light contained in sunlight depressed flavin autofluorescence, demonstrating that the visible component of sunlight has a physiologically significant effect on human skin. The ROS produced by blue light is probably superoxide, but not singlet oxygen. These results suggest that blue light contributes to skin aging similar to UVA. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Sundaram, Bhuvaneshwari; Aggarwal, Aanchal; Sandhir, Rajat

    2013-04-01

    Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50mg/kg body weight) and chromium was administered orally as chromium picolinate (1mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes. Copyright © 2012 Elsevier GmbH. All rights reserved.

  7. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats.

    PubMed

    Salim, Samina; Sarraj, Nada; Taneja, Manish; Saha, Kaustuv; Tejada-Simon, Maria Victoria; Chugh, Gaurav

    2010-04-02

    Recent work has suggested correlation of oxidative stress with anxiety-like behavior. There also is evidence for anxiolytic effects of physical exercise. However, a direct role of oxidative stress in anxiety is not clear and a protective role of physical exercise in oxidative stress-mediated anxiety has never been addressed. In this study, we have utilized rats to test direct involvement of oxidative stress with anxiety-like behavior and have identified oxidative stress mechanisms likely involved in anxiolytic effects of physical exercise. Intraperitoneal injections at non-toxic dose of l-buthionine-(S,R)-sulfoximine (BSO), an agent that increases oxidative stress markers, increased anxiety-like behavior of rats compared to vehicle-treated control rats. Prior 2 weeks treatment with the antioxidant, tempol attenuated BSO-induced anxiety-like behavior of rats suggesting a role of oxidative stress in this phenomenon. Moreover, moderate treadmill exercise prevented BSO-induced anxiety-like behavior of rats and also prevented BSO-mediated increase in oxidative stress markers in serum, urine and brain tissue homogenates from hippocampus, amygdala and locus coeruleus. Thus increasing oxidative stress increases anxiety-like behavior of rats. Moreover, antioxidant or treadmill exercise training both reduce oxidative stress in the rat brain regions implicated in anxiety response and prevent anxiety-like behavior of rats. Published by Elsevier B.V.

  8. Peroxisome proliferator-activated receptor delta (PPARdelta) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis.

    PubMed

    Pesant, Matthieu; Sueur, Stéphanie; Dutartre, Patrick; Tallandier, Mireille; Grimaldi, Paul A; Rochette, Luc; Connat, Jean-Louis

    2006-02-01

    Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied. We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we also showed that the selective PPARdelta agonist GW501516 protected cells from H(2)O(2)-induced cell death. The protective effect of GW501516 was due to an inhibition of H(2)O(2)-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARdelta that the protection induced by GW501516 was totally dependent on PPARdelta. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H(2)O(2)-triggered apoptosis, as evidenced by annexin-V labeling. Taken together, our results account for an important role of PPARdelta in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARdelta appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences.

  9. The effect of grape seed extract on radiation-induced oxidative stress in the rat liver.

    PubMed

    Cetin, Aysun; Kaynar, Leylagül; Koçyiğit, Ismail; Hacioğlu, Sibel Kabukçu; Saraymen, Recep; Oztürk, Ahmet; Orhan, Okan; Sağdiç, Osman

    2008-06-01

    The tolerance of the liver is considerably low when an effective radiation (RTx) dose needs to be delivered in patients in whom either their liver or whole body area has to be irradiated. The aim of this study was to evaluate the possible protective effect of grape seed extract on liver toxicity induced by RTx in the rat liver. We used four groups, each consisting of 12 healthy male Wistar rats. RTx-grape seed extract group: rats were given grape seed extract (100 mg/kg) orally for seven days, following 8 Gy whole body irradiation, and grape seed extract was maintained for four days. RTx group: the same protocol was applied in this group; however, they received distilled water instead of grape seed extract. Grape seed extract group: only grape seed extract solution was administered for 11 consecutive days in the same fashion. only distilled water (orally) was administered in a similar manner. The level of malondialdehyde, an end product of lipid peroxidation, and the activities of superoxide dismutase and catalase, two important endogenous antioxidants, were evaluated in tissue homogenates. Grape seed extract was seen to protect the cellular membrane from oxidative damage and consequently from protein and lipid oxidation. In the RTx group, malondialdehyde levels were extremely higher than those of the grape seed extract-RTx group (p<0.001). Grape seed extract administration moderately reserved the malondialdehyde levels. RTx therapy decreased superoxide dismutase and catalase activities in the liver homogenates (p<0.001), and these alterations were significantly reversed by grape seed extract treatment (p<0.001). There were no differences between the grape seed extract- RTx, grape seed extract and control groups with regard to antioxidant activity (p>0.05). The levels of antioxidant parameters on RTx-induced liver toxicity were restored to control values with grape seed extract therapy. Grape seed extract may be promising as a therapeutic option in RTx-induced

  10. Oxidative Stress in Schizophrenia: An Integrated Approach

    PubMed Central

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

    2010-01-01

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

  11. How Magnetotactic Bacteria Respond to Radiation Induced Stress and Damage: Comparative Genomics Evidences for Evolutionary Adaptation

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Pan, Y.

    2015-12-01

    Solar radiation and galactic cosmic radiation is believed to be major restriction factors influencing survival and evolution of life. On planet earth, geomagnetic field along with atmosphere protect living beings from the harmful radiation. During a geomagnetic reversal or excursion, however, the efflux of charged particles on earth surface would increase as the shielding effect of magnetic field decrease. The stratospheric ozone can also be partially stripped away by solar wind when the strength of the field is weak, leading to an increasing ultraviolet radiation penetration to the earth surface. However, studies on the mechanism of radiation induced stress and damage are focused only on bacteria that have no response to magnetic field. This study was motivated by the need to fill the gap upon knowledge of that on magnetic field sensitive microorganism. Magnetotactic bacteria (MTB) are a group of microbes that are able to synthesis intracellular nano-sized magnetic particles (named magnetosomes). These chain-arranged magnetosomes help MTB sense and swim along the magnetic field to find their optimal living environment efficiently. In this paper, in silico prediction of stress and damage repair genes in response to different radiation were carried out on the complete genome of four nonmagnetotactic and four magnetotactic spirilla. In silico analyses of the genomes of magnetic field sensitive and non-sensitive spirilla revealed: 1) all strains contain genes for regulate responses superoxide and peroxide stress, DNA pyrimidine dimer and string breaks; 2) non-magnetotactic spirilla have more genes dealing with oxidative stress, while magnetotactic spirilla may benefit from magnetotaxis by swimming into oxic-anoxic zone away from oxidative stress and direct radiation damage; yet, the lipid hydroperoxide peroxidase gene in MTB may be responsible for possible ROS generated by the membrane enveloped magnetite magnetosome; 3) magnetotactic spirilla possess SOS rec

  12. Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

    PubMed

    Shukla, Pratiksha; Singh, A K

    2015-09-01

    The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

  13. Physiological changes induced in four bacterial strains following oxidative stress.

    PubMed

    Baatout, S; De Boever, P; Mergeay, M

    2006-01-01

    In order to study the behaviour and resistance of bacteria under extreme conditions, physiological changes associated with oxidative stress were monitored using flow cytometry. The study was conducted to assess the maintenance of membrane integrity and potential as well as the esterase activity, the intracellular pH and the production of superoxide anions in four bacterial strains (Ralstonia metallidurans, Escherichia coli, Shewanella oneidensis and Deinococcus radiodurans). The strains were chosen for their potential usefulness in bioremediation. Suspensions of R. metallidurans, E. coli, S. oneidensis and D. radiodurans were submitted to 1 h oxidative stress (H2O2 at various concentrations from 0 to 880 mM). Cell membrane permeability (propidium iodide) and potential (rhodamine-123, 3,3'-dihexyloxacarbocyanine iodide), intracellular esterase activity (fluorescein diacetate), intracellular reactive oxygen species concentration (hydroethidine) and intracellular pH (carboxyflurorescein diacetate succinimidyl ester (5(6)) were monitored to evaluate the physiological state and the overall fitness of individual bacterial cells under oxidative stress. The four bacterial strains exhibited varying sensitivities towards H2O2. However, for all bacterial strains, some physiological damage could already be observed from 13.25 mM H2O2 onwards, in particular with regard to their membrane permeability. Depending on the bacterial strains, moderate to high physiological damage could be observed between 13.25 mM and 220 mM H2O2. Membrane potential, esterase activity, intracellular pH and production of superoxide anion production were considerably modified at high H2O2 concentrations in all four strains. In conclusion, we show that a range of significant physiological alterations occurs when bacteria are challenged with H2O2 and fluorescent staining methods coupled with flow cytometry are useful for monitoring the changes induced not only by oxidative stress but also by other

  14. Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

    PubMed

    Garnacho-Castaño, Manuel Vicente; Alva, Norma; Sánchez-Nuño, Sergio; Bardallo, Raquel G; Palomeque, Jesús; Carbonell, Teresa

    2016-12-01

    Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O 2 ), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

  15. Effects of Dietary Iron and Gamma Radiation on the Rat Retina

    NASA Technical Reports Server (NTRS)

    Morgan, Jennifer; Marshall, Grace; Theriot, Corey A.; Chacon, Natalia; Zwart, Sara; Zanello, Susana B.

    2012-01-01

    A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes

  16. Nano lead oxide and epdm composite for development of polymer based radiation shielding material: Gamma irradiation and attenuation tests

    NASA Astrophysics Data System (ADS)

    Özdemir, T.; Güngör, A.; Akbay, I. K.; Uzun, H.; Babucçuoglu, Y.

    2018-03-01

    It is important to have a shielding material that is not easily breaking in order to have a robust product that guarantee the radiation protection of the patients and radiation workers especially during the medical exposure. In this study, nano sized lead oxide (PbO) particles were used, for the first time, to obtain an elastomeric composite material in which lead oxide nanoparticles, after the surface modification with silane binding agent, was used as functional material for radiation shielding. In addition, the composite material including 1%, 5%, 10%, 15% and 20% weight percent nano sized lead oxide was irradiated with doses of 81, 100 and 120 kGy up to an irradiation period of 248 days in a gamma ray source with an initial dose rate of 21.1 Gy/h. Mechanical, thermal properties of the irradiated materials were investigated using DSC, DMA, TGA and tensile testing and modifications in thermal and mechanical properties of the nano lead oxide containing composite material via gamma irradiation were reported. Moreover, effect of bismuth-III oxide addition on radiation attenuation of the composite material was investigated. Nano lead oxide and bismuth-III oxide particles were mixed with different weight ratios. Attenuation tests have been conducted to determine lead equivalent values for the developed composite material. Lead equivalent thickness values from 0.07 to 0.65 (2-6 mm sample thickness) were obtained.

  17. Scavenging and antioxidant properties of different grape cultivars against ionizing radiation-induced liver damage ex vivo.

    PubMed

    Singha, Indrani; Das, Subir Kumar

    2016-04-01

    Ionizing radiation (IR) has become an integral part of the modern medicine--both for diagnosis as well as therapy. However, normal tissues or even distant cells also suffer IR-induced free radical insult. It may be more damaging in longer term than direct radiation exposure. Antioxidants provide protection against IR-induced damage. Grapes are the richest source of antioxidants. Here, we assessed the scavenging properties of four grape (Vitis vinifera) cultivars, namely Flame seedless (Black), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Green), and also evaluated their protective action against γ-radiation-induced oxidative stress in liver tissue ex vivo. The scavenging abilities of grape seeds [2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀ = 0.008 ± 0.001 mg/mL), hydrogen peroxide (IC₅₀ = 0.49 to 0.8 mg/mL), hydroxyl radicals (IC₅₀ = 0.08 ± 0.008 mg/mL), and nitric oxide (IC₅₀ = 0.8 ± 0.08 mg/mL)] were higher than that of skin or pulp. Gamma (γ) radiation exposure to sliced liver tissues ex vivo from goat, @ 6 Gy significantly (P < 0.001) decreased reduced glutathione (GSH) content by 21.2% and also activities of catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST) by 49.5, 66.0, 70.3, 73.6%, respectively. However, it increased thiobarbituric acid reactive substances (TBARS) by 2.04-fold and nitric oxide level by 48.6% compared to untreated group. Further increase in doses (10 or 16 Gy) of γ-radiation correspondingly decreased GSH content and enzyme activities, and increased TBARS and nitric oxide levels. Grape extract treatment prior to ionizing radiation exposure ameliorated theses effects at varying extent. The seed extracts exhibited strong antioxidant potential compared to skin or pulp extracts of different grape cultivars against oxidative damage by ionizing radiation (6 Gy, 10 Gy and 16 Gy) in sliced liver tissues ex vivo. Grape extracts at

  18. "Cumulative Stress": The Effects of Maternal and Neonatal Oxidative Stress and Oxidative Stress-Inducible Genes on Programming of Atopy.

    PubMed

    Manti, Sara; Marseglia, Lucia; D'Angelo, Gabriella; Cuppari, Caterina; Cusumano, Erika; Arrigo, Teresa; Gitto, Eloisa; Salpietro, Carmelo

    2016-01-01

    Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes. Analyzing the role of maternal and neonatal oxidative stress and oxidative stress-inducible genes, the purpose of this review was to summarize what is known about the relationship between maternal and neonatal OS-related genes and the development of atopic diseases.

  19. H2S protects against methionine-induced oxidative stress in brain endothelial cells.

    PubMed

    Tyagi, Neetu; Moshal, Karni S; Sen, Utpal; Vacek, Thomas P; Kumar, Munish; Hughes, William M; Kundu, Soumi; Tyagi, Suresh C

    2009-01-01

    Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nomega-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress.

  20. Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species.

    PubMed

    Choi, Kyungsun; Kim, Jinho; Kim, Gyung W; Choi, Chulhee

    2009-11-01

    Oxidative stress is deeply involved in various brain diseases, including neurodegenerative diseases, stroke, and ischemia/reperfusion injury. Mitochondria are thought to be the target and source of oxidative stress. We investigated the role of mitochondria in oxidative stress-induced necrotic neuronal cell death in a neuroblastoma cell line and a mouse model of middle cerebral artery occlusion. The exogenous administration of hydrogen peroxide was used to study the role of oxidative stress on neuronal cell survival and mitochondrial function in vitro. Hydrogen peroxide induced non-apoptotic neuronal cell death in a c-Jun N-terminal kinase- and poly(ADP-ribosyl) polymerase-dependent manner. Unexpectedly, hydrogen peroxide treatment induced transient hyperpolarization of the mitochondrial membrane potential and a subsequent delayed burst of endogenous reactive oxygen species (ROS). The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo. The inhibition of mitochondrial hyperpolarization can protect neuronal cells from oxidative stress-induced necrotic cell death, suggesting a novel method of therapeutic intervention in oxidative stress-induced neurological disease.

  1. Oxidative stress induces senescence in human mesenchymal stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brandl, Anita; Meyer, Matthias; Bechmann, Volker

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

  2. Oxidative Stress Induces Disruption of the Axon Initial Segment

    PubMed Central

    Clark, Kareem C.; Sword, Brooke A.; Dupree, Jeffrey L.

    2017-01-01

    The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex. PMID:29228786

  3. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

    PubMed Central

    Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

    2013-01-01

    Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. PMID:22915786

  4. Oxygen radical absorbance capacity (ORAC) and exercise-induced oxidative stress in trotters.

    PubMed

    Kinnunen, Susanna; Hyyppä, Seppo; Lehmuskero, Arja; Oksala, Niku; Mäenpää, Pekka; Hänninen, Osmo; Atalay, Mustafa

    2005-12-01

    Strenuous exercise is a potent inducer of oxidative stress, which has been suggested to be associated with disturbances in muscle homeostasis, fatigue and injury. There is no comprehensive or uniform view of the antioxidant status in horses. We have previously shown that moderate exercise induces protein oxidation in trotters. The aim of this study was to measure the antioxidative capacity of the horse in relation to different antioxidant components and oxidative stress markers after a single bout of moderate exercise to elucidate the mechanisms of antioxidant protection in horses. Eight clinically normal and regularly trained standard-bred trotters were treadmill-exercised for 53 min at moderate intensity. Blood samples were collected prior to and immediately after exercise and at 4 and 24 h of recovery. Muscle biopsies from the middle gluteal muscle were taken before exercise and after 4 h of recovery. Acute induction of oxygen radical absorbance capacity (ORAC) did not prevent exercise-induced oxidative stress, which was demonstrated by increased lipid hydroperoxides (LPO). Pre-exercise ORAC levels were, however, a determinant of total glutathione content of the blood after 4 and 24 h of recovery. Furthermore, baseline ORAC level correlated negatively with 4-h recovery LPO levels. Our results imply that horses are susceptible to oxidative stress, but a stronger antioxidant capacity may improve coping with exercise-induced oxidative stress.

  5. Modulation of ionizing radiation induced oxidative imbalance by semi-fractionated extract of Piper betle

    PubMed Central

    Verma, Savita; Dutta, Ajaswrata; Sankhwar, Sanghmitra; Shukla, Sandeep Kumar

    2010-01-01

    The study was planned to evaluate modulatory effect of aqueous extract of Piper betle leaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract, we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP ) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 µg/ml) and superoxide radicals (up to 95% at 80 µg/ml), chelated metal ions (up to 83% at 50 µg/ml) and inhibited lipid peroxidation (up to 45.65% at 500 µg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of radiation

  6. Reduction of Radiation-Induced Vascular Nitrosative Stress by the Vitamin E Analog {gamma}-Tocotrienol: Evidence of a Role for Tetrahydrobiopterin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Berbee, Maaike; Fu Qiang; Boerma, Marjan

    2011-03-01

    Purpose: The vitamin E analog {gamma}-tocotrienol (GT3) is a powerful radioprotector. GT3 reduces postradiation vascular peroxynitrite production, an effect dependent on inhibition of hydroxy-methylglutaryl-coenzyme A reductase. Hydroxy-methylglutaryl-coenzyme A reductase inhibitors mediate their pleiotropic effects via endothelial nitric oxide synthase that requires the cofactor tetrahydrobiopterin (BH4). This study investigated the effects of radiation on BH4 bioavailability and of GT3 on BH4 metabolism. Methods and Materials: Mice were exposed to 8.5 Gy of total body irradiation (TBI). Lung BH4 and total biopterin concentrations were measured 0, 3.5, 7, 14, and 21 days after TBI by use of differential oxidation followed by high-performancemore » liquid chromatography. The effect of exogenous GT3 and BH4 treatment on postradiation vascular oxidative stress and bone marrow colony-forming units were assessed in vivo. The effect of GT3 on endothelial cell apoptosis and endothelial expression of guanosine triphosphate (GTP) cyclohydrolase 1 (GTPCH), GTPCH feedback regulatory protein (GFRP), GFRP transcription, GFRP protein levels, and GFRP-GTPCH protein binding was determined in vitro. Results: Compared with baseline levels, lung BH4 concentrations decreased by 24% at 3.5 days after TBI, an effect that was reversed by GT3. At 14 and 21 days after TBI, compensatory increases in BH4 (58% and 80%, respectively) were observed. Relative to vehicle-treated controls, both GT3 and BH4 supplementation reduced postirradiation vascular peroxynitrite production at 3.5 days (by 66% and 33%, respectively), and BH4 resulted in a 68% increase in bone marrow colony-forming units. GT3 ameliorated endothelial cell apoptosis and reduced endothelial GFRP protein levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene. Conclusions: BH4 bioavailability is reduced in the early postradiation phase. Exogenous administration of BH4 reduces postirradiation vascular

  7. Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

    PubMed

    Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

    2014-12-01

    The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.

  8. H2S Protects Against Methionine–Induced Oxidative Stress in Brain Endothelial Cells

    PubMed Central

    Tyagi, Neetu; Moshal, Karni S.; Sen, Utpal; Vacek, Thomas P.; Kumar, Munish; Hughes, William M.; Kundu, Soumi

    2009-01-01

    Abstract Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nω-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress. Antioxid. Redox Signal. 11, 25–33. PMID:18837652

  9. Evaluation of the Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

    2011-01-01

    NASA is concerned with the health risks to astronauts, particularly those risks related to radiation exposure. Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of (A) peripheral leukocyte distribution; (B) plasma cytokine levels; (C) cytokine production profiles following whole blood stimulation of either T cells or monocytes.

  10. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

    PubMed

    Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

    2009-06-01

    In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy.

  11. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

    PubMed

    Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

    2017-03-15

    It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shin, Jung Ar; Chung, Jin Sil; Cho, Sang-Ho

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain.more » Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.« less

  13. Hydrogen-peroxide-induced oxidative stress responses in Desulfovibrio vulgaris Hildenborough

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, A.; He, Z.; Redding-Johanson, A.M.

    2010-07-01

    To understand how sulphate-reducing bacteria respond to oxidative stresses, the responses of Desulfovibrio vulgaris Hildenborough to H{sub 2}O{sub 2}-induced stresses were investigated with transcriptomic, proteomic and genetic approaches. H{sub 2}O{sub 2} and induced chemical species (e.g. polysulfide, ROS) and redox potential shift increased the expressions of the genes involved in detoxification, thioredoxin-dependent reduction system, protein and DNA repair, and decreased those involved in sulfate reduction, lactate oxidation and protein synthesis. A gene coexpression network analysis revealed complicated network interactions among differentially expressed genes, and suggested possible importance of several hypothetical genes in H{sub 2}O{sub 2} stress. Also, most of themore » genes in PerR and Fur regulons were highly induced, and the abundance of a Fur regulon protein increased. Mutant analysis suggested that PerR and Fur are functionally overlapped in response to stresses induced by H{sub 2}O{sub 2} and reaction products, and the upregulation of thioredoxin-dependent reduction genes was independent of PerR or Fur. It appears that induction of those stress response genes could contribute to the increased resistance of deletion mutants to H{sub 2}O{sub 2}-induced stresses. In addition, a conceptual cellular model of D. vulgaris responses to H{sub 2}O{sub 2} stress was constructed to illustrate that this bacterium may employ a complicated molecular mechanism to defend against the H{sub 2}O{sub 2}-induced stresses.« less

  14. Protective effects of Nano-elemental selenium against chromium-vi-induced oxidative stress in broiler liver.

    PubMed

    Xueting, L; Rehman, M U; Zhang, H; Tian, X; Wu, X; Shixue; Mehmood, K; Zhou, D

    2018-01-01

    The valuable role of selenium in mitigation of oxidative stress and heavy metal toxicity is well-known. Thus, the aim of the current study on broiler chickens was to examine whether nano elemental selenium (Nano-Se) supplementation can reduce the effects of chromium VI (K2Cr2O7) toxicity. For this purpose, a total of 150, one-day-old broiler chickens were allotted to five groups with three replicates: control group (standard diet), poisoned group (K2Cr2O7 via drinking water), protection group (K2Cr2O7 + Nano- Se), cure group (K2Cr2O7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group). The broilers were detected by the activities of marker enzymes and oxidative stress markers including, aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and superoxide dismutase (SOD), glutathione peroxidase (GSH-px), malondialdehyde (MDA), respectively. The (K2Cr2O7 administration caused histopathological damage in the liver of the chickens. Moreover, changes in serum biochemical indicators and oxidative stress parameters were also observed. Nano-Se supplementation increased the levels of GSH-px but reduced the activities of SOD, MDA, GGT, ALT and AST in the experimental groups (P less than 0.05). Our results showed that Nano-Se plays a protective role by preventing the oxidative stress induced by the chromium VI in broiler chickens.

  15. Stress induction in the bacteria Shewanella oneidensis and Deinococcus radiodurans in response to below-background ionizing radiation.

    PubMed

    Castillo, Hugo; Schoderbek, Donald; Dulal, Santosh; Escobar, Gabriela; Wood, Jeffrey; Nelson, Roger; Smith, Geoffrey

    2015-01-01

    The 'Linear no-threshold' (LNT) model predicts that any amount of radiation increases the risk of organisms to accumulate negative effects. Several studies at below background radiation levels (4.5-11.4 nGy h(-1)) show decreased growth rates and an increased susceptibility to oxidative stress. The purpose of our study is to obtain molecular evidence of a stress response in Shewanella oneidensis and Deinococcus radiodurans grown at a gamma dose rate of 0.16 nGy h(-1), about 400 times less than normal background radiation. Bacteria cultures were grown at a dose rate of 0.16 or 71.3 nGy h(-1) gamma irradiation. Total RNA was extracted from samples at early-exponential and stationary phases for the rt-PCR relative quantification (radiation-deprived treatment/background radiation control) of the stress-related genes katB (catalase), recA (recombinase), oxyR (oxidative stress transcriptional regulator), lexA (SOS regulon transcriptional repressor), dnaK (heat shock protein 70) and SOA0154 (putative heavy metal efflux pump). Deprivation of normal levels of radiation caused a reduction in growth of both bacterial species, accompanied by the upregulation of katB, recA, SOA0154 genes in S. oneidensis and the upregulation of dnaK in D. radiodurans. When cells were returned to background radiation levels, growth rates recovered and the stress response dissipated. Our results indicate that below-background levels of radiation inhibited growth and elicited a stress response in two species of bacteria, contrary to the LNT model prediction.

  16. Excess copper induced oxidative stress and response of antioxidants in rice.

    PubMed

    Thounaojam, Thorny Chanu; Panda, Piyalee; Panda, P; Mazumdar, Purabi; Mazumdar, P; Kumar, Devanand; Sharma, Gauri Dutta; Sharma, G D; Sahoo, Lingaraj; Sahoo, L; Panda, Sanjib Kumar; Panda, S K

    2012-04-01

    To investigate the effects of copper (Cu), rice plant (Oryza sativa. L. var. MSE-9) was treated with different Cu concentrations (0, 10, 50 and 100 μM) for 5 days in hydroponic condition. Gradual decrease in shoot and root growth was observed with the increase of Cu concentration and duration of treatment where maximum inhibition was recorded in root growth. Cu was readily absorbed by the plant though the maximum accumulation was found in root than shoot. Hydrogen peroxide (H(2)O(2)) production and lipid peroxidation were found increased with the elevated Cu concentration indicating excess Cu induced oxidative stress. Antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) and glutathione reductase (GR) were effectively generated at the elevated concentrations of Cu though catalase (CAT) did not show significant variation with respect to control. Ascorbate (ASH), glutathione (GSH) and proline contents were also increased in all the Cu treated plants compared with the control. SOD isoenzyme was greatly affected by higher concentration of Cu and it was consistent with the changes of the activity assayed in solution. The present study confirmed that excess Cu inhibits growth, induced oxidative stress by inducing ROS formation while the stimulated antioxidative system appears adaptive response of rice plant against Cu induced oxidative stress. Moreover proline accumulation in Cu stress plant seems to provide additional defense against the oxidative stress. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Protective role of Vernonia cinerea L. against gamma radiation--induced immunosupression and oxidative stress in mice.

    PubMed

    Pratheeshkumar, P; Kuttan, Girija

    2011-08-01

    The radioprotective effect of Vernonia cinerea extract was studied in balb/c mice. Whole-body irradiation of γ-rays (6 Gy) given to animals reduced the white blood cell count, bone marrow cellularity and α-esterase positive cells in control animals, which were elevated by the administration of V. cinerea extract (20 mg/kg body weight [b.wt.], intraperitoneally [i.p.]). The elevated levels of serum enzymes alkaline phosphatase (ALP), glutamate pyruvate transferases (GPT) and lipid peroxidation (LPO) after irradiation were also reduced with V. cineria extract administration. V. cinerea treatment also significantly enhanced the animal's antioxidant status by enhancing the activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) level in irradiated animals. Histopathological analysis of liver and small intestine also suggests that V. cinerea could reduce the tissue damages induced by radiation. The level of pro-inflammatory cytokines such as interleukin 1β (IL-1β), tumour necrosis factor α (TNF-α) and C-reactive protein (CRP) elevated after irradiation, which were significantly reduced by V. cinerea extract administration. On the other hand, the extract stimulated the production of other cytokines such as granulocyte monocyte-colony stimulating factor (GM-CSF) and interferon-γ (IFN-γ) in animals exposed to radiation. Agarose gel electrophoresis of DNA isolated from bone marrow of control animals showed heavy DNA damage, but a reduced DNA damage was seen in animals treated with V. cinerea extract. Administration of V. cinerea did not compromise the anti-neoplastic efficiency of radiation. In fact, there was a synergistic action of radiation and V. cinerea in reducing the solid tumours in mice. Methanolic extract of V. cinerea given i.p. showed a significant radioprotective activity without compromising the radiotherapeutic efficacy of radiation, indicating its possible use as an adjuvant during

  18. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.

    PubMed

    Brown, Charles O; Salem, Kelley; Wagner, Brett A; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R; Goel, Apollina

    2012-06-15

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.

  19. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    PubMed Central

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy. PMID:22471522

  20. Oxidative stress is involved in Dasatinib-induced apoptosis in rat primary hepatocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xue, Tao; Luo, Peihua; Zhu, Hong

    2012-06-15

    Dasatinib, a multitargeted inhibitor of BCR–ABL and SRC kinases, exhibits antitumor activity and extends the survival of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). However, some patients suffer from hepatotoxicity, which occurs through an unknown mechanism. In the present study, we found that Dasatinib could induce hepatotoxicity both in vitro and in vivo. Dasatinib reduced the cell viability of rat primary hepatocytes, induced the release of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in vitro, and triggered the ballooning degeneration of hepatocytes in Sprague–Dawley rats in vivo. Apoptotic markers (chromatin condensation, cleaved caspase-3 andmore » cleaved PARP) were detected to indicate that the injury induced by Dasatinib in hepatocytes in vitro was mediated by apoptosis. This result was further validated in vivo using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Here we found that Dasatinib dramatically increased the level of reactive oxygen species (ROS) in hepatocytes, reduced the intracellular glutathione (GSH) content, attenuated the activity of superoxide dismutase (SOD), generated malondialdehyde (MDA), a product of lipid peroxidation, decreased the mitochondrial membrane potential, and activated nuclear factor erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinases (MAPK) related to oxidative stress and survival. These results confirm that oxidative stress plays a pivotal role in Dasatinib-mediated hepatotoxicity. N-acetylcysteine (NAC), a typical antioxidant, can scavenge free radicals, attenuate oxidative stress, and protect hepatocytes against Dasatinib-induced injury. Thus, relieving oxidative stress is a viable strategy for reducing Dasatinib-induced hepatotoxicity. -- Highlights: ►Dasatinib shows potential hepatotoxicity both in vitro and in vivo. ►Apoptosis plays a vital role in

  1. Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

    PubMed

    Akolkar, Gauri; da Silva Dias, Danielle; Ayyappan, Prathapan; Bagchi, Ashim K; Jassal, Davinder S; Salemi, Vera Maria Cury; Irigoyen, Maria Claudia; De Angelis, Katia; Singal, Pawan K

    2017-10-01

    Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1β, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins. NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy

  2. Oxidative stress involvement in Physalis angulata-induced apoptosis in human oral cancer cells.

    PubMed

    Lee, H-Z; Liu, W-Z; Hsieh, W-T; Tang, F-Y; Chung, J-G; Leung, Henry W-C

    2009-03-01

    In this report, we investigated the role of oxidative stress in Physalis angulata-induced apoptosis of human oral cancer cells. P. angulata-induced apoptosis was characterized by nuclear morphological changes, membrane blebbing and activation of caspase-9. Exposure of HSC-3 cells to P. angulata caused production of reactive oxygen species and up-regulation of oxidative stress markers heme oxygenase-1 (HO-1), superoxide dismutase (SOD), heat shock protein 70 (HSP70) and caspase-4. Down-regulation of HO-1, SOD and HSP70 proteins expression by attenuation of oxidative stress, pretreatment with glutathione or N-acetylcysteine, significantly decreased P. angulata-triggered cell death. The present study also demonstrated that the mitochondria and the endoplasmic reticulum are the targets of P. angulata in HSC-3 cells. Our results revealed that: (1) reactive oxygen species may play a dominant role in this process, (2) P. angulata induces oxidative stress in HSC-3 cells, (3) P. angulata-initiated apoptosis is caused through oxidative stress-dependent induction of heme oxygenase-1, Cu/Zn SOD and HSP70 proteins expression and (4) antioxidants inhibited P. angulata-induced cell death through inhibition of the proteins expression of HO-1, Cu/Zn SOD and HSP70.

  3. Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis

    PubMed Central

    Wang, Yan; Xu, Yingqiong; Liu, Qian; Zhang, Yuanyuan; Gao, Zhen; Yin, Mingzhu; Jiang, Nan; Cao, Guosheng; Yu, Boyang; Cao, Zhengyu; Kou, Junping

    2017-01-01

    Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H2O2), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear. We demonstrate that myosin IIA was required for neuronal contraction, while myosin IIB was required for neuronal outgrowth in normal conditions. During H2O2-induced neuronal apoptosis, myosin IIA, rather than IIB, interacted with actin filaments to generate contractile forces that lead to morphological changes. Moreover, myosin IIA knockout using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) reduced H2O2-induced neuronal apoptosis and the associated morphological changes. We further demonstrate that caspase-3/Rho-associated kinase 1 (ROCK1) dependent phosphorylation of myosin light chain (MLC) was required for the formation of the myosin IIA-actin complex. Meanwhile, either inhibition of myosin II ATPase with blebbistatin or knockdown of myosin IIA with siRNA reversely attenuated caspase-3 activation, suggesting a positive feedback loop during oxidative stress-induced apoptosis. Based on our observation, myosin IIA-actin complex contributes to actomyosin contractility and is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. This study unravels the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases. PMID:28352215

  4. Live-cell Imaging Approaches for the Investigation of Xenobiotic-Induced Oxidant Stress

    EPA Science Inventory

    BACKGROUND: Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular t...

  5. NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent

    EPA Science Inventory

    Exposure to metallic environmental toxicants has been demonstrated to induce a variety of oxidative stress responses in mammalian cells. The transcription factor Nrf2 is activated in response to oxidative stress and coordinates the expression of antioxidant gene products. In this...

  6. Interferon-gamma enhances radiation-induced cell death via downregulation of Chk1

    PubMed Central

    Kim, Kwang Seok; Choi, Kyu Jin; Bae, Sangwoo

    2012-01-01

    Interferon-gamma (IFNγ) is a cytokine with roles in immune responses as well as in tumor control. Interferon is often used in cancer treatment together with other therapies. Here we report a novel approach to enhancement of cancer cell killing by combined treatment of IFNγ with ionizing radiation. We found that IFNγ treatment alone in HeLa cells induced phosphorylation of Chk1 in a time- and dose-dependent manner, and resulted in cell arrest. Moreover IFNγ treatment was correlated with attenuation of Chk1 as the treatment shortened protein half-life of Chk1. As Chk1 is an essential cell cycle regulator for viability after DNA damage, attenuation of Chk1 by IFNγ pre-treatment in HeLa cells resulted in increased cell death following ionizing radiation about 2-folds than ionizing radiation treatment alone whereas IFNγ treatment alone had little effect on cell death. X-linked inhibitor of apoptosis-associated factor 1 (XAF1), an IFN-induced gene, seems to partly regulate IFNγ-induced Chk1 destabilization and radiation sensitivity because transient depletion of XAF1 by siRNA prevented IFNγ-induced Chk1 attenuation and partly protected cells from IFNγ-enhanced radiation cell killing. Therefore the results provide a novel rationale to combine IFNγ pretreatment and DNA-damaging anti-cancer drugs such as ionizing radiation to enhance cancer cell killing. PMID:22825336

  7. Nanoparticle-induced oxidation of corona proteins initiates an oxidative stress response in cells†

    PubMed Central

    Jayaram, Dhanya T.; Runa, Sabiha; Kemp, Melissa L.

    2017-01-01

    Titanium dioxide nanoparticles (TiO2 NPs), used as pigments and photocatalysts, are ubiquitous in our daily lives. Previous work has observed cellular oxidative stress in response to the UV-excitation of photocatalytic TiO2 NPs. In comparison, most human exposure to TiO2 NPs takes place in the dark, in the lung following inhalation or in the gut following consumption of TiO2 NP food pigment. Our spectroscopic characterization shows that both photocatalytic and food grade TiO2 NPs, in the dark, generate low levels of reactive oxygen species (ROS), specifically hydroxyl radicals and superoxides. These ROS oxidize serum proteins that form a corona of proteins on the NP surface. This protein layer is the interface between the NP and the cell. An oxidized protein corona triggers an oxidative stress response, detected with PCR and western blotting. Surface modification of TiO2 NPs to increase or decrease surface defects correlates with ROS generation and oxidative stress, suggesting that NP surface defects, likely oxygen vacancies, are the underlying cause of TiO2 NP-induced oxidative stress. PMID:28537609

  8. Dual behavior of N-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains.

    PubMed

    Bauer, Alison K; Fitzgerald, Mary; Ladzinski, Adam T; Lenhart Sherman, Sydney; Maddock, Benjamin H; Norr, Zoe M; Miller, Robert R

    2017-10-01

    Ethanol (EtOH) causes oxidative stress in embryos. Because N-acetylcysteine (NAC) failures and successes in ameliorating EtOH-induced oxidative stress have been reported, the objective was to determine if exogenous NAC ameliorated EtOH-induced oxidative stress within embryonic chick brains. Control eggs were injected with approximately 25 µl of water on day 0, 1, and 2 of development (E 0-2 ). Experimental eggs were injected with dosages of either 3.0 mmol EtOH/kg egg; 747 µmol NAC/kg egg; 3.0 mmol EtOH and 747 µmol NAC/kg egg; 1000 µmol NAC/kg egg; or 3.0 mmol EtOH and 1000 µmol NAC/kg during the first 3 days of development (E 0-2 ). At 11 days of development (E 11 ; late embryogenesis), brains were harvested and subsequently assayed for oxidative stress markers including the loss of long-chain membrane polyunsaturated fatty acids (PUFAs); the accumulation of lipid hydroperoxides (LPO); decreased glutathione (GSH) and glutathione/glutathione disulfide (GSSG) levels; and decreased glutathione peroxidase (GPx) activities. EtOH (3 mmol/kg egg), medium NAC (747 µmol/kg egg), and EtOH and medium NAC promoted oxidative stress. These treatments caused decreased brain membrane long-chain PUFAs; increased LPO levels; decreased GSH levels and GSH/GSSG levels; and decreased Se-dependent GPx activities. High NAC dosages (1000 µmol/kg egg) attenuated EtOH-induced oxidative stress within EtOH and high NAC-treated chick brains. Exogenous EtOH and/or medium NAC propagated oxidative stress. Meanwhile, high NAC ameliorated EtOH-induced oxidative stress.

  9. Role of Oxidative Stress in Transformation Induced by Metal Mixture

    PubMed Central

    Martín, Silva-Aguilar; Emilio, Rojas; Mahara, Valverde

    2011-01-01

    Metals are ubiquitous pollutants present as mixtures. In particular, mixture of arsenic-cadmium-lead is among the leading toxic agents detected in the environment. These metals have carcinogenic and cell-transforming potential. In this study, we used a two step cell transformation model, to determine the role of oxidative stress in transformation induced by a mixture of arsenic-cadmium-lead. Oxidative damage and antioxidant response were determined. Metal mixture treatment induces the increase of damage markers and the antioxidant response. Loss of cell viability and increased transforming potential were observed during the promotion phase. This finding correlated significantly with generation of reactive oxygen species. Cotreatment with N-acetyl-cysteine induces effect on the transforming capacity; while a diminution was found in initiation, in promotion phase a total block of the transforming capacity was observed. Our results suggest that oxidative stress generated by metal mixture plays an important role only in promotion phase promoting transforming capacity. PMID:22191014

  10. Betanodavirus induces oxidative stress-mediated cell death that prevented by anti-oxidants and zfcatalase in fish cells.

    PubMed

    Chang, Chih-Wei; Su, Yu-Chin; Her, Guor-Mour; Ken, Chuian-Fu; Hong, Jiann-Ruey

    2011-01-01

    The role of oxidative stress in the pathogenesis of RNA nervous necrosis virus infection is still unknown. Red-spotted grouper nervous necrosis virus (RGNNV) induced free radical species (ROS) production at 12-24 h post-infection (pi; early replication stage) in fish GF-1 cells, and then at middle replication stage (24-48 h pi), this ROS signal may upregulate some expressions of the anti-oxidant enzymes Cu/Zn SOD and catalase, and eventually expression of the transcription factor Nrf2. Furthermore, both antioxidants diphenyliodonium and N-acetylcysteine or overexpression of zebrafish catalase in GF-1 cells also reduced ROS production and protected cells for enhancing host survival rate due to RGNNV infection. Furthermore, localization of ROS production using esterase activity and Mitotracker staining assays found that the ROS generated can affect mitochondrial morphology changes and causes ΔΨ loss, both of which can be reversed by antioxidant treatment. Taken together, our data suggest that RGNNV induced oxidative stress response for playing dual role that can initiate the host oxidative stress defense system to upregulate expression of antioxidant enzymes and induces cell death via disrupting the mitochondrial morphology and inducing ΔΨ loss, which can be reversed by anti-oxidants and zfcatalase, which provide new insight into betanodavirus-induced ROS-mediated pathogenesis.

  11. Antioxidant power, lipid oxidation, color, and viability of Listeria monocytogenes in beef bologna treated with gamma radiation and containing various levels of glucose.

    PubMed

    Sommers, Christopher H; Fan, Xuetong

    2002-11-01

    Ionizing radiation can be used to pasteurize ready-to-eat (RTE) meat products. Thermal processing of RTE meats that contain dextrose results in the production of antioxidants that may interfere with ionizing radiation pasteurization of RTE meat products. Beef bologna was manufactured with dextrose concentrations of 0, 2, 4, 6, and 8%. Antioxidant activity, as measured by the Ferric Reducing Antioxidant Power assay, increased with dextrose concentration but was unaffected by ionizing radiation. Lipid oxidation increased significantly in irradiated bologna (4 kGy) that contained dextrose. Hunter color analysis indicated that the addition of dextrose reduced the ionizing radiation-induced loss of redness (a-value) but promoted the loss of brightness (L-value). The radiation resistance, D10-value, of Listeria monocytogenes that was surface-inoculated onto bologna slices was not affected by dextrose concentration. L. monocytogenes strains isolated from RTE meats after listeriosis outbreaks were utilized. Increased antioxidant activity generated by thermal processing of dextrose in fine emulsion sausages does not present a barrier to radiation pasteurization of RTE meats. However, a high dextrose concentration in combination with gamma irradiation increases lipid oxidation significantly.

  12. Radiation-induced desulfurization of Arabian crude oil and straight-run diesel

    NASA Astrophysics Data System (ADS)

    Basfar, A. A.; Mohamed, K. A.

    2011-11-01

    Radiation-induced desulfurization of four types of Arabian crude oils (heavy, medium, light and extra light) and straight-run diesel (SRD) was investigated over the range of 10-200 kGy. Results show that gamma radiation processing at absorbed doses up to 200 kGy without further treatment is not sufficient for desulfurization. However, the combination of gamma-irradiation with other physical/chemical processes (i.e. L/L extraction, adsorption and oxidation) may be capable of removing considerable levels of sulfur compounds in the investigated products. Currently, this approach of combined radiation/physical/chemical processes is under investigation. The findings of these attempts will be reported in the future.

  13. Potential Protective Effects of Ursolic Acid against Gamma Irradiation-Induced Damage Are Mediated through the Modulation of Diverse Inflammatory Mediators

    PubMed Central

    Wang, Hong; Sim, Meng-Kwoon; Loke, Weng Keong; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Tang, Feng Ru; Sethi, Gautam

    2017-01-01

    This study was aimed to evaluate the possible protective effects of ursolic acid (UA) against gamma radiation induced damage both in vitro as well as in vivo. It was observed that the exposure to gamma radiation dose- and time-dependently caused a significant decrease in the cell viability, while the treatment of UA attenuated this cytotoxicity. The production of free radicals including reactive oxygen species (ROS) and NO increased significantly post-irradiation and further induced lipid peroxidation and oxidative DNA damage in cells. These deleterious effects could also be effectively blocked by UA treatment. In addition, UA also reversed gamma irradiation induced inflammatory responses, as indicated by the decreased production of TNF-α, IL-6, and IL-1β. NF-κB signaling pathway has been reported to be a key mediator involved in gamma radiation-induced cellular damage. Our results further demonstrated that gamma radiation dose- and time-dependently enhanced NF-κB DNA binding activity, which was significantly attenuated upon UA treatment. The post-irradiation increase in the expression of both phospho-p65, and phospho-IκBα was also blocked by UA. Moreover, the treatment of UA was found to significantly prolong overall survival in mice exposed to whole body gamma irradiation, and reduce the excessive inflammatory responses. Given its radioprotective efficacy as described here, UA as an antioxidant and NF-κB pathway blocker, may function as an important pharmacological agent in protecting against gamma irradiation-induced injury. PMID:28670276

  14. Novel sila-amide derivatives of N-acetylcysteine protects platelets from oxidative stress-induced apoptosis.

    PubMed

    Paul, Manoj; Thushara, Ram M; Jagadish, Swamy; Zakai, Uzma I; West, Robert; Kemparaju, Kempaiah; Girish, Kesturu S

    2017-02-01

    Oxidative stress-induced platelet apoptosis is one among the many causes for the development and progression of many disorders like cardiovascular diseases, arthritis, Alzheimer's disease and many chronic inflammatory responses. Many studies have demonstrated the less optimal effect of N-acetyl cysteine (NAC) in oxidative stress-induced cellular damage. This could be due to its less lipophilicity which makes it difficult to enter the cellular membrane. Therefore in the present study, lipophilic sila-amide derivatives (6a and 6b) synthesized through the reaction of NAC with 3-Aminopropyltrimethylsilane and aminomethyltrimethylsilane were used to determine their protective property against oxidative stress-induced platelet apoptosis. At a concentration of 10 µM, compound 6a and 6b were able to significantly inhibit Rotenone/H 2 O 2 induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cytochrome c release from mitochondrial to the cytosol, caspase-9 and -3 activity and phosphatidylserine externalization. Therefore, the compounds can be extrapolated as therapeutic agents to protect platelets from oxidative stress-induced platelet apoptosis and its associated complications.

  15. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

    PubMed

    Lorimore, S A; Wright, E G

    2003-01-01

    To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

  16. Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

    PubMed

    Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

    2015-08-01

    The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI.

  17. Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

    PubMed Central

    Uchino, Yuichi; Kawakita, Tetsuya; Miyazawa, Masaki; Ishii, Takamasa; Onouchi, Hiromi; Yasuda, Kayo; Ogawa, Yoko; Shimmura, Shigeto; Ishii, Naoaki; Tsubota, Kazuo

    2012-01-01

    Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease. PMID:23071526

  18. Modulation of stress-induced neurobehavioral changes and brain oxidative injury by nitric oxide (NO) mimetics in rats.

    PubMed

    Gulati, Kavita; Chakraborti, Ayanabha; Ray, Arunabha

    2007-11-02

    The present study evaluated the effects of NO mimetics on stress-induced neurobehavioral changes and the possible involvement of ROS-RNS interactions in rats. Restraint stress (RS) suppressed both percent open arm entries and time spent in the open arms in the elevated plus maze (EPM) test. These RS-induced changes in EPM activity were attenuated by the NO mimetics, l-arginine, isosorbide dinitrate and molsidomine, in a differential manner. RS-exposed rats showed (a) increased lipid peroxidation (MDA) and (b) lowered reduced glutathione (GSH) and NO metabolites (NOx), in brain homogenates of these animals. Pretreatment with the NO mimetics also differentially influenced RS-induced changes in brain oxidative stress markers. The results suggest that NO may protect against stress-induced anxiogenic behavior and oxidative injury in the brain and highlight the significance of ROS-RNS interactions.

  19. Anti-Oxidative Effects of Rooibos Tea (Aspalathus linearis) on Immobilization-Induced Oxidative Stress in Rat Brain

    PubMed Central

    Kim, Hyun-Pyo

    2014-01-01

    Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS) or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea’s ability to (i) reverse the increase in stress-related metabolites (5-HIAA and FFA), (ii) prevent lipid peroxidation (LPO), (iii) restore stress-induced protein degradation (PD), (iv) regulate glutathione metabolism (GSH and GSH/GSSG ratio), and (v) modulate changes in the activities of antioxidant enzymes (SOD and CAT). PMID:24466326

  20. Early growth rates and their relationships to mortalities of five breeds of chickens following exposure to acute gamma radiation stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Latimer, B.E.; Brisbin, I.L. Jr.

    Growth and mortality responses were recorded for 541 chicks, representing five different breeds of chickens, following acute exposures to gamma radiation stress at two days of age. Although there were no statistically significant differences in the LD50/30 of the five breeds studied, Cobb broilers showed the highest (1580R) and White Leghorn bantams the lowest (980R) levels, respectively. Other breeds studied included the standard White Leghorn, Athens Randombreds and a strain of feral bantam. Growth rates of body weights were proportionately more depressed by radiation stress than were body sizes, as measured by the lengths of the culmen, tarsus, middle toemore » and longest primary wing feather of all 32 day-old survivors. Among these structures, the length of the culmen seemed to be the least affected by radiation stress in all of the breeds studied. Feral bantams were able to tolerate the greatest depression in weight gain before exhibiting mortality at exposures below their LD50/30' while Cobb broilers tolerated the greatest depression of weight gain at higher exposure levels. There was a suggestion that those characteristics which were strongly selected for in the course of a particular breed's development were those which experienced the greatest proportional depressions following exposure to gamma radiation stress.« less

  1. Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells.

    PubMed

    He, Ruijun; Cui, Min; Lin, Hui; Zhao, Lei; Wang, Jiayu; Chen, Songfeng; Shao, Zengwu

    2018-04-15

    Intervertebral disc degeneration (IVDD) is thought to be the major cause of low back pain (LBP), which is still in lack of effective etiological treatment. Oxidative stress has been demonstrated to participate in the impairment of nucleus pulposus cells (NPCs). As the most important neuroendocrine hormone in biological clock regulation, melatonin (MLT) is also featured by good antioxidant effect. In this study, we investigated the effect and mechanisms of melatonin on oxidative stress-induced damage in rat NPCs. Cytotoxicity of H 2 O 2 and protecting effect of melatonin were analyzed with Cell Counting kit-8 (CCK-8). Cell apoptosis rate was detected by Annexin V-FITC/PI staining. DCFH-DA probe was used for the reactive oxygen species (ROS) detection. The mitochondrial membrane potential (MMP) changes were analyzed with JC-1 probe. Intracellular oxidation product and reductants were measured through enzymatic reactions. Extracellular matrix (ECM) and apoptosis associated proteins were analyzed with Western blot assays. Melatonin preserved cell viability of NPCs under oxidative stress. The apoptosis rate, ROS level and malonaldehyde (MDA) declined with melatonin. MLT/H 2 O 2 group showed higher activities of GSH and SOD. The fall of MMP receded and the expression of ECM protein increased with treatment of melatonin. The mitochondrial pathway of apoptosis was inhibited by melatonin. Melatonin alleviated the oxidative stress-induced apoptosis of NPCs. Melatonin could be a promising alternative in treatment of IVDD. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation.

    PubMed

    Tseng, Bertrand P; Lan, Mary L; Tran, Katherine K; Acharya, Munjal M; Giedzinski, Erich; Limoli, Charles L

    2013-01-01

    Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs). We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS), reactive nitrogen species (RNS), nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

  3. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    PubMed Central

    Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

    2015-01-01

    We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

  4. The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration.

    PubMed

    Botella, Jose A; Ulschmid, Julia K; Gruenewald, Christoph; Moehle, Christoph; Kretzschmar, Doris; Becker, Katja; Schneuwly, Stephan

    2004-05-04

    A growing body of evidence suggests that oxidative stress is a common underlying mechanism in the pathogenesis of neurodegenerative disorders such as Alzheimer's, Huntington's, Creutzfeld-Jakob and Parkinson's diseases. Despite the increasing number of reports finding a causal relation between oxidative stress and neurodegeneration, little is known about the genetic elements that confer protection against the deleterious effects of oxidation in neurons. We have isolated and characterized the Drosophila melanogaster gene sniffer, whose function is essential for preventing age-related neurodegeneration. In addition, we demonstrate that oxidative stress is a direct cause of neurodegeneration in the Drosophila central nervous system and that reduction of sniffer activity leads to neuronal cell death. The overexpression of the gene confers neuronal protection against oxygen-induced apoptosis, increases resistance of flies to experimental normobaric hyperoxia, and improves general locomotor fitness. Sniffer belongs to the family of short-chain dehydrogenase/reductase (SDR) enzymes and exhibits carbonyl reductase activity. This is the first in vivo evidence of the direct and important implication of this enzyme as a neuroprotective agent in the cellular defense mechanisms against oxidative stress.

  5. Assessment of Eccentric Exercise-Induced Oxidative Stress Using Oxidation-Reduction Potential Markers

    PubMed Central

    Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K.; Poulios, Athanasios; Jamurtas, Athanasios Z.; Bar-Or, David; Kouretas, Dimitrios

    2015-01-01

    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. PMID:25874019

  6. Betanodavirus Induces Oxidative Stress-Mediated Cell Death That Prevented by Anti-Oxidants and Zfcatalase in Fish Cells

    PubMed Central

    Chang, Chih-Wei; Su, Yu-Chin; Her, Guor-Mour; Ken, Chuian-Fu; Hong, Jiann-Ruey

    2011-01-01

    The role of oxidative stress in the pathogenesis of RNA nervous necrosis virus infection is still unknown. Red-spotted grouper nervous necrosis virus (RGNNV) induced free radical species (ROS) production at 12–24 h post-infection (pi; early replication stage) in fish GF-1 cells, and then at middle replication stage (24–48 h pi), this ROS signal may upregulate some expressions of the anti-oxidant enzymes Cu/Zn SOD and catalase, and eventually expression of the transcription factor Nrf2. Furthermore, both antioxidants diphenyliodonium and N-acetylcysteine or overexpression of zebrafish catalase in GF-1 cells also reduced ROS production and protected cells for enhancing host survival rate due to RGNNV infection. Furthermore, localization of ROS production using esterase activity and Mitotracker staining assays found that the ROS generated can affect mitochondrial morphology changes and causes ΔΨ loss, both of which can be reversed by antioxidant treatment. Taken together, our data suggest that RGNNV induced oxidative stress response for playing dual role that can initiate the host oxidative stress defense system to upregulate expression of antioxidant enzymes and induces cell death via disrupting the mitochondrial morphology and inducing ΔΨ loss, which can be reversed by anti-oxidants and zfcatalase, which provide new insight into betanodavirus-induced ROS-mediated pathogenesis. PMID:21991373

  7. Effects of gamma-Radiation on Select Lipids and Antioxidants

    NASA Technical Reports Server (NTRS)

    Gandolph, Jacob; Mauer, Lisa; Perchonok, Michele

    2006-01-01

    Radiation encountered on an extended duration space mission (estimates of 3 Sieverts for a mission to Mars) poses a threat not only to human health, but also to the quality, nutritional value, and palatability of the food system. Free radicals generated by radiation interaction with foods may initiate many unwanted reactions including: 1) autoxidation in lipids that alters flavor, odor, and concentrations of essential fatty acids, and 2) depletion of antioxidants food products and dietary supplements. Studies have shown that antioxidants may provide long term health protection from oxidative stress caused by radiation exposure; therefore, consumption of antioxidants will be important. Stability of essential fatty acids is also important for astronauts long-term health status. The objectives of this study were to characterize the effects of low dose gamma-radiation on lipids and antioxidants by monitoring oxidation and reducing power, respectively, in model systems. Select oils and antioxidants were exposed to levels of gamma-radiation ranging from 0 to 1000 Gy (1 Gy = 1 Sv) using a Gammacell 220 and stored at ambient or elevated temperatures (65 C) for up to 3 months prior to analysis. A Fricke dosimeter was used to verify differences between the radiation doses administered. Primary and secondary products of lipid oxidation in soybean and peanut oils were monitored using conjugated diene and 2-thiobarbituric acid (TBARs) assays. Changes in fatty acid composition and formation and vitamin E levels were also measured. The reducing power of antioxidant compounds, including vitamins C and E and beta-carotene, was determined using the ferric reducing antioxidant power (FRAP) assay. Significant differences (alpha =0.05) were present between all radiation doses tested using the Fricke dosimeter. Increasing radiation doses above 3 Sv resulted in significantly (alpha =0.05) elevated levels of oxidation and free fatty acids in soybean and peanut oils. Decreases in

  8. Dimethyl sulfoxide induces oxidative stress in the yeast Saccharomyces cerevisiae.

    PubMed

    Sadowska-Bartosz, Izabela; Pączka, Aleksandra; Mołoń, Mateusz; Bartosz, Grzegorz

    2013-12-01

    Dimethyl sulfoxide (DMSO) is used as a cryoprotectant for the preservation of cells, including yeast, and as a solvent for chemical compounds. We report that DMSO induces oxidative stress in the yeast. Saccharomyces cerevisiae wt strain EG-103 and its mutants Δsod1, Δsod2, and Δsod1 Δsod2 were used. Yeast were subjected to the action of 1-14% DMSO for 1 h at 28 °C. DMSO induced a concentration-dependent inhibition of yeast growth, the effect being more pronounced for mutants devoid of SOD (especially Δsod1 Δsod2). Cell viability was compromised. DMSO-concentration-dependent activity loss of succinate dehydrogenase, a FeS enzyme sensitive to oxidative stress, was observed. DMSO enhanced formation of reactive oxygen species, estimated with dihydroethidine in a concentration-dependent manner, the effect being again more pronounced in mutants devoid of superoxide dismutases. The content of cellular glutathione was increased with increasing DMSO concentrations, which may represent a compensatory response. Membrane fluidity, estimated by fluorescence polarization of DPH, was decreased by DMSO. These results demonstrate that DMSO, although generally considered to be antioxidant, induces oxidative stress in yeast cells. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  9. Low-dose γ-radiation-induced oxidative stress response in mouse brain and gut: regulation by NFκB-MnSOD cross-signaling.

    PubMed

    Veeraraghavan, Jamunarani; Natarajan, Mohan; Herman, Terence S; Aravindan, Natarajan

    2011-01-10

    Radiation-induced amplification of reactive oxygen species (ROS) may be a sensing mechanism for activation of signaling cascades that influence cell fate. However, the regulated intrinsic mechanisms and targets of low-dose ionizing radiation (LDIR) are still unclear. Accordingly, we investigated the effects of LDIR on NFκB signal transduction and manganese superoxide dismutase (SOD2) activity in mice brain and gut. LDIR resulted in both dose-dependent and persistent NFκB activation in gut and brain. QPCR displayed a dose- and tissue-dependent differential modulation of 88 signaling molecules. With stringent criteria, a total of 15 (2cGy), 43 (10cGy) and 19 (50cGy) genes were found to be commonly upregulated between brain and gut. SOD2 immunostaining showed a LDIR-dose dependent increase. Consistent with the NFκB results, we observed a persistent increase in SOD2 activity after LDIR. Moreover, muting of LDIR-induced NFκB attenuated SOD2 transactivation and cellular localization. These results imply that exposure of healthy tissues to LDIR results in induced NFκB and SOD2 activity and transcriptional activation of NFκB-signal transduction/target molecules. More importantly, the results suggest that NFκB initiates a feedback response through transcriptional activation of SOD2 that may play a key role in the LDIR-induced oxidative stress response and may control the switch that directs cell fate. 2010 Elsevier B.V. All rights reserved.

  10. Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.

    PubMed

    Landis, Gary; Shen, Jie; Tower, John

    2012-11-01

    Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.

  11. Clustered DNA damages induced by high and low LET radiation, including heavy ions

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

    2001-01-01

    Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

  12. Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response.

    PubMed

    Kim, Sou Hyun; Oh, Dal-Seok; Oh, Ji Youn; Son, Tae Gen; Yuk, Dong Yeon; Jung, Young-Suk

    2016-04-01

    Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins. Our recent study suggested that silymarin induces hepatic synthesis of glutathione by increasing cysteine availability, which may consequently contribute to increased antioxidant capacity of the liver. In the present study, we investigated the effects of silymarin on acute liver injury induced by restraint stress. Silymarin (100 mg/kg) was orally administered to BALB/c mice every 12 h (3 times in total). After the last dose, mice were subjected to restraint stress for 6 h, and serum levels of aspartate and alanine aminotransferases, and hepatic levels of lipid peroxidation were determined. Hepatic levels of sulfur-containing metabolites such as methionine, S-adenosylmethionine, cysteine, and glutathione were also measured. The level of pro-inflammatory mediators in both liver and serum was determined. To study the mechanism of the effects of silymarin, we assessed Jun N-terminal kinase (JNK) activation and apoptotic signaling. Restraint stress induced severe oxidative stress and increased mRNA levels of pro-inflammatory mediators; both effects of restraint stress were significantly inhibited by silymarin. Moreover, administration of silymarin significantly prevented acute liver injury induced by restraint stress by blocking JNK activation and subsequently apoptotic signaling. In conclusion, these results suggest that the inhibition of restraint stress-induced liver injury by silymarin is due at least in part to its anti-oxidant activity and its ability to suppress the inflammatory response.

  13. Administration of the peroxisomal proliferator-activated receptor {gamma} agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao Weiling; Payne, Valerie; Tommasi, Ellen

    2007-01-01

    Purpose: We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor {gamma} (PPAR{gamma}) agonist pioglitazone (Pio) to adult male rats would inhibit radiation-induced cognitive impairment. Methods and Materials: Young adult male F344 rats received one of the following: (1) fractionated whole brain irradiation (WBI); 40 or 45 Gy {gamma}-rays in 4 or 4.5 weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h after completion of WBI. Results: Administration ofmore » Pio before, during, and for 4 or 54 weeks after WBI prevented Radiation-induced cognitive impairment. Administration of Pio for 54 weeks starting after completion of fractionated WBI substantially but not significantly reduced Radiation-induced cognitive impairment. Conclusions: These findings offer the promise of improving the quality of life and increasing the therapeutic window for brain tumor patients.« less

  14. Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes.

    PubMed

    Singh, Abhishek Kumar; Singh, Sandeep; Garg, Geetika; Rizvi, Syed Ibrahim

    2016-10-01

    An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl 2 (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca 2+ influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl 2 . Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl 2 -induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca 2+ influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.

  15. Combined effects of gamma radiation doses and sodium nitrite content on the lipid oxidation and color of mortadella.

    PubMed

    Dutra, Monalisa Pereira; Cardoso, Giselle Pereira; Fontes, Paulo Rogério; Silva, Douglas Roberto Guimarães; Pereira, Marcio Tadeu; Ramos, Alcinéia de Lemos Souza; Ramos, Eduardo Mendes

    2017-12-15

    The effects of different doses of gamma radiation (0-20kGy) on the color and lipid oxidation of mortadella prepared with increasing nitrite levels (0-300ppm) were evaluated using a central composite rotatable design. Higher radiation doses increased the redox potential, promoted the lipid oxidation and elevating the hue color of the mortadellas. Nevertheless, higher addition of sodium nitrite elevated the residual nitrite content, reduced the lipid oxidation and promoted the increase of redness and the reduce of hue color of the mortadellas, regardless of the radiation dose applied. Nitrite addition had a greater effect than irradiation on the quality parameters evaluated, and even at low levels (∼75ppm), its use decreased the deleterious effects of irradiation at doses as high as 20kGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 4-(4-Hydroxy-3-methoxyphenyl)-2-butanone modulates redox signal in gamma-irradiation-induced nephrotoxicity in rats.

    PubMed

    Abozaid, Omayma A R; Moawed, Fatma S M; Farrag, Mostafa A; Abdel Aziz, Abdel Aziz A

    2017-12-01

    Cellular exposure to ionising radiation leads to oxidative stress events, which refer to elevated intracellular levels of reactive oxygen species (ROS). The elevated levels of ROS significantly contributed to γ-radiation (IR) induced cytotoxicity. In an attempt to minimise these cytotoxic effects, antioxidant compounds have been identified to counteract radiation- associated toxicities. We mainly aimed to study the protective effect of 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (HMB) on IR-induced nephrotoxicity, whereas it was previously shown to have anti-inflammatory effects in different inflammation models. Animals were treated orally with HMB (25 mg/kg b.wt daily) then performed by whole-body gamma-irradiation of animals with 6 Gy; a single dose applied on the 15th day and animals were sacrificed at the end of the 23rd day. It was found that IR exposure significantly induced renal oxidative injury that accompanied by inflammatory disturbance. Also, NADPH oxidase and iNOS gene expressions were significantly up-regulated, while the mitochondrial enzymes (complex I & II) were significantly down-regulated in IR exposed animals. Additionally, Western immunoblotting analysis of signalling growth factor protein; p38 MAPK was significantly overexpressed. Interestingly, HMB treatment showed statistically significant amelioration in parameters with an improved histological structure upon the IR-induced nephrotoxicity. It can be concluded that modulation of NADPH-oxidase, iNOS and mitochondrial enzymes by HMB might be responsible for the amendment of the antioxidant status and impairment of p38 MAPK signal, thus attenuate the nephrotoxicity induced post IR exposure.

  17. Fly ash leachate induces oxidative stress in freshwater fish Channa punctata (Bloch).

    PubMed

    Ali, M; Parvez, S; Pandey, S; Atif, F; Kaur, M; Rehman, H; Raisuddin, S

    2004-09-01

    Oxidative stress inducing potential of fly ash leachate (FAL) was studied in a freshwater fish, Channa punctata (Bloch). Fish were exposed to fly ash leachate for 24 h and lipid peroxidation (LPO) was studied as a marker of oxidative stress. Catalase (CAT), glutathione S-transferase (GST) activities and levels of reduced glutathione (GSH) were also estimated in the exposed fish. FAL (1 ml/l) induced LPO in all the organs and most prominent response was in the gill. It also caused induction of enzymes and glutathione. Liver showed highest level of induction of enzyme activities. The results of this study demonstrate that fly ash constituents have potential to induce oxidative stress in fish and gills are the most vulnerable organs. It is also suggested that in case of exposure to FAL, along with LPO antioxidant defense is also activated to counteract the reactive oxygen species (ROS) at least partly in the initial stages of exposure.

  18. Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

    PubMed

    Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

    2015-01-01

    It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

  19. Dietary Approaches to Protect Against Eye Blast Induced Oxidative Stress and Vision Loss

    DTIC Science & Technology

    2016-11-01

    supplementation of antioxidants and antioxidant enzymes. The ultimate goal of this study was to identify a dietary intervention that could protect...AWARD NUMBER: W81XWH-15-1-0096 TITLE: Dietary Approaches to Protect Against Eye Blast-Induced Oxidative Stress and Vision Loss PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Dietary Approaches to Protect Against Eye Blast-Induced Oxidative Stress and Vision Loss 5b. GRANT NUMBER

  20. Nrf2 protects against oxidative stress induced by SiO2 nanoparticles.

    PubMed

    Liu, Wei; Hu, Tao; Zhou, Li; Wu, Desheng; Huang, Xinfeng; Ren, Xiaohu; Lv, Yuan; Hong, Wenxu; Huang, Guanqin; Lin, Zequn; Liu, Jianjun

    2017-10-01

    The aim of our study was to explore the role of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) on the exposure of SiO 2 nanoparticles (NPs) and its influence. To understand the mechanism of NP-induced oxidative stress, the involvement of oxidative-stress-responding transcription factors and the Nrf2/antioxidant reactive element (ARE) signaling pathway in the toxicity of SiO 2 NPs' exposure was investigated via in vivo and in vitro models. A549 cells showed a significant cytotoxic effect while A549-shNrf2 cells showed decreased cell viability after nm-SiO 2 exposure. SiO 2 NPs' exposure activated the Nrf2/ARE signaling pathway. Nrf2 -/- exposed mice showed increased reactive oxygen species, 8-hydroxyl deoxyguanosine level and decreased total antioxidant capacity. Nrf2/ARE signaling pathway activation disrupted, leading inhibition of heme oxygenase-1 and upregulation of PKR-like endoplasmic-reticulum-regulated kinase. Our findings suggested that Nrf2 could protect against oxidative stress induced by SiO 2 NPs, and the Nrf2/ARE pathway might be involved in mild-to-moderate SiO 2 NP-induced oxidative stress that was evident from dampened activity of Nrf2.

  1. Mitochondrial dependent oxidative stress in cell culture induced by laser radiation at 1265 nm.

    PubMed

    Saenko, Yury V; Glushchenko, Eugenia S; Zolotovskii, Igor O; Sholokhov, Evgeny; Kurkov, Andrey

    2016-04-01

    Photodynamic therapy is the main technique applied for surface carcinoma treatment. This technique employs singlet oxygen generated via a laser excited photosensitizer as a main damaging agent. However, prolonged sensitivity to intensive light, relatively low tissue penetration by activating light the cost of photosensitizer (PS) administration can limit photodynamic therapy applications. Early was reported singlet oxygen generation without photosensitizer induced by a laser irradiation at the wavelength of 1250-1270 nm. Here, we study the dynamics of oxidative stress, DNA damage, changes of mitochondrial potential, and mitochondrial mass induced by a laser at 1265 nm have been studied in HCT-116 and CHO-K cells. Laser irradiation of HCT-116 and CHO-K cells has induced a dose-dependent cell death via increasing intracellular reactive oxygen species (ROS) concentration, increase of DNA damage, decrease of mitochondrial potential, and reduced glutathione. It has been shown that, along with singlet oxygen generation, the increase of the intracellular ROS concentration induced by mitochondrial damage contributes to the damaging effect of the laser irradiation at 1265 nm.

  2. Lowering Effects of Onion Intake on Oxidative Stress Biomarkers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Azuma, Keiko; Minami, Yuko; Ippoushi, Katsunari; Terao, Junji

    2007-01-01

    The protective effect of onion against oxidative stress in streptozotosin-induced diabetic rats was investigated in comparison with that of quercetin aglycone. We measured oxidative stress biomarkers involving the susceptibility of the plasma against copper ion-induced lipid peroxidation, which was estimated by the amounts of thiobarbituric acid-reactive substances (TBARS) and cholesteryl ester hydroperoxides, and urine TBARS and 8-hydroxydeoxyguanosine contents. After the 12-week feeding period, plasma glucose levels and these biomarkers increased in diabetic rats compared to normal rats. In diabetic rats fed a 6.0% onion diet (quercetin equivalent: 0.023%), quercetin metabolites accumulated in the plasma at concentrations of approximately 35 µM. Onion intake decreased plasma glucose levels and lowered the oxidative stress biomarkers. On the other hand, quercetin metabolites in the plasma of rats fed a diet with 0.023% quercetin aglycone were found at lower concentrations (14.2 µM) than the rats fed the onion diet. Furthermore, oxidative stress biomarkers were higher in the quercetin diet group compared to the onion diet group. These results strongly suggest that onion intake suppresses diabetes-induced oxidative stress more effectively than the intake of the same amount of quercetin aglycone alone. PMID:18188415

  3. Gamma radiation-induced synthesis and characterization of Polyvinylpyrrolidone nanogels

    NASA Astrophysics Data System (ADS)

    Ges, A. A.; Viltres, H.; Borja, R.; Rapado, M.; Aguilera, Y.

    2017-01-01

    Due to the importance of bioactive peptides, proteins and drug for pharmaceutical purpose, there is a growing interest for suitable delivery systems, able to increase their bioavailability and to target them to the desired location. Some of the most studied delivery systems involve encapsulation or entrapment of drugs into biocompatible polymeric devices. A multitude of techniques have been described for the synthesis of nanomaterials from polymers, however, the use of ionizing radiation (γ, e-), to obtain nano- and microgels polymer is characterized by the possibility of obtaining products with a high degree of purity. Although, in the world, electronic radiation is used for this purpose, gamma radiation has not been utilized for these purposes. In this paper is developed the formulation the formulation of Polyvinylpyrrolidone (PVP) nanogels synthesized by gamma radiation techniques, for their evaluation as potential system of drug delivery. Experiments were performed in absence of oxygen using aqueous solutions of PVP (0.05% -1%). Crosslinking reactions were carried out at 25° C in a gamma irradiation chamber with a 60Co source (MPX-γ 30). The Viscosimetry, Light Scattering, X-Ray Diffraction and Transmission Electron Microscopy (TEM), were used as characterization techniques.

  4. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis.

    PubMed

    Sun, Xin-Zhi; Liao, Ying; Li, Wei; Guo, Li-Mei

    2017-06-01

    Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H 2 O 2 ) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H 2 O 2 -induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.

  5. Gamma Radiation Effects on Peanut Skin Antioxidants

    PubMed Central

    de Camargo, Adriano Costa; de Souza Vieira, Thais Maria Ferreira; Regitano-D’Arce, Marisa Aparecida Bismara; Calori-Domingues, Maria Antonia; Canniatti-Brazaca, Solange Guidolin

    2012-01-01

    Peanut skin, which is removed in the peanut blanching process, is rich in bioactive compounds with antioxidant properties. The aims of this study were to measure bioactive compounds in peanut skins and evaluate the effect of gamma radiation on their antioxidant activity. Peanut skin samples were treated with 0.0, 5.0, 7.5, or 10.0 kGy gamma rays. Total phenolics, condensed tannins, total flavonoids, and antioxidant activity were evaluated. Extracts obtained from the peanut skins were added to refined-bleached-deodorized (RBD) soybean oil. The oxidative stability of the oil samples was determined using the Oil Stability Index method and compared to a control and synthetic antioxidants (100 mg/kg BHT and 200 mg/kg TBHQ). Gamma radiation changed total phenolic content, total condensed tannins, total flavonoid content, and the antioxidant activity. All extracts, gamma irradiated or not, presented increasing induction period (h), measured by the Oil Stability Index method, when compared with the control. Antioxidant activity of the peanut skins was higher than BHT. The present study confirmed that gamma radiation did not affect the peanut skin extracts’ antioxidative properties when added to soybean oil. PMID:22489142

  6. Buffer Modulation of Menadione-Induced Oxidative Stress in Saccharomyces cerevisiae

    PubMed Central

    Lushchak, Oleh V.; Bayliak, Maria M.; Korobova, Olha V.; Levine, Rodney L.; Lushchak, Volodymyr I.

    2012-01-01

    The objective of this study was to compare in vivo the effects of bicarbonate and phosphate buffers on surviving and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. If at 25 mM concentration of buffers menadione only slightly reduced yeast surviving, at 50 mM concentration cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed. PMID:19843376

  7. Buffer modulation of menadione-induced oxidative stress in Saccharomyces cerevisiae.

    PubMed

    Lushchak, Oleh V; Bayliak, Maria M; Korobova, Olha V; Levine, Rodney L; Lushchak, Volodymyr I

    2009-01-01

    The objective of this study was to compare, in vivo, the effects of bicarbonate and phosphate buffers on survival and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. At 25 mM concentration of buffers, menadione only slightly reduced yeast surviving; at 50 mM concentration, cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed.

  8. Novel Radiomitigator for Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  9. The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment

    PubMed Central

    Tian, Ye; Ma, Xiaoli; Yang, Chaofei; Su, Peihong; Yin, Chong

    2017-01-01

    The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut’s health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors—namely radiation and microgravity—in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe. PMID:29023398

  10. The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment.

    PubMed

    Tian, Ye; Ma, Xiaoli; Yang, Chaofei; Su, Peihong; Yin, Chong; Qian, Ai-Rong

    2017-10-12

    The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut's health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors-namely radiation and microgravity-in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe.

  11. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes.

    PubMed

    Zana, Marianna; Szécsényi, Anita; Czibula, Agnes; Bjelik, Annamária; Juhász, Anna; Rimanóczy, Agnes; Szabó, Krisztina; Vetró, Agnes; Szucs, Péter; Várkonyi, Agnes; Pákáski, Magdolna; Boda, Krisztina; Raskó, István; Janka, Zoltán; Kálmán, János

    2006-06-30

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n=7) and adults (n=18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

  12. Radiation-induced cardiovascular effects

    NASA Astrophysics Data System (ADS)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  13. Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gebhard, Catherine; Staehli, Barbara E.; Zurich Center for Integrative Human Physiology

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer The nuclear enzyme PARP-1 is a downstream effector of oxidative stress. Black-Right-Pointing-Pointer PARP-1 protects from oxidative stress induced endothelial dysfunction. Black-Right-Pointing-Pointer This effect is mediated through inhibition of vasoconstrictor prostanoid production. Black-Right-Pointing-Pointer Thus, PARP-1 may play a protective role as antioxidant defense mechanism. -- Abstract: Background: Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress. Methods: PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings weremore » suspended in organ chambers for isometric tension recording to analyze vascular function. Results: PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p < 0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, L-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3-fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p < 0.001 vs. PQ treated PARP-1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p < 0.05 vs. PQ treated PARP-1(+/+). Conclusion: PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids.« less

  14. Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells.

    PubMed

    Bigagli, Elisabetta; Cinci, Lorenzo; D'Ambrosio, Mario; Luceri, Cristina

    2017-08-01

    Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in oxidative stress, inflammation and cell death. The aim of this study was to investigate the potential protective effects of a commercial eye drop (Dacriovis™) containing Matricaria chamomilla and Euphrasia officinalis extracts on human corneal epithelial cells (HCEC-12) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the eye drops was evaluated by measuring the ferric reducing antioxidant power and the total phenolic content by Folin-Ciocalteu reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye drops at various concentrations. Cell viability, wound healing assay, reactive oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL-1β, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were able to protect corneal epithelial cells from UVB-induced cell death and ameliorated the wound healing; the eye drops exhibited a strong antioxidant activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops also exerted anti-inflammatory activities by decreasing COX-2, IL-1β, iNOS expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1 expression to control levels. These findings suggest that an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects against UVB induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from UVB exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. p53 as a retrovirus-induced oxidative stress modulator.

    PubMed

    Kim, Soo Jin; Wong, Paul K Y

    2015-01-01

    Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator. © 2015 The Authors.

  16. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

    PubMed Central

    Shin, Jihyun; Yang, Soo Jin

    2016-01-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. PMID:28211759

  17. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

    PubMed

    Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

    2017-03-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

  18. [Increasing oxidative stress in aging].

    PubMed

    Shimosawa, Tatsuo

    2005-06-01

    The balance between reactive oxigen species (ROS) production and degradation is important in defining oxidative stress. In aging process, ROS production increases and degradation is impaired and thus oxidative stress is accumulated. Oxidative stress damages organs both directly and indirectly. Protein, lipid, as well as DNA are directly react with ROS, more over, ROS interact with intracellular signaling system. It is reported that several transcription factors such as NF-kappaB, AP-1 and ASK-1 and also it interferes MAPK activity. Besides these signaling, we recently showed that insulin resistance is induced by accumulated oxidative stress in aged mice. Adrenomedullin deficient mice accumulate higher oxidative stress and insulin resistance developed in aging. Oxidative stress in aging relates not only direct organ damage but also induce risk factors for vascular damage such as metabolic syndrome.

  19. Uranium induces oxidative stress in lung epithelial cells

    PubMed Central

    Periyakaruppan, Adaikkappan; Kumar, Felix; Sarkar, Shubhashish; Sharma, Chidananda S.

    2009-01-01

    Uranium compounds are widely used in the nuclear fuel cycle, antitank weapons, tank armor, and also as a pigment to color ceramics and glass. Effective management of waste uranium compounds is necessary to prevent exposure to avoid adverse health effects on the population. Health risks associated with uranium exposure includes kidney disease and respiratory disorders. In addition, several published results have shown uranium or depleted uranium causes DNA damage, mutagenicity, cancer and neurological defects. In the current study, uranium toxicity was evaluated in rat lung epithelial cells. The study shows uranium induces significant oxidative stress in rat lung epithelial cells followed by concomitant decrease in the antioxidant potential of the cells. Treatment with uranium to rat lung epithelial cells also decreased cell proliferation after 72 h in culture. The decrease in cell proliferation was attributed to loss of total glutathione and superoxide dismutase in the presence of uranium. Thus the results indicate the ineffectiveness of antioxidant system’s response to the oxidative stress induced by uranium in the cells. PMID:17124605

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu; Patel-Vayas, Kinal; Shen, Jianliang

    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 andmore » 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

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

    PubMed Central

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

    2015-01-01

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

  2. Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.

    PubMed

    Wang, Jun; Wu, Yajing; Yuan, Fang; Liu, Yixian; Wang, Xuefeng; Cao, Feng; Zhang, Yi; Wang, Sheng

    2016-09-01

    Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

    DTIC Science & Technology

    2010-01-01

    mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

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

    PubMed

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

    2014-04-01

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

  5. Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster

    PubMed Central

    Landis, Gary; Shen, Jie; Tower, John

    2012-01-01

    Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging. PMID:23211361

  6. Mercury-induced oxidative stress in Indian mustard (Brassica juncea L.).

    PubMed

    Shiyab, Safwan; Chen, Jian; Han, Fengxiang X; Monts, David L; Matta, Fank B; Gu, Mengmeng; Su, Yi; Masad, Motasim A

    2009-10-01

    Mercury, a potent neurotoxin, is released to the environment in significant amounts by both natural processes and anthropogenic activities. No natural hyperaccumulator plant has been reported for mercury phytoremediation. Few studies have been conducted on the physiological responses of Indian mustard, a higher biomass plant with faster growth rates, to mercury pollution. This study investigated the phytotoxicity of mercury to Indian mustard (Brassica juncea L.) and mercury-induced oxidative stress in order to examine the potential application of Indian mustard to mercury phytoremediation. Two common cultivars (Florida Broadleaf and Longstanding) of Indian mustard were grown hydroponically in a mercury-spiked solution. Plant uptake, antioxidative enzymes, peroxides, and lipid peroxidation under mercury stress were investigated. Antioxidant enzymes (catalase, CAT; peroxidase, POD; and superoxide dismutase, SOD) were the most sensitive indices of mercury-induced oxidative response of Indian mustard plants. Indian mustard effectively generated an enzymatic antioxidant defense system (especially CAT) to scavenge H(2)O(2), resulting in lower H(2)O(2) in shoots with higher mercury concentrations. These two cultivars of Indian mustard demonstrated an efficient metabolic defense and adaptation system to mercury-induced oxidative stress. A majority of Hg was accumulated in the roots and low translocations of Hg from roots to shoots were found in two cultivars of Indian mustard. Thus Indian mustard might be a potential candidate plant for phytofiltration/phytostabilization of mercury contaminated waters and wastewater.

  7. Improving degradation of paracetamol by integrating gamma radiation and Fenton processes.

    PubMed

    Cruz-González, Germán; Rivas-Ortiz, Iram B; González-Labrada, Katia; Rapado-Paneque, Manuel; Chávez-Ardanza, Armando; Nuevas-Paz, Lauro; Jáuregui-Haza, Ulises J

    2016-10-14

    Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters.

  8. Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

    PubMed Central

    Shvedova, Anna A.; Pietroiusti, Antonio; Fadeel, Bengt; Kagan, Valerian E.

    2015-01-01

    Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. PMID:22513272

  9. Comparison of degradation effects induced by gamma radiation and electron beam radiation in two cable jacketing materials

    NASA Astrophysics Data System (ADS)

    Bartoníček, B.; Plaček, V.; Hnát, V.

    2007-05-01

    The radiation degradation behavior of commercial low density polyethylene (LDPE) and ethylene-vinylacetate (EVA) cable materials has been investigated. The changes of mechanical properties, thermooxidative stability and density exhibit different radiation stability towards 60Co-gamma radiation and 160 keV electron beam radiation. This difference reflects much higher penetration of the gamma radiation through the polymeric material as a function of sample thickness. These results are discussed with respect to the role of beta radiation during design basis events in a nuclear power plants. In case when total accidental design basis event (DBE) dose (involving about 80% soft beta radiation) is simulated by 60Co-gamma radiation the conservatism is reached.

  10. High temperature induces apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells.

    PubMed

    Cheng, Chang-Hong; Yang, Fang-Fang; Liao, Shao-An; Miao, Yu-Tao; Ye, Chao-Xia; Wang, An-Li; Tan, Jia-Wen; Chen, Xiao-Yan

    2015-10-01

    Water temperature is an important environmental factor in aquaculture farming that affects the survival and growth of organisms. The change in culture water temperature may not only modify various chemical and biological processes but also affect the status of fish populations. In previous studies, high temperature induced apoptosis and oxidative stress. However, the precise mechanism and the pathways that are activated in fish are still unclear. In the present study, we investigated the effects of high temperature (34°C) on the induction of apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells. The data showed that high temperature exposure increased oxygen species (ROS), cytoplasmic free-Ca(2+) concentration and cell apoptosis. To test the apoptotic pathway, the expression pattern of some key apoptotic related genes including P53, Bax, caspase 9 and caspase 3 were examined. The results showed that acute high temperature stress induced up-regulation of these genes, suggesting that the p53-Bax pathway and the caspase-dependent apoptotic pathway could be involved in apoptosis induced by high temperature stress. Furthermore, the gene expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, CAT, GPx, and GR) and heat shock proteins (HSP90 and HSP70) in the blood cells were induced by high temperature stress. Taken together, our results showed that high temperature-induced oxidative stress may cause pufferfish blood cells apoptosis, and cooperatively activated p53-Bax and caspase-dependent apoptotic pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Expression of Aluminum-Induced Genes in Transgenic Arabidopsis Plants Can Ameliorate Aluminum Stress and/or Oxidative Stress1

    PubMed Central

    Ezaki, Bunichi; Gardner, Richard C.; Ezaki, Yuka; Matsumoto, Hideaki

    2000-01-01

    To examine the biological role of Al-stress-induced genes, nine genes derived from Arabidopsis, tobacco (Nicotiana tabacum L.), wheat (Triticum aestivum L.), and yeast (Saccharomyces cerevisiae) were expressed in Arabidopsis ecotype Landsberg. Lines containing eight of these genes were phenotypically normal and were tested in root elongation assays for their sensitivity to Al, Cd, Cu, Na, Zn, and to oxidative stresses. An Arabidopsis blue-copper-binding protein gene (AtBCB), a tobacco glutathione S-transferase gene (parB), a tobacco peroxidase gene (NtPox), and a tobacco GDP-dissociation inhibitor gene (NtGDI1) conferred a degree of resistance to Al. Two of these genes, AtBCB and parB, and a peroxidase gene from Arabidopsis (AtPox) also showed increased resistance to oxidative stress induced by diamide, while parB conferred resistance to Cu and Na. Al content of Al-treated root tips was reduced in the four Al-resistant plant lines compared with wild-type Ler-0, as judged by morin staining. All four Al-resistant lines also showed reduced staining of roots with 2′,7′-dichloro fluorescein diacetate (H2DCFDA), an indicator of oxidative stress. We conclude that Al-induced genes can serve to protect against Al toxicity, and also provide genetic evidence for a link between Al stress and oxidative stress in plants. PMID:10712528

  12. Gamma inert sterilization: a solution to polyethylene oxidation?

    PubMed

    Medel, Francisco J; Kurtz, Steven M; Hozack, William J; Parvizi, Javad; Purtill, James J; Sharkey, Peter F; MacDonald, Daniel; Kraay, Matthew J; Goldberg, Victor; Rimnac, Clare M

    2009-04-01

    In the 1990s, oxidation was found to occur in ultra-high molecular weight polyethylene total joint replacement components following gamma irradiation and prolonged shelf aging in air. Orthopaedic manufacturers developed barrier packaging to reduce oxidation during and after radiation sterilization. The present study explores the hypothesis that polyethylene components sterilized in a low-oxygen environment undergo similar in vivo oxidative mechanisms as inserts sterilized in air. In addition, the potential influence of the different sterilization processes on the wear performance of the polyethylene components was examined. An analysis of oxidation, wear, and surface damage was performed for forty-eight acetabular liners and 123 tibial inserts. The mean implantation time was 12.3+/-3.7 years for thirty-one acetabular liners that had been gamma sterilized in air and 4.0+/-2.5 years for the seventeen acetabular liners that had been gamma sterilized in inert gas. The mean implantation time was 11.0+/-3.2 years for the twenty-six tibial inserts that had been sterilized in air and 2.8+/-2.2 years for the ninety-seven tibial inserts that had been gamma sterilized in inert gas. Oxidation and hydroperoxide levels were characterized in loaded and unloaded regions of the inserts. Measurable oxidation and oxidation potential were observed in all cohorts. The oxidation and hydroperoxide levels were regional. Surfaces with access to body fluids were more heavily oxidized than protected bearing surfaces were. This variation appeared to be greater in historical (gamma-in-air-sterilized) components. Regarding wear performance, historical and conventional acetabular liners showed similar wear penetration rates, whereas a low incidence of delamination was confirmed for the conventional tibial inserts in the first decade of implantation. The present study explores the impact of industry-wide changes in sterilization practices for polyethylene. We found lower oxidation and oxidation

  13. Gamma radiation induced changes in nuclear waste glass containing Eu

    NASA Astrophysics Data System (ADS)

    Mohapatra, M.; Kadam, R. M.; Mishra, R. K.; Kaushik, C. P.; Tomar, B. S.; Godbole, S. V.

    2011-10-01

    Gamma radiation induced changes were investigated in sodium-barium borosilicate glasses containing Eu. The glass composition was similar to that of nuclear waste glasses used for vitrifying Trombay research reactor nuclear waste at Bhabha Atomic Research Centre, India. Photoluminescence (PL) and electron paramagnetic resonance (EPR) techniques were used to study the speciation of the rare earth (RE) ion in the matrix before and after gamma irradiation. Judd-Ofelt ( J- O) analyses of the emission spectra were done before and after irradiation. The spin counting technique was employed to quantify the number of defect centres formed in the glass at the highest gamma dose studied. PL data suggested the stabilisation of the trivalent RE ion in the borosilicate glass matrix both before and after irradiation. It was also observed that, the RE ion distributes itself in two different environments in the irradiated glass. From the EPR data it was observed that, boron oxygen hole centre based radicals are the predominant defect centres produced in the glass after irradiation along with small amount of E’ centres. From the spin counting studies the concentration of defect centres in the glass was calculated to be 350 ppm at 900 kGy. This indicated the fact that bulk of the glass remained unaffected after gamma irradiation up to 900 kGy.

  14. Aluminium oxide nanoparticles induced morphological changes, cytotoxicity and oxidative stress in Chinook salmon (CHSE-214) cells.

    PubMed

    Srikanth, Koigoora; Mahajan, Amit; Pereira, Eduarda; Duarte, Armando Costa; Venkateswara Rao, Janapala

    2015-10-01

    Aluminium oxide nanoparticles (Al2 O3 NPs) are increasingly used in diverse applications that has raised concern about their safety. Recent studies suggested that Al2 O3 NPs induced oxidative stress may be the cause of toxicity in algae, Ceriodaphnia dubia, Caenorhabditis elegans and Danio rerio. However, there is paucity on the toxicity of Al2 O3 NPs on fish cell lines. The current study was aimed to investigate Al2 O3 NPs induced cytotoxicity, oxidative stress and morphological abnormality of Chinnok salmon cells (CHSE-214). A dose-dependent decline in cell viability was observed in CHSE-214 cells exposed to Al2 O3 NPs. Oxidative stress induced by Al2 O3 NPs in CHSE-214 cells has resulted in the significant reduction of superoxide dismutase, catalase and glutathione in a dose-dependent manner. However, a significant increase in glutathione sulfo-transferase and lipid peroxidation was observed in CHSE-214 cells exposed to Al2 O3 NPs in a dose-dependent manner. Significant morphological changes in CHSE-214 cells were observed when exposed to Al2 O3 NPs at 6, 12 and 24 h. The cells started to detach and appear spherical at 6 h followed by loss of cellular contents resulting in the shrinking of the cells. At 24 h, the cells started to disintegrate and resulted in cell death. Our data demonstrate that Al2 O3 NPs induce cytotoxicity and oxidative stress in a dose-dependent manner in CHSE-214 cells. Thus, our current work may serve as a base-line study for future evaluation of toxicity studies using CHSE-214 cells. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Interferon Gamma potentiates the injury caused by MPP(+) on SH-SY5Y cells, which is attenuated by the nitric oxide synthases inhibition.

    PubMed

    Titze-de-Almeida, Simoneide S; Lustosa, Cátia Faria; Horst, Camila Hillesheim; Bel, Elaine Del; Titze-de-Almeida, Ricardo

    2014-12-01

    This study examined whether the cytokine interferon (IFN) gamma plays a role in the injury of SH-SY5Y cells caused by MPP(+) (1-methyl-4-phenylpyridinium). First of all, IFN-gamma sensitized cells to the neurotoxin MPP(+), as determined by MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide) assay. MPP(+)-injured cells showed higher reactive oxygen species (ROS) levels, which was reinforced by IFN-gamma. The injury triggered a marked expression of the neuronal NOS (nNOS) enzyme. L-NAME [N(ω)-nitro-L-arginine methyl ester, a non-specific NOS inhibitor] reestablished the cell viability after IFN-gamma challenging, and recovered cells from MPP(+) injury (95.0 vs. 84.7 %; P < 0.05). Seven-NI (7-nitroindazole, a nNOS inhibitor) protected cells against the injury by MPP(+) co-administered with IFN-gamma. Both inhibitors restrained the apoptosis of SH-SY5Y cells caused by MPP(+)/IFN-gamma. Regarding oxidative stress, L-NAME and 7-NI attenuated the increase in ROS levels caused by MPP(+) (45.3 or 48.4 vs. 87.9 %, P < 0.05). Indeed, L-NAME was more effective than 7-NI for reducing oxidative stress caused by MPP(+) under IFN-gamma exposition. The nNOS gene silencing by small-interfering RNAs recovered cells challenged by IFN-gamma (24 h), or MPP(+) (8 h). In conclusion, IFN-gamma sensitizes cells to MPP(+)-induced injury, also causing an increase in ROS levels. Pretreating cells with L-NAME or 7-NI reverts both the oxidative stress and apoptosis triggered by the neurotoxin MPP(+). Taking together, our data reinforce that IFN-gamma and NOS enzymes play a role in oxidative stress and dopaminergic cell death triggered by MPP(+).

  16. Protective potential of Black grapes against lead induced oxidative stress in rats.

    PubMed

    Lakshmi, B V S; Sudhakar, M; Aparna, M

    2013-05-01

    From time immemorial Vitis vinifera (Black grapes) have been used both for medicinal and nourishment purposes. The aim of this study is to investigate the protective effect of Black grapes against lead nitrate induced oxidative stress. Exposure to lead significantly increased malondialdehyde levels with a significant decrease in superoxide dismutase and catalase activities, and the concentration of GSH in the liver and kidneys of rats. Significantly increased levels of AST, ALT, ALP, BUN and serum creatinine and decreased levels of total protein were observed. The administration of lead significantly decreased the body weight and organ weights at the end of the experimental period. Statistically significant decrease in hemoglobin, red blood cell and total leukocyte count was observed. Pretreatment of hydroalcoholic extract of Black grapes to lead exposed rats significantly ameliorated lead-induced oxidative stress in tissues and produced improvement in hematological parameters over lead-exposed rats, indicating the beneficial role of Black grapes to counteract the lead-induced oxidative stress. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

    PubMed Central

    Ivanov, Alexander V.; Valuev-Elliston, Vladimir T.; Tyurina, Daria A.; Ivanova, Olga N.; Kochetkov, Sergey N.; Bartosch, Birke; Isaguliants, Maria G.

    2017-01-01

    Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review. PMID:27965466

  18. Bis is Induced by Oxidative Stress via Activation of HSF1

    PubMed Central

    Yoo, Hyung Jae; Im, Chang-Nim; Youn, Dong-Ye; Yun, Hye Hyeon

    2014-01-01

    The Bis protein is known to be involved in a variety of cellular processes including apoptosis, migration, autophagy as well as protein quality control. Bis expression is induced in response to a number of types of stress, such as heat shock or a proteasome inhibitor via the activation of heat shock factor (HSF)1. We report herein that Bis expression is increased at the transcriptional level in HK-2 kidney tubular cells and A172 glioma cells by exposure to oxidative stress such as H2O2 treatment and oxygen-glucose deprivation, respectively. The pretreatment of HK-2 cells with N-acetyl cysteine, suppressed Bis induction. Furthermore, HSF1 silencing attenuated Bis expression that was induced by H2O2, accompaniedby increase in reactive oxygen species (ROS) accumulation. Using a series of deletion constructs of the bis gene promoter, two putative heat shock elements located in the proximal region of the bis gene promoter were found to be essential for the constitutive expression is as well as the inducible expression of Bis. Taken together, our results indicate that oxidative stress induces Bis expression at the transcriptional levels via activation of HSF1, which might confer an expansion of antioxidant capacity against pro-oxidant milieu. However, the possible role of the other cis-element in the induction of Bis remains to be determined. PMID:25352760

  19. Protective Role of Intracellular Melatonin Against Oxidative Stress and UV Radiation in Saccharomyces cerevisiae.

    PubMed

    Bisquert, Ricardo; Muñiz-Calvo, Sara; Guillamón, José M

    2018-01-01

    Melatonin (Mel) is considered a potent natural antioxidant molecule given its free-radical scavenging ability. Its origin is traced back to the origin of aerobic life as early defense against oxidative stress and radiation. More complex signaling functions have been attributed to Mel as a result of evolution in different biological kingdoms, which comprise gene expression modulation, enzyme activity, and mitochondrial homeostasis regulation processes, among others. Since Mel production has been recently reported in wine yeast, we tested the protective effect of Mel on Saccharomyces cerevisiae against oxidative stress and UV light. As the optimal conditions for S. cerevisiae to synthesize Mel are still unknown, we developed an intracellular Mel-charging method to test its effect against stresses. To assess Mel's ability to protect S. cerevisiae from both stresses, we ran growth tests in liquid media and viability assays by colony count after Mel treatment, followed by stress. We also analyzed gene expression by qPCR on a selection of genes involved in stress protection in response to Mel treatment under oxidative stress and UV radiation. The viability in the Mel-treated cells after H 2 O 2 stress was up to 35% greater than for the untreated controls, while stress amelioration reached 40% for UVC light (254 nm). Mel-treated cells showed a significant shortened lag phase compared to the control cells under the stress and normal growth conditions. The gene expression analysis showed that Mel significantly modulated gene expression in the unstressed cells in the exponential growth phase, and also during various stress treatments.

  20. Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes

    PubMed Central

    Bavarva, Jasmin H.; Tae, Hongseok; McIver, Lauren; Garner, Harold R.

    2014-01-01

    Although the connection between cancer and cigarette smoke is well established, nicotine is not characterized as a carcinogen. Here, we used exome sequencing to identify nicotine and oxidative stress-induced somatic mutations in normal human epithelial cells and its correlation with cancer. We identified over 6,400 SNVs, indels and microsatellites in each of the stress exposed cells relative to the control, of which, 2,159 were consistently observed at all nicotine doses. These included 429 nsSNVs including 158 novel and 79 cancer-associated. Over 80% of consistently nicotine induced variants overlap with variations detected in oxidative stressed cells, indicating that nicotine induced genomic alterations could be mediated through oxidative stress. Nicotine induced mutations were distributed across 1,585 genes, of which 49% were associated with cancer. MUC family genes were among the top mutated genes. Analysis of 591 lung carcinoma tumor exomes from The Cancer Genome Atlas (TCGA) revealed that 20% of non-small-cell lung cancer tumors in smokers have mutations in at least one of the MUC4, MUC6 or MUC12 genes in contrast to only 6% in non-smokers. These results indicate that nicotine induces genomic variations, promotes instability potentially mediated by oxidative stress, implicating nicotine in carcinogenesis, and establishes MUC genes as potential targets. PMID:24947164

  1. Mentha piperita as a pivotal neuro-protective agent against gamma irradiation induced DNA fragmentation and apoptosis : Mentha extract as a neuroprotective against gamma irradiation.

    PubMed

    Hassan, Hanaa A; Hafez, Hani S; Goda, Mona S

    2013-01-01

    Ionizing radiation is classified as a potent carcinogen, and its injury to living cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell death. Our present study aimed to characterize and semi-quantify the radiation-induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective agent. Our results through flow cytometry exhibited the significant disturbance and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p < 0.05). Significant increase in % of apoptosis and P53 protein expression as apoptotic biomarkers were coincided with significant decrease in Bcl(2) as an anti-apoptotic marker. The biochemical analysis recorded a significant decrease in the levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA) and ribonucleic acid contents. Moreover, numerous histopathological alterations were detected in brain tissues of gamma irradiated mice such as signs of chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice pretreated with Mentha extract showed largely an improvement in all the above tested parameters through a homeostatic state for the content of brain apoptosis and stabilization of DNA cycle with a distinct improvement in cell cycle analysis and antioxidant defense system. Furthermore, the aforementioned effects of Mentha extracts through down-regulation of P53 expression and up-regulation of Bcl(2) domain protected brain structure from extensive damage. Therefore, Mentha extract seems to have a significant role to ameliorate the neuronal injury induced by gamma irradiation.

  2. Chlorogenic acid attenuates hydrogen peroxide-induced oxidative stress in lens epithelial cells

    PubMed Central

    Song, Jike; Guo, Dadong; Bi, Hongsheng

    2018-01-01

    Oxidative stress has an important role in the degradation, oxidation, cross-linking and aggregation of lens proteins, and can trigger lens epithelial cell apoptosis. To investigate the protective effect of chlorogenic acid (CGA) against hydrogen peroxide (H2O2)-induced oxidative stress, human lens epithelial cells (hLECs) were exposed to various concentrations of H2O2 in the presence and absence of CGA. Using MTT assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA techniques, cell viability, and protein/mRNA levels of BCL2 apoptosis regulator (Bcl-2) and BCL2 associated X apoptosis regulator (Bax) were investigated. Additionally, the levels of intracellular reactive oxygen species (ROS) and apoptosis within cells were measured using flow cytometry to determine the protective effect of CGA on H2O2-induced oxidative stress. Furthermore, the protective effect of CGA on H2O2-induced apoptosis was also examined using rabbit lenses ex vivo. The results indicated that CGA reduced H2O2-induced cytotoxicity in a dose-dependent manner. Flow cytometry analysis demonstrated that simultaneous exposure of hLECs to H2O2 and CGA significantly decreased apoptosis and the levels of ROS. RT-qPCR analysis revealed a decrease in Bcl-2 and an increase in Bax in hLECs following exposure to H2O2 for 24 h, regardless of CGA presence. Furthermore, ELISA results indicate that CGA increased Bcl-2 expression and decreased Bax expression following treatment with H2O2 for 24 h and the Bax/Bcl-2 ratio was significantly decreased by CGA treatment. Lens organ culture experiments indicated a dose-dependent decrease in H2O2-induced lens opacity following CGA treatment. These results suggest that CGA suppresses hLECs apoptosis and prevents lens opacity induced by H2O2 via Bax/Bcl-2 signaling pathway. CGA may provide effective defenses against oxidative stress and, thus, haσ potential as treatment for a variety of diseases in clinical practice. PMID:29207051

  3. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage.

    PubMed

    Akıncı, Ayşin; Eşrefoğlu, Mukaddes; Taşlıdere, Elif; Ateş, Burhan

    2017-01-01

    Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Animal experimentation. Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals' stomachs were arranged for microscopic and biochemical examinations. Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system.

  4. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    PubMed Central

    Akıncı, Ayşin; Eşrefoğlu, Mukaddes; Taşlıdere, Elif; Ateş, Burhan

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system. PMID:28251024

  5. Detection of oxidative stress biomarker-induced assembly of gold nanoparticles in retinal pigment epithelial cells

    NASA Astrophysics Data System (ADS)

    Yasmin, Z.; Lee, Y.; Maswadi, S.; Glickman, R.; Nash, K. L.

    2013-02-01

    Oxidative stress (OS) is increasingly implicated as an underlying pathogenic mechanism in a wide range of diseases, resulting from an imbalance between the production of reactive oxygen species (ROS) and the system's ability to detoxify the reactive intermediates or repair the resulting damage. ROS can be difficult to detect directly; however, they can be detected indirectly from the effects on oxidative stress biomarkers (OSB), such as glutathione (GSH), 3-nitrotyrosine, homocysteine, and cysteine. Moreover the reaction of transition metals with thiol-containing amino acids (for example GSH) oxidized by ROS can yield reactive products that accumulate with time and contribute to aging and diseases. The study of the interaction between OSB using functionalized nanoparticles (fNPs) has attracted interest because of potential applications in bio-sensors and biomedical diagnostics. A goal of the present work is to use fNPs to detect and ultimately quantitate OS in retinal pigment epithelial (RPE) cells subjected to external stressors, e.g. nonionizing (light) and ionizing (gamma) radiation. Specifically, we are investigating the assembly of gold fNPs mediated by the oxidation of GSH in irradiated RPE cells. The dynamic interparticle interactions had been characterized in previously reported work by monitoring the evolution of the surface plasmon resonance band using spectroscopic analysis (UV-VIS absorption). Here we are comparing the dynamic evolution of fNP assembly using photoacoustic spectroscopy (PAS). We expect that PAS will provide a more sensitive measure allowing these fNP sensors to measure OS in cell-based models without the artifacts limiting the use of current methods, such as fluorescent indicators.

  6. Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats.

    PubMed

    Lee, Yen-Mei; Cheng, Pao-Yun; Hong, Su-Fen; Chen, Shu-Ying; Lam, Kwok-Keung; Sheu, Joen-Rong; Yen, Mao-Hsiung

    2005-07-01

    Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17beta-Estradiol (E(2)) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E(2) depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.

  7. Quercetin ameliorates liver injury induced with Tripterygium glycosides by reducing oxidative stress and inflammation.

    PubMed

    Wang, Junming; Miao, Mingsan; Zhang, Yueyue; Liu, Ruixin; Li, Xaobing; Cui, Ying; Qu, Lingbo

    2015-06-01

    Quercetin (Que) is one of main compounds in Lysimachia christinae Hance (Christina loosestrife), and has both medicinal and nutritional value. Glycosides from Tripterygium wilfordii Hook.f. (léi gōng téng [the thunder duke vine]; TG) have diverse and broad bioactivities but with a high incidence of liver injury. Our previous study reported on the hepatoprotective properties of an ethanol extract from L. christinae against TG-induced liver injury in mice. This research is designed to observe, for the first time, the possible protective properties of the compound Que against TG-induced liver injury, and the underlying mechanisms that are involved in oxidative stress and anti-inflammation. The results indicated that TG caused excessive elevation in serum levels of alanine/aspartate transaminase (ALT/AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), as well as hepatic lipid peroxidation (all P < 0.01). On the other hand, following TG exposure, we observed significantly reduced levels of biomarkers, including hepatic glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and the anti-inflammatory cytokine interleukin (IL)-10, as well as the enzyme activity and mRNA expression of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) (all P < 0.01). Nevertheless, all of these alterations were reversed by the pre-administration of Que or the drug bifendate (positive control) for 7 consecutive days. Therefore, this study suggests that Que ameliorates TG-induced acute liver injury, probably through its ability to reduce oxidative stress and its anti-inflammatory properties.

  8. Effects of gamma radiation on the chromosomes of Gryllidae (orthoptera)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lim, H.C.; Kevan, D.K.; Vickery, V.R.

    1972-12-01

    BS>Six species if Gryllidae (orthoptera), Gryllus assimilis, G, Bim aculatus, G. pennsylvanicus, Acheta domesticus, Scapipedus marginatus, and Allonemobius allardi, were subjected to gamma radiation treatment (dosages varied from 1000 rads to 2446 rads) in order to induce chromosomal abnormalities. Gamma radiation was found to affect development, survival, and reproduction. Effects of gamma rays were similar in all of the species studied, but sensitivity varied between the different species. (auth)

  9. Co-expression of antioxidant enzymes with expression of p53, DNA repair, and heat shock protein genes in the gamma ray-irradiated hermaphroditic fish Kryptolebias marmoratus larvae.

    PubMed

    Rhee, Jae-Sung; Kim, Bo-Mi; Kim, Ryeo-Ok; Seo, Jung Soo; Kim, Il-Chan; Lee, Young-Mi; Lee, Jae-Seong

    2013-09-15

    To investigate effects of gamma ray irradiation in the hermaphroditic fish, Kryptolebias marmoratus larvae, we checked expression of p53, DNA repair, and heat shock protein genes with several antioxidant enzyme activities by quantitative real-time RT-PCR and biochemical methods in response to different doses of gamma radiation. As a result, the level of gamma radiation-induced DNA damage was initiated after 4Gy of radiation, and biochemical and molecular damage became substantial from 8Gy. In particular, several DNA repair mechanism-related genes were significantly modulated in the 6Gy gamma radiation-exposed fish larvae, suggesting that upregulation of such DNA repair genes was closely associated with cell survival after gamma irradiation. The mRNA expression of p53 and most hsps was also significantly upregulated at high doses of gamma radiation related to cellular damage. This finding indicates that gamma radiation can induce oxidative stress with associated antioxidant enzyme activities, and linked to modulation of the expression of DNA repair-related genes as one of the defense mechanisms against radiation damage. This study provides a better understanding of the molecular mode of action of defense mechanisms upon gamma radiation in fish larvae. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress.

    PubMed

    Alzoubi, Karem H; Mayyas, Fadia A; Mahafzah, Rania; Khabour, Omar F

    2018-01-15

    Consumption of high-fat diet (HFD) induces oxidative stress in the hippocampus that leads to memory impairment. Melatonin has antioxidant and neuroprotective effects. In this study, we hypothesized that chronic administration of melatonin can prevent memory impairment induced by consumption of HFD. Melatonin was administered to rats via oral gavage (100mg/kg/day) for 4 weeks. HFD was also instituted for the same duration. Behavioral studies were conducted to test spatial memory using the radial arm water maze. Additionally, oxidative stress biomarkers were assessed in the hippocampus. Results showed that HFD impaired both short- and long- term memory (P<0.05), while melatonin treatment prevented such effects. Furthermore, melatonin prevented HFD-induced reduction in levels of GSH, and ratio of GSH/GSSG, and increase in GSSG in the hippocampus. Melatonin also prevented reduction in the catalase activity in hippocampus of animals on HFD. In conclusion, HFD induced memory impairment and melatonin prevented this impairment probably by preventing alteration of oxidative stress in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes

    PubMed Central

    Gonzalez, Eric J.; Peterson, Abbey; Malley, Susan; Daniel, Mitchel; Lambert, Daniel; Kosofsky, Michael; Vizzard, Margaret A.

    2015-01-01

    We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P ≤ 0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P ≤ 0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P ≤ 0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation. PMID:25973443

  12. Induced oxidative stress management in wounds through phenolic acids engineered fibrous protein: An in vitro assessment using polymorphonuclear (PMN) cells.

    PubMed

    Thiruselvi, T; Thirupathi Kumara Raja, S; Shanuja, S K; Iswarya, S; Gnanamani, A

    2017-03-01

    The present study explores the preparation, characterization and the role of phenolic acid tethered fibrous protein in the management of induced oxidative stress studied under in vitro conditions. In brief, the biomaterial is prepared by engineering the fibrous protein with dihydroxy and trihydroxy phenolic acid moieties and subjected to characterization to ensure the tethering. The resultant biomaterial studied for its efficacy as a free radical scavenger using polymorphonuclear (PMN) cells with induced oxidative stress and also as an agent for cell migration using fibroblasts cells. Results revealed that induced oxidative stress in PMN cells after exposure to UVB radiation managed well with the prepared biomaterial by reducing the levels of superoxide anion, oxygen and hydroxyl radicals. Further, the protein and the phenolic acid interaction supports the cell migration as evidenced from the scratch assay. In conclusion, though phenolic acids are well known for their antimicrobial and antioxidant potential, indenting these acids directly to the wounds is not sensible, but tethering to protein explored the scavenging activity as expected. The present study infers that phenolic acid engineered protein has a significant role in managing the imbalance in the redox state prevailing in wounds and supports the healing at appreciable level. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

    PubMed

    Ren, Jiayi; Liu, Chunpeng; Zhao, Dan; Fu, Jing

    2018-05-15

    The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p < 0.05) after chronic cold stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p < 0.05) in both of the acute and chronic cold stress groups. Malondialdehyde (MDA) content was significantly increased (p < 0.05) under cold stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

  14. Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats.

    PubMed

    Coban, Funda Karabag; Ince, Sinan; Kucukkurt, Ismail; Demirel, Hasan Huseyin; Hazman, Omer

    2015-10-01

    Organophosphorus compounds cause oxidative stress and lead to alterations in antioxidant status in organisms. In this study, the effects of subchronic exposure to malathion and the protective effects of boron (B) were evaluated in 48 Wistar rats, which were divided equally into six groups. For 28 d, the control group received a normal diet and tap water, the corn oil group received a normal diet and 0.5 mL of corn oil by gastric gavage and the malathion group received a normal diet and malathion (100 mg/kg/d) by gastric gavage. During the same period, each of the three other groups received a different dosage of B (5, 10 and 20 mg/kg/d, respectively) and malathion (100 mg/kg/d) by gastric gavage. Malathion administration during the period increased malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as markers of liver function, yet decreased acetylcholinesterase, reduced glutathione, superoxide dismutase, and catalase activities in blood, liver, kidney and brain tissues. Administration of B in a dose-dependent manner also reversed malathion-induced oxidative stress, lipid peroxidation (LPO) and antioxidant enzyme activity. Moreover, B exhibited protective action against malathion-induced histopathological changes in liver, kidney and brain tissues. These results demonstrate that, if used in a dose-dependent manner, B decreases malathion-induced oxidative stress, enhances the antioxidant defense mechanism and regenerates tissues in rats.

  15. In vitro stimulatory effect of N-acetyl tryptophan-glucopyranoside against gamma radiation induced immunosuppression.

    PubMed

    Malhotra, Poonam; Singh, Darshana; Kumar, Raj

    2018-03-01

    Radiation-induced manifestations like free radical burst, oxidative damage and apoptosis leading to cell death. In present study, N-acetyl tryptophan glucopyranoside (NATG) was assessed for its immune-radioprotective activities using J774A.1 cells. Clonogenic cell survival, cell cycle progression and cytokines i.e. IFN-γ, TNF-α, IL-2, IL-10, IL-12, IL-13 and IL-17A expression were evaluated in irradiated and NATG pretreated cells using clonogenic formation ability, flow cytometry and ELISA assay. Results indicated that 0.25μg/ml NATG exhibited maximum radioprotection against gamma-radiation (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus irradiated cells showed significant elevation in IFN-γ (∼38.2%), IL-17A (∼53.7%) and IL-12 (∼58.8%) expression as compared to only irradiated cells. Conversely, significant decrease in TNF-α (∼21.6%), IL-10 (∼31.2%), IL-2 (∼23.7%) and IL-13 expression (∼17.8%) were observed in NATG pretreated plus irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment to irradiated J774A.1 cells, stimulate Th 1 while diminish Th 2 cytokines that contributes to radioprotection. © 2017 Wiley Periodicals, Inc.

  16. Ascorbyl stearate and ionizing radiation potentiate apoptosis through intracellular thiols and oxidative stress in murine T lymphoma cells.

    PubMed

    Mane, Shirish D; Kamatham, Akhilender Naidu

    2018-02-01

    Ascorbyl stearate (Asc-s) is a derivative of ascorbic acid with better anti-tumour efficacy compared to its parent compound ascorbic acid. In this study, we have examined radio-sensitizing effect of Asc-s in murine T cell lymphoma (EL4) cells at 4 Gy. Asc-s and radiation treatment reduced cell proliferation, induced apoptosis in a dose dependent manner by arresting the cells at S/G2-M phase of cell cycle. It also decreased the frequency of cancer stem cells per se, with significantly higher decrease in combination with radiation treatment./Further, Asc-s and radiation treatment increased the level of reactive oxygen species (ROS), drop in mitochondrial membrane potential (MMP) and increased caspase-3 activity resulting in apoptosis of EL4 cells. Further it also significantly decreased GSH/GSSG ratio due to binding of Asc-s with thiols. The increase in oxidative stress induced by Asc-s and radiation treatment was abrogated by thiol antioxidants in EL4 cells. Interestingly, this redox modulation triggered significant increase in protein glutathionylation in a time dependent manner. Asc-s treatment resulted in glutathionylation of IKK, p50-NF-kB and mutated p53, thereby inhibiting cancer progression during oxidative stress. Asc-s quenches GSH ensuing Asc-s + GSH adduct thereby further modulating GSH/GSSG ratio as evident from HPLC and docking studies. The anti-tumour effect of Asc-s along with radiation was studied by injecting EL4 cells in synegenicC57/BL6 male mice. Intraperitoneal injection of Asc-s followed by radiation exposure at 4 Gy to the tumour bearing mice resulted in radio-sensitization which is evident from significant regression of tumour as evident from tumour burden index. The survival study supports the data that Asc-s pre-treatment enhances radio-sensitization in murine lymphoma. Our data, suggest that Asc-s and ionizing radiation induced cell cycle arrest and apoptosis by perturbing redox balance through irreversible complexes of thiols with Asc

  17. Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways.

    PubMed

    Li, Xiang; Michaeloudes, Charalambos; Zhang, Yuelin; Wiegman, Coen H; Adcock, Ian M; Lian, Qizhou; Mak, Judith C W; Bhavsar, Pankaj K; Chung, Kian Fan

    2018-05-01

    Oxidative stress-induced mitochondrial dysfunction can contribute to inflammation and remodeling in patients with chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. We sought to examine the effect of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo. ASMCs were cocultured with iPSC-MSCs in the presence of cigarette smoke medium (CSM), and mitochondrial reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), and apoptosis were measured. Conditioned medium from iPSC-MSCs and transwell cocultures were used to detect any paracrine effects. The effect of systemic injection of iPSC-MSCs on airway inflammation and hyperresponsiveness in ozone-exposed mice was also investigated. Coculture of iPSC-MSCs with ASMCs attenuated CSM-induced mitochondrial ROS, apoptosis, and ΔΨm loss in ASMCs. iPSC-MSC-conditioned medium or transwell cocultures with iPSC-MSCs reduced CSM-induced mitochondrial ROS but not ΔΨm or apoptosis in ASMCs. Mitochondrial transfer from iPSC-MSCs to ASMCs was observed after direct coculture and was enhanced by CSM. iPSC-MSCs attenuated ozone-induced mitochondrial dysfunction, airway hyperresponsiveness, and inflammation in mouse lungs. iPSC-MSCs offered protection against oxidative stress-induced mitochondrial dysfunction in human ASMCs and in mouse lungs while reducing airway inflammation and hyperresponsiveness. These effects are, at least in part, dependent on cell-cell contact, which allows for mitochondrial transfer, and paracrine regulation. Therefore iPSC-MSCs show promise as a therapy for oxidative stress-dependent lung diseases, such as COPD. Copyright © 2017 American Academy of Allergy

  18. Gender comparisons of exercise-induced oxidative stress: influence of antioxidant supplementation.

    PubMed

    Goldfarb, Allan H; McKenzie, Michael J; Bloomer, Richard J

    2007-12-01

    The purpose of this study was to determine the influence of gender and antioxidant supplementation on exercise-induced oxidative stress. Twenty-five men and 23 women ran for 30 min at 80% VO2 max, once before and once after 2 weeks of supplementation, and again after a 1-week wash-out period. Subjects were randomly assigned to either placebo (P), antioxidant (A: 400 IU vitamin E+1 g vitamin C), or a fruit and vegetable powder (FV) treatment. Blood was obtained at rest and immediately after exercise. Before supplementation, women had higher resting reduced glutathione, total glutathione, and plasma vitamin E compared with men. With both A and FV supplementations, plasma vitamin E gender differences disappeared. Protein carbonyls, oxidized glutathione, and malondialdehyde all increased similarly for both genders in response to exercise. Both A and FV attenuated the reduced glutathione decrease and the oxidized glutathione and protein carbonyls increase compared with P, with no gender differences. 8-hydroxydeoxyguanosine was lower with treatment A compared with FV and P only for men. Plasma vitamin C increased 39% (A) and 21% (FV) compared with P. These data indicate that women have higher resting antioxidant levels than men. Markers of oxidative stress increased similarly in both genders in response to exercise of similar intensity and duration. Two weeks of antioxidant supplementation can attenuate exercise-induced oxidative stress equally in both genders.

  19. Metal-induced oxidative stress in terrestrial macrolichens.

    PubMed

    Kováčik, Jozef; Dresler, Sławomir; Peterková, Viera; Babula, Petr

    2018-07-01

    Short-term (24 h) responses of Cladonia arbuscula subsp. mitis and Cladonia furcata to copper (CuII) or chromium (CrIII) excess (10 or 100 μM) were compared. C. arbuscula accumulated more Cu and Cr at higher metal doses but both species revealed depletion of K and/or Ca amount. Not only Cu but also Cr typically elevated reactive oxygen species (ROS) formation (fluorescence microscopy detection of total ROS and hydrogen peroxide) and depleted nitric oxide (NO) signal, with Cu showing more negative impact on lipid peroxidation (BODIPY 581/591 C11 staining reagent). Metals and staining reagents also affected anatomical responses and photobiont/mycobiont visibility. Principally different impact of Cu and Cr was observed at antioxidative metabolites level, indicating various ways of metal-induced ROS removal and/or metal chelation: Cu strongly depleted glutathione (GSH) and stimulated phytochelatin 2 (PC2) content while ascorbic acid accumulation was depleted by Cu and stimulated by Cr. Subsequent experiment with GSH biosynthetic inhibitor (buthionine sulfoximine, BSO) revealed that 48 h of exposure is needed to deplete GSH and BSO-induced depletion of GSH and PC2 amounts under Cu or Cr excess elevated ROS but depleted NO. These data suggest close relations between thiols, NO and appearance of oxidative stress (ROS generation) under metallic stress also in lichens. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Gamma radiation-induced blue shift of resonance peaks of Bragg gratings in pure silica fibres

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faustov, A V; Mégret, P; Wuilpart, M

    2016-02-28

    We report the first observation of a significant gamma radiation-induced blue shift of the reflection/transmission peak of fibre Bragg gratings inscribed into pure-silica core fibres via multiphoton absorption of femtosecond pulses. At a total dose of ∼100 kGy, the shift is ∼20 pm. The observed effect is attributable to the ionising radiation-induced decrease in the density of the silica glass when the rate of colour centre formation is slow. We present results of experimental measurements that provide the key parameters of the dynamics of the gratings for remote dosimetry and temperature sensing. (laser crystals and braggg ratings)

  1. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Technical Reports Server (NTRS)

    Plaza-Rosado, Heriberto

    1991-01-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  2. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Astrophysics Data System (ADS)

    Plaza-Rosado, Heriberto

    1991-09-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  3. Evaluation of the gamma radiation shielding parameters of bismuth modified quaternary glass system

    NASA Astrophysics Data System (ADS)

    Kaur, Parminder; Singh, K. J.; Thakur, Sonika

    2018-05-01

    Glasses modified with heavy metal oxides (HMO) are an interesting area of research in the field of gamma-ray shielding. Bismuth modified lithium-zinc-borate glasses have been studied whereby bismuth oxide is added from 0 to 50 mol%. The gamma ray shielding properties of the glasses were evaluated at photon energy 662 keV with the help of XMuDat computer program by using the Hubbell and Seltzer database. Various gamma ray shielding parameters such as attenuation coefficient, shield thickness in terms of half and tenth value layer, effective atomic number have been studied in this work. A useful comparison of this glass system has been made with standard radiation shielding concretes viz. ordinary, barite and iron concrete. The glass samples containing 20 to 50 mol% bismuth oxide have shown better gamma ray shielding properties and hence have the potential to become good radiation absorbers.

  4. Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

    PubMed

    Zacarias, Aline Cruz; Barbosa, Maria Andrea; Guerra-Sá, Renata; De Castro, Uberdan Guilherme Mendes; Bezerra, Frank Silva; de Lima, Wanderson Geraldo; Cardoso, Leonardo M; Santos, Robson Augusto Souza Dos; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2017-11-01

    Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.

  5. Preventive or Potential Therapeutic Value of Nutraceuticals against Ionizing Radiation-Induced Oxidative Stress in Exposed Subjects and Frequent Fliers

    PubMed Central

    Giardi, Maria Teresa; Touloupakis, Eleftherios; Bertolotto, Delfina; Mascetti, Gabriele

    2013-01-01

    Humans are constantly exposed to ionizing radiation deriving from outer space sources or activities related to medical care. Absorption of ionizing radiation doses over a prolonged period of time can result in oxidative damage and cellular dysfunction inducing several diseases, especially in ageing subjects. In this report, we analyze the effects of ionizing radiation, particularly at low doses, in relation to a variety of human pathologies, including cancer, and cardiovascular and retinal diseases. We discuss scientific data in support of protection strategies by safe antioxidant formulations that can provide preventive or potential therapeutic value in response to long-term diseases that may develop following exposure. PMID:23965979

  6. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    NASA Astrophysics Data System (ADS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  7. Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

    NASA Technical Reports Server (NTRS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2007-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  8. Protective effects of resveratrol on calcium-induced oxidative stress in rat heart mitochondria.

    PubMed

    Gutiérrez-Pérez, Areli; Cortés-Rojo, Christian; Noriega-Cisneros, Ruth; Calderón-Cortés, Elizabeth; Manzo-Avalos, Salvador; Clemente-Guerrero, Mónica; Godínez-Hernández, Daniel; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2011-04-01

    Trans-resveratrol is a nutraceutical with known antioxidant, anti-inflammatory, cardioprotective, and anti-apoptotic properties. The aim of this study was to evaluate the effects of resveratrol on heart mitochondria. Resveratrol significantly decreased Fe(2+) + ascorbate oxidant system-induced lipid peroxide levels, preserved physiological levels of glutathione, and increased nitric oxide (NO) levels in mitochondria. Under calcium-mediated stress, there was a 2.7-fold increase in the NO levels, and a mild decoupling in the mitochondrial respiratory chain. These results provide a mechanism for and support the beneficial effects of resveratrol under pathological conditions induced by oxidative stress and calcium overload. In addition, these findings underscore the usefulness of resveratrol in the prevention of cardiovascular diseases.

  9. Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

    NASA Technical Reports Server (NTRS)

    Westby, Christian M.; Seawright, John W.; Wu, Honglu

    2011-01-01

    One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio

  10. Galactic plane gamma-radiation

    NASA Technical Reports Server (NTRS)

    Hartman, R. C.; Kniffen, D. A.; Thompson, D. J.; Fichtel, C. E.; Ogelman, H. B.; Tumer, T.; Ozel, M. E.

    1979-01-01

    Analysis of the SAS 2 data together with the COS B results shows that the distribution of galactic gamma-radiation has several similarities to that of other large-scale tracers of galactic structure. The radiation is primarily confined to a thin disc which exhibits offsets from b = 0 degrees similar to warping at radio frequencies. The principal distinction of the gamma-radiation is a stronger contrast in intensity between the region from 310 to 45 degrees in longitude and the regions away from the center that can be attributed to a variation in cosmic-ray density as a function of position in Galaxy. The diffuse galactic gamma-ray energy spectrum shows no significant variation in direction, and the spectrum seen along the plane is the same as that for the galactic component of the gamma-radiation at high altitudes. The uniformity of the galactic gamma-ray spectrum, the smooth decrease in intensity as a function of altitude, and the absence of any galactic gamma-ray sources at high altitudes indicate a diffuse origin for bulk of the galactic gamma-radiation rather than a collection of localized sources.

  11. Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

    PubMed Central

    2016-01-01

    The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms. PMID:26949445

  12. Role of Oxidative Damage in Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  13. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.

    PubMed

    Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

    2014-01-01

    Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.

  14. Chloride Secretion Induced by Rotavirus Is Oxidative Stress-Dependent and Inhibited by Saccharomyces boulardii in Human Enterocytes

    PubMed Central

    Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

    2014-01-01

    Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics. PMID:24918938

  15. Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach

    PubMed Central

    Misdaq, Misbah; Ziegler, Sonia; von Ahsen, Nicolas; Asif, Abdul R.

    2015-01-01

    Thiopurines are extensively used immunosuppressants for the treatment of inflammatory bowel disease (IBD). The polymorphism of thiopurine S-methyltransferase (TPMT) influences thiopurine metabolism and therapy outcome. We used a TPMT knockdown (kd) model of human Jurkat T-lymphocytes cells to study the effects of treatment with 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) on proteome and phosphoproteome. We identified thirteen proteins with altered expression and nine proteins with altered phosphorylation signals. Three proteins (THIO, TXD17, and GSTM3) with putative functions in cellular oxidative stress responses were altered by 6-TG treatment and another protein PRDX3 was differentially phosphorylated in TPMT kd cells. Furthermore, reactive oxygen species (ROS) assay results were consistent with a significant induction of oxidative stress by both TPMT knockdown and thiopurine treatments. Immunoblot analyses showed treatment altered expression of key antioxidant enzymes (i.e., SOD2 and catalase) in both wt and kd groups, while SOD1 was downregulated by 6-TG treatment and TPMT knockdown. Collectively, increased oxidative stress might be a mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e., hepatotoxicity) and an antioxidant cotherapy might help to combat this. Results highlight the significance of oxidative stress in thiopurines' actions and could have important implications for the treatment of IBD patients. PMID:25873760

  16. Halobenzoquinone-Induced Alteration of Gene Expression Associated with Oxidative Stress Signaling Pathways.

    PubMed

    Li, Jinhua; Moe, Birget; Liu, Yanming; Li, Xing-Fang

    2018-06-05

    Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) that effectively induce reactive oxygen species and oxidative damage in vitro. However, the impacts of HBQs on oxidative-stress-related gene expression have not been investigated. In this study, we examined alterations in the expression of 44 genes related to oxidative-stress-induced signaling pathways in human uroepithelial cells (SV-HUC-1) upon exposure to six HBQs. The results show the structure-dependent effects of HBQs on the studied gene expression. After 2 h of exposure, the expression levels of 9 to 28 genes were altered, while after 8 h of exposure, the expression levels of 29 to 31 genes were altered. Four genes ( HMOX1, NQO1, PTGS2, and TXNRD1) were significantly upregulated by all six HBQs at both exposure time points. Ingenuity pathway analysis revealed that the Nrf2 pathway was significantly responsive to HBQ exposure. Other canonical pathways responsive to HBQ exposure included GSH redox reductions, superoxide radical degradation, and xenobiotic metabolism signaling. This study has demonstrated that HBQs significantly alter the gene expression of oxidative-stress-related signaling pathways and contributes to the understanding of HBQ-DBP-associated toxicity.

  17. Detection of gamma-neutron radiation by solid-state scintillation detectors. Detection of gamma-neutron radiation by novel solid-state scintillation detectors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryzhikov, V.; Grinyov, B.; Piven, L.

    It is known that solid-state scintillators can be used for detection of both gamma radiation and neutron flux. In the past, neutron detection efficiencies of such solid-state scintillators did not exceed 5-7%. At the same time it is known that the detection efficiency of the gamma-neutron radiation characteristic of nuclear fissionable materials is by an order of magnitude higher than the efficiency of detection of neutron fluxes alone. Thus, an important objective is the creation of detection systems that are both highly efficient in gamma-neutron detection and also capable of exhibiting high gamma suppression for use in the role ofmore » detection of neutron radiation. In this work, we present the results of our experimental and theoretical studies on the detection efficiency of fast neutrons from a {sup 239}Pu-Be source by the heavy oxide scintillators BGO, GSO, CWO and ZWO, as well as ZnSe(Te, O). The most probable mechanism of fast neutron interaction with nuclei of heavy oxide scintillators is the inelastic scattering (n, n'γ) reaction. In our work, fast neutron detection efficiencies were determined by the method of internal counting of gamma-quanta that emerge in the scintillator from (n, n''γ) reactions on scintillator nuclei with the resulting gamma energies of ∼20-300 keV. The measured efficiency of neutron detection for the scintillation crystals we considered was ∼40-50 %. The present work included a detailed analysis of detection efficiency as a function of detector and area of the working surface, as well as a search for new ways to create larger-sized detectors of lower cost. As a result of our studies, we have found an unusual dependence of fast neutron detection efficiency upon thickness of the oxide scintillators. An explanation for this anomaly may involve the competition of two factors that accompany inelastic scattering on the heavy atomic nuclei. The transformation of the energy spectrum of neutrons involved in the (n, n'γ) reactions

  18. Augmentation of aluminum-induced oxidative stress in rat cerebrum by presence of pro-oxidant (graded doses of ethanol) exposure.

    PubMed

    Nayak, Prasunpriya; Sharma, Shiv Bhushan; Chowdary, Nadella Vijaya Subbaraya

    2010-11-01

    Both aluminum and ethanol are pro-oxidants and neurotoxic. Considering the possibilities of co-exposure and sharing mechanisms of producing neurotoxicity, the present study was planned to identify the level of aluminum-induced oxidative stress in altered pro-oxidant (ethanol exposure) status of cerebrum. Male rats were coexposed to aluminum and ethanol for 4 weeks. After the exposure period, cerebral levels of protein, reduced glutathione (GSH), lipid peroxidation (TBARS) were measured. Activities of catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione perioxidase (GPx) of cerebrum were estimated. In most of the cases significant correlations were observed between the alterations and graded ethanol doses, suggesting a dose-dependency in pushing the oxidant equilibrium toward pro-oxidants. Aluminum is found to influence significantly all the studied parameters of oxidative stress. Likewise, ethanol also influenced these parameters significantly, except GR, while the interaction between ethanol and aluminum could significantly influence only the GSH content and GR activity of cerebrum. Present study demonstrate that coexposure of aluminum with pro-oxidant might favor development of aluminum-induced oxidative stress in cerebrum. This observation might be helpful in understanding of mechanism of neurodegenerative disorders and ameliorate them.

  19. Trivalent chromium induces oxidative stress in goldfish brain.

    PubMed

    Lushchak, Oleh V; Kubrak, Olha I; Torous, Ihor M; Nazarchuk, Tetyana Yu; Storey, Kenneth B; Lushchak, Volodymyr I

    2009-03-01

    Although information on the effects of Cr(6+) in biological systems is abundant, Cr(3+) has received less attention. Toxic effects of chromium compounds are partially associated with activation of redox processes. Recently we found that Cr(6+) induced oxidative stress in goldfish tissues and the glutathione system was shown to play a protective role. The present study aimed to investigate free radical processes in brain of goldfish exposed to CrCl(3). Trivalent chromium at a concentration of 50 mg L(-1) was lethal and therefore we chose to examine sublethal dosages of 1.0-10.0 mg L(-1) in aquarium water. The levels of lipid peroxides and protein carbonyls (measures of oxidative damage to lipids and proteins) in brain increased after 96 h exposure of goldfish to Cr(3+). However, exposure to 1.0-10.0 mg L(-1) Cr(3+) decreased total glutathione concentration in brain by approximately 50-60%. Oxidized glutathione levels also fell by approximately 40-60% except at the 10.0 mg L(-1) dosage where they decreased by 85%. Therefore, 10.0 mg L(-1) Cr(3+) significantly reduced the ratio [GSSG]/[totalGSH] to 35% of the control value. Chromium treatment did not affect the activity of superoxide dismutase, but reduced the activities of catalase by 55-62% and glutathione-S-transferase by 14-21%. The activities of glucose-6-phosphate dehydrogenase and glutathione reductase were unchanged under any experimental conditions used. Therefore, it can be concluded that although Cr(3+) exposure induced oxidative stress in goldfish brain, it failed to enhance the efficiency of the antioxidant system in the organ.

  20. Protective effect of Opuntia ficus-indica L. cladodes against UVA-induced oxidative stress in normal human keratinocytes.

    PubMed

    Petruk, Ganna; Di Lorenzo, Flaviana; Imbimbo, Paola; Silipo, Alba; Bonina, Andrea; Rizza, Luisa; Piccoli, Renata; Monti, Daria Maria; Lanzetta, Rosa

    2017-12-15

    Opuntia ficus-indica L. is known for its beneficial effects on human health, but still little is known on cladodes as a potent source of antioxidants. Here, a direct, economic and safe method was set up to obtain water extracts from Opuntia ficus-indica cladodes rich in antioxidant compounds. When human keratinocytes were pre-treated with the extract before being exposed to UVA radiations, a clear protective effect against UVA-induced stress was evidenced, as indicated by the inhibition of stress-induced processes, such as free radicals production, lipid peroxidation and GSH depletion. Moreover, a clear protective effect against apoptosis in pre-treated irradiated cells was evidenced. We found that eucomic and piscidic acids were responsible for the anti-oxidative stress action of cladode extract. In conclusion, a bioactive, safe, low-cost and high value-added extract from Opuntia cladodes was obtained to be used for skin health/protection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. OXIDATIVE STRESS PARTICIPATES IN PARTICULATE MATTER (PM) INDUCED LUNG INJURY

    EPA Science Inventory

    Oxidative stress participates in particulate matter (PM) induced acute lung injury.
    Elizabeth S. Roberts1, Judy L. Richards2, Kevin L. Dreher2. 1College of Veterinary Medicine, NC State University, Raleigh, NC, 2US Environmental Protection Agency, NHEERL, RTP, NC.
    Epidemiol...

  2. Mechanism of H₂O₂-induced oxidative stress regulating viability and biocontrol ability of Rhodotorula glutinis.

    PubMed

    Chen, Jian; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2015-01-16

    The use of antagonistic yeasts to control postharvest pathogens is a promising alternative to fungicides. The effectiveness of the antagonists against fungal pathogens is greatly dependent on their viability, which is usually mediated by reactive oxygen species (ROS). Here, we investigated the effects of H₂O₂-induced oxidative stress on the viability and biocontrol efficacy of Rhodotorula glutinis and, using flow cytometric analysis, observed the changes of ROS accumulation and apoptosis in the yeast cells with or without H₂O₂ treatment. We found that the viability of R. glutinis decreased in a time- and dose-dependent manner under H₂O₂-induced oxidative stress. Compared to the control, yeast cells exposed to oxidative stress exhibited more accumulation of ROS and higher levels of protein oxidative damage, but showed lower efficacy for biocontrol of Penicillium expansum causing blue mold rot on peach fruit. The results indicate that apoptosis is a main cause of the cell viability loss in R. glutinis, which is attributed to ROS accumulation under oxidative stress. These findings offer a plausible explanation that oxidative stress affects biocontrol efficacy of R. glutinis via regulating its viability and cell apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Passive smoking reduces and vitamin C increases exercise-induced oxidative stress: does this make passive smoking an anti-oxidant and vitamin C a pro-oxidant stimulus?

    PubMed

    Theodorou, Anastasios A; Paschalis, Vassilis; Kyparos, Antonios; Panayiotou, George; Nikolaidis, Michalis G

    2014-11-07

    The current interpretative framework states that, for a certain experimental treatment (usually a chemical substance) to be classified as "anti-oxidant", it must possess the property of reducing (or even nullifying) exercise-induced oxidative stress. The aim of the study was to compare side by side, in the same experimental setup, redox biomarkers responses to an identical acute eccentric exercise session, before and after chronic passive smoking (considered a pro-oxidant stimulus) or vitamin C supplementation (considered an anti-oxidant stimulus). Twenty men were randomly assigned into either passive smoking or vitamin C group. All participants performed two acute eccentric exercise sessions, one before and one after either exposure to passive smoking or vitamin C supplementation for 12 days. Vitamin C, oxidant biomarkers (F2-isoprostanes and protein carbonyls) and the non-enzymatic antioxidant (glutathione) were measured, before and after passive smoking, vitamin C supplementation or exercise. It was found that chronic exposure to passive smoking increased the level of F2-isoprostanes and decreased the level of glutathione at rest, resulting in minimal increase or absence of oxidative stress after exercise. Conversely, chronic supplementation with vitamin C decreased the level of F2-isoprostanes and increased the level of glutathione at rest, resulting in marked exercise-induced oxidative stress. Contrary to the current scientific consensus, our results show that, when a pro-oxidant stimulus is chronically delivered, it is more likely that oxidative stress induced by subsequent exercise is decreased and not increased. Reversely, it is more likely to find greater exercise-induced oxidative stress after previous exposure to an anti-oxidant stimulus. We believe that the proposed framework will be a useful tool to reach more pragmatic explanations of redox biology phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

    PubMed

    Hirata, Yoko; Yamada, Chika; Ito, Yuki; Yamamoto, Shotaro; Nagase, Haruna; Oh-Hashi, Kentaro; Kiuchi, Kazutoshi; Suzuki, Hiromi; Sawada, Makoto; Furuta, Kyoji

    2018-03-15

    The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca 2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. α-Syntrophin is involved in the survival signaling pathway in myoblasts under menadione-induced oxidative stress.

    PubMed

    Lim, Jeong-A; Choi, Su Jin; Moon, Jae Yun; Kim, Hye Sun

    2016-05-15

    Dystrophin-deficient muscle is known to be more vulnerable to oxidative stress, but not much is known about the signaling pathway(s) responsible for this phenomenon. α-Syntrophin, a component of the dystrophin-glycoprotein complex, can function as a scaffold protein because of its multiple protein interaction domains. In this study, we investigated the role of α-syntrophin in C2 myoblasts under menadione-induced oxidative stress. We found that the protein level of α-syntrophin was elevated when cells were exposed to menadione. To investigate the function of α-syntrophin during oxidative stress, we established α-syntrophin-overexpressing and knockdown cell lines. The α-syntrophin-overexpressing cells were resistant to the menadione-induced oxidative stress. In addition, survival signalings such as protein kinase B (Akt) phosphorylation and the Bcl-2/BAX ratio were increased in these cells. On the other hand, apoptotic signals such as cleavage of caspase-3 and poly ADP ribose polymerase (PARP) were increased in the α-syntrophin knockdown cells. Furthermore, Ca(2+)influx, which is known to increase when cells are exposed to oxidative stress, decreased in the α-syntrophin-overexpressing cells, but increased in the knockdown cells. These results suggest that α-syntrophin plays a pivotal role in the survival pathway triggered by menadione-induced oxidative stress in cultured myoblasts. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria.

    PubMed

    Cueno, Marni E; Imai, Kenichi; Matsukawa, Noriko; Tsukahara, Takamitsu; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2013-09-01

    Butyric acid (BA) is a major extracellular metabolite produced by anaerobic periodontopathic bacteria and is commonly deposited in the gingival tissue. BA induces mitochondrial oxidative stress in vitro; however, its effects in vivo were never elucidated. Here, we determined the effects of butyric acid retention in the gingival tissues on oxidative stress induction in the jugular blood mitochondria. We established that BA injected in the rat gingival tissue has prolonged retention in gingival tissues. Blood taken at 0, 60, and 180 min after BA injection was used for further analysis. We isolated blood mitochondria, verified its purity, and measured hydrogen peroxide (H2O2), heme, superoxide (SOD), and catalase (CAT) to determine BA effects. We found that H2O2, heme, SOD, and CAT levels all increased after BA injection. This would insinuate that mitochondrial oxidative stress was induced ascribable to BA.

  7. Thyroid hormone-induced oxidative stress.

    PubMed

    Venditti, P; Di Meo, S

    2006-02-01

    Hypermetabolic state in hyperthyroidism is associated with tissue oxidative injury. Available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS production. The increased mitochondrial ROS generation is a side effect of the enhanced level of electron carriers, by which hyperthyroid tissues increase their metabolic capacity. Investigations of antioxidant defence system have returned controversial results. Moreover, other thyroid hormone-linked biochemical changes increase tissue susceptibility to oxidative challenge, which exacerbates the injury and dysfunction they suffer under stressful conditions. Mitochondria, as a primary target for oxidative stress, might account for hyperthyroidism linked tissue dysfunction. This is consistent with the inverse relationship found between functional recovery of ischemic hyperthyroid hearts and mitochondrial oxidative damage and respiration impairment. However, thyroid hormone-activated mitochondrial mechanisms provide protection against excessive tissue dysfunction, including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulate opening of permeability transition pores.

  8. Evidence That the Capacity of Nongenotoxic Carcinogens to Induce Oxidative Stress Is Subject to Marked Variability

    PubMed Central

    Henderson, Colin J.; Cameron, Amy R.; Chatham, Lynsey; Stanley, Lesley A.; Wolf, Charles Roland

    2015-01-01

    Many drugs and environmental chemicals which are not directly mutagenic have the capacity to increase the incidence of tumors in the liver and other tissues. For this reason, such compounds are known as nongenotoxic carcinogens. The mechanisms underlying their effects remain unclear; however, their capacity to induce oxidative stress is considered to be a critical step in the carcinogenic process, although the evidence that this is actually the case remains equivocal and sparse. We have exploited a novel heme oxygenase-1 reporter mouse to evaluate the capacity of nongenotoxic carcinogens with different mechanisms of action to induce oxidative stress in the liver in vivo. When these compounds were administered at doses reported to cause liver tumors, marked differences in activation of the reporter were observed. 1,4-Dichlorobenzene and nafenopin were strong inducers of oxidative stress, whereas phenobarbital, piperonyl butoxide, cyproterone acetate, and WY14,643 were, at best, only very weak inducers. In the case of phenobarbital and thioacetamide, the number of LacZ-positive hepatocytes increased with time, and for the latter also with dose. The data obtained demonstrate that although some nongenotoxic carcinogens can induce oxidative stress, it is not a dominant feature of the response to these compounds. Therefore in contrast to the current models, these data suggest that oxidative stress is not a key determinant in the mechanism of nongenotoxic carcinogenesis but may contribute to the effects in a compound-specific manner. PMID:25690736

  9. Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial damage mediated apoptosis in cardiomyoblasts.

    PubMed

    Jadaun, Pratiksha; Yadav, Dhananjay; Bisen, Prakash Singh

    2018-04-01

    The current study was undertaken to study the effect of Spirulina platensis (Spirulina) extract on enhanced oxidative stress during high glucose induced cell death in H9c2 cells. H9c2 cultured under high glucose (33 mM) conditions resulted in a noteworthy increase in oxidative stress (free radical species) accompanied by loss of mitochondrial membrane potential, release of cytochrome c, increase in caspase activity and pro-apoptotic protein (Bax). Spirulina extract (1 μg/mL), considerably inhibited increased ROS and RNS levels, reduction in cytochrome c release, raise in mitochondrial membrane potential, decreased the over expression of proapoptotic protein Bax and suppressed the Bax/Bcl2 ratio with induced apoptosis without affecting cell viability. Overall results suggest that Spirulina extract plays preventing role against enhanced oxidative stress during high glucose induced apoptosis in cardiomyoblasts as well as related dysfunction in H9c2 cells.

  10. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells.

    PubMed

    Benameur, Laila; Charif, Naceur; Li, Yueying; Stoltz, Jean-François; de Isla, Natalia

    2015-01-01

    Under physiological conditions, there is a production of limited range of free radicals. However, when the cellular antioxidant defence systems, overwhelm and fail to reverse back the free radicals to their normal basal levels, there is a creation of a condition of redox disequilibrium termed "oxidative stress", which is implicated in a very wide spectrum of genetic, metabolic, and cellular responses. The excess of free radicals can, cause unfavourable molecular alterations to biomolecules through oxidation of lipids, proteins, RNA and DNA, that can in turn lead to mutagenesis, carcinogenesis, and aging. Mesenchymal stem cells (MSCs) have been proven to be a promising source of cells for regenerative medicine, and to be useful in the treatment of pathologies in which tissue damage is linked to oxidative stress. Moreover, MSCs appeared to efficiently manage oxidative stress and to be more resistant to oxidative insult than normal somatic cells, making them an interesting and testable model for the role of oxidative stress in the aging process. In addition, aging is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Also, there is an obvious link between intracellular reactive oxygen species levels and cellular senescence. To date, few studies have investigated the promotion of aging by oxidative stress on human MSCs, and the mechanism by which oxidative stress induce stem cell aging is poorly understood. In this context, the aim of this review is to gain insight the current knowledge about the molecular mechanisms of aging-induced oxidative stress in human MSCs.

  11. SIRT1 activation inhibits hyperglycemia-induced apoptosis by reducing oxidative stress and mitochondrial dysfunction in human endothelial cells.

    PubMed

    Wang, Shengqiang; Wang, Jian; Zhao, Airong; Li, Jigang

    2017-09-01

    Sustained hyperglycemic stimulation of vascular cells is involved in the pathogenesis of diabetes mellitus‑induced cardiovascular complications. Silent information regulator T1 (SIRT1), a mammalian sirtuin, has been previously recognized to protect endothelial cells against hyperglycemia‑induced oxidative stress. In the present study, human umbilical vein endothelial cells (HUV‑EC‑C) were treated with D‑glucose, and the levels of oxidative stress, mitochondrial dysfunction, the rate of apoptosis and SIRT1 activity were measured. The effect of manipulated SIRT1 activity on hyperglycemia‑induced oxidative stress, mitochondrial dysfunction and apoptosis was then assessed using the SIRT1 activator, resveratrol (RSV), and the SIRT1 inhibitor, sirtinol. The present study confirmed that hyperglycemia promotes oxidative stress and mitochondrial dysfunction in HUV‑EC‑C cells. The accumulation of reactive oxygen species, the swelling of mitochondria, the ratio of adenosine 5'‑diphosphate to adenosine 5'‑triphosphate and localized mitochondrial superoxide levels were all increased following D‑glucose treatment, whereas the mitochondrial membrane potential was significantly reduced by >50 mg/ml D‑glucose treatment. In addition, hyperglycemia was confirmed to induce apoptosis in HUV‑EC‑C cells. Furthermore, the results confirmed the prevention and aggravation of hyperglycemia‑induced apoptosis by RSV treatment and sirtinol treatment, via the amelioration and enhancement of oxidative stress and mitochondrial dysfunction in HUV‑EC‑C cells, respectively. In conclusion, the present study revealed that hyperglycemia promotes oxidative stress, mitochondrial dysfunction and apoptosis in HUV‑EC‑C cells, and manipulation of SIRT1 activity regulated hyperglycemia‑induced mitochondrial dysfunction and apoptosis in HUV‑EC‑C cells. The data revealed the protective effect of SIRT1 against hyperglycemia‑induced apoptosis via the alleviation of

  12. Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

    PubMed

    Arck, Petra Clara; Overall, Rupert; Spatz, Katharina; Liezman, Christiane; Handjiski, Bori; Klapp, Burghard F; Birch-Machin, Mark A; Peters, Eva Milena Johanne

    2006-07-01

    Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

  13. Silibinin Attenuates Sulfur Mustard Analog-Induced Skin Injury by Targeting Multiple Pathways Connecting Oxidative Stress and Inflammation

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants. PMID:23029417

  14. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  15. Iodinated contrast media can induce long-lasting oxidative stress in hemodialysis patients.

    PubMed

    Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel; Yoon, Soo Young

    2013-11-01

    Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients.

  16. Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

    PubMed Central

    Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel

    2013-01-01

    Purpose Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. Materials and Methods We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. Results In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Conclusion Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients. PMID:24142649

  17. [Use of terahertz electromagnetic radiation at nitric oxide frequencies for the correction of thyroid functional state during stress].

    PubMed

    Kirichuk, V F; Tsymbal, A A

    2010-01-01

    The influence of terahertz electromagnetic radiation at nitric oxide frequencies (150.176-150.664 Ghz) on the functional activity of rat thyroid gland subjected to acute immobilization stress has been studied. It is shown that terahertz radiation totally normalizes thyroid activity in stressed animals within 30 min after application.

  18. Cocoa flavonoids protect hepatic cells against high-glucose-induced oxidative stress: relevance of MAPKs.

    PubMed

    Cordero-Herrera, Isabel; Martín, María Angeles; Goya, Luis; Ramos, Sonia

    2015-04-01

    Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection. EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high-glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Hyperglycemia-induced diaphragm weakness is mediated by oxidative stress

    PubMed Central

    2014-01-01

    Introduction A major consequence of ICU-acquired weakness (ICUAW) is diaphragm weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced respiratory muscle weakness are not known. Excessive reactive oxygen species (ROS) injure multiple tissues during HG, but only one study suggests that excessive ROS generation may be linked to HG-induced diaphragm weakness. We hypothesized that HG-induced diaphragm dysfunction is mediated by excessive superoxide generation and that administration of a specific superoxide scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these effects. Methods HG was induced in rats using streptozotocin (60 mg/kg intravenously) and the following groups assessed at two weeks: controls, HG, HG + PEG-SOD (2,000U/kg/d intraperitoneally for seven days), and HG + denatured (dn)PEG-SOD (2000U/kg/d intraperitoneally for seven days). PEG-SOD and dnPEG-SOD were administered on day 8, we measured diaphragm specific force generation in muscle strips, force-pCa relationships in single permeabilized fibers, contractile protein content and indices of oxidative stress. Results HG reduced diaphragm specific force generation, altered single fiber force-pCa relationships, depleted troponin T, and increased oxidative stress. PEG-SOD prevented HG-induced reductions in diaphragm specific force generation (for example 80 Hz force was 26.4 ± 0.9, 15.4 ± 0.9, 24.0 ± 1.5 and 14.9 ± 0.9 N/cm2 for control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups, respectively, P <0.001). PEG-SOD also restored HG-induced reductions in diaphragm single fiber force generation (for example, Fmax was 182.9 ± 1.8, 85.7 ± 2.0, 148.6 ± 2.4 and 90.9 ± 1.5 kPa in control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups, respectively, P <0.001). HG-induced troponin T depletion, protein nitrotyrosine formation

  20. Relationship between genotoxicity and oxidative stress induced by mercury on common carp (Cyprinus carpio) tissues.

    PubMed

    García-Medina, Sandra; Galar-Martínez, Marcela; Gómez-Oliván, Leobardo Manuel; Ruiz-Lara, Karina; Islas-Flores, Hariz; Gasca-Pérez, Eloy

    2017-11-01

    Mercury is one of the most toxic metals in aquatic systems since it is able to induce neurobehavioral disorders as well as renal and gastrointestinal tract damage. The common carp Cyprinus carpio is an important species from both an ecological and economic viewpoint as it is consumed in many countries, the top producers being Mexico, China, India and Japan. The present study aimed to evaluate the relation between Hg-induced oxidative stress and genotoxicity in diverse tissues of C. carpio. Specimens were exposed to 0.01mgHg/L (the maximum permissible limit for aquatic life protection), and lipid peroxidation, protein carbonyl content and the activity of antioxidant enzymes were evaluated at 96h. Micronuclei frequency and DNA damage by comet assay were determined at 12, 24, 48, 72 and 96h. Hg induced oxidative stress and genotoxicity on exposed fish, since inhibition of antioxidant enzymes activity and increases in lipid peroxidation, DNA damage and micronuclei frequency occurred. Blood, gill and liver were more susceptible to oxidative stress, while blood were more sensitive to genotoxicity. In conclusion, Hg at concentrations equal to the maximum permissible limit for aquatic life protection induced oxidative stress and genotoxicity on C. carpio, and these two effects prove to be correlated. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

    PubMed

    Stier, Antoine; Massemin, Sylvie; Criscuolo, François

    2014-12-01

    Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

  2. Chitooligosaccharides protect human embryonic hepatocytes against oxidative stress induced by hydrogen peroxide.

    PubMed

    Xu, Qingsong; Ma, Pan; Yu, Weiting; Tan, Chengyu; Liu, Hongtao; Xiong, Chuannan; Qiao, Ying; Du, Yuguang

    2010-06-01

    Chitooligosaccharides (COS) has many biological activities, such as antitumor activity and hepatoprotective effect. Herein, we investigated the protective effect of COS against hydrogen peroxide (H2O2)-induced oxidative stress on human embryonic hepatocytes (L02 cells) and its scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical in vitro. The results showed that the lost cell viability induced by H2O2 was markedly restored after 24 h pre-incubation with COS (0.1-0.4 mg/ml). This rescue effect could be related to the antioxidant property of COS, in which we showed that the radical scavenging activity of COS reached 80% at concentration of 2 mg/ml. In addition, COS could prevent cell apoptosis induced by H2O2, as shown by the inhibition of the cleavage of poly (adenosine diphosphate-ribose) polymerase and increased expression of the anti-apoptotic protein Bcl-xL. Furthermore, we have utilized confocal laser microscopy to observe cellular uptake of COS, an important step for COS to exert its effects on target cells. Taken together, our findings suggested that COS could effectively protect L02 cells against oxidative stress, which might be useful in clinical setting during the treatment of oxidative stress-related liver damages.

  3. Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

    PubMed

    Smina, T P; Joseph, Jini; Janardhanan, K K

    2016-11-01

    The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

  4. Procyanidins protect Fao cells against hydrogen peroxide-induced oxidative stress.

    PubMed

    Roig, Roser; Cascón, Esther; Arola, Lluis; Bladé, Cinta; Salvadó, M Josepa

    2002-08-15

    In this paper, we evaluate the extent to which flavonoids in red wine (catechin, epicatechin, quercetin and procyanidins) protect against hydrogen peroxide-induced oxidative stress in Fao cells. When cells were exposed to H(2)O(2), malondialdehyde (MDA) levels, oxidized glutathione (GSSG) levels and lactate dehydrogenase (LDH) release increased, indicating membrane damage and oxidative stress. All the flavonoids studied, and in particular epicatechin and quercetin, protected the plasma membrane. Only procyanidins lowered MDA levels and LDH leakage, maintained a higher reduced/oxidized glutathione ratio, and increased catalase/superoxide dismutase and glutathione peroxidase/superoxide dismutase ratios, and glutathione reductase and glutathione transferase activities. These results show that the procyanidin mixture has a greater antioxidant effect than the individual flavonoids studied, probably due to its oligomer content and/or the additive/synergistic effect of its compounds. This suggests that the mixture of flavonoids found in wine has a greater effect than individual phenols, which may explain many of the healthy effects attributed to wine.

  5. Ultra Fine Particles from Diesel Engines Induce Vascular Oxidative Stress via JNK Activation

    PubMed Central

    Li, Rongsong; Ning, Zhi; Cui, Jeffery; Khalsa, Bhavraj; Ai, Lisong; Takabe, Wakako; Beebe, Tyler; Majumdar, Rohit; Sioutas, Constantinos; Hsiai, Tzung

    2011-01-01

    Exposure of particulate air pollution is linked to increased incidences of cardiovascular diseases. Ambient ultra fine particles (UFP) from diesel vehicle engines have been shown to be pro-atherogenic in apoE knockout mice and may constitute a major cardiovascular risk in humans. We posited that circulating nano-sized particles from traffic pollution sources induced vascular oxidative stress via JNK activation in endothelial cells. Diesel UFP were collected from a 1998 Kenworth truck. Intra-cellular superoxide assay revealed that these UFP dose-dependently induced superoxide (O2·-) production in human aortic endothelial cells (HAEC). Flow cytometry (FACS) showed that UFP increased MitoSOX Red intensity specific for mitochondrial superoxide. Protein carbonyl content is increased by UFP as an indication of vascular oxidative stress. UFP also up-regulated hemeoxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pre-treatment with antioxidant, N-acetyl cysteine (NAC), significantly decreased their expression. Furthermore, UFP transiently activated JNK in HAEC. Treatment with JNK inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP stimulated O2·- production and mRNA expression of HO-1 and TF. Our findings suggest that JNK activation play an important role in UFP-induced oxidative stress and stress response gene expression. PMID:19154785

  6. Hydrogen incorporation and radiation induced dynamics in metal-oxide-silicon structures: A study using nuclear reaction analysis

    NASA Astrophysics Data System (ADS)

    Briere, M. A.

    Resonant Nuclear Reaction Analysis (NRA), using the H-1/N-15, alpha gamma/c-12 reaction at 6.4 MeV, is successfully applied to the investigation of hydrogen incorporation and radiation induced migration in metal oxide silicon structures. The influence of processing parameters on the H content of thermal oxides, with and without gate material present, is studied. Hydrogen accumulation at the Si-SiO2 interface is reproducibly demonstrated for as-oxidized samples, as well as for oxides exposed to H2 containing atmospheres during subsequent thermal processing. The migration of hydrogen, from the bulk oxide to the silicon oxide interface during NRA, is investigated. It is found that the cross section for this migration, per incident N-15 ion, depends on the sample processing history. It is argued that the release is due to electron capture at Si-OH sites and that the migration is driven by reductions in the interfacial free energy associated with the incorporation of hydrogen within the strained oxide region. A similar migration of hydrogen during irradiation with 2.5 MeV electrons is presented, which suggests that the migration occurs preferentially under applied fields which are directed to the silicon interface. It is argued that this bias effect is due to holes, which modify the interfacial region so as to increase hydrogen solubility, that is explained by the diffusivity of the hydrogen species during N-15 irradiation, which suggest identification as neutral atomic hydrogen. The spatial distribution of hydrogen at the Si-SiO2 interface is shown to be confined to within ca. 2 nm of the metallurgical boundary, in agreement with measurements of the location of oxide charge states, paramagnetic centers, as well as the width of the strained transition region in the neighborhood of this interface. A direct correlation between the hydrogen content of the bulk oxide and the radiation generated oxide charges and interface states is presented. These data provide strong

  7. Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

    PubMed

    Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

    2018-08-01

    Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves against UVB-induced oxidative stress in fibroblasts and hairless mice.

    PubMed

    de Souza, Rebeca Oliveira; de Assis Dias Alves, Geórgia; Aguillera, Ana Luiza Scarano; Rogez, Hervé; Fonseca, Maria José Vieira

    2018-01-01

    Ultraviolet B (UVB) irradiation increases the risk of various skin disorders, leading to inflammation and oxidative stress and thereby increasing the risk of skin photoaging and carcinogenesis. The use of photochemoprotectors such as natural products with antioxidant and anti-inflammatory properties represents a strategy for preventing UVB-induced skin damage. We investigated the photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves (BCF) on fibroblasts and hairless mice exposed to UVB radiation. The mixture of phenolic compounds in BCF prevented the decrease in reduced glutathione (GSH) levels in fibroblast cultures induced by UVB radiation more than some of their individual standards ((+)-catechin (CAT), epigallocatechin gallate and quercetin 3-O-β-d-glucopyranoside). Prepared gel formulations increased skin antioxidant activity, and BCF components and the CAT standard were retained in the HRS/J hairless mice epidermis 2h after application. Topical treatment with the BCF or CAT formulations (1%) significantly reduced the decrease in GSH levels and decreased myeloperoxidase activity and the secretion of pro-inflammatory cytokines IL-1β and IL-6 induced by UVB radiation (P<0.05), indicating that both BCF and CAT had anti-inflammatory effects. BCF inhibited UVB-induced metalloproteinase (MMP)-9 secretion/activity, whereas CAT had no effect on MMP-9 activity in the skin of treated animals. These results therefore suggest that BCF can be used as a photochemoprotective agent and antioxidant in the prevention/treatment of inflammation and oxidative stress of the skin induced by UVB radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Protective effect of sulforaphane against oxidative stress: recent advances.

    PubMed

    Guerrero-Beltrán, Carlos Enrique; Calderón-Oliver, Mariel; Pedraza-Chaverri, José; Chirino, Yolanda Irasema

    2012-07-01

    Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy

    PubMed Central

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A.; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-01-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy. PMID:24398069

  11. Effects of Antioxidant N-acetylcysteine Against Paraquat-Induced Oxidative Stress in Vital Tissues of Mice

    PubMed Central

    Ortiz, Maricelly Santiago; Forti, Kevin Muñoz; Suárez Martinez, Edu B.; Muñoz, Lenin Godoy; Husain, Kazim

    2016-01-01

    Paraquat (PQ) is a commonly used herbicide that induces oxidative stress via reactive oxygen species (ROS) generation. This study aimed to investigate the effects of the antioxidant N-acetylcysteine (NAC) against PQ-induced oxidative stress in mice. Male Balb/C mice (24) were randomly divided into 4 groups and treated for 3 weeks: 1) control (saline), 2) NAC (0.5% in diet), 3) PQ (20 mg/kg, IP) and 4) combination (PQ + NAC). Afterwards mice were sacrificed and oxidative stress markers were analyzed. Our data showed no significant change in serum antioxidant capacity. PQ enhanced lipid peroxidation (MDA) levels in liver tissue compared to control whereas NAC decreased MDA levels (p<0.05). NAC significantly increased MDA in brain tissue (p<0.05). PQ significantly depleted glutathione (GSH) levels in liver (p=0.001) and brain tissue (p<0.05) but non-significant GSH depletion in lung tissue. NAC counteracted PQ, showing a moderate increase GSH levels in liver and brain tissues. PQ significantly increased 8-oxodeoxyguanosine (8-OH-dG) levels (p<0.05) in liver tissue compared to control without a significant change in brain tissue. NAC treatment ameliorated PQ-induced oxidative DNA damage in the liver tissue. PQ significantly decreased the relative mtDNA amplification and increased the frequency of lesions in liver and brain tissue (p<0.0001), while NAC restored the DNA polymerase activity in liver tissue but not in brain tissue. In conclusion, PQ induced lipid peroxidation, oxidative nuclear DNA and mtDNA damage in liver tissues and depleted liver and brain GSH levels. NAC supplementation ameliorated the PQ-induced oxidative stress response in liver tissue of mice. PMID:27398384

  12. Antioxidant potential of tea reduces arsenite induced oxidative stress in Swiss albino mice.

    PubMed

    Sinha, D; Roy, S; Roy, M

    2010-04-01

    Environmental arsenic (As) is a potent human carcinogen and groundwater As contamination is a major health concern in West Bengal, India. Oxidative stress has been one of the prime factors in As-induced carcinogenicity. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance cause a severe imbalance of the cellular antioxidant defence mechanism. Tea, a popular beverage has excellent chemopreventive and antioxidant properties. In this study it was investigated whether these flavonoids could ameliorate the arsenite (As III) induced oxidative stress in Swiss albino mice. Bio-monitoring with comet assay elicited that the increase in genotoxicity caused by As III was counteracted by both black tea and green tea. Elevated levels of lipid peroxides and protein carbonyl by As III were effectively reduced with green as well as black tea. They also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the tea polyphenols by virtue of their antioxidant potential may be used as an effective agent to reduce the As III induced oxidative stress in Swiss albino mice. 2010 Elsevier Ltd. All rights reserved.

  13. Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress.

    PubMed

    Chen, Wei; Li, Yuting; Bao, Tao; Gowd, Vemana

    2017-01-01

    Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin -3-O- glucoside and cyanidin -3-O- rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays) jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH) depletion and caused mitochondrial membrane potential (MMP) collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress.

  14. Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress

    PubMed Central

    Li, Yuting; Bao, Tao; Gowd, Vemana

    2017-01-01

    Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays) jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH) depletion and caused mitochondrial membrane potential (MMP) collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress. PMID:28819542

  15. Hesperidin, a citrus bioflavonoid, alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster.

    PubMed

    Abolaji, Amos Olalekan; Babalola, Oluwatoyin Victoria; Adegoke, Abimbola Kehinde; Farombi, Ebenezer Olatunde

    2017-10-01

    Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400mg/10g diet), TCE (10μM/10g diet) and TCE (10μM/10g diet)+HSP (400mg/10g diet) respectively in the diet for 5days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p<0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected inmore » the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.« less

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

    PubMed

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

    2014-10-02

    Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens. This study was performed to evaluate the hepatoprotective potential of PKC extract in heat-induced oxidative stress in chicken hepatocytes. The nature of the active metabolites and elucidation of the possible mechanism involved were also investigated. The PKC extract possessed free radical scavenging activity with values significantly (p < 0.05) lower than silymarin as the reference antioxidant. Heat-induced oxidative stress in chicken hepatocyte impaired the total protein, lipid peroxidation and antioxidant enzymes activity significantly (p < 0.05). Treatment of heat-induced hepatocytes with PKC extract (125 μg/ml) and silymarin as positive control increased these values significantly (p < 0.05). The real time PCR and western blot analyses revealed the significant (p < 0.05) up-regulation of oxidative stress biomarkers including TNF-like, IFN-γ and IL-1β genes; NF-κB, COX-2, iNOS and Hsp70 proteins expression upon heat stress in chicken hepatocytes. The PKC extract and silymarin were able to alleviate the expression of all of these biomarkers in heat-induced chicken hepatocytes. The gas chromatography-mass spectrometry analysis of PKC extract showed the presence of fatty acids, phenolic compounds, sugar derivatives and other organic compounds such as furfural which could be responsible for the observed hepatoprotective activity. Palm kernel cake extract could be a potential agent to protect hepatocytes function under heat induced oxidative stress.

  18. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid.

    PubMed

    Patra, Kartick; Bose, Samadrita; Sarkar, Shehnaz; Rakshit, Jyotirmoy; Jana, Samarjit; Mukherjee, Avik; Roy, Abhishek; Mandal, Deba Prasad; Bhattacharjee, Shamee

    2012-02-05

    Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Evaluation of basal DNA damage and oxidative stress in Wistar rat leukocytes after exposure to microwave radiation.

    PubMed

    Garaj-Vrhovac, Vera; Gajski, Goran; Trosić, Ivancica; Pavicić, Ivan

    2009-05-17

    The aim of this study was to assess whether microwave-induced DNA damage is basal or it is also generated through reactive oxygen species (ROS) formation. After having irradiated Wistar rats with 915MHz microwave radiation, we assessed different DNA alterations in peripheral leukocytes using standard and formamidopyrimidine DNA-glycosylase (Fpg)-modified comet assay. The first is a sensitive tool for detecting primary DNA damage, and the second is much more specific for detecting oxidative damage. The animals were irradiated for 1h a day for 2 weeks at a field power density of 2.4W/m(2), and the whole-body average specific absorption rate (SAR) of 0.6W/kg. Both the standard and the Fpg-modified comet assay detected increased DNA damage in blood leukocytes of the exposed rats. The significant increase in Fpg-detected DNA damage in the exposed rats suggests that oxidative stress is likely to be responsible. DNA damage detected by the standard comet assay indicates that some other mechanisms may also be involved. In addition, both methods served proved sensitive enough to measure basal and oxidative DNA damage after long-term exposure to 915MHz microwave radiation in vivo.

  20. Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat

    NASA Astrophysics Data System (ADS)

    Ghasemnezhad Targhi, Reza; Homayoun, Mansour; Mansouri, Somaieh; Soukhtanloo, Mohammad; Soleymanifard, Shokouhozaman; Seghatoleslam, Masoumeh

    2017-01-01

    Ionizing radiation by producing free radicals induces tissue oxidative stress and has clastogenic and cytotoxic effects. The radio protective effect of black mulberry extract (BME) has been investigated on liver tissue and bone marrow cells in the rat. Intraperitoneal (ip) administration of 200 mg/kg BME three days before and three days after 3 Gy and 6 Gy gamma irradiation significantly reduced the frequencies of micro nucleated polychromatic erythrocytes (MnPCEs) and micro nucleated norm chromatic erythrocyte (MnNCEs) and increased PCE/PCE+NCE ratio in rat bone marrow compared to the non-treated irradiated groups. Moreover, this concentration of BME extract decreased the level of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as enhanced the total thiol content and catalase activity in rat's liver compared to the non-treated irradiated groups. It seems that BME extract with antioxidant activity reduced the genotoxicity and cytotoxicity induced by gamma irradiation in bone marrow cells and liver in the rat.

  1. The NADPH oxidase inhibitor apocynin (acetovanillone) induces oxidative stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Riganti, Chiara; Costamagna, Costanzo; Bosia, Amalia

    Apocynin (acetovanillone) is often used as a specific inhibitor of NADPH oxidase. In N11 glial cells, apocynin induced, in a dose-dependent way, a significant increase of both malonyldialdehyde level (index of lipid peroxidation) and lactate dehydrogenase release (index of a cytotoxic effect). Apocynin evoked also, in a significant way, an increase of H{sub 2}O{sub 2} concentration and a decrease of the intracellular glutathione/glutathione disulfide ratio, accompanied by augmented efflux of glutathione and glutathione disulfide. Apocynin induced the activation of both pentose phosphate pathway and tricarboxylic acid cycle, which was blocked when the cells were incubated with glutathione together with apocynin.more » The cell incubation with glutathione prevented also the apocynin-induced increase of malonyldialdehyde generation and lactate dehydrogenase leakage. Apocynin exerted an oxidant effect also in a cell-free system: indeed, in aqueous solution, it evoked a faster oxidation of the thiols glutathione and dithiothreitol, and elicited the generation of reactive oxygen species, mainly superoxide anions. Our results suggest that apocynin per se can induce an oxidative stress and exert a cytotoxic effect in N11 cells and other cell types, and that some effects of apocynin in in vitro and in vivo experimental models should be interpreted with caution.« less

  2. Protein glutathionylation protects wheat (Triticum aestivum Var. Sonalika) against Fusarium induced oxidative stress.

    PubMed

    Mohapatra, Subhalaxmi; Mittra, Bhabatosh

    2016-12-01

    Fusarium induced oxidative stress could be recovered by reversible protein oxidative modification through the process of glutathionylation in co-stressed (low-dose (50 μM) Cd 2+ pre-treatment followed by Fusarium inoculation) wheat seedlings. Co-stressed seedlings showed low disease severity index as compared to Fusarium infected seedlings. A reduced level of hydrogen peroxide (H 2 O 2 ) and carbonyl contents due to irreversible protein oxidation were observed in co-stressed seedlings as compared to Fusarium infected seedlings. Further, a comparative biochemical assay showed an enhanced glutathione content in co-stressed tissues as compared to Fusarium infected tissues. In an investigation, reduced glutathione pre-coated agarose gel beads were used to pull down proteins having affinity with GSH. Fructose-1, 6-bisphosphate aldolase and 3-Phosphoglycerate kinase were observed to be co-existed in co-stressed seedlings when analysed by LC-MS/MS after being processed through protein-pull assay. Co-stressed tissues showed an enhanced free protein thiol content as compared to Fusarium infected tissues. The ratio of free thiol to thiol disulfides was also observed to be increased in co-stressed tissues as compared to Fusarium infected tissues. In contrast, the quantitative assay by Ellman's reagent and qualitative analysis by diagonal gel electrophoresis showed enhanced protein thiol disulfides in Fusarium infected tissues as compared to co-stressed tissues. Further, glutaredoxin, responsible for the reverse reduction of proteins was observed to be enhanced in co-stressed tissues as compared to Fusarium infected tissues. Thus, a low dose Cd 2+ triggered glutathionylation is suggestive of offering tolerance against Fusarium induced oxidative stress and protects target proteins from irreversible modification and permanent damage in wheat. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases.

    PubMed

    Akolkar, Gauri; Bagchi, Ashim K; Ayyappan, Prathapan; Jassal, Davinder S; Singal, Pawan K

    2017-04-01

    An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)-induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TNF-α and IL-10 in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were segregated into four groups: 1 ) control, 2 ) Vit C (25 µM), 3 ) Dox (10 µM), and 4 ) Vit C + Dox. Dox caused a significant increase in the generation of superoxide radical (O 2 ·- ), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced an increase in the ratio of monomeric/dimeric eNOS, promoting the production of O 2 ·- , which was prevented by Vit C by increasing the stability of the dimeric form of eNOS. Vit C protected against the Dox-induced increase in TNFα as well as a reduction in IL-10. These results suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stress and inflammation via a modulation of Dox-induced increase in the NO levels and NOS activity. Copyright © 2017 the American Physiological Society.

  4. [Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

    PubMed

    Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2010-01-01

    The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

  5. Cytotoxicity and the induction of the stress protein Hsp 70 in Chang liver cells in response to zearalenone-induced oxidative stress.

    PubMed

    Lee, Hyungkyoung; Kang, Changgeun; Yoo, Yong-San; Hah, Do-Yun; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

    2013-09-01

    Zearalenone (ZEN) has been implicated in several cases of mycotoxicosis in farm animals and humans. The toxic effects of ZEN have been well characterized, but little is known regarding the mechanisms of ZEN toxicity, including the involvement of the oxidative stress pathway. Using Chang liver cells as a model, the aim of this study was to determine if ZEN could elevate the expression of the heat shock protein Hsp 70, induce cytotoxicity and modulate the levels of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). In addition, the cytoprotective effects of N-acetylcysteine amide (NACA) pre-treatment were assessed. Finally, the involvement of oxidative stress in ZEN-induced toxicity was confirmed. The results of this study demonstrated that ZEN-induced Hsp 70 expression in a dose- and time-dependent manners. This effect occurred at low-ZEN concentrations, and could therefore be considered a biomarker of ZEN-induced toxicity. The cytotoxicity was reduced when Chang liver cells were exposed to sub-lethal heat shock prior to ZEN treatment, demonstrating a cytoprotective effect of Hsp 70. This cytoprotective effect suggested that Hsp 70 might play a key role in the cellular defense mechanism. When cells were pre-treated with NACA prior to ZEN treatment, the cells were also protected from toxicity. This NACA cytoprotective effect suggested the involvement of oxidative stress in ZEN-induced toxicity, and this mechanism was supported by reduced Hsp 70 expression, inhibited cytolethality, increased GSH levels and decreased TBARS formation when cells were pre-treated with NACA prior to ZEN exposure. Our data clearly demonstrated that ZEN induced cytotoxicity in Chang liver cells by inhibiting cell proliferation, decreasing GSH levels and increasing TBARS formation in a dose-dependent manner. ZEN also, induced Hsp 70 expression, and the side effects of ZEN were significantly alleviated by pre-treatment with NACA. Oxidative stress is likely to be one of the

  6. The effect of sunblock against oxidative stress in farmers: a pilot study

    PubMed Central

    Kim, Yong-Dae; Yim, Dong-Hyuk; Eom, Sang-Yong; Yeoun Lee, Ji; Kim, Heon

    2017-01-01

    Farmers are frequently exposed to ultraviolet (UV) radiation which causes various diseases by inducing oxidative stress. This study aimed to assess the effects of sunblock on oxidative stress in the body. Eighty-seven farmers were divided into two groups: those who wore sunblock for five days and those who did not. The total antioxidant capacity (TAC) in urine, which is an antioxidant indicator, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in urine, an oxidative stress indicator, were measured. The urinary TAC of sunblock users was significantly higher than that of non-users, but urinary 8-OHdG levels were not significantly different. Even after adjustment for potential confounders, urinary TAC was found to be markedly increased with sunblock usage. These results suggest that sunblock is effective in preventing oxidative stress among farmers. In addition, they show that urinary TAC can be used as a good effect marker of oxidative stress caused by UV exposure. PMID:28808206

  7. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    PubMed

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  8. Effects of curcumin on angiotensin-converting enzyme gene expression, oxidative stress and anti-oxidant status in thioacetamide-induced hepatotoxicity.

    PubMed

    Fazal, Yumna; Fatima, Syeda Nuzhat; Shahid, Syed Muhammad; Mahboob, Tabassum

    2015-12-01

    This study aimed to evaluate the protective effects of curcumin on angiotensin-converting enzyme (ACE) gene expression, oxidative stress and anti-oxidant status in thioacetamide (TAA)-induced hepatotoxicity in rats. Total 32 albino Wistar rats (male, 200-250 g) were divided into six groups (n=8). Group 1: untreated controls; Group 2: received TAA (200 mg/kg body weight (b.w.); i.p.) for 12 weeks; Group 3: received curcumin (75 mg/kg b.w.) for 24 weeks; Group 4: received TAA (200 mg/kg b.w.; i.p.) for 12 weeks+curcumin (75 mg/kg b.w.) for 12 weeks. A significantly higher ACE gene expression was observed in TAA-induced groups as compared with control, indicating more synthesis of ACE proteins. Treatment with curcumin suppressed ACE expression in TAA liver and reversed the toxicity produced. TAA treatment results in higher lipid peroxidation and lower GSH, SOD and CAT than the normal, and this produces oxidative stress in the liver. Cirrhotic conditions were confirmed by serum enzymes (ALT, AST and ALP) as well as histopathological observations. Curcumin treatment reduced oxidative stress in animals by scavenging reactive oxygen species, protecting the anti-oxidant enzymes from being denatured and reducing the oxidative stress marker lipid peroxidation. Curcumin treatment restores hepatocytes, damaged by TAA, and protects liver tissue approaching cirrhosis. © The Author(s) 2014.

  9. Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.

    PubMed

    Chen, Wan-Ju; Wu, Caiying; Xu, Zhenhua; Kuse, Yoshiki; Hara, Hideaki; Duh, Elia J

    2017-01-01

    Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6-24 h resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time-dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Measurement of exercise-induced oxidative stress in lymphocytes.

    PubMed

    Turner, James E; Bosch, Jos A; Aldred, Sarah

    2011-10-01

    Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

  11. Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

    PubMed

    Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

    2015-11-13

    The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

    PubMed

    Fuentes-Broto, Lorena; Miana-Mena, Francisco J; Piedrafita, Eduardo; Berzosa, César; Martínez-Ballarín, Enrique; García-Gil, Francisco A; Reiter, Russel J; García, Joaquín J

    2010-08-01

    Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl(3) and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA + 4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. Published 2010 Wiley-Liss, Inc.

  13. Interaction between cytotoxic effects of gamma-radiation and folate deficiency in relation to choline reserves.

    PubMed

    Batra, Vipen; Devasagayam, Thomas Paul Asir

    2009-01-08

    The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. Recent studies have indicated that bio-molecules such as folate and choline might be of radio-protective value as they are, within broad dose ranges, non-toxic to humans and experimental animals. The objective of the present study was to investigate choline dependent adaptive response to potential synergistic cytotoxic effect of folate deficiency and gamma-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93M formula, were subjected to 1-4Gy total body gamma-irradiation. To investigate liver DNA damage, apurinic/apyrimidinic sites (AP sites) were quantified. A significant increase in liver DNA AP sites with concomitant depletion of liver choline reserves was observed when gamma-radiation was combined with folate deficiency. Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Another major finding of these studies is that significant liver damage at higher doses of radiation (3-4Gy), might release considerable amounts of choline reserves to serum. In conclusion, a plausible interpretation of the present studies is that folate deprivation and gamma-radiation interact to mobilize additional choline reserves of hepatic tissue, for redistribution to other organs, which could not be utilized by folate deficiency alone. Present results clearly indicated a distinct choline pool in liver and kidney tissues that could be utilized by folate deficient animals only under radiation stress conditions.

  14. Gamma Radiation Sterilization Reduces the High-cycle Fatigue Life of Allograft Bone.

    PubMed

    Islam, Anowarul; Chapin, Katherine; Moore, Emily; Ford, Joel; Rimnac, Clare; Akkus, Ozan

    2016-03-01

    Sterilization by gamma radiation impairs the mechanical properties of bone allografts. Previous work related to radiation-induced embrittlement of bone tissue has been limited mostly to monotonic testing which does not necessarily predict the high-cycle fatigue life of allografts in vivo. We designed a custom rotating-bending fatigue device to answer the following questions: (1) Does gamma radiation sterilization affect the high-cycle fatigue behavior of cortical bone; and (2) how does the fatigue life change with cyclic stress level? The high-cycle fatigue behavior of human cortical bone specimens was examined at stress levels related to physiologic levels using a custom-designed rotating-bending fatigue device. Test specimens were distributed among two treatment groups (n = 6/group); control and irradiated. Samples were tested until failure at stress levels of 25, 35, and 45 MPa. At 25 MPa, 83% of control samples survived 30 million cycles (run-out) whereas 83% of irradiated samples survived only 0.5 million cycles. At 35 MPa, irradiated samples showed an approximately 19-fold reduction in fatigue life compared with control samples (12.2 × 10(6) ± 12.3 × 10(6) versus 6.38 × 10(5) ± 6.81 × 10(5); p = 0.046), and in the case of 45 MPa, this reduction was approximately 17.5-fold (7.31 × 10(5) ± 6.39 × 10(5) versus 4.17 × 10(4) ± 1.91 × 10(4); p = 0.025). Equations to estimate high-cycle fatigue life of irradiated and control cortical bone allograft at a certain stress level were derived. Gamma radiation sterilization severely impairs the high cycle fatigue life of structural allograft bone tissues, more so than the decline that has been reported for monotonic mechanical properties. Therefore, clinicians need to be conservative in the expectation of the fatigue life of structural allograft bone tissues. Methods to preserve the fatigue strength of nonirradiated allograft bone tissue are needed. As opposed to what monotonic tests might suggest, the cyclic

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

    PubMed

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

    2015-01-01

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

  16. Transport stress-induced cerebrum oxidative stress is not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.

    PubMed

    Ge, J; Li, H; Sun, F; Li, X-N; Lin, J; Xia, J; Zhang, C; Li, J-L

    2017-07-01

    Transportation of newly hatched chicks from the hatchery to the farm is inevitable, especially for parent stock and grandsire parent stock chicks. However, the possible effects of transport stress in the newly hatched chicks are poorly understood. The aim of this study was to determine the adaptive responses to transport stress by activing the nuclear factor-erythroid 2-related factor 2 (Nrf2)-induced antioxidant defense. One hundred twenty newly hatched chicks were divided into 3 groups (control group, transport group, and simulation transport group) for 2, 4, and 8 h of real or simulated transportation. Transport stress could cause oxidative stress in the cerebrum of newly hatched chicks by increasing lipid peroxidation and production of free radicals and decreasing the activities of antioxidant enzymes and the glutathione:oxidized glutathione ratio. Transport stress activated the Nrf2 signaling pathway and triggered the transcription of antioxidant parameters. However, transport stress-induced cerebrum oxidative stress was not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.

  17. S-Adenosylmethionine Attenuates Oxidative Stress and Neuroinflammation Induced by Amyloid-β Through Modulation of Glutathione Metabolism.

    PubMed

    Li, Qian; Cui, Jing; Fang, Chen; Liu, Min; Min, Guowen; Li, Liang

    2017-01-01

    Oxidative stress and neuroinflammation are mainly involved in the pathogenic mechanisms of Alzheimer's disease (AD). Amyloid-β (Aβ), the main component of senile plaques, is a kind of strong inducer of oxidative stress. Glutathione is an endogenous antioxidant protecting cells from oxidative injury. S-adenosylmethionine (SAM) produced in the methionine cycle is the primary methyl donor and the precursor of glutathione. In this study, the Aβ intrahippocampal injection rat model and cultured SH-SY5Y cells were used to explore the neuroprotective effect of SAM. We found that SAM could protect cells against Aβ-induced cellular injury by inhibition of oxidative stress and neuroinflammation. SAM administration could increase the endogenous antioxidant glutathione and potentiate the antioxidant enzymes activities. SAM might act as an antioxidant and be a potential candidate therapy for AD patients.

  18. Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377.

    PubMed

    Kim, Il-Sup; Sohn, Ho-Yong; Jin, Ingnyol

    2011-10-01

    The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time-dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7'-dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells.

  19. Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

    PubMed Central

    Bruder-Nascimento, Thiago; Silva, Samuel T.; Boer, Patrícia A.; Cordellini, Sandra

    2015-01-01

    Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load), stressed (2 h-immobilization), and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10). Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary). Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed). Indomethacin determined a decrease in sensitivity (EC50) in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination. PMID:26083604

  20. Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress.

    PubMed

    Ichinose, Masashi; Yonemochi, Hidetoshi; Sato, Toshiaki; Saikawa, Tetsunori

    2003-06-01

    Although mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels have been reported to reduce the extent of apoptosis, the critical timing of mitoK(ATP) channel opening required to protect myocytes against apoptosis remains unclear. In the present study, we examined whether the mitoK(ATP) channel serves as a trigger of cardioprotection against apoptosis induced by oxidative stress. Apoptosis of cultured neonatal rat cardiomyocytes was determined by flow cytometry (light scatter and propidium iodide/annexin V-FITC fluorescence) and by nuclear staining with Hoechst 33342. Mitochondrial membrane potential (DeltaPsi) was measured by flow cytometry of cells stained with rhodamine-123 (Rh-123). Exposure to H(2)O(2) (500 microM) induced apoptosis, and the percentage of apoptotic cells increased progressively and peaked at 2 h. This H(2)O(2)-induced apoptosis was associated with the loss of DeltaPsi, and the time course of decrease in Rh-123 fluorescence paralleled that of apoptosis. Pretreatment of cardiomyocytes with diazoxide (100 microM), a putative mitoK(ATP) channel opener, for 30 min before exposure to H(2)O(2) elicited transient and mild depolarization of DeltaPsi and consequently suppressed both apoptosis and DeltaPsi loss after 2-h exposure to H(2)O(2). These protective effects of diazoxide were abrogated by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 microM) but not by the sarcolemmal K(ATP) channel blocker HMR-1098 (30 microM). Our results suggest for the first time that diazoxide-induced opening of mitoK(ATP) channels triggers cardioprotection against apoptosis induced by oxidative stress in rat cardiomyocytes.

  1. Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress.

    PubMed

    Juškaitė, Vaida; Ramanauskienė, Kristina; Briedis, Vitalis

    2017-06-27

    Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

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

    PubMed

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

    2017-04-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Leaf extract of Wasabia japonica relieved oxidative stress induced by Helicobacter pylori infection and stress loading in Mongolian gerbils.

    PubMed

    Sekiguchi, Hirotaka; Takabayashi, Fumiyo; Deguchi, Yuya; Masuda, Hideki; Toyoizumi, Tomoyasu; Masuda, Shuichi; Kinae, Naohide

    2010-01-01

    Infection with Helicobacter pylori (H. pylori) can induce gastric disorders, and though its presence cannot explain disease pathogenesis and does not have associations with other factors, it is well known that H. pylori infection causes stomach inflammation following oxidative stress. We examined the suppressive effects of a leaf extract of Wasabia japonica on H. pylori infection and on stress loading in Mongolian gerbils. Following oral administration of wasabi extract of 50 and 200 mg/kg B.W./d for 10 d, the animals were exposed to restraint stress for 90 and 270 min. As for the results, the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the stomach and oxidative DNA damage in peripheral erythrocytes at 270 min significantly increased. That elevation was significantly suppressed by the addition of the leaf extract. We concluded that the simultaneous loading of H. pylori infection and physical stress loading might induce oxidative DNA damage additively, while a leaf extract attenuated this DNA damage in the stomach as well as the peripheral erythrocytes.

  4. AIR PARTICULATE POLLUTION EXPOSURE INDUCES SYSTEMIC OXIDATIVE STRESS IN HEALTHY MICE

    EPA Science Inventory

    Air particulate pollution exposure induces systemic oxidative stress in healthy mice

    Elizabeth S Roberts1 and Kevin L Dreher2. 1 College or Veterinary Medicine, NC State University, Raleigh, NC , 2US Environmental Protection Agency, NHEERL, RTP, NC

    Epidemiological s...

  5. Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats.

    PubMed

    Rehman, Shafiq Ur; Shah, Shahid Ali; Ali, Tahir; Chung, Jong Il; Kim, Myeong Ok

    2017-01-01

    Aging is a major factor involved in neurological impairments, decreased anti-oxidant activities, and enhanced neuroinflammation. D-galactose (D-gal) has been considered an artificial aging model which induces oxidative stress and inflammatory response resulting in memory and synaptic dysfunction. Dietary supplementation exerts valuable effects against oxidative stress and neuroinflammation. Polyphenolic flavonoids, such as anthocyanins, have been reported as an anti-inflammatory and anti-oxidant agents against various neurodegenerative diseases. Recently, our group reported anthocyanin neuroprotection of the developing rat brain against ethanol-induced oxidative stress and neurodegenaration and ethanol-induced neuronal apoptosis via GABA B1 receptor intracellular signaling in prenatal rat hippocampus. Here, we examined the protective effect of anthocyanin neuroprotection against D-gal-induced oxidative and inflammatory response in the hippocampus and cortex regions and explore the potential mechanism of its action. Our results indicated that anthocyanins treatment significantly improved behavioral performance of D-gal-treated rats in Morris water maze and Y-maze tests. One of the potential mechanisms of this action was decreased expression of the receptor for advance glycation end product, reduced level of reactive oxygen species (ROS) and lipid peroxidation as well as markers of the Alzheimer's disease. Furthermore, the results also indicated that anthocyanins inhibited activated astrocytes and neuroinflammation via suppression of various inflammatory markers including p-NF- K B, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α) in the hippocampus and cortex regions of D-gal-treated rats brain. Moreover, anthocyanins abrogated neuroapoptosis via C-jun N-terminal kinase (p-JNK) suppression and improved deregulated synaptic proteins including synaptophysin, synaptosomal-associated protein (SNAP)-23, SNAP-25, and phosphorylated CREB

  6. Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by oxidative stress-induced lysosome destabilization

    PubMed Central

    Zhang, Li; Sun, Yang; Fei, Mingjian; Tan, Cheng; Wu, Jing; Zheng, Jie; Tang, Jiqing; Sun, Wei; Lv, Zhaoliang; Bao, Jiandong; Xu, Qiang; Yu, Huixin

    2014-01-01

    Oxidative stress has been implicated in both normal aging and various neurodegenerative disorders and it may be a major cause of neuronal death. Chaperone-mediated autophagy (CMA) targets selective cytoplasmic proteins for degradation by lysosomes and protects neurons against various extracellular stimuli including oxidative stress. MEF2A (myocyte enhancer factor 2A), a key transcription factor, protects primary neurons from oxidative stress-induced cell damage. However, the precise mechanisms of how the protein stability and the transcriptional activity of MEF2A are regulated under oxidative stress remain unknown. In this study, we report that MEF2A is physiologically degraded through the CMA pathway. In pathological conditions, mild oxidative stress (200 μM H2O2) enhances the degradation of MEF2A as well as its activity, whereas excessive oxidative stress (> 400 μM H2O2) disrupts its degradation process and leads to the accumulation of nonfunctional MEF2A. Under excessive oxidative stress, an N-terminal HDAC4 (histone deacetylase 4) cleavage product (HDAC4-NT), is significantly induced by lysosomal serine proteases released from ruptured lysosomes in a PRKACA (protein kinase, cAMP-dependent, catalytic, α)-independent manner. The production of HDAC4-NT, as a MEF2 repressor, may account for the reduced DNA-binding and transcriptional activity of MEF2A. Our work provides reliable evidence for the first time that MEF2A is targeted to lysosomes for CMA degradation; oxidative stress-induced lysosome destabilization leads to the disruption of MEF2A degradation as well as the dysregulation of its function. These findings may shed light on the underlying mechanisms of pathogenic processes of neuronal damage in various neurodegenerative-related diseases. PMID:24879151

  7. Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

    PubMed Central

    Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

    2014-01-01

    It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

  8. Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse.

    PubMed

    Liu, Qianying; Lei, Zhixin; Guo, Jingchao; Liu, Aimei; Lu, Qirong; Fatima, Zainab; Khaliq, Haseeb; Shabbir, Muhammad A B; Maan, Muhammad Kashif; Wu, Qinghua; Dai, Menghong; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

    2018-01-01

    Mequindox (MEQ), belonging to quinoxaline-di- N -oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo .

  9. Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse

    PubMed Central

    Liu, Qianying; Lei, Zhixin; Guo, Jingchao; Liu, Aimei; Lu, Qirong; Fatima, Zainab; Khaliq, Haseeb; Shabbir, Muhammad A. B.; Maan, Muhammad Kashif; Wu, Qinghua; Dai, Menghong; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

    2018-01-01

    Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo. PMID:29765325

  10. A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.

    PubMed

    Khayyal, Mohamed T; Abdel-Naby, Doaa H; Abdel-Aziz, Heba; El-Ghazaly, Mona A

    2014-09-25

    Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

  11. Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

    PubMed

    Wang, Qian; Huang, Lihong; Yue, Jianbo

    2017-06-01

    High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.

    PubMed

    Zhang, Yu; Yang, Jian-Hong

    2013-11-01

    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia. © 2013 Wiley Periodicals, Inc.

  13. Long-term treatment of hydrogen-rich saline abates testicular oxidative stress induced by nicotine in mice.

    PubMed

    Li, Shu; Lu, DanDan; Zhang, Yaling; Zhang, Yi

    2014-01-01

    The present study was designed to test the hypothesis that long-term treatment with hydrogen-rich saline abated testicular oxidative stress induced by nicotine in mice. The effects of hydrogen-rich saline (6 ml/kg, i.p.), vitamin C (60 mg/kg, i.p.) and vitamin E (100 mg/kg, i.p.) on reproductive system and testicular oxidative levels in nicotine-treated (4.5 mg/kg, s.b.) mice were investigated. It was found that vitamin C and vitamin E attenuated serum oxidative level, but did not lower testicular oxidative levels in mice subjected to chronic nicotine treatment, and did not improve the male reproductive damage and apoptosis induced by nicotine. Different from normal antioxidants, vitamin C and vitamin E, hydrogen-rich saline abated oxidative stress in testis, and protected against nicotine-induced male reproductive damages. Our results first demonstrated that long-term treatment with hydrogen-rich saline attenuated testicular oxidative level and improved male reproductive function in nicotine-treated mice.

  14. Modulation of ionizing radiation induced oxidative imbalance by semi-fractionated extract of Piper betle: an in vitro and in vivo assessment.

    PubMed

    Verma, Savita; Gupta, Manju Lata; Dutta, Ajaswrata; Sankhwar, Sanghmitra; Shukla, Sandeep Kumar; Flora, Swaran J S

    2010-01-01

    The study was planned to evaluate modulatory effect of aqueous extract of Piper betle leaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 microg/ml) and superoxide radicals (up to 95% at 80 microg/ml), chelated metal ions (up to 83% at 50 microg/ml) and inhibited lipid peroxidation (up to 55.65% at 500 microg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of

  15. Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

    PubMed Central

    Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

    2016-01-01

    Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342

  16. N-Acetylcysteine amide protects against methamphetamine-induced oxidative stress and neurotoxicity in immortalized human brain endothelial cells.

    PubMed

    Zhang, Xinsheng; Banerjee, Atrayee; Banks, William A; Ercal, Nuran

    2009-06-12

    Oxidative stress plays an important role in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Methamphetamine (METH) is an amphetamine analog that causes degeneration of the dopaminergic system in mammals and subsequent oxidative stress. In our present study, we have used immortalized human brain microvascular endothelial (HBMVEC) cells to test whether N-acetylcysteine amide (NACA), a novel antioxidant, prevents METH-induced oxidative stress in vitro. Our studies showed that NACA protects against METH-induced oxidative stress in HBMVEC cells. NACA significantly protected the integrity of our blood brain barrier (BBB) model, as shown by permeability and trans-endothelial electrical resistance (TEER) studies. NACA also significantly increased the levels of intracellular glutathione (GSH) and glutathione peroxidase (GPx). Malondialdehyde (MDA) levels increased dramatically after METH exposure, but this increase was almost completely prevented when the cells were treated with NACA. Generation of reactive oxygen species (ROS) also increased after METH exposure, but was reduced to control levels with NACA treatment, as measured by dichlorofluorescin (DCF). These results suggest that NACA protects the BBB integrity in vitro, which could prevent oxidative stress-induced damage; therefore, the effectiveness of this antioxidant should be evaluated for the treatment of neurodegenerative diseases in the future.

  17. Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

    PubMed

    Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

    2017-02-01

    As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD + ) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD + could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD + were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD + at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD + administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD + might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The role of Nrf2 in oxidative stress-induced endothelial injuries.

    PubMed

    Chen, Bo; Lu, Yanrong; Chen, Younan; Cheng, Jingqiu

    2015-06-01

    Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Numerous antioxidant pathways are involved in cellular redox homeostasis, among which the nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is perhaps the most prominent. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Keap1 acts as an adapter for cullin 3/ring-box 1-mediated ubiquitination and degradation of Nrf2, which decreases the activity of Nrf2 under physiological conditions. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases. The aim of the present review is to briefly summarize the mechanisms that regulate the Nrf2/Keap1-ARE signaling pathway and the latest advances in understanding how Nrf2 protects against oxidative stress-induced endothelial injuries. Further studies regarding the precise mechanisms by which Nrf2-regulated endothelial protection occurs are necessary for determining whether Nrf2 can serve as a therapeutic target in the treatment of cardiovascular diseases. © 2015 Society for Endocrinology.

  19. Effect of Sophora subprosrate polysaccharide on oxidative stress induced by PCV2 infection in RAW264.7 cells.

    PubMed

    Su, Zi-Jie; Wei, Ying-Yi; Yin, Dan; Shuai, Xue-Hong; Zeng, Yun; Hu, Ting-Jun

    2013-11-01

    In this study, an oxidative stress model was first developed in a mouse macrophage cell line (RAW264.7 cells) by infecting the cells with porcine circovirus type 2 (PCV2). The regulatory effect of Sophora subprosrate polysaccharide (SSP) on PCV2-induced oxidative stress was investigated. The results showed that after infection with PCV2, reactive oxygen species (ROS) and nitric oxide (NO) production, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) expression were significantly increased. Meanwhile, the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and hydroxyl radical prevention capacity were greatly reduced. These data indicate successful creation of an oxidative stress model in RAW264.7 cells. A dramatic decrease in cell viability was observed in the cells exposed to oxidative stress compared to the control. When the cells were treated with SSP in concentrations of 100, 200 or 400 μg/mL post PCV2 infection, an increase in the GSH/GSSG ratio and hydroxyl radical prevention capacity was observed. We also observed decreased ROS and NO production, MPO activity, and iNOS expression in the infected cells. Our results demonstrated that PCV2 infection was able to induce oxidative stress in RAW264.7 cells and that SSP could reduce the negative effects resulting from the PCV2 infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress.

    PubMed

    Passaglia, Patrícia; Ceron, Carla S; Mecawi, André S; Antunes-Rodrigues, José; Coelho, Eduardo B; Tirapelli, Carlos R

    2015-11-01

    We hypothesized that chronic ethanol intake enhances vascular oxidative stress and induces hypertension through renin-angiotensin system (RAS) activation. Male Wistar rats were treated with ethanol (20% v/v). The increase in blood pressure induced by ethanol was prevented by losartan (10mg/kg/day; p.o. gavage), a selective AT1 receptor antagonist. Chronic ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels and serum aldosterone levels. No differences on plasma osmolality and sodium or potassium levels were detected after treatment with ethanol. Ethanol consumption did not alter ACE activity, as well as the levels of ANG I and ANG II in the rat aorta or mesenteric arterial bed (MAB). Ethanol induced systemic and vascular oxidative stress (aorta and MAB) and these effects were prevented by losartan. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was prevented by losartan. Ethanol intake did not alter protein expression of ACE, AT1 or AT2 receptors in both aorta and MAB. Aortas from ethanol-treated rats displayed decreased ERK1/2 phosphorylation and increased protein expression of SAPK/JNK. These responses were prevented by losartan. MAB from ethanol-treated rats displayed reduced phosphorylation of p38MAPK and ERK1/2 and losartan did not prevent these responses. Our study provides novel evidence that chronic ethanol intake increases blood pressure, induces vascular oxidative stress and decreases nitric oxide (NO) bioavailability through AT1-dependent mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Differential correlations between changes to glutathione redox state, protein ubiquitination, and stress-inducible HSPA chaperone expression after different types of oxidative stress.

    PubMed

    Girard, Pierre-Marie; Peynot, Nathalie; Lelièvre, Jean-Marc

    2018-05-12

    In primary bovine fibroblasts with an hspa1b/luciferase transgene, we examined the intensity of heat-shock response (HSR) following four types of oxidative stress or heat stress (HS), and its putative relationship with changes to different cell parameters, including reactive oxygen species (ROS), the redox status of the key molecules glutathione (GSH), NADP(H) NAD(H), and the post-translational protein modifications carbonylation, S-glutathionylation, and ubiquitination. We determined the sub-lethal condition generating the maximal luciferase activity and inducible HSPA protein level for treatments with hydrogen peroxide (H 2 O 2 ), UVA-induced oxygen photo-activation, the superoxide-generating agent menadione (MN), and diamide (DA), an electrophilic and sulfhydryl reagent. The level of HSR induced by oxidative stress was the highest after DA and MN, followed by UVA and H 2 O 2 treatments, and was not correlated to the level of ROS production nor to the extent of protein S-glutathionylation or carbonylation observed immediately after stress. We found a correlation following oxidative treatments between HSR and the level of GSH/GSSG immediately after stress, and the increase in protein ubiquitination during the recovery period. Conversely, HS treatment, which led to the highest HSR level, did not generate ROS nor modified or depended on GSH redox state. Furthermore, the level of protein ubiquitination was maximum immediately after HS and lower than after MN and DA treatments thereafter. In these cells, heat-induced HSR was therefore clearly different from oxidative stress-induced HSR, in which conversely early redox changes of the major cellular thiol predicted the level of HSR and polyubiquinated proteins.

  2. Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster.

    PubMed

    Hosamani, Ravikumar; Muralidhara

    2009-11-01

    Bacopa monnieri, Linn. (Brahmi, BM), traditionally used to improve mental health in Indian ayurvedic system of medicine is known to possess various neuropharmacolgical properties. In the recent past, Drosophila has been widely used as a model to study various neurodegenerative diseases. Environmental toxins like rotenone, a specific inhibitor of complex I is employed to increase oxidative stress mediated neuropathology and sporadic Parkinson's disease. In this study, we examined the neuroprotective properties of BM against rotenone induced oxidative damage and neurotoxicity. Flies (Oregon K strain, adult males) exposed to a standardized BM powder for 7 days in the diet exhibited significant diminution in the levels of endogenous oxidative markers viz., malondialdehyde, hydroperoxide and protein carbonyl content. Further, BM offered complete protection against rotenone (500 microM) induced oxidative stress and markedly inhibited dopamine depletion (head region, 33%; body region, 44%) in flies. Flies exposed to rotenone+BM exhibited a lower incidence of mortality (40-66% protection) and performed better in a negative geotaxis assay (45-65%) both suggesting the neuroprotective potential of BM. Interestingly, BM also conferred significant resistance (43-54% protection) in a paraquat oxidative stress bioassay. The neuroprotective effects of BM were highly comparable to those of a commercially available Brahmi preparation. Although the precise mechanism/s underlying the neuroprotective efficacy of BM are not clear, it is hypothesized that it is wholly or in part related to its ability to mitigate rotenone induced oxidative stress. Further, our approach confirms the utility of the Drosophila model in screening putative neuroprotective phytomedicines prior to their use in mammalian models.

  3. Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature.

    PubMed

    Trapp, Denise; Knez, Wade; Sinclair, Wade

    2010-10-01

    Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.

  4. Radiation-induced degradation of cyclohexanebutyric acid in aqueous solutions by gamma ray irradiation

    NASA Astrophysics Data System (ADS)

    Jia, Wenbao; He, Yanquan; Ling, Yongsheng; Hei, Daqian; Shan, Qing; Zhang, Yan; Li, Jiatong

    2015-04-01

    The radiation-induced degradation of cyclohexanebutyric acid under gamma ray irradiation was investigated. Degradation experiments were performed with 100 mL sealed Pyrex glass vessels loaded with 80 mL of cyclohexanebutyric acid solutions at various initial concentrations of 10, 20, and 40 mg L-1. The absorbed doses were controlled at 0, 0.65, 1.95, 3.25, 6.5, 9.75, and 13 kGy. The results showed that gamma ray irradiation could effectively degrade cyclohexanebutyric acid in aqueous solutions. The removal rate of cyclohexanebutyric acid increased significantly with the increase of absorbed dose and the decrease of its initial concentration. At the same time, the removal of chemical oxygen demand (COD) was as effective as that of cyclohexanebutyric acid. The kinetic studies showed that the degradation of cyclohexanebutyric acid followed pseudo first-order reaction. Above all, the proposed mechanism obtained when NaNO2, NaNO3 and tert-butanol were added showed that the •OH radical played a major role in the gamma degradation process of cyclohexanebutyric acid, while •H and eaq- played a minor role in the gamma degradation process. The degradation products were identified by Fourier transform infrared spectroscopy (FTIR) and gas chromatography/mass spectrometry (GC/MS) during cyclohexanebutyric acid degradation.

  5. Crosstalk Between Peroxisome Proliferator-Activated Receptor Gamma and the Canonical WNT/β-Catenin Pathway in Chronic Inflammation and Oxidative Stress During Carcinogenesis

    PubMed Central

    Vallée, Alexandre; Lecarpentier, Yves

    2018-01-01

    Inflammation and oxidative stress are common and co-substantial pathological processes accompanying, promoting, and even initiating numerous cancers. The canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPARγ) generally work in opposition. If one of them is upregulated, the other one is downregulated and vice versa. WNT/β-catenin signaling is upregulated in inflammatory processes and oxidative stress and in many cancers, although there are some exceptions for cancers. The opposite is observed with PPARγ, which is generally downregulated during inflammation and oxidative stress and in many cancers. This helps to explain in part the opposite and unidirectional profile of the canonical WNT/β-catenin signaling and PPARγ in these three frequent and morbid processes that potentiate each other and create a vicious circle. Many intracellular pathways commonly involved downstream will help maintain and amplify inflammation, oxidative stress, and cancer. Thus, many WNT/β-catenin target genes such as c-Myc, cyclin D1, and HIF-1α are involved in the development of cancers. Nuclear factor-kappaB (NFκB) can activate many inflammatory factors such as TNF-α, TGF-β, interleukin-6 (IL-6), IL-8, MMP, vascular endothelial growth factor, COX2, Bcl2, and inducible nitric oxide synthase. These factors are often associated with cancerous processes and may even promote them. Reactive oxygen species (ROS), generated by cellular alterations, stimulate the production of inflammatory factors such as NFκB, signal transducer and activator transcription, activator protein-1, and HIF-α. NFκB inhibits glycogen synthase kinase-3β (GSK-3β) and therefore activates the canonical WNT pathway. ROS activates the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling in many cancers. PI3K/Akt also inhibits GSK-3β. Many gene mutations of the canonical WNT/β-catenin pathway giving rise to cancers have been reported (CTNNB1, AXIN, APC

  6. Low dose radiation prevents doxorubicin-induced cardiotoxicity

    PubMed Central

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-01

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling. PMID:29416617

  7. Low dose radiation prevents doxorubicin-induced cardiotoxicity.

    PubMed

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-02

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

  8. Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

    PubMed Central

    Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

    2015-01-01

    Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload. PMID:25822525

  9. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    PubMed

    Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

    2015-01-01

    Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  10. Evidence that the capacity of nongenotoxic carcinogens to induce oxidative stress is subject to marked variability.

    PubMed

    Henderson, Colin J; Cameron, Amy R; Chatham, Lynsey; Stanley, Lesley A; Wolf, Charles Roland

    2015-05-01

    Many drugs and environmental chemicals which are not directly mutagenic have the capacity to increase the incidence of tumors in the liver and other tissues. For this reason, such compounds are known as nongenotoxic carcinogens. The mechanisms underlying their effects remain unclear; however, their capacity to induce oxidative stress is considered to be a critical step in the carcinogenic process, although the evidence that this is actually the case remains equivocal and sparse. We have exploited a novel heme oxygenase-1 reporter mouse to evaluate the capacity of nongenotoxic carcinogens with different mechanisms of action to induce oxidative stress in the liver in vivo. When these compounds were administered at doses reported to cause liver tumors, marked differences in activation of the reporter were observed. 1,4-Dichlorobenzene and nafenopin were strong inducers of oxidative stress, whereas phenobarbital, piperonyl butoxide, cyproterone acetate, and WY14,643 were, at best, only very weak inducers. In the case of phenobarbital and thioacetamide, the number of LacZ-positive hepatocytes increased with time, and for the latter also with dose. The data obtained demonstrate that although some nongenotoxic carcinogens can induce oxidative stress, it is not a dominant feature of the response to these compounds. Therefore in contrast to the current models, these data suggest that oxidative stress is not a key determinant in the mechanism of nongenotoxic carcinogenesis but may contribute to the effects in a compound-specific manner. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

  11. Mechanism of Hydrophilicity by Radiation-Induced Surface Activation

    NASA Astrophysics Data System (ADS)

    Honjo, Yoshio; Furuya, Masahiro; Takamasa, Tomoji; Okamoto, Koji

    When a metal oxide is irradiated by gamma rays, the irradiated surface becomes hydrophilic. This surface phenomenon is called as radiation-induced surface activation (RISA) hydrophilicity. In order to investigate gamma ray-induced and photoinduced hydrophilicity, the contact angles of water droplets on a titanium dioxide surface were measured in terms of irradiation intensity and time for gamma rays of cobalt-60 and for ultraviolet rays. Reciprocals of the contact angles increased in proportion to the irradiation time before the contact angles reached its super-hydrophilic state. The irradiation time dependency is equal to each other qualitatively. In addition, an effect of ambient gas was investigated. In pure argon gas, the contact angle remains the same against the irradiation time. This clearly indicates that certain humidity is required in ambient gas to take place of RISA hydrophilicity. A single crystal titanium dioxide (100) surface was analyzed by X-ray photoelectron spectrometry (XPS). After irradiation with gamma rays, a peak was found in the O1s spectrum, which indicates the adsorption of dissociative water to a surface 5-fold coordinate titanium site, and the formation of a surface hydroxyl group. We conclude that the RISA hydrophilicity is caused by chemisorption of the hydroxyl group on the surface.

  12. Synthesis of sphingosine is essential for oxidative stress-induced apoptosis of photoreceptors.

    PubMed

    Abrahan, Carolina E; Miranda, Gisela E; Agnolazza, Daniela L; Politi, Luis E; Rotstein, Nora P

    2010-02-01

    Oxidative stress is involved in inducing apoptosis of photoreceptors in many retinal neurodegenerative diseases. It has been shown that oxidative stress increases in photoreceptors the synthesis of ceramide, a sphingolipid precursor that then activates apoptosis. In several cell types, ceramide is converted by ceramidases to sphingosine (Sph), another apoptosis mediator; hence, this study was undertaken to determine whether Sph participates in triggering photoreceptor apoptosis. Rat retina neurons were incubated with [(3)H]palmitic acid and treated with the oxidant paraquat (PQ) to evaluate Sph synthesis. Sph was added to cultures with or without docosahexaenoic acid (DHA), the major retina polyunsaturated fatty acid and a photoreceptor survival factor, to evaluate apoptosis. Synthesis of Sph and sphingosine-1-phosphate (S1P), a prosurvival signal, were inhibited with alkaline ceramidase or sphingosine kinase inhibitors, respectively, before adding PQ, C(2)-ceramide, or Sph. Apoptosis, mitochondrial membrane polarization, cytochrome c localization, and reactive oxygen species (ROS) production were determined. PQ increased [(3)H]Sph synthesis in photoreceptors and blocking this synthesis by inhibiting alkaline ceramidase decreased PQ-induced apoptosis. Addition of Sph induced photoreceptor apoptosis, increased ROS production, and promoted cytochrome c release from mitochondria. Although DHA prevented this apoptosis, inhibiting Sph conversion to S1P blocked DHA protection. These results suggest that oxidative stress enhances formation of ceramide and its subsequent breakdown to Sph; ceramide and/or Sph would then trigger photoreceptor apoptosis. Preventing Sph synthesis or promoting its phosphorylation to S1P rescued photoreceptors, suggesting that Sph is a mediator of their apoptosis and modulation of Sph metabolism may be crucial for promoting photoreceptor survival.

  13. [Protective effects of astaxanthin against oxidative damage induced by 60Co gamma-ray irradiation].

    PubMed

    Zhao, Wei; Jing, Xuejun; Chen, Chen; Cui, Jie; Yang, Mo; Zhang, Zunzhen

    2011-09-01

    To investigate the protection effect of haematococcus pluvialis (containing astaxanthin) against the impairment of anti-oxidative system and DNA damage in mice induced by 60Co gamma-rays. Fifty mice were randomly divided into five groups, i.e. three haematococcus pluvialis groups (41.7, 83.3 and 166.7 mg/kg in vegetable oil, respectively), control group and model group (vegetable oil only). All mice except control group were irradiated by 8 Gy 60Co gamma-rays 30 days later, and executed in the 4th day after irradiation. Liver cells were collected for the analysis of the integrity of DNA by comet assay, as well as MDA contents, SOD and GSH-Px activities in liver by commercial kits. Peripheral granulocyte and bone marrow nucleated cells were counted by hematocyte counter. MDA contents of model group were higher than those of control group (P < 0.01), and SOD, GSH-Px activities of model group were lower than those of control group (P < 0.01). Compared with the model group, MDA contents were decreased (P < 0.01), and SOD and GSH-Px activities were increased (P < 0.01) in all haematococcus pluvialis groups, especially in the high haematococcus pluvialis group, and the more haematococcus pluvialis in the diet of mice, the lower rate of comet tail and OTM value were shown (P < 0.01). Furthermore, the counts of peripheral granulocyte and bone marrow nucleated cells of model group were lower than those of the control group, while the counts of peripheral granulocyte and bone marrow nucleated cells of medium and high haematococcus pluvialis groups were increased significantly when compared with the model group (P < 0.01). Astaxanthin might have some protective effect against oxidative impairment and DNA damage induced by 60Co gamma-rays in mice.

  14. Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen

    2009-03-03

    We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications.more » Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.« less

  15. Oxidative stress and NO generation in the rat pancreatitis induced by pancreatic duct ligation.

    PubMed

    Buchwalow, Igor; Schnekenburger, Jürgen; Atiakshin, Dmitri; Samoilova, Vera; Wolf, Eduard; Boecker, Werner; Tiemann, Katharina

    2017-04-01

    The interaction between nitric oxide (NO) and superoxides is critical in the development of an acute pancreatitis. Previously, we reported that the expression of superoxides and of the NO-generating enzyme (NO synthase, NOS) was up-regulated in the human pancreatitis, especially within the exocrine compartment indicating an exceptional susceptibility of the exocrine parenchyma to oxidative stress. The aim of the present study was to compare the regulation of NO signalling pathways in the human pancreatitis and in an animal model of an acute pancreatitis induced by pancreatic duct ligation (PDL) in rats. In the PDL-induced rat pancreatitis, we revealed a similar pattern of oxidative stress and NOS up-regulation in acinar and in ductal compartments, like in the human pancreatitis. This demonstrates that the PDL-induced rat pancreatitis is a proper model for further studies of acute pancreatitis development in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.

    PubMed

    Wages, Phillip A; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M

    2016-12-01

    Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

  17. Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice.

    PubMed

    Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

    2015-08-15

    Clinical and experimental studies have reported that short-term exposure to particulate air pollution is associated with inflammation, oxidative stress and impairment of lung function. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has a strong antioxidant and anti-inflammatory actions. Therefore, in the present study, we evaluated the possible ameliorative effect of emodin on diesel exhaust particles (DEP)-induced impairment of lung function, inflammation and oxidative stress in mice. Mice were intratracheally instilled with DEP (20 μg/mouse) or saline (control). Emodin was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty-four hours following DEP exposure, we evaluated airway resistance measured by forced oscillation technique, lung inflammation and oxidative stress. Emodin treatment abated the DEP-induced increase in airway resistance, and prevented the influx of neutrophils in bronchoalveolar lavage fluid. Similarly, lung histopathology confirmed the protective effect of emodin on DEP-induced lung inflammation. DEP induced a significant increase of proinflammatory cytokines in the lung including tumor necrosis factor α, interleukin 6 and interleukin 1β. The latter effect was significantly ameliorated by emodin. DEP caused a significant increase in lung lipid peroxidation, reactive oxygen species and a significant decrease of reduced glutathione concentration. These effects were significantly mitigated by emodin. We conclude that emodin significantly mitigated DEP-induced increase of airway resistance, lung inflammation and oxidative stress. Pending further pharmacological and toxicological studies, emodin may be considered a potentially useful pulmonary protective agent against particulate air pollution-induced lung toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster.

    PubMed

    Abolaji, Amos Olalekan; Kamdem, Jean Paul; Lugokenski, Thiago Henrique; Nascimento, Thallita Kalar; Waczuk, Emily Pansera; Farombi, Ebenezer Olatunde; Loreto, Élgion Lúcio da Silva; Rocha, João Batista Teixeira

    2014-06-01

    4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 µM-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (δ-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, δ-ALA-D, and AChE activities (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant balance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene.

    PubMed

    Bagchi, D; Bagchi, M; Stohs, S J

    2001-06-01

    Chromium (VI) is a widely used industrial chemical, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome, and wood treatment. On the contrary, chromium (III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been demonstrated to exhibit a significant number of health benefits in rodents and humans. However, the cause for the hexavalent chromium to induce cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that chromium (VI) induces an oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following chromium (VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. In this paper, we have demonstrated concentration- and time-dependent effects of sodium dichromate (chromium (VI) or Cr (VI)) on enhanced production of superoxide anion and hydroxyl radicals, changes in intracellular oxidized states as determined by laser scanning confocal microscopy, DNA fragmentation and apoptotic cell death (by flow cytometry) in human peripheral blood mononuclear cells. These results were compared with the concentration-dependent effects of chromium (VI) on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Chromium (VI)-induced enhanced production of ROS, as well as oxidative tissue and DNA damage were observed in these cells. More pronounced effect was observed on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Furthermore, we have assessed the effect of a

  20. Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

    PubMed

    Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

    2015-11-01

    Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  1. Aldose reductase is implicated in high glucose-induced oxidative stress in mouse embryonic neural stem cells.

    PubMed

    Fu, Jiang; Tay, S S W; Ling, E A; Dheen, S T

    2007-11-01

    Oxidative stress caused by hyperglycemia is one of the key factors responsible for maternal diabetes-induced congenital malformations, including neural tube defects in embryos. However, mechanisms by which maternal diabetes induces oxidative stress during neurulation are not clear. The present study was aimed to investigate whether high glucose induces oxidative stress in neural stem cells (NSCs), which compose the neural tube during development. We also investigated the mechanism by which high glucose disturbs the growth and survival of NSCs in vitro. NSCs were exposed to physiological d-glucose concentration (PG, 5 mmol/L), PG with l-glucose (25 mmol/L), or high d-glucose concentration (HG, 30 or 45 mmol/l). HG induced reactive oxygen species production and mRNA expression of aldose reductase (AR), which catalyzes the glucose reduction through polyol pathway, in NSCs. Expression of glucose transporter 1 (Glut1) mRNA and protein which regulates glucose uptake in NSCs was increased at early stage (24 h) and became down-regulated at late stage (72 h) of exposure to HG. Inhibition of AR by fidarestat, an AR inhibitor, decreased the oxidative stress, restored the cell viability and proliferation, and reduced apoptotic cell death in NSCs exposed to HG. Moreover, inhibition of AR attenuated the down-regulation of Glut1 expression in NSCs exposed to HG for 72 h. These results suggest that the activation of polyol pathway plays a role in the induction of oxidative stress which alters Glut1 expression and cell cycle in NSCs exposed to HG, thereby resulting in abnormal patterning of the neural tube in embryos of diabetic pregnancy.

  2. Protective Effect of Bacoside-A against Morphine-Induced Oxidative Stress in Rats.

    PubMed

    Sumathi, T; Nathiya, V C; Sakthikumar, M

    2011-07-01

    In the present study, we investigated the protective effect of bacoside-A the active principle isolated from the plant Bacopa monniera against oxidative damage induced by morphine in rat brain. Morphine intoxicated rats received 10-160 mg/kg b.w. of morphine hydrochloride intraperitoneally for 21 days. Bacoside-A pretreated rats were administered with bacoside-A (10 mg/kg b.w/day) orally, 2 h before the injection of morphine for 21 days. Pretreatment with bacoside-A has shown to possess a significant protective role against morphine induced brain oxidative damage in the antioxidant status (total reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and lipid peroxidation) and membrane bound ATP-ases(Na(+)/K(+)ATPase. Ca(2+) and Mg(2+) ATPases) activities in rat. The results of the present study indicate that bacoside-A protects the brain from oxidative stress induced by morphine.

  3. Protective effect of cinnamaldehyde against glutamate-induced oxidative stress and apoptosis in PC12 cells.

    PubMed

    Lv, Chao; Yuan, Xing; Zeng, Hua-Wu; Liu, Run-Hui; Zhang, Wei-Dong

    2017-11-15

    Cinnamaldehyde is a main ingredient of cinnamon oils from the stem bark of Cinnamomum cassia, which has been widely used in food and traditional herbal medicine in Asia. In the present study, the neuroprotective effects and the potential mechanisms of cinnamaldehyde against glutamate-induced oxidative stress in PC12 cells were investigated. Exposure to 4mM glutamate altered the GSH, MDA levels and SOD activity, caused the generation of reactive oxygen species, resulted in the induction of oxidative stress in PC12 cell, ultimately induced cell death. However, pretreatment with cinnamaldehyde at 5, 10 and 20μM significantly attenuated cell viability loss, reduced the generation of reactive oxygen species, stabilised mitochondrial membrane potential (MMP), decreased the release of cytochrome c and limited the activities of caspase-9 and -3. In addition, cinnamaldehyde also markedly increased Bcl-2 while inhibiting Bax expression,and decreased the LC3-II/LC3-I ratio. These results indicate that cinnamaldehyde exists a potential protective effect against glutamate-induced oxidative stress and apoptosis in PC12 cells. Copyright © 2017. Published by Elsevier B.V.

  4. The Degree of Radiation-Induced DNA Strand Breaks Is Altered by Acute Sleep Deprivation and Psychological Stress and Is Associated with Cognitive Performance in Humans.

    PubMed

    Moreno-Villanueva, Maria; von Scheven, Gudrun; Feiveson, Alan; Bürkle, Alexander; Wu, Honglu; Goel, Namni

    2018-03-27

    Sleep deprivation is associated with impaired immune responses, cancer, and morbidity and mortality, and can degrade cognitive performance, although individual differences exist in such responses. Sleep deprivation induces DNA strand breaks and DNA base oxidation in animals, and psychological stress is associated with increased DNA damage in humans. It remains unknown whether sleep deprivation or psychological stress in humans affects DNA damage response from environmental stressors, and whether these responses predict cognitive performance during sleep deprivation. Sixteen healthy adults (ages 29-52;mean age±SD, 36.4±7.1 years;7 women) participated in a 5-day experiment involving two 8 hour time-in-bed [TIB] baseline nights, followed by 39 hours total sleep deprivation (TSD), and two 8-10 hour TIB recovery nights. A modified Trier Social Stress Test was conducted on the day after TSD. Psychomotor Vigilance Tests measured behavioral attention. DNA damage was assessed in blood cells collected at 5 time points, and blood cells were irradiated ex-vivo. TSD, alone or in combination with psychological stress, did not induce significant increases in DNA damage. By contrast, radiation-induced DNA damage decreased significantly in response to TSD, but increased back to baseline when combined with psychological stress. Cognitively-vulnerable individuals had more radiation-induced DNA strand breaks before TSD, indicating their greater sensitivity to DNA damage from environmental stressors. Our results provide novel insights into the molecular consequences of sleep deprivation, psychological stress, and performance vulnerability. They are important for situations involving sleep loss, radiation exposure and cognitive deficits, including cancer therapy, environmental toxicology, and space medicine.

  5. Do antioxidants inhibit oxidative-stress-induced autophagy of tenofibroblasts?

    PubMed

    Kim, Ra-Jeong; Hah, Young-Sool; Sung, Chang-Meen; Kang, Jae-Ran; Park, Hyung Bin

    2014-07-01

    Recent research on tendinopathy has focused on its relationship to programmed cell death. Increased autophagy has been observed in ruptured rotator cuff tendon tissues, suggesting a causal relationship. We investigated whether autophagy occurs in human rotator cuff tenofibroblast death induced by oxidative stress and whether antioxidants protect against autophagic cell death. We used H2 O2 (0.75 mM) as oxidative stressor, cyanidin (100 µg/ml) as antioxidant, zVAD (20 µM) as apoptosis inhibitor, and 3-MA (10 mM) as autophagy inhibitor. We evaluated cell viability and known autophagic markers: LC3-II expression, GFP-LC3 puncta formation, autolysosomes, and Atg5-12 and Beclin 1 expression. H2 O2 exposure increased the rates of cell death, LC3-II expression, GFP-LC3 puncta formation, and autolysosomes. After we induced apoptosis arrest using zVAD, H2 O2 exposure still induced cell death, LC3-II expression, and GFP-LC3 puncta formation. H2 O2 exposure also increased Atg5-12 and Beclin 1 expressions, indicating autophagic cell death. However, cyanidin treatment reduced H2 O2 -induced cell death, LC3-II expression, GFP-LC3 puncta formation, and autolysosomes. Cyanidin and 3-MA similarly reduced the cell-death rate, and Atg5-12 and Beclin 1 expression. This study demonstrated that H2 O2 , an oxidative stressor, induces autophagic cell death in rotator cuff tenofibroblasts, and that cyanidin, a natural antioxidant, inhibits autophagic cell death. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. The effect of green, black and white tea on the level of alpha and gamma tocopherols in free radical-induced oxidative damage of human red blood cells.

    PubMed

    Gawlik, Małgorzata; Czajka, Aneta

    2007-01-01

    The present study was undertaken to investigate the effect of aqueous tea extracts on lipid peroxidation and alpha and gamma tocopherols concentration in the oxidative damage of human red blood cells (RBC). RBC was taken as the model for study of the oxidative damage was induced by cumene hydroperoxide (cumOOH). The antioxidative property of leaf green tea, leaf and granulate of black tea and white tea at levels 1, 2, 4 g/150 mL of water were evaluated. The correlation was observed between reducing power of tea extract and formation of malondialdehyde--MDA (an indicator of lipid peroxidation) in oxidative damage of RBC. All tea extracts at level of 4 g/150 mL of water significantly decreased concentration of MDA. The extract of green tea in comparison to black and white tea extracts at the same levels seems to be a better protective agent against oxidative stress. The antioxidant synergism between components extracted from leaves of green tea and endogenous alpha tocopherol in the oxidative damage of red blood cells was observed. The consumption of alpha tocopherol in oxidative damage of RBC was the lowest after treatment with the highest dose of green tea extract. All tea extracts did not protect against decrease of gamma tocopherol in human erythrocytes treated with cumOOH.

  7. Citrus peel extract attenuates acute cyanide poisoning-induced seizures and oxidative stress in rats.

    PubMed

    Abdel Moneim, Ahmed E

    2014-01-01

    The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

  8. 30 CFR 57.5047 - Gamma radiation surveys.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Gamma radiation surveys. 57.5047 Section 57..., Radiation, Physical Agents, and Diesel Particulate Matter Radiation-Underground Only § 57.5047 Gamma radiation surveys. (a) Gamma radiation surveys shall be conducted annually in all underground mines where...

  9. 30 CFR 57.5047 - Gamma radiation surveys.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Gamma radiation surveys. 57.5047 Section 57..., Radiation, Physical Agents, and Diesel Particulate Matter Radiation-Underground Only § 57.5047 Gamma radiation surveys. (a) Gamma radiation surveys shall be conducted annually in all underground mines where...

  10. Radiation-Resistant Micrococcus luteus SC1204 and Its Proteomics Change Upon Gamma Irradiation.

    PubMed

    Deng, Wuyuan; Yang, Yang; Gao, Peng; Chen, Hao; Wen, Wenting; Sun, Qun

    2016-06-01

    To explore the radiation-resistance mechanisms in bacteria, a radiation-resistant strain SC1204 was isolated from the surrounding area of a (60)Co-γ radiation facility. SC1204 could survive up to 8 kGy dose of gamma irradiation and was identified as Micrococcus luteus by phylogenetic analysis of 16S rRNA gene sequences. Its proteomic changes under 2-kGy irradiation were examined by two-dimensional electrophoresis followed by MALDI-TOF-TOF/MS analysis. The results showed that at least 24 proteins displayed significant changes (p < 0.05) at expression level under the radiation stress, among which 22 were successfully identified and classified into the major functional categories of metabolism, energy production and conservation, translation, ribosomal structure, and biogenesis. Among these proteins, leucyl aminopeptidase involved in synthesis of glutathione was the most abundant induced protein during postirradiation recovery, indicating that anti-oxidation protection was the most important line of defense in SC1204 against radiation. The next abundant protein was phosphoribosyl aminoimidazole carboxamide formyltransferase/IMP cyclohydrolase (AICAR Tfase/IMPCH), the key enzyme in the biosynthetic pathway of purine that is anti-radiation compound. Other proteins changing significantly (p < 0.05) after radiation exposure included urocanate hydratase, dihydrolipoyl dehydrogenase, succinyl-CoA synthetase subunit alpha, phosphoglycerate kinase, cell division protein FtsZ, elongation factor Ts and Tu, translation elongation factor Tu and G, 30S ribosomal protein S1, histidyl-tRNA synthetase, and arginyl-tRNA synthetase, which were considered to be the key proteins in urocanate metabolism, tricarboxylic acid cycle, glycolysis, cell division process, and synthesis process of proteins. Therefore, these proteins may also play important roles in radiation resistance in M. luteus.

  11. Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

    PubMed Central

    Panich, Uraiwan; Sittithumcharee, Gunya; Rathviboon, Natwarath

    2016-01-01

    Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells. PMID:27148370

  12. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feltens, Ralph, E-mail: ralph.feltens@ufz.d; UFZ- Helmholtz Centre for Environmental Research, Department of Proteomics, Permoserstrasse 15, D-04318 Leipzig; Moegel, Iljana, E-mail: iljana.moegel@ufz.d

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasismore » on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.« less

  13. IFN-gamma synergizes with LPS to induce nitric oxide biosynthesis through glycogen synthase kinase-3-inhibited IL-10.

    PubMed

    Lin, Chiou-Feng; Tsai, Cheng-Chieh; Huang, Wei-Ching; Wang, Chi-Yun; Tseng, Hsiang-Chi; Wang, Yi; Kai, Jui-In; Wang, Szu-Wen; Cheng, Yi-Lin

    2008-10-15

    Interferon-gamma (IFN-gamma) plays a crucial role in innate immunity and inflammation. It causes the synergistic effect on endotoxin lipopolysaccharide (LPS)-stimulated inducible nitric oxide synthase (iNOS)/NO biosynthesis; however, the mechanism remains unclear. In the present study, we investigated the effects of glycogen synthase kinase-3 (GSK-3)-mediated inhibition of anti-inflammatory interleukin-10 (IL-10). We found, in LPS-stimulated macrophages, that IFN-gamma increased iNOS expression and NO production in a time-dependent manner. In addition, ELISA analysis showed the upregulation of tumor necrosis factor-alpha and regulated on activation, normal T expressed and secreted, and the downregulation of IL-10. RT-PCR further showed changes in the IL-10 mRNA level as well. Treating cells with recombinant IL-10 showed a decrease in IFN-gamma/LPS-induced iNOS/NO biosynthesis, whereas anti-IL-10 neutralizing antibodies enhanced this effect, suggesting that IL-10 acts in an anti-inflammatory role. GSK-3-inhibitor treatment blocked IFN-gamma/LPS-induced iNOS/NO biosynthesis but upregulated IL-10 production. Inhibiting GSK-3 using short-interference RNA showed similar results. Additionally, treating cells with anti-IL-10 neutralizing antibodies blocked these effects. We further showed that inhibiting GSK-3 increased phosphorylation of transcription factor cyclic AMP response element binding protein. Inhibiting protein tyrosine kinase Pyk2, an upstream regulator of GSK-3beta, caused inhibition on IFN-gamma/LPS-induced GSK-3beta phosphorylation at tyrosine 216 and iNOS/NO biosynthesis. Taken together, these findings reveal the involvement of GSK-3-inhibited IL-10 on the induction of iNOS/NO biosynthesis by IFN-gamma synergized with LPS. (c) 2008 Wiley-Liss, Inc.

  14. Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation.

    PubMed

    Chung, Ki Wung; Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Kim, Dae Hyun; Park, Byung Hyun; Yu, Byung Pal; Chung, Hae Young

    2015-08-01

    Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased β-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3α (FOXO3α) by SIRT1 changed the transcriptional activity of FOXO3α and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.

    PubMed

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Maity, Pallab; Adhikari, Susanta S; Bandyopadhyay, Uday

    2010-07-15

    Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy. NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy. Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy. Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron. Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy. In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage. GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay. GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity. Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by whichmore » ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.« less

  17. p,p'-DDT induces testicular oxidative stress-induced apoptosis in adult rats.

    PubMed

    Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

    2017-05-26

    The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis. Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels. Antioxidant enzymes activities was assessed by determination of superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (H 2 O 2 ) production. In addition, glutathione-dependent enzymes and reducing power in testis was evaluated by glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione S-transferase (GST) activities and reduced and oxidized glutathione (GSH - GSSG) levels. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis and the apoptotic index was assessed through the TUNEL assay. After 10 days of treatment, an increase in LPO level and H 2 O 2 production occurred, while MTs level, SOD and CAT activities were decreased. Also, the Gpx, GR, GST, and GSH activities were decreased, whereas GSSG activity was increased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of DDT-exposed rats. In addition, the apoptotic index was significantly increased in testis of DDT-treated rats. These results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.

  18. Modulation of oxidative phosphorylation (OXPHOS) by radiation- induced biophotons.

    PubMed

    Le, Michelle; McNeill, Fiona E; Seymour, Colin B; Rusin, Andrej; Diamond, Kevin; Rainbow, Andrew J; Murphy, James; Mothersill, Carmel E

    2018-05-01

    Radiation-induced biophotons are an electromagnetic form of bystander signalling. In human cells, biophoton signalling is capable of eliciting effects in non-irradiated bystander cells. However, the mechanisms by which the biophotons interact and act upon the bystander cells are not clearly understood. Mitochondrial energy production and ROS are known to be involved but the precise interactions are not known. To address this question, we have investigated the effect of biophoton emission upon the function of the complexes of oxidative phosphorylation (OXPHOS). The exposure of bystander HCT116 p53 +/+ cells to biophoton signals emitted from β-irradiated HCT116 p53 +/+ cells induced significant modifications in the activity of Complex I (NADH dehydrogenase or NADH:ubiquinone oxidoreductase) such that the activity was severely diminished compared to non-irradiated controls. The enzymatic assay showed that the efficiency of NADH oxidation to NAD+ was severely compromised. It is suspected that this impairment may be linked to the photoabsorption of biophotons in the blue wavelength range (492-455 nm). The photobiomodulation to Complex I was suspected to contribute greatly to the inefficiency of ATP synthase function since it resulted in a lower quantity of H + ions to be available for use in the process of chemiosmosis. Other reactions of the ETC were not significantly impacted. Overall, these results provide evidence for a link between biophoton emission and biomodulation of the mitochondrial ATP synthesis process. However, there are many aspects of biological modulation by radiation-induced biophotons which will require further elucidation. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis.

    PubMed

    Isaak, Cara K; Petkau, Jay C; Blewett, Heather; O, Karmin; Siow, Yaw L

    2017-08-01

    Lingonberry grown in northern Manitoba, Canada, contains exceptionally high levels of anthocyanins and other polyphenols. Previous studies from our lab have shown that lingonberry anthocyanins can protect H9c2 cells from ischemia-reperfusion injury and anthocyanin-rich diets have been shown to be associated with decreased cardiovascular disease and mortality. Oxidative stress can impair function and trigger apoptosis in cardiomyocytes. This study investigated the protective effects of physiologically relevant doses of lingonberry extracts and pure anthocyanins against hydrogen-peroxide-induced cell death. Apoptosis and necrosis were detected in H9c2 cells after hydrogen peroxide treatment via flow cytometry using FLICA 660 caspase 3/7 combined with YO-PRO-1 and then confirmed with Hoechst staining and fluorescence microscopy. Each of the 3 major anthocyanins found in lingonberry (cyanidin-3-galactoside, cyanidin-3-glucoside, and cyanidin-3-arabinoside) was protective against hydrogen-peroxide-induced apoptosis in H9c2 cells at 10 ng·mL -1 (20 nmol·L -1 ) and restored the number of viable cells to match the control group. A combination of the 3 anthocyanins was also protective and a lingonberry extract tested at 3 concentrations produced a dose-dependent protective effect. Lingonberry anthocyanins protected cardiac cells from oxidative-stress-induced apoptosis and may have cardioprotective effects as a dietary modification.

  20. Cryopreservation affects ROS-induced oxidative stress and antioxidant response in Arabidopsis seedlings

    USDA-ARS?s Scientific Manuscript database

    Plant recovery status after cryopreservation by vitrification had a negative relationship to the oxidative stress induced by reactive oxygen species (ROS). Arabidopsis thaliana seedlings germinated for 48-h or 72-h with different cryopreservation survival tolerances were examined at five steps of a ...

  1. Evaluation of Cassia tora Linn. against Oxidative Stress-induced DNA and Cell Membrane Damage

    PubMed Central

    Kumar, R Sunil; Narasingappa, Ramesh Balenahalli; Joshi, Chandrashekar G; Girish, Talakatta K; Prasada Rao, Ummiti JS; Danagoudar, Ananda

    2017-01-01

    Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy. PMID:28584491

  2. Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells.

    PubMed

    Chen, Hai-Lan; Yang, Jian; Fu, Yuan-Fang; Meng, Xi-Nan; Zhao, Wei-Dan; Hu, Ting-Jun

    2017-05-02

    This study was carried out to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on PCV2 induced oxidative stress in RAW264.7 cells. Oxidative stress model was established in RAW264.7 cells by infecting with PCV2. Virus infected cells were then treated with various concentrations (25 mg/ml, 50 mg/ml and 100 mg/ml) of TFSD. The levels of oxidative stress related molecules (NO, ROS, GSH and GSSG) and activities of associated enzymes (SOD, MPO and XOD were analyzed using ultraviolet spectrophotometry, fluorescence method and commercialized detection kits. PCV2 infection induced significant increase of NO secretion, ROS generation, GSSG content, activities of both XOD and MPO, and dramatically decrease of GSH content and SOD activity in RAW264.7 cells (P < 0.05). After treating with TFSD, PCV2 induced alteration of oxidative stress related molecule levels and enzyme activities were recovered to a level similar to control. Our findings indicated that TFSD was able to regulate oxidative stress induced by PCV2 infection in RAW264.7 cells, which supports the ethnomedicinal use of this herb as an alternative or complementary therapeutic drug for reactive oxygen-associated pathologies.

  3. C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

    PubMed

    Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

    2017-08-20

    Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

  4. Ex-situ and in-situ observations of the effects of gamma radiation on lithium ion battery performance

    NASA Astrophysics Data System (ADS)

    Tan, Chuting; Bashian, Nicholas H.; Hemmelgarn, Chase W.; Thio, Wesley J.; Lyons, Daniel J.; Zheng, Yuan F.; Cao, Lei R.; Co, Anne C.

    2017-07-01

    Radiation effects induced by gamma rays on battery performance were investigated by measuring the capacity and resistance of a series of battery coin cells in-situ directly under gamma radiation and ex-situ. An experimental setup was developed to charge and discharge batteries directly under gamma radiation, equipped with precise temperature control, at The Ohio State University Nuclear Reactor Lab. Latent effects induced by gamma radiation on battery components directly influence their performance. Charge and discharge capacity and overall resistance throughout a time span of several weeks post irradiation were monitored and compared to control groups. It was found that exposure to gamma radiation does not significantly alter the available capacity and the overall cell resistance immediately, however, battery performance significantly decreases with time post irradiation. Also, batteries exposed to a higher cumulative dose showed close-to-zero capacity at two-week post irradiation.

  5. Neuroglobin protects astroglial cells from hydrogen peroxide-induced oxidative stress and apoptotic cell death.

    PubMed

    Amri, Fatma; Ghouili, Ikram; Amri, Mohamed; Carrier, Alice; Masmoudi-Kouki, Olfa

    2017-01-01

    Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in astroglial cell death occurring in diverse neuropathological conditions. Numerous studies indicate that neuroglobin (Ngb) promotes neuron survival, but nothing is known regarding the action of Ngb in astroglial cell survival. Thus, the purpose of this study was to investigate the potential glioprotective effect of Ngb on hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis in cultured mouse astrocytes. Incubation of cells with subnanomolar concentrations of Ngb (10 -14 -10 -10  M) was found to prevent both H 2 O 2 -evoked reduction in surviving cells number and accumulation of reactive oxygen species in a concentration-dependent manner. Furthermore, Ngb treatment abolishes H 2 O 2 -induced increase in mitochondrial oxygen consumption rates. Concomitantly, Ngb treatment rescues H 2 O 2 -associated reduced expression of endogenous antioxidant enzymes (superoxide dismutases and catalase) and prevents the stimulation of the expression of pro-inflammatory genes (inducible nitric oxide synthase, cyclooxygenase-2, and interleukin (IL) IL-6 and IL-33). Moreover, Ngb blocks the stimulation of Bax (pro-apoptotic) and the inhibition of Bcl-2 (anti-apoptotic) gene expression induced by H 2 O 2 , which in turn abolishes caspase 3 activation. The protective effect of Ngb upon H 2 O 2 induced activation of caspase 3 activity and cell death can be accounted for by activation of protein kinase A and mitogen-activated protein kinase transduction cascade. Finally, we demonstrate that Ngb increases Akt phosphorylation and prevents H 2 O 2 -provoked inhibition of ERK and Akt phosphorylation. Taken together, these data demonstrate for the first time that Ngb is a glioprotective agent that prevents H 2 O 2 -induced oxidative stress and apoptotic astroglial cell death. Protection of astrocytes from oxidative insult may thus contribute to the neuroprotective effect of Ngb.

  6. Nontypeable Haemophilus influenzae Induces Sustained Lung Oxidative Stress and Protease Expression

    PubMed Central

    King, Paul T.; Sharma, Roleen; O’Sullivan, Kim; Selemidis, Stavros; Lim, Steven; Radhakrishna, Naghmeh; Lo, Camden; Prasad, Jyotika; Callaghan, Judy; McLaughlin, Peter; Farmer, Michael; Steinfort, Daniel; Jennings, Barton; Ngui, James; Broughton, Bradley R. S.; Thomas, Belinda; Essilfie, Ama-Tawiah; Hickey, Michael; Holmes, Peter W.; Hansbro, Philip; Bardin, Philip G.; Holdsworth, Stephen R.

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps. PMID:25793977

  7. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

    PubMed Central

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-01-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

  8. 3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.

    PubMed

    Lahbib, Karima; Aouani, Iyadh; Cavalier, Jean-François; Touil, Soufiane

    2015-09-01

    Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications. © 2014 John Wiley & Sons A/S.

  9. Methamidophos induces cytotoxicity and oxidative stress in human peripheral blood mononuclear cells.

    PubMed

    Ramirez-Vargas, Marco Antonio; Huerta-Beristain, Gerardo; Guzman-Guzman, Iris Paola; Alarcon-Romero, Luz Del Carmen; Flores-Alfaro, Eugenia; Rojas-Garcia, Aurora Elizabeth; Moreno-Godinez, Ma Elena

    2017-01-01

    Previous studies have shown that organophosphate pesticide (OP) exposure is associated with oxidative stress. Methamidophos (MET) is an OP widely used in agriculture, which is regarded as a highly toxic pesticide and it is a potent inhibitor of acetylcholinesterase. The aim of this study was to evaluate whether MET can induce oxidative stress at low concentrations in primary cultures of human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy individuals were exposed to MET (0-80 mg/L) for 0-72 h. We performed the MTT and neutral-red assays to assess the cytotoxicity. As indicators of oxidative stress, the levels of reactive oxygen species (ROS) were assessed using flow cytometry, and the malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined. MET decreased the viability of PBMCs in a dose-dependent manner. At concentrations of 3, 10, or 20 mg/L for 24 h, MET increased the ROS production significantly compared with the vehicle control. Similarly, MET increased the levels of MDA at the same concentrations that increased ROS (10 and 20 mg/L); however, no changes in GSH levels were observed. These results suggest that MET increased the generation of oxidative stress in PBMCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 147-155, 2017. © 2015 Wiley Periodicals, Inc.

  10. Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Aggregation Causes Mitochondrial Dysfunction during Oxidative Stress-induced Cell Death*

    PubMed Central

    Itakura, Masanori; Kubo, Takeya; Kaneshige, Akihiro; Harada, Naoki; Izawa, Takeshi; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Yamaji, Ryouichi; Takeuchi, Tadayoshi

    2017-01-01

    Glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional protein that also mediates cell death under oxidative stress. We reported previously that the active-site cysteine (Cys-152) of GAPDH plays an essential role in oxidative stress-induced aggregation of GAPDH associated with cell death, and a C152A-GAPDH mutant rescues nitric oxide (NO)-induced cell death by interfering with the aggregation of wild type (WT)-GAPDH. However, the detailed mechanism underlying GAPDH aggregate-induced cell death remains elusive. Here we report that NO-induced GAPDH aggregation specifically causes mitochondrial dysfunction. First, we observed a correlation between NO-induced GAPDH aggregation and mitochondrial dysfunction, when GAPDH aggregation occurred at mitochondria in SH-SY5Y cells. In isolated mitochondria, aggregates of WT-GAPDH directly induced mitochondrial swelling and depolarization, whereas mixtures containing aggregates of C152A-GAPDH reduced mitochondrial dysfunction. Additionally, treatment with cyclosporin A improved WT-GAPDH aggregate-induced swelling and depolarization. In doxycycline-inducible SH-SY5Y cells, overexpression of WT-GAPDH augmented NO-induced mitochondrial dysfunction and increased mitochondrial GAPDH aggregation, whereas induced overexpression of C152A-GAPDH significantly suppressed mitochondrial impairment. Further, NO-induced cytochrome c release into the cytosol and nuclear translocation of apoptosis-inducing factor from mitochondria were both augmented in cells overexpressing WT-GAPDH but ameliorated in C152A-GAPDH-overexpressing cells. Interestingly, GAPDH aggregates induced necrotic cell death via a permeability transition pore (PTP) opening. The expression of either WT- or C152A-GAPDH did not affect other cell death pathways associated with protein aggregation, such as proteasome inhibition, gene expression induced by endoplasmic reticulum stress, or autophagy. Collectively, these results suggest that NO-induced GAPDH

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada

    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,more » 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.« less

  12. Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis

    PubMed Central

    Choudhury, Mahua G.; Saha, Nirmalendu

    2016-01-01

    The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in

  13. Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis.

    PubMed

    Choudhury, Mahua G; Saha, Nirmalendu

    2016-01-01

    The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in

  14. Protective Effect of Bacoside-A against Morphine-Induced Oxidative Stress in Rats

    PubMed Central

    Sumathi, T.; Nathiya, V. C.; Sakthikumar, M.

    2011-01-01

    In the present study, we investigated the protective effect of bacoside-A the active principle isolated from the plant Bacopa monniera against oxidative damage induced by morphine in rat brain. Morphine intoxicated rats received 10-160 mg/kg b.w. of morphine hydrochloride intraperitoneally for 21 days. Bacoside-A pretreated rats were administered with bacoside-A (10 mg/kg b.w/day) orally, 2 h before the injection of morphine for 21 days. Pretreatment with bacoside-A has shown to possess a significant protective role against morphine induced brain oxidative damage in the antioxidant status (total reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and lipid peroxidation) and membrane bound ATP-ases(Na+/K+ATPase. Ca2+ and Mg2+ ATPases) activities in rat. The results of the present study indicate that bacoside-A protects the brain from oxidative stress induced by morphine. PMID:22707825

  15. The glutathione mimic ebselen inhibits oxidative stress but not endoplasmic reticulum stress in endothelial cells.

    PubMed

    Ahwach, Salma Makhoul; Thomas, Melanie; Onstead-Haas, Luisa; Mooradian, Arshag D; Haas, Michael J

    2015-08-01

    Reactive oxygen species are associated with cardiovascular disease, diabetes, and atherosclerosis, yet the use of antioxidants in clinical trials has been ineffective at improving outcomes. In endothelial cells, high-dextrose-induced oxidative stress and endoplasmic reticulum stress promote endothelial dysfunction leading to the recruitment and activation of peripheral blood lymphocytes and the breakdown of barrier function. Ebselen, a glutathione peroxidase 1 (GPX1) mimic, has been shown to improve β-cell function in diabetes and prevent atherosclerosis. To determine if ebselen inhibits both oxidative stress and endoplasmic reticulum (ER) stress in endothelial cells, we examined its effects in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) with and without high-dextrose. Oxidative stress and ER stress were measured by 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence and ER stress alkaline phosphatase assays, respectively. GPX1 over-expression and knockdown were performed by transfecting cells with a GPX1 expression construct or a GPX1-specific siRNA, respectively. Ebselen inhibited dextrose-induced oxidative stress but not ER stress in both HUVEC and HCAEC. Ebselen also had no effect on tunicamycin-induced ER stress in HCAEC. Furthermore, augmentation of GPX1 activity directly by sodium selenite supplementation or transfection of a GPX1 expression plasmid decreased dextrose-induced oxidative stress but not ER stress, while GPX1 knockout enhanced oxidative stress but had no effect on ER stress. These results suggest that ebselen targets only oxidative stress but not ER stress. Copyright © 2015. Published by Elsevier Inc.

  16. Antioxidant Effect of CoQ(10) on N-nitrosodiethylamine-induced Oxidative Stress in Mice.

    PubMed

    Song, Ho Sun; Kim, Hee Rae; Park, Tae Wook; Cho, Bong Jae; Choi, Mi Young; Kim, Chang Jong; Sohn, Uy Dong; Sim, Sang Soo

    2009-08-01

    The antioxidant effect of CoQ(10) on N-nitrosodiethylamine (NDEA)-induced oxidative stress was investigated in mice. Food intake and body weight were similar in both CoQ(10) and control groups during the 3-week experimental period. NDEA significantly increased the activities of typical marker enzymes of liver function (AST, ALT and ALP) both in control and CoQ(10) groups. However, the increase of plasma aminotransferase activity was significantly reduced in the CoQ(10) group. Lipid peroxidation in various tissues, such as heart, lung, liver, kidney, spleen and plasma, was significantly increased by NDEA, but this increase was significantly reduced by 100 mg/kg of CoQ(10). Superoxide dismutase activity increased significantly upon NDEA-induced oxidative stress in both the control and CoQ(10) groups with the effect being less in the CoQ(10) group. Catalase activity decreased significantly in both the control and CoQ(10) groups treated with NDEA, again with the effect being less in the CoQ(10) group. The lesser effect on superoxide dismutase and catalase in the NDEA-treated CoQ(10) group is indicative of the protective effect CoQ(10). Thus, CoQ(10) can offer useful protection against NDEA-induced oxidative stress.

  17. Protective Effects of Houttuynia cordata Thunb. on Gentamicin-induced Oxidative Stress and Nephrotoxicity in Rats

    PubMed Central

    Kang, Changgeun; Lee, Hyungkyoung; Hah, Do-Yun; Heo, Jung Ho; Kim, Chung Hui; Kim, Euikyung

    2013-01-01

    Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d, oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration). Treatments were administered once daily for 12 d. After 12 d, biochemical and histopathological analyses were conducted to evaluate oxidative stress and renal nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant activity. Animals treated with GS alone showed a significant increase in serum levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and CAT. Treatment of rats with HC showed significant improvement in renal function, presumably as a result of decreased biochemical indices and oxidative stress parameters associated with GS-induced nephrotoxicity. Histopathological examination of the rat kidneys confirmed these observations. Therefore, the novel natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative stress in rats. PMID:24278630

  18. Protective Effects of Houttuynia cordata Thunb. on Gentamicin-induced Oxidative Stress and Nephrotoxicity in Rats.

    PubMed

    Kang, Changgeun; Lee, Hyungkyoung; Hah, Do-Yun; Heo, Jung Ho; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

    2013-03-01

    Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d, oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration). Treatments were administered once daily for 12 d. After 12 d, biochemical and histopathological analyses were conducted to evaluate oxidative stress and renal nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant activity. Animals treated with GS alone showed a significant increase in serum levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and CAT. Treatment of rats with HC showed significant improvement in renal function, presumably as a result of decreased biochemical indices and oxidative stress parameters associated with GS-induced nephrotoxicity. Histopathological examination of the rat kidneys confirmed these observations. Therefore, the novel natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative stress in rats.

  19. Alpha-crystallin-mediated protection of lens cells against heat and oxidative stress-induced cell death.

    PubMed

    Christopher, Karen L; Pedler, Michelle G; Shieh, Biehuoy; Ammar, David A; Petrash, J Mark; Mueller, Niklaus H

    2014-02-01

    In addition to their key role as structural lens proteins, α-crystallins also appear to confer protection against many eye diseases, including cataract, retinitis pigmentosa, and macular degeneration. Exogenous recombinant α-crystallin proteins were examined for their ability to prevent cell death induced by heat or oxidative stress in a human lens epithelial cell line (HLE-B3). Wild type αA- or αB-crystallin (WT-αA and WT-αB) and αA- or αB-crystallins, modified by the addition of a cell penetration peptide (CPP) designed to enhance the uptake of proteins into cells (gC-αB, TAT-αB, gC-αA), were produced by recombinant methods. In vitro chaperone-like assays were used to assay the ability of α-crystallins to protect client proteins from chemical or heat induced aggregation. In vivo viability assays were performed in HLE-B3 to determine whether pre-treatment with α-crystallins reduced death after exposure to oxidative or heat stress. Most of the five recombinant α-crystallin proteins tested conferred some in vitro protection from protein aggregation, with the greatest effect seen with WT-αB and gC-αB. All α-crystallins displayed significant protection to oxidative stress induced cell death, while only the αB-crystallins reduced cell death induced by thermal stress. Our findings indicate that the addition of the gC tag enhanced the protective effect of αB-crystallin against oxidative but not thermally-induced cell death. In conclusion, modifications that increase the uptake of α-crystallin proteins into cells, without destroying their chaperone-like activity and anti-apoptotic functions, create the potential to use these proteins therapeutically. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Gamma radiation effects on polydimethylsiloxane rubber foams under different radiation conditions

    NASA Astrophysics Data System (ADS)

    Sui, H. L.; Liu, X. Y.; Zhong, F. C.; Li, X. Y.; Wang, L.; Ju, X.

    2013-07-01

    Polydimethylsiloxane rubber foams were irradiated by gamma ray under different radiation conditions designed by orthogonal design method. Compression set measurement, infrared attenuated total reflectance spectroscopy (ATR) and X-ray induced photoelectron spectroscopy (XPS) were used. Three aging factors' influence effects on the mechanical property and chemical structure were studied. It was found that among the three factors and the chosen levels, both properties were affected most by radiation dose, while radiation dose rate had no obvious influence on both properties. The stiffening of the rubber foams was caused by cross-linking reactions in the Si-CH3. At the same radiation dose, the rigidity of the foams irradiated in air was lower than that in nitrogen. When polydimethylsiloxane was irradiated at a high dose in sealed nitrogen atmosphere, carbon element distribution would be changed. Hydrocarbons produced by gamma ray in the sealed tube would make the carbon content in the skin-deep higher than that in the middle, which indicated that polydimethylsiloxane rubber foams storing in a sealed atmosphere filled with enough hydrocarbons should be helpful to extend the service life.

  1. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress.

    PubMed

    Shokrzadeh, Mohammad; Sadat-Hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

    2017-05-01

    Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica , pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

  2. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress

    PubMed Central

    Shokrzadeh, Mohammad; Sadat-hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

    2017-01-01

    Objective(s): Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Materials and Methods: Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica, pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Results: Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Conclusion: Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN. PMID:28656084

  3. Quercetin protects human peripheral blood mononuclear cells from OTA-induced oxidative stress, genotoxicity, and inflammation.

    PubMed

    Periasamy, Ramyaa; Kalal, Iravathy Goud; Krishnaswamy, Rajashree; Viswanadha, VijayaPadma

    2016-07-01

    Ochratoxin A (OTA) is one of the most abundant food-contaminating mycotoxins world wide, and is detrimental to human and animal health. This study evaluated the protective effect of quercetin against OTA-induced cytotoxicity, genotoxicity, and inflammatory response in lymphocytes. Cytotoxicity determined by MTT assay revealed IC20 value of OTA to be 20 µM, which was restored to near control values by pretreatment with quercetin. Oxidative stress parameters such as antioxidant enzymes, LPO and PCC levels indicated that quercetin exerted a protective effect on OTA-induced oxidative stress. Quercetin exerted an antigenotoxic effect on OTA-induced genotoxicity, by significantly reducing the number of structural aberrations in chromosomes and comet parameters like, % olive tail moment from 2.76 ± 0.02 to 0.56 ± 0.02 and % tail DNA from 56.23 ± 2.56 to 12.36 ± 0.56 as determined by comet assay. OTA-induced NO, TNF-α, IL-6, and IL-8 were significantly reduced in the quercetin pretreated samples indicating its anti-inflammatory role. Our results demonstrate for the first time that quercetin exerts a cytoprotective effect against OTA-induced oxidative stress, genotoxicity, and inflammation in lymphocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 855-865, 2016. © 2014 Wiley Periodicals, Inc.

  4. Compartmentalized oxidative stress in dopaminergic cell death induced by pesticides and complex I inhibitors: Distinct roles of superoxide anion and superoxide dismutases

    PubMed Central

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Pickett, Chillian; Sumin, Li; Jones, Jocelyn; Chen, Han; Webb, Brian; Choi, Jae; Zhou, You; Zimmerman, Matthew C.; Franco, Rodrigo

    2013-01-01

    The loss of dopaminergic neurons induced by the parkinsonian toxins paraquat, rotenone and 1-methyl-4-phenylpyridinium (MPP+) is associated with oxidative stress. However, controversial reports exist regarding the source/compartmentalization of reactive oxygen species (ROS) generation and its exact role in cell death. We aimed to determine in detail the role of superoxide anion (O2•−), oxidative stress and their subcellular compartmentalization in dopaminergic cell death induced by parkinsonian toxins. Oxidative stress and ROS formation was determined in the cytosol, intermembrane (IMS) and mitochondrial matrix compartments, using dihydroethidine derivatives, the redox sensor roGFP, as well as electron paramagnetic resonance spectroscopy. Paraquat induced an increase in ROS and oxidative stress in both the cytosol and mitochondrial matrix prior to cell death. MPP+ and rotenone primarily induced an increase in ROS and oxidative stress in the mitochondrial matrix. No oxidative stress was detected at the level of the IMS. In contrast to previous studies, overexpression of manganese superoxide dismutase (MnSOD) or copper/zinc SOD (CuZnSOD) had no effect on ROS steady state levels, lipid peroxidation, loss of mitochondrial membrane potential (ΔΨm) and dopaminergic cell death induced by MPP+ or rotenone. In contrast, paraquat-induced oxidative stress and cell death were selectively reduced by MnSOD overexpression, but not by CuZnSOD or manganese-porphyrins. However, MnSOD also failed to prevent ΔΨm loss. Finally, paraquat, but not MPP+ or rotenone, induced the transcriptional activation the redox-sensitive antioxidant response elements (ARE) and nuclear factor kappa-B (NF-κB). These results demonstrate a selective role of mitochondrial O2•− in dopaminergic cell death induced by paraquat, and show that toxicity induced by the complex I inhibitors rotenone and MPP+ does not depend directly on mitochondrial O2•− formation. PMID:23602909

  5. Indirect effects of radiation induce apoptosis and neuroinflammation in neuronal SH-SY5Y cells.

    PubMed

    Saeed, Yasmeen; Xie, Bingjie; Xu, Jin; Wang, Hailong; Hassan, Murtaza; Wang, Rui; Hong, Ma; Hong, Qing; Deng, Yulin

    2014-12-01

    Recent studies have evaluated the role of direct radiation exposure in neurodegenerative disorders; however, association among indirect effects of radiation and neurodegenerative diseases remains rarely discussed. The objective of this study was to estimate the relative risk of neurodegeneration due to direct and indirect effects of radiation. (60)Co gamma ray was used as source of direct radiation whereas irradiated cell conditioned medium (ICCM) was used to mimic the indirect effect of radiation. To determine the potency of ICCM to inhibit neuronal cells survival colony forming assay was performed. The role of ICCM to induce apoptosis in neuronal SH-SY5Y cells was estimated by TUNEL assay and Annexin V/PI assay. Level of oxidative stress and the concentration of inflammatory cytokines after exposing to direct radiation and ICCM were evaluated by ELISA method. Expression of key apoptotic protein following direct and indirect radiation exposure was investigated by western blot technique. Experimental data manifest that ICCM account loss of cell survival and increase apoptotic induction in neuronal SH-SY5Y cells that was dependent on time and dose. Moreover, ICCM stimulate significant release of inflammatory cytokines i.e., tumor necrosis factor TNF-alpha (P < 0.01), Interleukin-1 (IL-1, P < 0.001), and Interleukin-6 (IL-6, P < 0.001) in neuronal SH-SY5Y cells and elevate the level of oxidative stress (MDA, P < 0.01). Up-regulation of key apoptotic protein expression i.e., Bax, Bid, cytochrome C, caspase-8 and caspase-3 confirms the toxicity of ICCM to neuronal cells. This study provides the evidence that indirect effect of radiation can be as much damaging to neuronal cells as direct radiation exposure can be. Hence, more focused research on estimation risks of indirect effect of radiation to CNS at molecular level may help to reduce the uncertainty about cure and cause of several neurodegenerative disorders.

  6. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway.

    PubMed

    Wen, Di; An, Meiling; Gou, Hongyan; Liu, Xia; Liu, Li; Ma, Chunling; Cong, Bin

    2016-12-01

    As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (METH) abuse may lead to long-lasting abnormalities in brain structure and function. We found that pretreatment of cholecystokinin-8 (CCK-8) inhibited METH-induced brain cellular dopaminergic (DA) damage in the striatum and substantia nigra, and related behavioural deficits and hyperthermia. However, the mechanism of CCK-8 action on METH-induced toxicity is not clear. The aim of this study was to explore whether the possible protective effect of CCK-8 on METH-induced neurotoxicity involved anti-oxidative stress mechanisms. The subtypes of CCK receptors mediating the regulatory action of CCK-8 were also investigated. The present results revealed that CCK-8 dose-dependently inhibited METH-induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells. Pre-treatment of CCK-8 before METH stimulation significantly attenuated the generation of reactive oxygen species and NADPH oxidase activation in PC12 cells. In conclusion, our study demonstrated a protective effect of CCK-8 on METH-induced neurotoxicity in vitro and suggested that a possible mechanism of this action was dependent on the activation of the CCK2 receptor to reduce the neurotoxicity and oxidative stress induced by METH stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tetz, Lauren M., E-mail: ltetz@umich.edu; Cheng, Adrienne A.; Korte, Cassandra S.

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and thenmore » measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yanyan; Gao, Chao; Shi, Yanru

    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.more » 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.« less

  9. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

    PubMed Central

    Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

    2015-01-01

    Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

  10. Mechanisms of Mycotoxin-Induced Neurotoxicity through Oxidative Stress-Associated Pathways

    PubMed Central

    Doi, Kunio; Uetsuka, Koji

    2011-01-01

    Among many mycotoxins, T-2 toxin, macrocyclic trichothecenes, fumonisin B1 (FB1) and ochratochin A (OTA) are known to have the potential to induce neurotoxicity in rodent models. T-2 toxin induces neuronal cell apoptosis in the fetal and adult brain. Macrocyclic trichothecenes bring about neuronal cell apoptosis and inflammation in the olfactory epithelium and olfactory bulb. FB1 induces neuronal degeneration in the cerebral cortex, concurrent with disruption of de novo ceramide synthesis. OTA causes acute depletion of striatal dopamine and its metabolites, accompanying evidence of neuronal cell apoptosis in the substantia nigra, striatum and hippocampus. This paper reviews the mechanisms of neurotoxicity induced by these mycotoxins especially from the viewpoint of oxidative stress-associated pathways. PMID:21954354

  11. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

    PubMed Central

    2014-01-01

    Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

  12. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes.

    PubMed

    Zapolska-Downar, Danuta; Zapolski-Downar, Andrzej; Naruszewicz, Marek; Siennicka, Aldona; Krasnodebska, Barbara; Kołdziej, Blanka

    2002-11-01

    It is currently believed that oxidative stress and inflammation play a significant role in atherogenesis. Artichoke extract exhibits hypolipemic properties and contains numerous active substances with antioxidant properties in vitro. We have studied the influence of aqueous and ethanolic extracts from artichoke on intracellular oxidative stress stimulated by inflammatory mediators (TNFalpha and LPS) and ox-LDL in endothelial cells and monocytes. Oxidative stress which reflects the intracellular production of reactive oxygen species (ROS) was followed by measuring the oxidation of 2', 7'-dichlorofluorescin (DCFH) to 2', 7'-dichlorofluorescein (DCF). Agueous and ethanolic extracts from artichoke were found to inhibit basal and stimulated ROS production in endothelial cells and monocytes in dose dependent manner. In endothelial cells, the ethanolic extract (50 microg/ml) reduced ox-LDL-induced intracellular ROS production by 60% (p<0,001) while aqueous extract (50 microg/ml) by 43% (p<0,01). The ethanolic extract (50 microg/ml) reduced ox-LDL-induced intracellular ROS production in monocytes by 76% (p<0,01). Effective concentrations (25-100 microg/ml) were well below the cytotoxic levels of the extracts which started at 1 mg/ml as assessed by LDH leakage and trypan blue exclusion. Penetration of some active substances into the cells was necessary for inhibition to take place as juged from the effect of preincubation time. These results demonstrate that artichoke extracts have marked protective properties against oxidative stress induced by inflammatory mediators and ox-LDL in cultured endothelial cells and monocytes.

  13. Responsiveness of entomopathogenic fungi to menadione-induced oxidative stress.

    PubMed

    Azevedo, Rosana F F; Souza, Roberta K F; Braga, Gilberto U L; Rangel, Drauzio E N

    2014-12-01

    Entomopathogenic fungi are predisposed to ROS induced by heat and UV-A radiation when outside the insect host. When inside the host, they are subject to phagocytic cells that generate ROS to eliminate invading pathogens. The oxidative stress tolerance of the entomopathogenic fungi Aschersonia aleyrodis (ARSEF 430 and 10276), Aschersonia placenta (ARSEF 7637), Beauveria bassiana (ARSEF 252), Isaria fumosorosea (ARSEF 3889), Lecanicillium aphanocladii (ARSEF 6433), Metarhizium acridum (ARSEF 324), Metarhizium anisopliae (ARSEF 5749), Metarhizium brunneum (ARSEF 1187 and ARSEF 5626), Metarhizium robertsii (ARSEF 2575), Tolypocladium cylindrosporum (ARSEF 3392), Tolypocladium inflatum (ARSEF 4877), and Simplicillium lanosoniveum (ARSEF 6430 and ARSEF 6651) was studied based on conidial germination on a medium supplemented with menadione. Conidial germination was evaluated 24 h after inoculation on potato dextrose agar (PDA) (control) or PDA supplemented with menadione. The two Aschersonia species (ARSEF 430, 7637, and 10276) were the most susceptible fungi, followed by the two Tolypocladium species (ARSEF 3392 and 4877) and the M. acridum (ARSEF 324). Metarhizium brunneum (ARSEF 5626) and M. anisopliae (ARSEF 5749) were the most tolerant isolates with MIC 0.28 mM. All fungal isolates, except ARSEF 5626 and ARSEF 5749, were not able to germinate at 0.20 mM. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  14. Cosmic rays, gamma rays and synchrotron radiation from the Galaxy

    DOE PAGES

    Orlando, Elena

    2012-07-30

    Galactic cosmic rays (CR), interstellar gamma-ray emission and synchrotron radiation are related topics. CR electrons propagate in the Galaxy and interact with the interstellar medium, producing inverse-Compton emission measured in gamma rays and synchrotron emission measured in radio. I present an overview of the latest results with Fermi/LAT on the gamma-ray diffuse emission induced by CR nuclei and electrons. Then I focus on the recent complementary studies of the synchrotron emission in the light of the latest gamma-ray results. Relevant observables include spectral indices and their variations, using surveys over a wide range of radio frequencies. As a result, thismore » paper emphasizes the importance of using the parallel study of gamma rays and synchrotron radiation in order to constrain the low-energy interstellar CR electron spectrum, models of propagation of CRs, and magnetic fields.« less

  15. A Salt-Inducible Mn-Catalase (KatB) Protects Cyanobacterium from Oxidative Stress.

    PubMed

    Chakravarty, Dhiman; Banerjee, Manisha; Bihani, Subhash C; Ballal, Anand

    2016-02-01

    Catalases, enzymes that detoxify H2O2, are widely distributed in all phyla, including cyanobacteria. Unlike the heme-containing catalases, the physiological roles of Mn-catalases remain inadequately characterized. In the cyanobacterium Anabaena, pretreatment of cells with NaCl resulted in unusually enhanced tolerance to oxidative stress. On exposure to H2O2, the NaCl-treated Anabaena showed reduced formation of reactive oxygen species, peroxides, and oxidized proteins than the control cells (i.e. not treated with NaCl) exposed to H2O2. This protective effect correlated well with the substantial increase in production of KatB, a Mn-catalase. Addition of NaCl did not safeguard the katB mutant from H2O2, suggesting that KatB was indeed responsible for detoxifying the externally added H2O2. Moreover, Anabaena deficient in KatB was susceptible to oxidative effects of salinity stress. The katB gene was strongly induced in response to osmotic stress or desiccation. Promoter-gfp analysis showed katB to be expressed only in the vegetative cells but not in heterocysts. Biochemically, KatB was an efficient, robust catalase that remained active in the presence of high concentrations of NaCl. Our findings unravel the role of Mn-catalase in acclimatization to salt/oxidative stress and demonstrate that the oxidative stress resistance of an organism can be enhanced by a simple compound such as NaCl. © 2016 American Society of Plant Biologists. All Rights Reserved.

  16. Mangiferin induces cell death against rhabdomyosarcoma through sustained oxidative stress.

    PubMed

    Padma, Vishwanadha Vijaya; Kalaiselvi, Palanisamy; Yuvaraj, Rangasamy; Rabeeth, M

    2015-06-01

    Embryonic rhabdomyosarcoma (RD) is the most prevalent type of cancer among children. The present study aimed to investigate cell death induced by mangiferin in RD cells. The Inhibitory concentration (IC 50 ) value of mangiferin was determined by an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Cell death induced by mangiferin against RD cells was determined through lactate dehydrogenase and nitric oxide release, intracellular calcium levels, reactive oxygen species generation, antioxidant status, mitochondrial calcium level, and mitochondrial membrane potential. Furthermore, acridine orange/ethidium bromide staining was performed to determine early/late apoptotic event. Mangiferin induced cell death in RD cells with an IC 50 value of 70 μM. The cytotoxic effect was reflected in a dose-dependent increase in lactate dehydrogenase leakage and nitric oxide release during mangiferin treatment. Mangiferin caused dose dependent increase in reactive oxygen species generation, intracellular calcium levels with subsequent decrease in antioxidant status (catalase, superoxide dismutase, glutathione-S-transferase, and glutathione) and loss of mitochondrial membrane potential in RD cells. Further data from fluorescence microscopy suggest that mangiferin caused cell shrinkage and nuclear condensation along with the occurrence of a late event of apoptosis. Results of the present study shows that mangiferin can act as a promising chemopreventive agent against RD by inducing sustained oxidative stress.

  17. Targeted overexpression of mitochondrial catalase prevents radiation-induced cognitive dysfunction.

    PubMed

    Parihar, Vipan K; Allen, Barrett D; Tran, Katherine K; Chmielewski, Nicole N; Craver, Brianna M; Martirosian, Vahan; Morganti, Josh M; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M; Nelson, Gregory A; Allen, Antiño R; Limoli, Charles L

    2015-01-01

    Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain.

  18. Protective effect of cerium ion against ultraviolet B radiation-induced water stress in soybean seedlings.

    PubMed

    Mao, Chun Xia; Chen, Min Min; Wang, Lei; Zou, Hua; Liang, Chan Juan; Wang, Li Hong; Zhou, Qing

    2012-06-01

    Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants.

  19. Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.

    PubMed

    Saulsbury, Marilyn D; Heyliger, Simone O; Wang, Kaiyu; Johnson, Deadre J

    2009-05-02

    There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

  20. Gamma radiation effects on seed germination, growth and pigment content, and ESR study of induced free radicals in maize (Zea mays).

    PubMed

    Marcu, Delia; Damian, Grigore; Cosma, Constantin; Cristea, Victoria

    2013-09-01

    The effects of gamma radiation are investigated by studying plant germination, growth and development, and biochemical characteristics of maize. Maize dry seeds are exposed to a gamma source at doses ranging from 0.1 to 1 kGy. Our results show that the germination potential, expressed through the final germination percentage and the germination index, as well as the physiological parameters of maize seedlings (root and shoot lengths) decreased by increasing the irradiation dose. Moreover, plants derived from seeds exposed at higher doses (≤0.5 kGy) did not survive more than 10 days. Biochemical differences based on photosynthetic pigment (chlorophyll a, chlorophyll b, carotenoids) content revealed an inversely proportional relationship to doses of exposure. Furthermore, the concentration of chlorophyll a was higher than chlorophyll b in both irradiated and non-irradiated seedlings. Electron spin resonance spectroscopy used to evaluate the amount of free radicals induced by gamma ray treatment demonstrates that the relative concentration of radiation-induced free radicals depends linearly on the absorbed doses.

  1. Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine–Induced Chronic Renal Failure in Rats

    PubMed Central

    Ali, Badreldin H.; Al-Husseni, Isehaq; Beegam, Sumyia; Al-Shukaili, Ahmed; Nemmar, Abderrahim; Schierling, Simone; Queisser, Nina; Schupp, Nicole

    2013-01-01

    Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in chronic renal failure (CRF) in rats. The aim of this work was to study the role of inflammation and oxidative stress in adenine-induced CRF and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in feed (0.75%, w/w), GA in drinking water (15%, w/v) and adenine+GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration). In addition, the concentrations of the pro-inflammatory cytokine TNF-α and the oxidative stress markers glutathione and superoxide dismutase, renal apoptosis, superoxide formation and DNA double strand break frequency, detected by immunohistochemistry for γ-H2AX, were measured. Adenine significantly increased the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance and induced significant increases in the concentration of the measured inflammatory mediators. Further, it caused oxidative stress and DNA damage. Treatment with GA significantly ameliorated these actions. The mechanism of the reported salutary effect of GA in adenine-induced CRF is associated with mitigation of the adenine-induced inflammation and generation of free radicals. PMID:23383316

  2. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    PubMed

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  3. Methane alleviates copper-induced seed germination inhibition and oxidative stress in Medicago sativa.

    PubMed

    Samma, Muhammad Kaleem; Zhou, Heng; Cui, Weiti; Zhu, Kaikai; Zhang, Jing; Shen, Wenbiao

    2017-02-01

    Recent results discovered the protective roles of methane (CH 4 ) against oxidative stress in animals. However, the possible physiological roles of CH 4 in plants are still unknown. By using physiological, histochemical and molecular approaches, the beneficial role of CH 4 in germinating alfalfa seeds upon copper (Cu) stress was evaluated. Endogenous production of CH 4 was significantly increased in Cu-stressed alfalfa seeds, which was mimicked by 0.39 mM CH 4 . The pretreatment with CH 4 significantly alleviated the inhibition of seed germination and seedling growth induced by Cu stress. Cu accumulation was obviously blocked as well. Meanwhile, α/β amylase activities and sugar contents were increased, all of which were consistent with the alleviation of seed germination inhibition triggered by CH 4 . The Cu-triggered oxidative stress was also mitigated, which was confirmed by the decrease of lipid peroxidation and reduction of Cu-induced loss of plasma membrane integrity in CH 4 -pretreated alfalfa seedlings. The results of antioxidant enzymes, including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (POD) total or isozymatic activities, and corresponding transcripts (APX1/2, Cu/Zn SOD and Mn-SOD), indicated that CH 4 reestablished cellular redox homeostasis. Further, Cu-induced proline accumulation was partly impaired by CH 4 , which was supported by the alternation of proline metabolism. Together, these results indicated that CH 4 performs an advantageous effect on the alleviation of seed germination inhibition caused by Cu stress, and reestablishment of redox homeostasis mainly via increasing antioxidant defence.

  4. Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

    NASA Technical Reports Server (NTRS)

    Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

    2017-01-01

    Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

  5. Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays.

    PubMed

    Lee, S H; Jo, S H; Lee, S M; Koh, H J; Song, H; Park, J W; Lee, W H; Huh, T L

    2004-09-01

    To investigate the regulation of NADPH-producing isocitrate dehydrogenase (ICDH) in cytosol (IDPc) and mitochondria (IDPm) upon gamma-ray irradiation, and the roles of IDPc and IDPm in the protection against cellular damage induced by gamma-ray irradiation. Changes of IDPc and IDPm proteins upon gamma-ray irradiation to NIH3T3 cells were analysed by immunoblotting. To increase or decrease the expression of IDPc or IDPm, NIH3T3 cells were stably transfected with mouse IDPc or IDPm cDNA in either the sense or the antisense direction. The transfected cells with either increased or decreased IDPc or IDPm were exposed to gamma-rays, and the levels of reactive oxygen species generation, protein oxidation and lipid peroxidation were measured. Both IDPc and IDPm activities were induced by gamma-ray in NIH3T3 cells. Cells with decreased expression of IDPc or IDPm had elevated reactive oxygen species generation, lipid peroxidation and protein oxidation. Conversely, overproduction of IDPc or IDPm protein partially protected the cells from oxidative damage induced by gamma-ray irradiation. The protective role of IDPc and IDPm against gamma-ray-induced cellular damage can be attributed to elevated NADPH, reducing equivalents needed for recycling reduced glutathione in the cytosol and mitochondria. Thus, a primary biological function of the ICDHs may be production of NADPH, which is a prerequisite for some cellular defence systems against oxidative damage.

  6. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ

    PubMed Central

    Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F.; Kanthasamy, Anumantha G.; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2014-01-01

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (–/–) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (–/–) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (–/–) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. PMID:22512859

  7. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ.

    PubMed

    Shin, Eun-Joo; Duong, Chu Xuan; Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F; Kanthasamy, Anumantha G; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2012-06-15

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (-/-) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (-/-) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (-/-) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

    PubMed

    M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

    2017-10-01

    The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

  9. Microscopic observations of X-ray and gamma-ray induced decomposition of ammonium perchlorate crystals

    NASA Technical Reports Server (NTRS)

    Herley, P. J.; Levy, P. W.

    1972-01-01

    The X-ray and gamma-ray induced decomposition of ammonium perchlorate was studied by optical, transmission, and scanning electron microscopy. This material is a commonly used oxidizer in solid propellents which could be employed in deep-space probes, and where they will be subjected to a variety of radiations for as long as ten years. In some respects the radiation-induced damage closely resembles the effects produced by thermal decomposition, but in other respects the results differ markedly. Similar radiation and thermal effects include the following: (1) irregular or ill-defined circular etch pits are formed in both cases; (2) approximately the same size pits are produced; (3) the pit density is similar; (4) the c face is considerably more reactive than the m face; and (5) most importantly, many of the etch pits are aligned in crystallographic directions which are the same for thermal or radiolytic decomposition. Thus, dislocations play an important role in the radiolytic decomposition process.

  10. DNA damage in cells exhibiting radiation-induced genomic instability

    DOE PAGES

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  11. Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: modulation of Nrf-2 and COX-2 expression.

    PubMed

    Qin, Wang-Sen; Deng, Yu-Hui; Cui, Fa-Cai

    2016-08-01

    Acrolein (2-propenal) is a reactive α, β-unsaturated aldehyde which causes a health hazard to humans. The present study focused on determining the protection offered by sulforaphane against acrolein-induced damage in peripheral blood mononuclear cells (PBMC). Acrolein-induced oxidative stress was determined through evaluating the levels of reactive oxygen species, protein carbonyl and sulfhydryl content, thiobarbituric acid reactive species, total oxidant status and antioxidant status (total antioxidant capacity, glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activity). Also, Nrf-2 expression levels were determined using western blot analysis. Acrolein-induced inflammation was determined through analyzing expression of cyclooxygenase-2 by western blot and PGE2 levels by ELISA. The protection offered by sulforaphane against acrolein-induced oxidative stress and inflammation was studied. Acrolein showed a significant (p < 0.001) increase in the levels of oxidative stress parameters and down-regulated Nrf-2 expression. Acrolein-induced inflammation was observed through upregulation (p < 0.001) of COX-2 and PGE2 levels. Pretreatment with sulforaphane enhanced the antioxidant status through upregulating Nrf-2 expression (p < 0.001) in PBMC. Acrolein-induced inflammation was significantly inhibited through suppression of COX-2 (p < 0.001) and PGE2 levels (p < 0.001). The present study provides clear evidence that pre-treatment with sulforaphane completely restored the antioxidant status and prevented inflammatory responses mediated by acrolein. Thus the protection offered by sulforaphane against acrolein-induced damage in PBMC is attributed to its anti-oxidant and anti-inflammatory potential.

  12. Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney.

    PubMed

    Arany, Istvan; Hall, Samuel; Reed, Dustin K; Reed, Caitlyn T; Dixit, Mehul

    2016-07-01

    Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 μg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity-associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese

  13. Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

    PubMed Central

    Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao

    2017-01-01

    Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF-α, IL-1β, MIP-1α, and MIP-2) along with their master regulator NFκB. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries. PMID:28828145

  14. Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy.

    PubMed

    Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao; Hao, Enkui

    2017-01-01

    Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF- α , IL-1 β , MIP-1 α , and MIP-2) along with their master regulator NF κ B. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries.

  15. Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: a potentially lethal complication

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lewin, A.A.; Serago, C.F.; Schwade, J.G.

    1984-10-01

    New multi-programmable pacemakers frequently employ complementary metal oxide semiconductors (CMOS). This circuitry appears more sensitive to the effects of ionizing radiation when compared to the semiconductor circuits used in older pacemakers. A case of radiation induced runaway pacemaker in a CMOS device is described. Because of this and other recent reports of radiation therapy-induced CMOS type pacemaker failure, these pacemakers should not be irradiated. If necessary, the pacemaker can be shielded or moved to a site which can be shielded before institution of radiation therapy. This is done to prevent damage to the CMOS circuit and the life threatening arrythmiasmore » which may result from such damage.« less

  16. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages.

    PubMed

    Lara-Guzmán, Oscar J; Gil-Izquierdo, Ángel; Medina, Sonia; Osorio, Edison; Álvarez-Quintero, Rafael; Zuluaga, Natalia; Oger, Camille; Galano, Jean-Marie; Durand, Thierry; Muñoz-Durango, Katalina

    2018-05-01

    Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and significantly induced in macrophages stimulated with oxLDL. Importantly, the main metabolites responsible for the THP1-macrophage response to oxLDL exposure were the oxidative stress markers 5-epi-5-F 2t -IsoP, 15-E 1t -IsoP, 8-F 3t -IsoP and 15-keto-15-F 2t -IsoP as well as inflammatory markers PGDM, 17-trans-PGF 3α , and 11β-PGF 2α , all of which are reported here, for the first time, to function in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage pathway mediated by anti-inflammatory PGs (PGE 1 and 17-trans-PGF 3α ) was also identified, suggesting a response to oxLDL-induced injury. In conclusion, when THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers related to oxidative stress and inflammation was triggered. This work contributes to our understanding of initial atherogenic events mediated by oxLDL-macrophage interactions and helps to generate new approaches for their modulation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. A combination of He-Ne laser irradiation and exogenous NO application efficiently protect wheat seedling from oxidative stress caused by elevated UV-B stress.

    PubMed

    Li, Yongfeng; Gao, Limei; Han, Rong

    2016-12-01

    The elevated ultraviolet-B (UV-B) stress induces the accumulation of a variety of intracellular reactive oxygen species (ROS), which seems to cause oxidative stress for plants. To date, very little work has been done to evaluate the biological effects of a combined treatment with He-Ne laser irradiation and exogenous nitric oxide (NO) application on oxidative stress resulting from UV-B radiation. Thus, our study investigated the effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative damages in wheat seedlings under elevated UV-B stress. Our data showed that the reductions in ROS levels, membrane damage parameters, while the increments in antioxidant contents and antioxidant enzyme activity caused by a combination with He-Ne laser and exogenous NO treatment were greater than those of each individual treatment. Furthermore, these treatments had a similar effect on transcriptional activities of plant antioxidant enzymes. This implied that the protective effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative stress resulting from UV-B radiation was more efficient than each individual treatment with He-Ne laser or NO molecule. Our findings might provide beneficial theoretical references for identifying some effective new pathways for plant UV-B protection.

  18. Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle.

    PubMed

    Zaccaria, Marco; Ludovici, Matteo; Sanzani, Simona Marianna; Ippolito, Antonio; Cigliano, Riccardo Aiese; Sanseverino, Walter; Scarpari, Marzia; Scala, Valeria; Fanelli, Corrado; Reverberi, Massimo

    2015-10-23

    Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B₁, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile) to transcriptional analysis (RNA-seq). There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies.

  19. Hepatoprotective properties of kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis.

    PubMed

    Bhattacharya, Semantee; Gachhui, Ratan; Sil, Parames C

    2011-06-01

    Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. Recent studies have suggested that KT prevents paracetamol and carbon tetrachloride-induced hepatotoxicity. We investigated the beneficial role of KT was against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in murine hepatocytes. TBHP is a well known reactive oxygen species (ROS) inducer, and it induces oxidative stress in organ pathophysiology. In our experiments, TBHP caused a reduction in cell viability, enhanced the membrane leakage and disturbed the intra-cellular antioxidant machineries while simultaneous treatment of the cells with KT and this ROS inducer maintained membrane integrity and prevented the alterations in the cellular antioxidant status. These findings led us to explore the detailed molecular mechanisms involved in the protective effect of KT. TBHP introduced apoptosis as the primary phenomena of cell death as evidenced by flow cytometric analyses. In addition, ROS generation, changes in the mitochondrial membrane potential, cytochrome c release, activation of caspases (3 and 9) and Apaf-1 were detected confirming involvement of mitochondrial pathway in this pathophysiology. Simultaneous treatment of KT with TBHP, on the other hand, protected the cells against oxidative injury and maintained their normal physiology. In conclusion, KT was found to modulate the oxidative stress induced apoptosis in murine hepatocytes probably due to its antioxidant activity and functioning via mitochondria dependent pathways and could be beneficial against liver diseases, where oxidative stress is known to play a crucial role. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Cyanidin-3-glucoside attenuates angiotensin II-induced oxidative stress and inflammation in vascular endothelial cells.

    PubMed

    Sivasinprasasn, Sivanan; Pantan, Rungusa; Thummayot, Sarinthorn; Tocharus, Jiraporn; Suksamrarn, Apichart; Tocharus, Chainarong

    2016-10-28

    Angiotensin II (Ang II) causes oxidative stress and vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of inflammatory cardiovascular diseases such as atherosclerosis. Therefore, interventions of oxidative stress and inflammation may contribute to the reduction of cardiovascular diseases. Cyanidin-3-glucoside (C3G) plays a role in the prevention of oxidative damage in several diseases. Here, we investigated the effect of C3G on Ang II-induced oxidative stress and vascular inflammation in human endothelial cells (EA.hy926). C3G dose-dependently suppressed the free radicals and inhibited the nuclear factor-kappa B (NF-κB) signaling pathway by protecting the degradation of inhibitor of kappa B-alpha (IκB-α), inhibiting the expression and translocation of NF-κB into the nucleus through the down-regulation of NF-κB p65 and reducing the expression of inducible nitric oxide synthase (iNOS). Pretreatment with C3G not only prohibited the NF-κB signaling pathway but also promoted the activity of the nuclear erythroid-related factor 2 (Nrf2) signaling pathway through the upregulation of endogenous antioxidant enzymes. Particularly, we observed that C3G significantly enhanced the production of superoxide dismutase (SOD) and induced the expression of heme oxygenase (HO-1). Our findings confirm that C3G can protect against vascular endothelial cell inflammation induced by AngII. C3G may represent a promising dietary supplement for the prevention of inflammation, thereby decreasing the risk for the development of atherosclerosis. Copyright © 2016. Published by Elsevier Ireland Ltd.

  1. Ciprofloxacin induces oxidative stress in duckweed (Lemna minor L.): Implications for energy metabolism and antibiotic-uptake ability.

    PubMed

    Gomes, Marcelo Pedrosa; Gonçalves, Cíntia Almeida; de Brito, Júlio César Moreira; Souza, Amanda Miranda; da Silva Cruz, Fernanda Vieira; Bicalho, Elisa Monteze; Figueredo, Cleber Cunha; Garcia, Queila Souza

    2017-04-15

    We investigate the physiological responses and antibiotic-uptake capacity of Lemna minor exposed to ciprofloxacin. Ciprofloxacin (Cipro) induced toxic effects and hormesis in plants by significantly modifying photosynthesis and respiration pathways. A toxic effect was induced by a concentration ≥1.05mg ciprofloxacin l -1 while hormesis occurs at the lowest concentration studied (0.75mg ciprofloxacin l -1 ). By impairing normal electron flow in the respiratory electron transport chain, ciprofloxacin induces hydrogen peroxide (H 2 O 2 ) production. The ability of plants to cope with H 2 O 2 accumulation using antioxidant systems resulted in stimulation/deleterious effects to photosynthesis by Cipro. Cipro-induced oxidative stress was also associated with the ability of L. minor plants to uptake the antibiotic and, therefore, with plant-uptake capacity. Our results indicate that instead of being a photosystem II binding molecule, Cipro induces oxidative stress by targeting the mitochondrial ETC, which would explain the observed effects of the antibiotic on non-target eukaryotic organisms. The selection of plants species with a high capacity to tolerate oxidative stress may constitute a strategy to be used in Cipro-remediation programs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

    PubMed

    Mamalis, A; Fiadorchanka, N; Adams, L; Serravallo, M; Heilman, E; Siegel, D; Brody, N; Jagdeo, J

    2014-05-01

    Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation.

  3. Effects of tempol and redox-cycling nitroxides in models of oxidative stress

    PubMed Central

    Wilcox, Christopher S.

    2010-01-01

    Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia. PMID:20153367

  4. Blue light irradiation-induced oxidative stress in vivo via ROS generation in rat gingival tissue.

    PubMed

    Yoshida, Ayaka; Shiotsu-Ogura, Yukako; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Toyama, Toshizo; Yoshino, Fumihiko

    2015-10-01

    It has been reported that oxidative stress with reactive oxygen species (ROS) generation is induced by blue light irradiation to a living body. Only limited research has been reported in dental field on the dangers of blue light, mostly focusing on cytotoxicity associated with heat injury of dental pulp. We thus performed an in vivo study on oral tissue exposed to blue light. ROS generated upon blue light irradiation of flavin adenine dinucleotide were measured by electron spin resonance spectroscopy. After blue light irradiation, the palatal gingiva of Wistar rats were isolated. Collected samples were subjected to biochemical analysis of lipid peroxidation and glutathione. Singlet oxygen was generated by blue light irradiation, but was significantly quenched in an N-acetyl-L-cysteine (NAC) concentration-dependent manner. Blue light significantly accelerated oxidative stress and increased the oxidized glutathione levels in gingival tissue. These effects were also inhibited by NAC pre-administration. The results suggest that blue light irradiation at clinical levels of tooth bleaching treatment may enhance lipid peroxidation by the induction of oxidative stress and the consumption of a significant amount of intracellular glutathione. In addition, NAC might be an effective supplement for the protection of oral tissues against blue light irradiation-induced oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Evaluation of the Potential of Brazilian Propolis against UV-Induced Oxidative Stress

    PubMed Central

    Fonseca, Yris Maria; Marquele-Oliveira, Franciane; Vicentini, Fabiana T. M. C.; Furtado, Niege Araçari J. C.; Sousa, João Paulo B.; Lucisano-Valim, Yara M.; Fonseca, Maria José Vieira

    2011-01-01

    This study investigated the potential use of topically and orally administered propolis extracts to prevent UV irradiation-induced oxidative stress in skin. The results illustrated that green propolis extract (GPE) contained greater amounts of polyphenols, coumaric acid, drupanin, baccharin and artepillin C than did brown propolis extract (BPE). GPE showed higher antioxidant activity than BPE when the IC50 (concentration that caused 50% inhibition) values were compared. Interesting, the oral treatment of hairless mice demonstrated a recovery of 30.0% for GPE and 22.8% for BPE with respect to UV irradiation-induced GSH depletion. The topical pretreatment of animals with both propolis extract solutions recovered around 14.0% of the depleted GSH. However, the employed treatments did not inhibit the increase of cutaneous proteinase secretion/activity caused by irradiation. These findings indicate that despite differences in composition and antioxidant properties, GPE and BPE both successfully prevent UV-induced GSH depletion in vivo and are both promising antioxidant systems against oxidative stress in skin. Based on these findings, complementary studies should be performed to enhance our understanding of the protective effects of propolis extracts in skin. PMID:20953396

  6. Gamma radiation field intensity meter

    DOEpatents

    Thacker, Louis H.

    1994-01-01

    A gamma radiation intensity meter measures dose rate of a radiation field. The gamma radiation intensity meter includes a tritium battery emitting beta rays generating a current which is essentially constant. Dose rate is correlated to an amount of movement of an electroscope element charged by the tritium battery. Ionizing radiation decreases the voltage at the element and causes movement. A bleed resistor is coupled between the electroscope support element or electrode and the ionization chamber wall electrode.

  7. Gamma radiation field intensity meter

    DOEpatents

    Thacker, Louis H.

    1995-01-01

    A gamma radiation intensity meter measures dose rate of a radiation field. The gamma radiation intensity meter includes a tritium battery emitting beta rays generating a current which is essentially constant. Dose rate is correlated to an amount of movement of an electroscope element charged by the tritium battery. Ionizing radiation decreases the voltage at the element and causes movement. A bleed resistor is coupled between the electroscope support element or electrode and the ionization chamber wall electrode.

  8. Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development.

    PubMed

    Al-Gubory, Kaïs H

    2014-07-01

    Developmental toxicity caused by exposure to a mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviours, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase susceptibility of offspring to diseases. There is evidence to suggest that the developmental toxicological mechanisms of chemicals and lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased ROS generation overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Data on the involvement of oxidative stress in the mechanism of developmental toxicity following exposure to environmental pollutants are reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on post-natal development and health outcomes. Developmental toxicity caused by exposure to mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviors, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase the susceptibility of offspring to development complications and diseases. There is evidence to suggest that the developmental toxicological mechanisms

  9. Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

    PubMed

    Han, C H; Guan, Z B; Zhang, P X; Fang, H L; Li, L; Zhang, H M; Zhou, F J; Mao, Y F; Liu, W W

    2018-01-15

    Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI. Copyright © 2017. Published by Elsevier Inc.

  10. Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction.

    PubMed

    Lord, Kevin C; Shenouda, Sylvia K; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A; Varner, Kurt J

    2010-07-01

    Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Echocardiography and Millar pressure-volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased -dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction.

  11. Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

    PubMed Central

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

    2010-01-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

  12. The high-fat diet induces myocardial fibrosis in the metabolically healthy obese minipigs-The role of ER stress and oxidative stress.

    PubMed

    Li, Sin-Jin; Liu, Chia-Hsin; Chu, Hsien-Pin; Mersmann, Harry J; Ding, Shih-Torng; Chu, Chun-Han; Wang, Chia-Yu; Chen, Ching-Yi

    2017-06-01

    The cellular mechanisms of obesity-induced cardiomyopathy are multiple and not completely elucidated. The objective of this study was to differentiate two obesity-associated cardiomyopathy miniature pig models: one with the metabolic syndrome (MetS), and one with a metabolically healthy obesity (MHO). The cellular responses during the development of obesity-induced cardiomyopathy were investigated. Five-month-old Lee-Sung (MetS) and Lanyu (MHO) minipigs were made obese by feeding a high-fat diet (HFD) for 6 months. Obese pigs exhibited a greater heart weight than control pigs. Interstitial and perivascular fibrosis developed in the myocardium of obese pigs. The HFD induced cardiac lipid accumulation and oxidative stress and also decreased the antioxidant defense in MetS pigs. This diet activated oxidative stress without changing cardiac antioxidant defense and lipid content in MHO pigs. The HFD upregulated the expression of Grp94, CHOP, caspase 12, p62, and LC3II, and increased the ratio of LC3II to LC3I in the left ventricle (LV) of MetS pigs. Compared to obese MetS pigs, less Grp94 and elevated CHOP expression was found in the obese MHO heart. The HFD did not change the ratio of LC3II to LC3I and p62 expression in obese MHO pigs. The obese MetS pigs had an extensive and greater inflammatory response in the plasma than the obese MHO pigs, which had a lesser and milder inflammation. Oxidative stress and ER stress were involved in the progression of MHO-related cardiomyopathy. Inflammation, autophagy, ER stress, oxidative stress, and lipotoxicity participated in the pathological mechanism of MetS-related cardiomyopathy. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells

    PubMed Central

    Shahid, Muhammad; Gao, Jian; Zhou, Yanan; Liu, Gang; Ali, Tariq; Deng, Youtian; Sabir, Naveed; Su, Jingliang; Han, Bo

    2017-01-01

    Bovine protothecal mastitis results in considerable economic losses worldwide. However, Prototheca zopfii induced morphological alterations and oxidative stress in bovine mammary epithelial cells (bMECs) is not comprehensively studied yet. Therefore, the aim of this current study was to investigate the P. zopfii induced pathomorphological changes, oxidative stress and apoptosis in bMECs. Oxidative stress was assessed by evaluating catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) contents and lactate dehydrogenase (LDH) activity, while ROS generation and apoptosis was measured by confocal laser scanning microscopy. The results revealed that infection of P. zopfii genotype II (GTII) significantly changed bMECs morphology, increased apoptotic rate and MDA contents at 12 h (p < 0.05) and 24 h (p < 0.01) in comparison with control group, in time-dependent manner. LDH activity and ROS generation was also increased (p < 0.01) at 12 h and 24 h. However, SOD and CAT contents in bMECs infected with GTII were decreased (p < 0.05) at 12 h, while GPx (p < 0.01), SOD (p < 0.05) and CAT (p < 0.01) levels were reduced at 24 h. In case of GTI, only CAT and GPx activities were significantly decreased when the duration prolonged to 24 h but lesser than GTII. This suggested that GTII has more devastating pathogenic effects in bMECs, and the findings of this study concluded that GTII induced apoptosis and oxidative stress in bMECs via the imbalance of oxidant and antioxidant defenses as well as the production of intracellular ROS. PMID:28404882

  14. Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells.

    PubMed

    Shahid, Muhammad; Gao, Jian; Zhou, Yanan; Liu, Gang; Ali, Tariq; Deng, Youtian; Sabir, Naveed; Su, Jingliang; Han, Bo

    2017-05-09

    Bovine protothecal mastitis results in considerable economic losses worldwide. However, Prototheca zopfii induced morphological alterations and oxidative stress in bovine mammary epithelial cells (bMECs) is not comprehensively studied yet. Therefore, the aim of this current study was to investigate the P. zopfii induced pathomorphological changes, oxidative stress and apoptosis in bMECs. Oxidative stress was assessed by evaluating catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) contents and lactate dehydrogenase (LDH) activity, while ROS generation and apoptosis was measured by confocal laser scanning microscopy. The results revealed that infection of P. zopfii genotype II (GTII) significantly changed bMECs morphology, increased apoptotic rate and MDA contents at 12 h (p < 0.05) and 24 h (p < 0.01) in comparison with control group, in time-dependent manner. LDH activity and ROS generation was also increased (p < 0.01) at 12 h and 24 h. However, SOD and CAT contents in bMECs infected with GTII were decreased (p < 0.05) at 12 h, while GPx (p < 0.01), SOD (p < 0.05) and CAT (p < 0.01) levels were reduced at 24 h. In case of GTI, only CAT and GPx activities were significantly decreased when the duration prolonged to 24 h but lesser than GTII. This suggested that GTII has more devastating pathogenic effects in bMECs, and the findings of this study concluded that GTII induced apoptosis and oxidative stress in bMECs via the imbalance of oxidant and antioxidant defenses as well as the production of intracellular ROS.

  15. Effect of gamma radiation on the stability of UV replicated composite mirrors

    NASA Astrophysics Data System (ADS)

    Zaldivar, Rafael J.; Kim, Hyun I.; Ferrelli, Geena L.

    2018-04-01

    Composite replicated mirrors are gaining increasing attention for space-based applications due to their lower density, tailorable mechanical properties, and rapid manufacturing times over state-of-the-art glass mirrors. Ultraviolet (UV)-cured mirrors provide a route by which high-quality mirrors can be manufactured at relatively low processing temperatures that minimize residual stresses. The successful utilization of these mirrors requires nanometer scale dimensional stability after both thermal cycling and hygrothermal exposure. We investigate the effect of gamma irradiation as a process to improve the stability of UV replicated mirrors. Gamma radiation exposure was shown to increase the cure state of these mirrors as evidenced by an increase in modulus, glass transition temperature, and the thermal degradation behavior with dosage. Gas chromatography-mass spectroscopy also showed evidence of consumption of the primary monomers and initiation of the photosensitive agent with gamma exposure. The gamma-exposed mirrors exhibited significant improvement in stability even after multiple thermal cycling in comparison with nonirradiated composite mirrors. Though improvements in the cure state contribute to the overall stability, the radiation dosage was also shown to reduce the film stress of the mirror by over 80% as evidenced using Stoney replicated specimens. This reduction in residual stress is encouraging considering the utilization of these structures for space applications. This paper shows that replicated composite mirrors are a viable alternative to conventional optical structures.

  16. Nanomaterial induction of oxidative stress in lung epithelial cells and macrophages

    NASA Astrophysics Data System (ADS)

    Wang, Lin; Pal, Anoop K.; Isaacs, Jacqueline A.; Bello, Dhimiter; Carrier, Rebecca L.

    2014-09-01

    Oxidative stress in the lung epithelial A549 cells and macrophages J774A.1 due to contact with commercially important nanomaterials [i.e., nano-silver (nAg), nano-alumina (nAl2O3), single-wall carbon nanotubes (CNT), and nano-titanium oxide anatase (nTiO2)] was evaluated. Nanomaterial-induced intracellular oxidative stress was analyzed by both H2DCFDA fluorescein probe and GSH depletion, extracellular oxidative stress was assessed by H2HFF fluorescein probes, and the secretion of chemokine IL-8 by A549 cells due to elevation of cellular oxidative stress was also monitored, in order to provide a comprehensive in vitro study on nanomaterial-induced oxidative stress in lung. In addition, results from this study were also compared with an acellular "ferric reducing ability of serum" (FRAS) assay and a prokaryotic cell-based assay in evaluating oxidative damage caused by the same set of nanomaterials, for comparison purposes. In general, it was found that nanomaterial-induced oxidative stress is highly cell-type dependent. In A549 lung epithelial cells, nAg appeared to induce highest level of oxidative stress and cell death followed by CNT, nTiO2, and nAl2O3. Different biological oxidative damage (BOD) assays' (i.e., H2DCFA, GSH, and IL-8 release) results generally agreed with each other, and the same trends of nanomaterial-induced BOD were also observed in acellular FRAS and prokaryotic E. coli K12-based assay. In macrophage J774A.1 cells, nAl2O3 and nTiO2 appeared to induce highest levels of oxidative stress. These results suggest that epithelial and macrophage cell models may provide complimentary information when conducting cell-based assays to evaluate nanomaterial-induced oxidative damage in lung.

  17. Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

    2013-11-01

    Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

  18. Acoustic-radiation stress in solids. I - Theory

    NASA Technical Reports Server (NTRS)

    Cantrell, J. H., Jr.

    1984-01-01

    The general case of acoustic-radiation stress associated with quasi-compressional and quasi-shear waves propagating in infinite and semiinfinite lossless solids of arbitrary crystalline symmetry is studied. The Boussinesq radiation stress is defined and found to depend directly on an acoustic nonlinearity parameter which characterizes the radiation-induced static strain, a stress-generalized nonlinearity parameter which characterizes the stress nonlinearity, and the energy density of the propagating wave. Application of the Boltzmann-Ehrenfest principle of adiabatic invariance to a self-constrained system described by the nonlinear equations of motion allows the acoustic-radiation-induced static strain to be identified with a self-constrained variation in the time-averaged product of the internal energy density and displacement gradient. The time-averaged product is scaled by the acoustic nonlinearity parameter and represents the first-order nonlinearity in the virial theorem. Finally, the relationship between the Boussinesq and the Cauchy radiation stress is obtained in a closed three-dimensional form.

  19. The ameliorative effect of thymol against hydrocortisone-induced hepatic oxidative stress injury in adult male rats.

    PubMed

    Aboelwafa, Hanaa R; Yousef, Hany N

    2015-08-01

    The aim of the present study was to investigate whether hydrocortisone induces oxidative stress in hepatocytes and to evaluate the possible ameliorative effect of thymol against such hepatic injury. Twenty-four adult male rats were divided into control, thymol, hydrocortisone, and hydrocortisone+thymol groups. The 4 groups were treated daily for 15 days. Hydrocortisone significantly induced oxidative stress in the liver tissues, marked by increased serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total oxidative capacity (TOC), and tumor necrosis factor-alpha (TNF-α) accompanied by marked decline of serum levels of total protein, albumin, and total antioxidant capacity (TAC). Also, marked elevation in the levels of the thiobarbituric acid reactive substances (TBARS) and TNF-α, beside significant decrease in the level of glutathione (GSH) in hepatic tissues were recorded. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal hepatic architecture, in addition to ultrastructural alterations represented by degenerative features covering almost all the cytoplasmic organelles of the hepatocytes. Supplementation of hydrocortisone-treated rats with thymol reversed most of the biochemical, histological, and ultrastructural alterations. The results of our study confirm that thymol has strong ameliorative effect against hydrocortisone-induced oxidative stress injury in hepatic tissues.

  20. Heavy metals induce oxidative stress and trigger oxidative stress-mediated heat shock protein (hsp) modulation in the intertidal copepod Tigriopus japonicus.

    PubMed

    Kim, Bo-Mi; Rhee, Jae-Sung; Jeong, Chang-Bum; Seo, Jung Soo; Park, Gyung Soo; Lee, Young-Mi; Lee, Jae-Seong

    2014-11-01

    Heat shock proteins (hsps) are induced by a wide range of environmental stressors including heavy metals in aquatic organisms. However, the effect of heavy metals on zooplankton at the molecular level remains still unclear. In this study, we measured the intracellular reactive oxygen species (ROS) level and the antioxidant enzyme activities for 96 h after exposure to five heavy metals: arsenic (As), cadmium (Cd), copper (Cu), silver (Ag), and zinc (Zn) in the intertidal copepod Tigriopus japonicus. Activities of the antioxidant enzymes were highly elevated in metal-exposed copepods, indicating that heavy metals can induce oxidative stress by generating ROS, and stimulate the involvement of antioxidant enzymes as cellular defense mechanisms. Subsequently, transcriptional changes in hsp gene families were further investigated in the metal-exposed groups for 96 h. The ROS level and glutathione (GSH) content were significantly increased in Ag-, As-, and Cu-exposed copepods, while they were only slightly elevated in Cd- and Zn-exposed groups. Based on the numbers of significantly modulated hsp genes and their expression levels for 96 h, we measured the effect of heavy metals to stress genes of T. japonicus in the following order: Cu > Zn > Ag > As > Cd, implying that Cu acts as a stronger oxidative stress inducer than other heavy metals. Of them, the expression of hsp20 and hsp70 genes was substantially modulated by exposure to heavy metals, indicating that these genes would provide a sensitive molecular biomarker for aquatic monitoring of heavy metal pollution. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Butyric acid induces apoptosis via oxidative stress in Jurkat T-cells.

    PubMed

    Kurita-Ochiai, T; Ochiai, K

    2010-07-01

    Reactive oxygen species (ROS) are essential for the induction of T-cell apoptosis by butyric acid, an extracellular metabolite of periodontopathic bacteria. To determine the involvement of oxidative stress in apoptosis pathways, we investigated the contribution of ROS in mitochondrial signaling pathways, death-receptor-initiated signaling pathway, and endoplasmic reticulum stress in butyric-acid-induced T-cell apoptosis. N-acetyl-L-Cysteine (NAC) abrogated mitochondrial injury, cytochrome c, AIF, and Smac release, and Bcl-2 and Bcl-xL suppression and Bax and Bad activation induced by butyric acid. However, the decrease in cFLIP expression by butyric acid was not restored by treatment with NAC; increases in caspase-4 and -10 activities by butyric acid were completely abrogated by NAC. NAC also affected the elevation of GRP78 and CHOP/GADD153 expression by butyric acid. These results suggest that butyric acid is involved in mitochondrial-dysfunction- and endoplasmic reticulum stress-mediated apoptosis in human Jurkat T-cells via a ROS-dependent mechanism.

  2. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

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

    2013-01-01

    Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

  3. Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Siddiqui, Maqsood A; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; AlSalhi, Mohamad S; Alrokayan, Salman A

    2011-05-10

    Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Gamma radiation field intensity meter

    DOEpatents

    Thacker, L.H.

    1995-10-17

    A gamma radiation intensity meter measures dose rate of a radiation field. The gamma radiation intensity meter includes a tritium battery emitting beta rays generating a current which is essentially constant. Dose rate is correlated to an amount of movement of an electroscope element charged by the tritium battery. Ionizing radiation decreases the voltage at the element and causes movement. A bleed resistor is coupled between the electroscope support element or electrode and the ionization chamber wall electrode. 4 figs.

  5. Gamma radiation field intensity meter

    DOEpatents

    Thacker, L.H.

    1994-08-16

    A gamma radiation intensity meter measures dose rate of a radiation field. The gamma radiation intensity meter includes a tritium battery emitting beta rays generating a current which is essentially constant. Dose rate is correlated to an amount of movement of an electroscope element charged by the tritium battery. Ionizing radiation decreases the voltage at the element and causes movement. A bleed resistor is coupled between the electroscope support element or electrode and the ionization chamber wall electrode. 4 figs.

  6. Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis.

    PubMed

    Murakami, Yayoi; Ito, Masafumi; Ohsawa, Ikuroh

    2017-01-01

    Inhalation of molecular hydrogen (H2) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H2 also prevents chronic neurodegenerative diseases including Parkinson's disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain unclear. Here, we investigated the effect of H2 on mitochondria in cultured human neuroblastoma SH-SY5Y cells. H2 increased the mitochondrial membrane potential and the cellular ATP level, which were accompanied by a decrease in the reduced glutathione level and an increase in the superoxide level. Pretreatment with H2 suppressed H2O2-induced cell death, whereas post-treatment did not. Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H2-treated cells indicated that mild stress caused by H2 induced increased resistance to exacerbated oxidative stress. We propose that H2 functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Qian; Ma, Ruonan; Tian, Ying

    2013-05-20

    Ar/O{sub 2} (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.

  8. β-Radiation Stress Responses on Growth and Antioxidative Defense System in Plants: A Study with Strontium-90 in Lemna minor

    PubMed Central

    Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

    2015-01-01

    In the following study, dose dependent effects on growth and oxidative stress induced by β-radiation were examined to gain better insights in the mode of action of β-radiation induced stress in plant species. Radiostrontium (90Sr) was used to test for β-radiation induced responses in the freshwater macrophyte Lemna minor. The accumulation pattern of 90Sr was examined for L. minor root and fronds separately over a seven-day time period and was subsequently used in a dynamic dosimetric model to calculate β-radiation dose rates. Exposing L. minor plants for seven days to a 90Sr activity concentration of 25 up to 25,000 kBq·L−1 resulted in a dose rate between 0.084 ± 0.004 and 97 ± 8 mGy·h−1. After seven days of exposure, root fresh weight showed a dose dependent decrease starting from a dose rate of 9.4 ± 0.5 mGy·h−1. Based on these data, an EDR10 value of 1.5 ± 0.4 mGy·h−1 was estimated for root fresh weight and 52 ± 17 mGy·h−1 for frond fresh weight. Different antioxidative enzymes and metabolites were further examined to analyze if β-radiation induces oxidative stress in L. minor. PMID:26198226

  9. β-Radiation Stress Responses on Growth and Antioxidative Defense System in Plants: A Study with Strontium-90 in Lemna minor.

    PubMed

    Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

    2015-07-07

    In the following study, dose dependent effects on growth and oxidative stress induced by β-radiation were examined to gain better insights in the mode of action of β-radiation induced stress in plant species. Radiostrontium (⁹⁰Sr) was used to test for β-radiation induced responses in the freshwater macrophyte Lemna minor. The accumulation pattern of 90Sr was examined for L. minor root and fronds separately over a seven-day time period and was subsequently used in a dynamic dosimetric model to calculate β-radiation dose rates. Exposing L. minor plants for seven days to a ⁹⁰Sr activity concentration of 25 up to 25,000 kBq·L⁻¹ resulted in a dose rate between 0.084 ± 0.004 and 97 ± 8 mGy·h⁻¹. After seven days of exposure, root fresh weight showed a dose dependent decrease starting from a dose rate of 9.4 ± 0.5 mGy·h⁻¹. Based on these data, an EDR10 value of 1.5 ± 0.4 mGy·h⁻¹ was estimated for root fresh weight and 52 ± 17 mGy·h⁻¹ for frond fresh weight. Different antioxidative enzymes and metabolites were further examined to analyze if β-radiation induces oxidative stress in L. minor.

  10. Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages

    PubMed Central

    Deng, Song-Yun; Zhang, Le-Meng; Ai, Yu-hang; Pan, Pin-Hua; Zhao, Shuang-Ping; Su, Xiao-Li; Wu, Dong-Dong; Tan, Hong-Yi; Zhang, Li-Na; Tsung, Allan

    2017-01-01

    Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages. PMID:28849179

  11. Distinctive functions of Syk N-terminal and C-terminal SH2 domains in the signaling cascade elicited by oxidative stress in B cells.

    PubMed

    Ding, J; Takano, T; Hermann, P; Gao, S; Han, W; Noda, C; Yanagi, S; Yamamura, H

    2000-05-01

    Syk plays a crucial role in the transduction of oxidative stress signaling. In this paper, we investigated the roles of Src homology 2 (SH2) domains of Syk in oxidative stress signaling, using Syk-negative DT40 cells expressing the N- or C-terminal SH2 domain mutant [mSH2(N) or mSH2(C)] of Syk. Tyrosine phosphorylation of Syk in cells expressing mSH2(N) Syk after H(2)O(2) treatment was higher than that in cells expressing wild-type Syk or mSH2(C) Syk. The tyrosine phosphorylation of wild-type Syk and mSH2(C) Syk, but not that of mSH2(N), was sensitive to PP2, a specific inhibitor of Src-family protein-tyrosine kinase. In oxidative stress, the C-terminal SH2 domain of Syk was demonstrated to be required for induction of tyrosine phosphorylation of cellular proteins, phospholipase C (PLC)-gamma2 phosphorylation, inositol 1,4, 5-triphosphate (IP(3)) generation, Ca(2)(+) release from intracellular stores, and c-Jun N-terminal kinase activation. In contrast, in mSH2(N) Syk-expressing cells, tyrosine phosphorylation of intracellular proteins including PLC-gamma2 was markedly induced in oxidative stress. The enhanced phosphorylation of mSH2(N) Syk and PLC-gamma2, however, did not link to Ca(2)(+) mobilization from intracellular pools and IP(3) generation. Thus, the N- and C-terminal SH2 domains of Syk possess distinctive functions in oxidative stress signaling.

  12. Oxidative stress response in SH-SY5Y cells exposed to short-term 1800 MHz radiofrequency radiation.

    PubMed

    Marjanovic Cermak, Ana Marija; Pavicic, Ivan; Trosic, Ivancica

    2018-01-28

    The exact mechanism that could explain the effects of radiofrequency (RF) radiation exposure at non-thermal level is still unknown. Increasing evidence suggests a possible involvement of reactive oxygen species (ROS) and development of oxidative stress. To test the proposed hypothesis, human neuroblastoma cells (SH-SY5Y) were exposed to 1800 MHz short-term RF exposure for 10, 30 and 60 minutes. Electric field strength within Gigahertz Transverse Electromagnetic cell (GTEM) was 30 V m -1 and specific absorption rate (SAR) was calculated to be 1.6 W kg -1 . Cellular viability was measured by MTT assay and level of ROS was determined by fluorescent probe 2',7'-dichlorofluorescin diacetate. Concentrations of malondialdehyde and protein carbonyls were used to assess lipid and protein oxidative damage and antioxidant activity was evaluated by measuring concentrations of total glutathione (GSH). After radiation exposure, viability of irradiated cells remained within normal physiological values. Significantly higher ROS level was observed for every radiation exposure time. After 60 min of exposure, the applied radiation caused significant lipid and protein damage. The highest GSH concentration was detected after 10 minute-exposure. The results of our study showed enhanced susceptibility of SH-SY5Y cells for development of oxidative stress even after short-term RF exposure.

  13. Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle

    PubMed Central

    Zaccaria, Marco; Ludovici, Matteo; Sanzani, Simona Marianna; Ippolito, Antonio; Aiese Cigliano, Riccardo; Sanseverino, Walter; Scarpari, Marzia; Scala, Valeria; Fanelli, Corrado; Reverberi, Massimo

    2015-01-01

    Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B1, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile) to transcriptional analysis (RNA-seq). There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies. PMID:26512693

  14. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    PubMed Central

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  15. Efficacy of grape seed and skin extract against doxorubicin-induced oxidative stress in rat liver.

    PubMed

    Mokni, Meherzia; Hamlaoui, Sonia; Kadri, Safouen; Limam, Ferid; Amri, Mohamed; Marzouki, Lamjed; Aouani, Ezzedine

    2015-11-01

    Doxorubicin (Dox) is an anthracycline used in chemotherapy, although it causes toxicity and oxidative stress. Grape seed and skin extract (GSSE) is a mixture of polyphenolic compounds with antioxidant properties. To evaluate the hepato-toxicity of Dox on healthy rats as well as the protective effect of GSSE, rats were treated with GSSE (500mg/kg bw) during 8 days. At the 4th day of treatment, they received a single dose of Dox (20 mg/kg bw). After the treatment (9th day), livers were collected and processed for oxidative stress status. Dox increased MDA (+ 900%), decreased catalase (-60%) and increased peroxidase (+90%) and superoxide dismutase (+100%) activities. In this latter case Dox mainly increased the iron isoform. Furthermore Dox altered intracellular mediators as catalytic free iron (-75%), H₂O₂(-75%) and calcium (+30%). Dox also affected liver function by elevating plasma triacylglycerol and transaminases and liver morphology by altering its typical architecture. Importantly all Dox-induced liver disturbances were alleviated upon GSSE treatment. Dox induced liver toxicity and an oxidative stress mainly characterized by increased lipoperoxidation but not protein carbonylation. GSSE efficiently protected the liver from Dox-induced toxicity and appeared as a safe adjuvant that could be incorporated into chemotherapy protocols.

  16. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

    PubMed Central

    Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

    2013-01-01

    Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

  17. Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress.

    PubMed

    Chen, Shizhu; Hou, Yingjian; Cheng, Gong; Zhang, Cuimiao; Wang, Shuxiang; Zhang, Jinchao

    2013-07-01

    Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H2O2. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H2O2. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.

  18. High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats.

    PubMed

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Ideris, Aini; Abdullah, Maizaton Atmadini

    2015-10-24

    Serum sialic acid levels are positively correlated with coronary artery disease and inflammation. Although sialic acid is a non-specific marker, it is considered sensitive likely due to its influence in sialylation of glycoprotein structures all over the body. We hypothesized that dietary supplementation with N-acetylneuraminic acid (Neu5Ac), a type of sialic acid, will have profound effects on high fat diet- (HFD-) induced inflammation and oxidative stress in view of the widespread incorporation of sialic acid into glycoprotein structures in the body. HFD-fed rats with or without simvastatin or Neu5Ac (50 and 400 mg/kg/day) were followed up for 12 weeks. Lipid profiles, and markers of inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor alpha), insulin resistance (serum insulin and adiponectin, oral glucose tolerance test and homeostatic model of insulin resistance) and oxidative stress (total antioxidant status and thiobarbituric acid reactive species) in the serum and liver were determined, while mRNA levels of hepatic antioxidant and inflammation genes were also quantified. Serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, urea, creatinine and uric acid were also assessed. HFD feeding caused hyperlipidemia and insulin resistance, and worsened liver and kidney functions. HFD feeding also potentiated inflammation and oxidative stress, partly through modulation of hepatic gene expression, while Neu5Ac especially at higher doses and simvastatin attenuated HFD-induced changes, although Neu5Ac showed better outcomes. Based on the present results, we surmised that Neu5Ac can prevent HFD-induced inflammation and oxidative stress, and may in fact be useful in the prevention of hyperlipidemia-associated inflammation and oxidative stress. However, the translational implications of these findings can only be determined after long-term effects are established. Hence, the use of Neu5Ac on obesity-related diseases

  19. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats.

    PubMed

    Hajiluian, Ghazaleh; Abbasalizad Farhangi, Mahdieh; Nameni, Ghazaleh; Shahabi, Parviz; Megari-Abbasi, Mehran

    2017-07-06

    There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.

  20. Classification of oxidative stress based on its intensity

    PubMed Central

    Lushchak, Volodymyr I.

    2014-01-01

    In living organisms production of reactive oxygen species (ROS) is counterbalanced by their elimination and/or prevention of formation which in concert can typically maintain a steady-state (stationary) ROS level. However, this balance may be disturbed and lead to elevated ROS levels called oxidative stress. To our best knowledge, there is no broadly acceptable system of classification of oxidative stress based on its intensity due to which proposed here system may be helpful for interpretation of experimental data. Oxidative stress field is the hot topic in biology and, to date, many details related to ROS-induced damage to cellular components, ROS-based signaling, cellular responses and adaptation have been disclosed. However, it is common situation when researchers experience substantial difficulties in the correct interpretation of oxidative stress development especially when there is a need to characterize its intensity. Careful selection of specific biomarkers (ROS-modified targets) and some system may be helpful here. A classification of oxidative stress based on its intensity is proposed here. According to this classification there are four zones of function in the relationship between “Dose/concentration of inducer” and the measured “Endpoint”: I – basal oxidative stress (BOS); II – low intensity oxidative stress (LOS); III – intermediate intensity oxidative stress (IOS); IV – high intensity oxidative stress (HOS). The proposed classification will be helpful to describe experimental data where oxidative stress is induced and systematize it based on its intensity, but further studies will be in need to clear discriminate between stress of different intensity. PMID:26417312

  1. Radiation-induced enzyme efflux from rat heart: sedentary animals. [Gamma radiation, lactate dehydrogenase, creative kinase, glutamate oxaloacetate transaminase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    MacWilliam, L.D.; Bhakthan, N.M.G.

    1976-01-01

    Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of ..gamma..-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of ..gamma..-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in themore » dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell.« less

  2. Targeted Overexpression of Mitochondrial Catalase Prevents Radiation-Induced Cognitive Dysfunction

    PubMed Central

    Parihar, Vipan K.; Allen, Barrett D.; Tran, Katherine K.; Chmielewski, Nicole N.; Craver, Brianna M.; Martirosian, Vahan; Morganti, Josh M.; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M.; Nelson, Gregory A.; Allen, Antiño R.

    2015-01-01

    Abstract Aims: Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Results: Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Innovation: Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Conclusion: Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain. Antioxid. Redox Signal. 22, 78–91. PMID:24949841

  3. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  4. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

    PubMed

    Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

    2014-08-01

    Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups

  5. Analysis of drought-tolerant sugar beet (Beta vulgaris L.) mutants induced with gamma radiation using SDS-PAGE and ISSR markers.

    PubMed

    Sen, Ayse; Alikamanoglu, Sema

    2012-01-01

    Drought is one of the major environmental stresses which greatly affect the plant growth and productivity. In the present study, various doses (0-75Gy) of gamma rays were applied to investigate the effect of radiation on shoot tip explants. It was observed that the regeneration rates and plant fresh weights decreased significantly with an increase in radiation dose. The optimal irradiation doses for mutation induction were determined at 15 and 20Gy. Afterwards, the induction of somatic mutation in sugar beet (Beta vulgaris L.) was investigated by irradiation of shoot tips with 15 and 20Gy gamma rays. Irradiated shoot tips were sub-cultured and M(1)V(1)-M(1)V(3) generations were obtained. Mutants tolerant to drought stress were selected on MS medium, supplemented with 10 and 20gl(-1) PEG6000. Of the M(1)V(3) plantlets, drought-tolerant mutants were selected. Leaf soluble proteins obtained from the control and drought-tolerant mutants were analyzed by SDS-PAGE. A total of 22 protein bands were determined and 2 of them were observed to be drought-tolerant mutants except the control. Polymorphism was also detected among the control and drought-tolerant mutants by DNA fingerprinting using ISSR markers. A total of 106 PCR fragments were amplified with 19 ISSR primers and 91 of them were polymorphic. The dendrograms were separated into two main clusters. First cluster included M8 mutant plant, which was applied 20Gy gamma radiation and regenerated on selective culture media containing 10gl(-1) PEG6000 concentration, and the second cluster was further divided into five sub-clusters. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

    PubMed

    Yang, Long; Dong, Xiujuan

    2017-06-01

    We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in prostate cancer cells.

    PubMed

    Li, Lingyun; Steinauer, Kirsten K; Dirks, Amie J; Husbeck, Bryan; Gibbs, Iris; Knox, Susan J

    2003-12-01

    Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in arachidonate metabolism and the conversion of arachidonic acid (AA) to prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated that the COX2 protein is up-regulated in prostate cancer cells after irradiation and that this results in elevated levels of PGE(2). In the present study, we further investigated whether radiation-induced COX2 up-regulation is dependent on the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS), and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to modulate the cellular redox status. BSO decreased the cellular GSH level and increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha-lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up-regulation is secondary to the production of ROS. The relative increases in COX2 expression and PGE(2) production induced by radiation and H(2)O(2) were even greater when PC-3 cells were pretreated with BSO. When the cells were pretreated with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2 up-regulation and PGE(2) production were markedly inhibited. These results demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is modulated by the cellular redox status. Radiation-induced increases in ROS levels contribute to the adaptive response of PC-3 cells, resulting in elevated levels of COX2.

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

    PubMed

    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.

  9. Characterization of non-CG genomic hypomethylation associated with gamma-ray-induced suppression of CMT3 transcription in Arabidopsis thaliana.

    PubMed

    Kim, Ji Eun; Lee, Min Hee; Cho, Eun Ju; Kim, Ji Hong; Chung, Byung Yeoup; Kim, Jin-Hong

    2013-12-01

    Ionizing radiation causes various epigenetic changes, as well as a variety of DNA lesions such as strand breaks, cross-links, oxidative damages, etc., in genomes. However, radiation-induced epigenetic changes have rarely been substantiated in plant genomes. The current study investigates whether DNA methylation of Arabidopsis thaliana genome is altered by gamma rays. We found that genomic DNA methylation decreased in wild-type plants with increasing doses of gamma rays (5, 50 and 200 Gy). Irradiation with 200 Gy significantly increased the expression of transcriptionally inactive centromeric 180-bp (CEN) and transcriptionally silent information (TSI) repeats. This increase suggested that there was a substantial release of transcriptional gene silencing by gamma rays, probably by induction of DNA hypomethylation. High expression of the DNA demethylase ROS1 and low expression of the DNA methyltransferase CMT3 supported this hypothesis. Moreover, Southern blot analysis following digestion of genomic DNA with methylation-sensitive enzymes revealed that the DNA hypomethylation occured preferentially at CHG or CHH sites rather than CG sites, depending on the radiation dose. Unlike CEN and TSI repeats, the number of Ta3, AtSN1 and FWA repeats decreased in transcription but increased in non-CG methylation. In addition, the cmt3-11 mutant showed neither DNA hypomethylation nor transcriptional activation of silenced repeats upon gamma irradiation. Furthermore, profiles of genome-wide transcriptomes in response to gamma rays differed between the wild-type and cmt3-11 mutant. These results suggest that gamma irradiation induced DNA hypomethylation preferentially at non-CG sites of transcriptionally inactive repeats in a locus-specific manner, which depends on CMT3 activity.

  10. Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

    PubMed

    Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

    2017-09-01

    Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn 2+ through influx of extracellular Zn 2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.

  11. Sensitivity to Antibiotics of Bacteria Exposed to Gamma Radiation Emitted from Hot Soils of the High Background Radiation Areas of Ramsar, Northern Iran.

    PubMed

    Mortazavi, Seyed Mohammad Javad; Zarei, Samira; Taheri, Mohammad; Tajbakhsh, Saeed; Mortazavi, Seyed Alireza; Ranjbar, Sahar; Momeni, Fatemeh; Masoomi, Samaneh; Ansari, Leila; Movahedi, Mohammad Mehdi; Taeb, Shahram; Zarei, Sina; Haghani, Masood

    2017-04-01

    Over the past several years our laboratories have investigated different aspects of the challenging issue of the alterations in bacterial susceptibility to antibiotics induced by physical stresses. To explore the bacterial susceptibility to antibiotics in samples of Salmonella enterica subsp. enterica serovar Typhimurium ( S. typhimurium ), Staphylococcus aureus , and Klebsiella pneumoniae after exposure to gamma radiation emitted from the soil samples taken from the high background radiation areas of Ramsar, northern Iran. Standard Kirby-Bauer test, which evaluates the size of the zone of inhibition as an indicator of the susceptibility of different bacteria to antibiotics, was used in this study. The maximum alteration of the diameter of inhibition zone was found for K. pneumoniae when tested for ciprofloxacin. In this case, the mean diameter of no growth zone in non-irradiated control samples of K. pneumoniae was 20.3 (SD 0.6) mm; it was 14.7 (SD 0.6) mm in irradiated samples. On the other hand, the minimum changes in the diameter of inhibition zone were found for S. typhimurium and S. aureus when these bacteria were tested for nitrofurantoin and cephalexin, respectively. Gamma rays were capable of making significant alterations in bacterial susceptibility to antibiotics. It can be hypothesized that high levels of natural background radiation can induce adaptive phenomena that help microorganisms better cope with lethal effects of antibiotics.

  12. Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.

    PubMed

    Rincón, J; Correia, D; Arcaya, J L; Finol, E; Fernández, A; Pérez, M; Yaguas, K; Talavera, E; Chávez, M; Summer, R; Romero, F

    2015-03-01

    Activation of the renin-angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with N(w)-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown. The current study was designed to test the hypothesis that AT1R activation promotes renal NAD(P)H oxidase up-regulation, oxidative stress and cytokine production during L-NAME induced-hypertension. Male Sprague-Dawley rats were distributed in three groups: L-NAME, receiving 70 mg/100ml of L-NAME, L-NAME+Los, receiving 70 mg/100ml of L-NAME and 40 mg/kg/day of Losartan; and Controls, receiving water instead of L-NAME or L-NAME and Losartan. After two weeks, L-NAME induced high blood pressure, renal overexpression of AT1R, NAD(P)H oxidase sub-units gp91, p22 and p47, increased levels of oxidative stress, interleukin-6 (IL-6) and interleukin-17 (IL-17). Also, we found increased renal accumulation of lymphocytes and macrophages. Losartan treatment abolished the renal expression of gp91, p22, p47, oxidative stress and reduced NF-κB activation and IL-6 expression. These findings indicate that NO induced-hypertension is associated with up-regulation of NADPH oxidase, oxidative stress production and overexpression of key inflammatory mediators. These events are associated with up-regulation of AT1R, as evidenced by their reversal with AT1R blocker treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Protective effects of Sesamum indicum extract against oxidative stress induced by vanadium on isolated rat hepatocytes.

    PubMed

    Hosseini, Mir-Jamal; Shahraki, Jafar; Tafreshian, Saman; Salimi, Ahmad; Kamalinejad, Mohammad; Pourahmad, Jalal

    2016-08-01

    Vanadium toxicity is a challenging problem to human and animal health with no entirely understanding cytotoxic mechanisms. Previous studies in vanadium toxicity showed involvement of oxidative stress in isolated liver hepatocytes and mitochondria via increasing of ROS formation, release of cytochrome c and ATP depletion after incubation with different concentrations (25-200 µM). Therefore, we aimed to investigate the protective effects of Sesamum indicum seed extract (100-300 μg/mL) against oxidative stress induced by vanadium on isolated rat hepatocytes. Our results showed that quite similar to Alpha-tocopherol (100 µM), different concentrations of extract (100-300 μg/mL) protected the isolated hepatocyte against all oxidative stress/cytotoxicity markers induced by vanadium in including cell lysis, ROS generation, mitochondrial membrane potential decrease and lysosomal membrane damage. Besides, vanadium induced mitochondrial/lysosomal toxic interaction and vanadium reductive activation mediated by glutathione in vanadium toxicity was significantly (P < 0.05) ameliorated by Sesamum indicum extracts. These findings suggested a hepato-protective role for extracts against liver injury resulted from vanadium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 979-985, 2016. © 2015 Wiley Periodicals, Inc.

  14. Fatty Acid Composition as a Predictor for the Oxidation Stability of Korean Vegetable Oils with or without Induced Oxidative Stress

    PubMed Central

    Yun, Jung-Mi; Surh, Jeonghee

    2012-01-01

    This study was designed to investigate whether the fatty acid composition could make a significant contribution to the oxidation stability of vegetable oils marketed in Korea. Ten kinds, 97 items of vegetable oils that were produced in either an industrialized or a traditional way were collected and analyzed for their fatty acid compositions and lipid oxidation products, in the absence or presence of oxidative stress. Peroxidability index (PI) calculations based on the fatty acid composition ranged from 7.10 to 111.87 with the lowest value found in olive oils and the highest in perilla oils. In the absence of induced oxidative stress, malondialdehyde (MDA), the secondary lipid oxidation product, was generated more in the oils with higher PI (r=0.890), while the tendency was not observed when the oils were subjected to an oxidation-accelerating system. In the presence of the oxidative stress, the perilla oils produced in an industrialized manner generated appreciably higher amounts of MDA than those produced in a traditional way, although both types of oils presented similar PIs. The results implicate that the fatty acid compositions could be a predictor for the oxidation stability of the vegetable oils at the early stage of oil oxidation, but not for those at a later stage of oxidation. PMID:24471078

  15. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

    PubMed

    Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

    2016-09-01

    Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene

  16. Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage.

    PubMed

    Yu, Yang; Cui, Yuxiang; Niedernhofer, Laura J; Wang, Yinsheng

    2016-12-19

    A variety of endogenous and exogenous agents can induce DNA damage and lead to genomic instability. Reactive oxygen species (ROS), an important class of DNA damaging agents, are constantly generated in cells as a consequence of endogenous metabolism, infection/inflammation, and/or exposure to environmental toxicants. A wide array of DNA lesions can be induced by ROS directly, including single-nucleobase lesions, tandem lesions, and hypochlorous acid (HOCl)/hypobromous acid (HOBr)-derived DNA adducts. ROS can also lead to lipid peroxidation, whose byproducts can also react with DNA to produce exocyclic DNA lesions. A combination of bioanalytical chemistry, synthetic organic chemistry, and molecular biology approaches have provided significant insights into the occurrence, repair, and biological consequences of oxidatively induced DNA lesions. The involvement of these lesions in the etiology of human diseases and aging was also investigated in the past several decades, suggesting that the oxidatively induced DNA adducts, especially bulky DNA lesions, may serve as biomarkers for exploring the role of oxidative stress in human diseases. The continuing development and improvement of LC-MS/MS coupled with the stable isotope-dilution method for DNA adduct quantification will further promote research about the clinical implications and diagnostic applications of oxidatively induced DNA adducts.

  17. Protective effect of vanilloids against tert-butyl hydroperoxide-induced oxidative stress in vero cells culture.

    PubMed

    Rosa, Antonella; Atzeri, Angela; Deiana, Monica; Melis, M Paola; Incani, Alessandra; Corona, Giulia; Loru, Debora; Appendino, Giovanni; Dessì, M Assunta

    2008-05-28

    This study investigated the effect of synthetic capsiate, a simplified analogue of capsiate, and vanillyl alcohol on the oxidative stress induced by tert-butyl hydroperoxide (TBH) in a line of fibroblasts derived from monkey kidney (Vero cells). In response to the TBH-mediated oxidative stress, a reduction of the levels of total unsaturated fatty acids and cholesterol was observed, and a rise in the concentrations of conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with both synthetic capsiate and vanillyl alcohol preserved Vero cells from oxidative damage and showed a remarkable protective effect on the reduction of the levels of total unsaturated fatty acids and cholesterol, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides, and 7-ketocholesterol. Both compounds were effective against peroxidation of cell membrane lipids induced by TBH, with synthetic capsiate essentially acting as a pro-drug of vanillyl alcohol, its hydrophilic hydrolytic derivative.

  18. Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice.

    PubMed

    Meng, Shanshan; Quan, Wuxing; Qi, Xu; Su, Zhiqiang; Yang, Shanshan

    2014-01-01

    A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABA(B) receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Chronic stress was induced by restraining mice for 2 h for seven consecutive days. We first investigated whether chronic stress influenced morphine-induced CPP, extinction, and stress-induced relapse in the stressed mice. Next, we investigated whether three different doses of baclofen influenced chronic stress as measured by the expression of morphine-induced CPP. We chose the most effective dose for subsequent extinction and reinstatement experiments. Reinstatement of morphine-induced CPP was induced by a 6-min forced swim stress. Locomotor activity was also measured for each test. Chronic stress facilitated the expression of morphine-induced CPP and prolonged extinction time. Forced swim stress primed the reinstatement of morphine-induced CPP in mice. Baclofen treatment affected the impact of chronic stress on different phases of morphine-induced CPP. Our results showed that baclofen antagonized the effects of chronic stress on morphine-induced CPP. These findings suggest the potential clinical utility of GABA(B) receptor-positive modulators as an anti-addiction agent in people suffering from chronic stress.

  19. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

    PubMed

    Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment.

  20. Argon laser phototherapy could eliminate the damage effects induced by the ionizing radiation "gamma radiation" in irradiated rabbits.

    PubMed

    Abdul-Aziz, Karolin Kamel; Tuorkey, M J

    2010-04-02

    The ionizing radiations could be taken in considerate as an integral part in our life, since, living organisms are actually exposed to a constant shower of ionizing radiations whether from the natural or artificial resources. The radio-protective efficiency of several chemicals has been confirmed in animal trails, whereas, due to their accumulative toxicity, their clinical utility is limited. Therefore, we aimed in the present work to investigate the possibility of using argon laser to recuperate the damaged tissues due to exposing to the ionizing radiation. The rabbits were used in this study, and they were designed as control, gamma irradiated, laser, and gamma plus laser groups. Lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glucose-6-phosphate dehydrogenase (G-6-PD) in blood and liver were evaluated. As well as, the level of protein thiol was evaluated in the plasma among each group. Results of this study revealed the potential therapeutic performance of the treatment by laser argon to decline the damaging effect of the ionized radiation whether at systematic or local levels. In conclusion, argon laser therapy appears propitious protective effect against the hazard effects of gamma radiation. Copyright 2010 Elsevier B.V. All rights reserved.