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Superoxide Anion (superoxide + anion)
Terms modified by Superoxide Anion Selected AbstractsPhotosensitized Oxidation of Sulfides: Discriminating between the Singlet-Oxygen Mechanism and Electron Transfer Involving Superoxide Anion or Molecular OxygenCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2006Sergio M. Bonesi Dr. Abstract The oxidation of diethyl and diphenyl sulfide photosensitized by dicyanoanthracene (DCA), N -methylquinolinium tetrafluoroborate (NMQ+), and triphenylpyrylium tetrafluoroborate (TPP+) has been explored by steady-state and laser flash photolysis studies in acetonitrile, methanol, and 1,2-dichloroethane. In the Et2S/DCA system sulfide-enhanced intersystem crossing leads to generation of 1O2, which eventually gives the sulfoxide via a persulfoxide; this mechanism plays no role with Ph2S, though enhanced formation of 3DCA has been demonstrated. In all other cases an electron-transfer (ET) mechanism is involved. Electron-transfer sulfoxidation occurs with efficiency essentially independent of the sulfide structure, is subject to quenching by benzoquinone, and does not lead to Ph2SO cooxidation. Formation of the radical cations R2S.+ has been assessed by flash photolysis (medium-dependent yield, dichloroethane,CH3CN>CH3OH) and confirmed by quenching with 1,4-dimethoxybenzene. Electron-transfer oxidations occur both when the superoxide anion is generated by the reduced sensitizer (DCA.,, NMQ.) and when this is not the case (TPP.). Although it is possible that different mechanisms operate with different ET sensitizers, a plausible unitary mechanism can be proposed. This considers that reaction between R2S.+ and O2., mainly involves back electron transfer, whereas sulfoxidation results primarily from the reaction of the sulfide radical cation with molecular oxygen. Calculations indeed show that the initially formed fleeting complex RS2+,,,OO. adds to a sulfide molecule and gives strongly stabilized R2SO.+OSR2 via an accessible transition state. This intermediate gives the sulfoxide, probably via a radical cation chain path. This mechanism explains the larger scope of ET sulfoxidation with respect to the singlet-oxygen process. [source] Analysis Of Agonist-Evoked Nitric Oxide Release From Human Endothelial Cells: Role Of Superoxide AnionCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001Monique David-Dufilho SUMMARY 1. Dichlorofluorescein oxidation and electrochemical monitoring of in situ nitric oxide (NO) release from cultured human endothelial cells reveals that agonists such as thrombin and histamine simultaneously stimulate transient superoxide production. 2. The duration of ·NO release was increased only in the simultaneous presence of extracellular L -arginine and exogenous superoxide dismutase. In contrast, the inhibition of membrane reduced nicotinamide adenine dinucleotide (phosphate) oxidases, the major source of ·O2, in endothelial cells, did not prolong ·NO release, although extracellular L -arginine was also present. Comparison of these two experimental conditions suggested that H2O2 was involved in the extension of the ·NO signal. 3. The present study demonstrates that, in the absence of external L -arginine, ·O2, production does not constitute the major pathway controlling the duration of agonist-induced ·NO signal. These results suggest that L -arginine and H2O2 act jointly to maintain nitric oxide synthase in an activated form. [source] Free radical generation during the activation of hemolymph prepared from the homopteran Dactylopius coccusARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2007F. García-Gil De Muñoz Abstract Superoxide anion (O,2) and nitric oxide (NO) generation in Dactylopius coccus hemolymph obtained by perfusion and activated with zymosan was studied. Activated hemolymph reduced 3-[4,5 dimethylthiazolil-2]-2,5-diphenyl tetrazolium bromide. This reduction was prevented by superoxide dismutase (SOD) indicating O,2 generation. This activity was dependent on temperature, and hemolymph incubated at 75°C lost its activity. Chromatocytes incubated with zymosan released their content and produced O,2. Activated hemolymph also produced NO and this activity was prevented in the presence of NG-nitro-L-arginine methyl ester, suggesting that nitric oxide synthase (NOS) might be present in D. coccus hemolymph. The probable source of O,2 in the D. coccus hemolymph is the anthraquinone oxidation, since commercial carminic dye produced O,2 during its oxidation by Agaricus bisporus tyrosinase. Gram+ Micrococcus luteus exposed to activated hemolymph were killed in vitro, and addition of NG-nitro-L-arginine methyl ester and D-Mannitol (a hydroxyl radical scavenger) prevented their killing. The cytotoxic effect produced by the activated hemolymph was not observed with the Gram, bacteria Serratia marcescens. These results suggest that D. coccus activated hemolymph generates reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that may limit M. luteus growth. Arch. Insect Biochem. Physiol. 65:20,28, 2007. © 2007 Wiley-Liss, Inc. [source] High glucose levels enhance platelet activation: involvement of multiple mechanismsBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2006Dzana Sudic Summary Diabetes mellitus (DM) and hyperglycaemia are associated with platelet activation. The present study was designed to investigate how high glucose levels influence platelet function. Fasting human blood was incubated with different concentrations of d -glucose (5, 15 and 30 mmol/l) and other sugars without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30 mmol/l l -glucose, sucrose and galactose. Hyperglycaemia also increased TRAP-induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not counteract the enhancement of platelet P-selectin expression, but abolished the enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia. Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the hyperglycaemic enhancement of platelet P-selectin expression, but did not counteract the enhancement of TRAP-induced platelet fibrinogen binding. Hyperglycaemia did not alter platelet intracellular calcium responses to agonist stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3) kinase, or nitric oxide synthase, or the addition of insulin did not influence the effect of hyperglycaemia. In conclusion, high glucose levels enhanced platelet reactivity to agonist stimulation through elevated osmolality. This occurred via superoxide anion production, which enhanced platelet P-selectin expression (secretion), and PKC signalling, which enhanced TRAP-induced fibrinogen binding (aggregablity). [source] Increased vascular endothelial growth factor expression, CD3-positive cell infiltration, and oxidative stress in premalignant lesions of the cervixCANCER, Issue 16 2009Yenddy Carrero MSc Abstract BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in cervical intraepithelial neoplasia (CIN) progression. The occurrence of leukocytes has been documented in CIN; however, their role in VEGF production remains unknown. Oxidative stress has been involved in the progression of malignant neoplasias, but to the authors' knowledge tissue oxidative stress in CIN has not been documented. The objective of the current study was to investigate the expression of VEGF, leukocyte infiltration, leukocyte VEGF expression, and nitrogen/oxygen metabolism in cervical tissues from patients with CIN. METHODS: Indirect immunofluorescence was used to study the expression of VEGF and leukocyte infiltration in cervical samples from 55 patients with CIN and 7 normal controls. Superoxide anion (O2,) expression was determined by a cytochemical method, and tissue and serum nitric oxide by the Griess reaction. Human papillomavirus (HPV) DNA and HPV types were identified by the hybrid capture 2 HPV DNA test. RESULTS: Increased expression of VEGF was observed related to the progression of CIN. A significant increment of CD3 lymphocytes was found in CIN type 3 (CIN 3) and coexpression of CD3/VEGF and monocyte-macrophage/VEGF in CIN 2 and 3. Increased O2, -positive cells were found in CIN 2 and 3; however, tissue nitrate-nitrite content remained similar to controls. The incidence of HPV infection was 16% in patients with CIN. No significant differences were observed in the values of HPV-positive or HPV-negative patients. CONCLUSIONS: Different factors leading to cervical neoplasia progression may be involved in the evolution of CIN, and the presence of these factors is most likely not related to the HPV infection status. Cancer 2009. © 2009 American Cancer Society. [source] Superoxide anions and hydrogen peroxide inhibit proliferation of activated rat stellate cells and induce different modes of cell deathLIVER INTERNATIONAL, Issue 6 2009Sandra Dunning Abstract Background: In chronic liver injury, hepatic stellate cells (HSCs) proliferate and produce excessive amounts of connective tissue causing liver fibrosis and cirrhosis. Oxidative stress has been implicated as a driving force of HSC activation and proliferation, although contradictory results have been described. Aim: To determine the effects of oxidative stress on activated HSC proliferation, survival and signalling pathways. Methods: Serum-starved culture-activated rat HSCs were exposed to the superoxide anion donor menadione (5,25 ,mol/L) or hydrogen peroxide (0.2,5 mmol/L). Haem oxygenase-1 mRNA expression, glutathione status, cell death, phosphorylation of mitogen-activated protein (MAP) kinases and proliferation were investigated. Results: Menadione induced apoptosis in a dose- and time-dependent, but caspase-independent manner. Hydrogen peroxide induced necrosis only at extremely high concentrations. Both menadione and hydrogen peroxide activated Jun N-terminal kinase (JNK) and p38. Hydrogen peroxide also activated extracellular signal-regulated protein. Menadione, but not hydrogen peroxide, reduced cellular glutathione levels. Inhibition of JNK or supplementation of glutathione reduced menadione-induced apoptosis. Non-toxic concentrations of menadione or hydrogen peroxide inhibited platelet-derived growth factor- or/and serum-induced proliferation. Conclusion: Reactive oxygen species (ROS) inhibit HSC proliferation and promote HSC cell death in vitro. Different ROS induce different modes of cell death. Superoxide anion-induced HSC apoptosis is dependent on JNK activation and glutathione status. [source] Metformin decreases platelet superoxide anion production in diabetic patientsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2002P. Gargiulo Abstract Background Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans. Methods We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O2,) elicited by collagen, was determined by lucigenin assay. Results Patients with diabetes had higher platelet O2, production than controls; no correlation was observed between blood glucose and platelet O2, production. Group A patients had platelet O2, production similar to that of healthy subjects but lower than Group B and Group C patients. Conclusion The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis. Copyright © 2002 John Wiley & Sons, Ltd. [source] Thymol analogues with antioxidant and L-type calcium current inhibitory activityDRUG DEVELOPMENT RESEARCH, Issue 4 2005Ai-Yu Shen Abstract Thymol is a natural product, which has antioxidant activity. 4-Morpholinomethyl-2-isopropyl-5-methylphenol (THMO), and 4-Pyrrolidinomethyl-2-isopropyl- 5-methylphenol (THPY) were synthesized by reacting thymol with formaldehyde and, respectively, morpholine or pyrrolidine. Since there is a relationship between the antioxidative status and incidence of human disease, anti-superoxidation, free radical scavenger activity, and anti-lipid peroxidation of the thymol analogues were determined by xanthine oxidase inhibition, cytochrome C system with superoxide anion releasing with formyl-Met-Leu-Phe (fMLP)/cytochalasin (CB) or phorbol myristate acetate (PMA) activating pathway in human neutrophils. All compounds studied had antioxidant activity. Mannich bases derived from thymol were generally found to be more potent compounds than thymol. THMO demonstrated the greatest antioxidant activity with IC50 values for xanthine oxidase inhibition and anti-lipid peroxidation being 21±2.78 and 61.29±5.83 µM, respectively. Moreover, since oxidative stress by free radical regulates the activity of L-type Ca2+ channel, the whole-cell configuration of the patch-clamp technique was used to investigate the effect of THMO upon ionic currents within NG108-15 cells. THMO (10 µM) suppressed the peak amplitude of L-type Ca2+ inward current (ICa,L), indicating that the antioxidative potential of the thymol analogues might be related to calcium current inhibition. The present studies suggest that THMO-dependent antioxidant and calcium ion current inhibition activity may be useful in treating free radical-related disorders. Drug Dev Res 64:195,202, 2005. © 2005 Wiley-Liss, Inc. [source] Anthracene photoinduced toxicity to plhc-1 cell line (Poeciliopsis lucida) and the role of lipid peroxidation in toxicityENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000Jonghoon Choi Abstract Many polycyclic aromatic hydrocarbons (PAHs) are acutely toxic to fish and other aquatic organisms in the presence of solar ultraviolet radiation (SUVR) of environmentally realistic intensities. In the present study, the photoinduced toxicity of a PAH (anthracene; ANT) to topminnow hepatoma cell line (PLHC-1) was assessed. After the toxicity was characterized, the role of lipid peroxidation in PAH photoinduced toxicity was examined by measuring lipid peroxidation products and by assessing the effect of lipid peroxidation antagonist (Trolox) treatment. In cytotoxicity tests using two assays (MTT, neutral red), the SUVR/ANT treatment elicited toxicity to PLHC-1 cells in a concentration- and SUVR (exposure duration and intensity)-dependent pattern. As found in previous organism-level studies, no significant cytotoxicity was observed in the cells exposed either to fluorescent light/ANT or to SUVR only. The SUVR/ANT treatment elicited the lipid peroxidation process and Trolox pretreatment significantly reduced SUVR/ANT-induced cell mortality. Microscopic observation showed that Trolox pretreatment relieved the SUVR/ANT-inflicted damage, such as cell shrinkage and membrane disruption. Together with a recent finding in our lab that increased production of superoxide anion and a lipid peroxidation product (malondialdehyde) was found in SUVR/ANT-treated fish microsomes, the present study suggests that reactive oxygen radical-induced lipid peroxidation is an important factor in PAH photoinduced toxicity to fish. [source] Evidence of oxidative stress in bluegill sunfish (Lepomis macrochirus) liver microsomes simultaneously exposed to solar ultraviolet radiation and anthraceneENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2000Jonghoon Choi Abstract Many polycyclic aromatic hydrocarbons (PAHs) are acutely toxic to fish and other aquatic organisms in the presence of environmentally realistic intensities of solar ultraviolet radiation (SUVR). However, the biochemical mechanism of this toxicity is not well established. In this study, increased levels of both reactive oxygen species production and lipid peroxidation were hypothesized as a toxic mechanism. To test this hypothesis, the production of superoxide anion and of a lipid peroxidation product (malondialdehyde) was measured in bluegill sunfish (Lepomis machrochirus) liver microsomes. These microsomes were exposed to a representative phototoxic PAH (anthracene [ANT]) and to SUVR and normal laboratory fluorescent light (FLU) in four different combinations: FLU + no ANT, FLU + ANT, SUVR + no ANT, and SUVR + ANT. The highest mean levels of both superoxide anion and malondialdehyde production were observed in the SUVR + ANT group, and these levels were significantly different (p < 0.05) from those in all other treatment groups. We conclude that the photoinduced toxicity of ANT, and possibly of other phototoxic PAHs, manifests at least in part through lipid peroxidation after increased production of reactive oxygen species. [source] Biological activity associated with noncoplanar polychlorinated biphenyls after microbial dechlorination of aroclor 1242® and aroclor 1254®ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2000Patricia E. Ganey Abstract Bioremediation of polychlorinated biphenyls (PCBs) byanaerobic microbial dechlorination occurring naturally in the subsurface and in engineered systems results in mixtures of lower-chlorinated, primarily ortho-substituted biphenyls. The purpose of this study was to determine whether this process of bacterial dechlorination results in a mixture that differs in biological activity from that of the parent PCB mixture. Two biological assays sensitive to the action of ortho-substituted PCBs were employed: insulin release by RINm5F cells, and superoxide anion (O2) production by rat neutrophils. The PCB mixtures Aroclor 1242® and Aroclor 1254® were incubated for nine months with microbes from PCB-contaminated sites (Silver Lake, MA, USA, or River Raisin, MI, USA), and the products of dechlorination were then extracted. Exposure of RINm5F cells to dechlorinated Aroclor 1242 or 1254 product mixtures caused an increase in insulin release similar to the hormone release from cells exposed to non-dechlorinated Aroclors. When tested alone, several of the major products identified in the dechlorination mixture (i.e., 2,2,,4,4,-tetrachlorobiphenyl, 2,2,,4-trichlorobiphenyl [TCB], 2,3,,4-TCB, 2,3,,5-TCB, and 2,2,-dichlorobiphenyl) caused an increase in insulin release. In studies using neutrophils isolated from rat peritoneum, the amount of O2 produced on exposure to product mixtures resulting from dechlorination of Aroclor 1242 was not different from the amount produced in nondechlorinated controls. The product mixture resulting from Aroclor 1254 dechlorination by organisms from River Raisin increased generation of O2, relative to the parent Aroclor. Taken together, these results suggest that anaerobic dechlorination of Aroclor mixtures of PCBs does not reduce the biological activities associated with lightly chlorinated and ortho -substituted PCBs. This observation has implications for the usefulness of PCB bioremediation efforts that involve only anaerobic dechlorination. [source] Laminar xanthine oxidase, superoxide dismutase and catalase activities in the prodromal stage of black-walnut induced equine laminitisEQUINE VETERINARY JOURNAL, Issue 1 2007J. P. LOFTUS Summary Reasons for study: Xanthine oxidase (XO)-dependent production of superoxide anion and hydrogen peroxide, a characteristic of ischaemia-reperfusion injury, may contribute to the development of equine laminitis. Objective: To determine the levels of XO and antioxidant enzymes (catalase, superoxide dismutase [SOD]) in the digital laminae of normal horses (CON) and horses in the developmental stage of laminitis using the black walnut extract (BWE) model. Methods: Healthy horses (n = 12) were administered BWE (BWE group, n = 6), or water (CON group, n = 6) through a nasogastric tube. At the onset of leucopenia in the BWE-treated animals, all horses were anaesthetised, digital laminae and other samples collected rapidly and flash frozen, and the animals subjected to euthanasia. Extracts of the frozen tissues were assayed for the 2 conformational forms of xanthine: oxygen oxidoreductase (XOR), namely, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), as well as the antioxidant enzymes, SOD and catalase. Results: Extracts of liver, lungs and skin, but not digital laminae, from either CON or BWE-treated horses had endogenous SOD, whereas all had endogenous XO and catalase. The levels of XDH, XO and catalase were similar in extracts of laminae from CON and BWE-treated horses as was the ratio of XDH to XO in extracts. Conclusions and potential relevance: The absence of increased XO activity suggest against the involvement of this reactive oxygen intermediate-generating system in the development of laminar pathology in BWE-treated horses. Conversely, the absence of SOD from extracts of equine digital laminae, but not other tissues, suggests that the equine digital laminae are highly susceptible to damage by superoxide anion, produced, for example, by emigrant inflammatory leucocytes. [source] Efficient DNA Cleavage Induced by Copper(II) Complexes of Hydrolysis Derivatives of 2,4,6-Tri(2-pyridyl)-1,3,5-triazine in the Presence of Reducing AgentsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 6 2007Joaquín Borrás Abstract The reaction of 2,4,6-tri(pyridyl)-1,3,5-triazine (ptz) and copper(II) salts in dmf/water (1:1) results in the hydrolysis of ptz and formation of the anions bis(2-pyridylcarbonyl)amide (ptO2,) and bis(2-pyridylamine)amide (ptN2,), which are found in the complexes [Cu(ptN2)(OAc)]·3H2O (1), [Cu(ptO2)(OAc)(H2O)]·H2O (2), [Cu(ptN2)(for)]·3H2O (3) (for = formate), [Cu(ptO2)(for)(H2O)] (4), [Cu(ptO2)(benz)]·H2O (5) (benz = benzoate), and [Cu(ptO2)F(H2O)]2·3H2O (6). This report includes the chemical and spectroscopic characterization of all these complexes along with the crystal structures of 4,6. The coordination spheres of CuII in 4 and 5 are best described as distorted tetragonal square pyramidal for the former and distorted square planar for the latter. The crystal structure of 6 shows the presence of two discrete monomeric [Cu(ptO2)F(H2O)] entities in the crystallographic asymmetric unit in which both copper(II) ions have a distorted square-pyramidal coordination geometry. The binding of the complexes to DNA has been investigated with the aid of viscosity and thermal denaturation studies, both of which indicate that the interaction is probably due to the outer-sphere mechanism. The ability of the compounds to cleave DNA has also been tested. Efficient oxidative cleavage was observed in the presence of a mild reducing agent (ascorbate) and dioxygen. Mechanistic studies with reactive oxygen species (ROS) scavengers confirm that hydrogen peroxide, the hydroxyl radical, singlet oxygen-like species, and the superoxide anion are necessary diffusible intermediates in the scission process. A mechanism involving either the Fenton or theHaber,Weiss reaction plus the formation of copper oxene species is proposed for the DNA cleavage mediated by these compounds.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Antioxidative activity of water extracts from the yam (Dioscorea opposita Thunb.) tuber mucilage tororoEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 6 2006Takeshi Nagai Abstract A water extract as a viscous solution was obtained from the yam Dioscorea opposita tuber mucilage tororo, and its functional properties were demonstrated. The protein content was about 280,,g/mL extract, and the main protein bands with an MW of ,33,kDa without 2-mercaptoethanol (2-ME) and ,31,kDa with 2-ME were detected by SDS-PAGE. The water extract possessed high antioxidative activity and scavenging activities against superoxide anion and hydroxyl radicals. However, it showed no inhibitory activity against angiotensin,I-converting enzyme. The yam tuber contains relatively high contents of vitamins, different micro- and macroelements, enzymes, and dietary fibers. The yam D.,opposita tuber will be increasingly regarded as a health-promoting food. [source] Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skinEXPERIMENTAL DERMATOLOGY, Issue 3 2002László Virág Abstract: In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO,), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO, on various cellular processes may explain the ,double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing ,cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases. [source] Possible role of exogenous cAMP to improve vascular endothelial dysfunction in hypertensive ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2006Dhvanit I. Shah Abstract The study has been designed to investigate the effect of 8-Br-cAMP, an activator of protein kinase A, in hypertension-induced vascular endothelial dysfunction. Rats were uninephroctomized and desoxycortisone acetate (DOCA) (40 mg/kg, s.c.) was administered to rats to produce hypertension (mean arterial blood pressure > 140 mmHg). Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta and serum concentration of nitrite/nitrate. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration and aortic superoxide anion concentration were estimated to assess oxidative stress. 8-Br-cAMP (5 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) prevented hypertension-induced attenuation of acetylcholine-induced endothelium-dependent relaxation, impairment of vascular endothelial lining, decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), serum nitrite/nitrate concentration and increase in expression of mRNA for p22phox, superoxide anion and serum TBARS. The ameliorative effect of 8-Br-cAMP was prevented by N -nitro- l -arginine methyl ester (25 mg/kg, i.p.) and glibenclamide (30 mg/kg, i.p.). It may be concluded that 8-Br-cAMP may stimulate expression and activity of eNOS and suppress expression of p22phox subunit of NADPH oxidase to reduce oxidative stress and subsequently improve vascular endothelial dysfunction. [source] Fluorescent Gold Nanoprobe Sensitive to Intracellular Reactive Oxygen SpeciesADVANCED FUNCTIONAL MATERIALS, Issue 12 2009Hyukjin Lee Abstract Gold nanoprobes immobilized with fluorescein-hyaluronic acid (HA) conjugates are fabricated and utilized for monitoring intracellular reactive oxygen species (ROS) generation in live cells via nanoparticle surface energy transfer. A bio-inspired adhesive molecule, dopamine, is used to robustly end-immobilize HA onto the surface of gold nanoparticles (AuNPs) for securing intracellular stability against glutathione. ROS induces cleavage and fragmentation of the HA chains immobilized on the surface of the AuNPs allows rapid and specific detection of intracellular ROS by emitting strong fluorescence-recovery signals. In particular, fluorescence-quenched gold nanoprobes exhibit selective and dose-dependent fluorescence-recovery signals upon exposure to certain oxygen species such as superoxide anion () and hydroxyl radical (·OH). The fluorescent gold nanoprobe is usefully exploited for real-time intracellular ROS detection and antioxidant screening assay, and has exciting potential for various biomedical applications as a new class of ROS imaging probes. [source] Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthmaIMMUNOLOGY, Issue 2 2006Marian L. Kruzel Summary Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases and in contact with mucosal surfaces generate superoxide anion (O2,,). In the presence of iron, O2,, may be converted to more reactive oxygen radicals, such as to H2O2 and/or ,OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NAD(P)H oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2,, to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders. [source] Antioxidant properties of methanolic extracts from Diospyros mespiliformis (jackal berry), Flacourtia indica (Batoka plum), Uapaca kirkiana (wild loquat) and Ziziphus mauritiana (yellow berry) fruitsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2008Ashwell R. Ndhlala Summary Four wild fruits, Diospyros mespiliformis, Flacourtia indica, Uapaca kirkiana and Ziziphus mauritiana, were extracted with methanol and analysed for radical-scavenging effect of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, reducing power and anion radical effect on superoxide anion using colorimetric method. There was an increase in the radical-scavenging effect, reducing power and superoxide anion radical-scavenging effect as the concentration of sample increased. Diospyros mespiliformis had high DPPH radical-scavenging capacity. The peels of F. indica and U. kirkiana had higher DPPH radical-scavenging effects, reducing power and superoxide-scavenging effects compared with the pulp while the pulp of Z. mauritiana had high DPPH radical-scavenging effects, reducing power and superoxide-scavenging effects compared with the peel. [source] Dichloroacetate- and trichloroacetate-induced oxidative stress in the hepatic tissues of mice after long-term exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010Ezdihar A. Hassoun Abstract Dichoroacetate (DCA) and trichloroacetate (TCA) were found to be hepatotoxic and hepatocarcinogenic in rodents. To investigate the role of oxidative stress in the long-term hepatotoxicity of the compounds, groups of mice were administered 7.7, 77, 154 and 410,mg,kg,1 per day, of either DCA or TCA, by gavage, for 4 weeks (4-W) and 13 weeks (13-W), and superoxide anion (SA), lipid peroxidation (LP) and DNA-single strand breaks (SSBs) were determined in the hepatic tissues. Significant increases in all of the biomarkers were observed in response to the tested doses of both compounds in the two test periods, with significantly greater increases observed in the 13-W, as compared with the 4-W, period. Hepatomegaly was only observed with a DCA dose of 410,mg,kg,1 per day in the 13-W treatment period, and that was associated with significant declines in the biomarkers, when compared with the immediately lower dose. With the exception of LP production in the 13-W treatment period that was similarly induced by the two compounds, the DCA-induced increases in all of the biomarkers were significantly greater than those of TCA. Since those biomarkers were significantly induced by the compounds' doses that were shown to be carcinogenic but at earlier periods than those demonstrating hepatotoxicity/haptocarcinogencity, they can be considered as initial events that may lead to later production of those long-term effects. The results also suggest LP to be a more significant contributing mechanism than SA and DNA damage to the long-term hepatotoxicity of TCA. Copyright © 2010 John Wiley & Sons, Ltd. [source] Mechanisms underlying the inhibition of the cytochrome P450 system by copper ionsJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2009M. E. Letelier Abstract Copper toxicity has been associated to the capacity of free copper ions to catalyze the production of superoxide anion and hydroxyl radical, reactive species that modify the structure and/or function of biomolecules. In addition, nonspecific Cu2+ -binding to thiol enzymes, which modifies their catalytic activities, has been reported. Cytochrome P450 (CYP450) monooxygenase is a thiol protein that binds substrates in the first and limiting step of CYP450 system catalytic cycle, necessary for the metabolism of lipophilic xenobiotics. Therefore, copper ions have the potential to oxidize and bind to cysteinyl residues of this monooxygenase, altering the CYP450 system activity. To test this postulate, we studied the effect of Cu2+ alone and Cu2+/ascorbate in rat liver microsomes, to independently evaluate its nonspecific binding and its pro-oxidant effects, respectively. We assessed these effects on the absorbance spectrum of the monooxygenase, as a measure of structural damage, and p -nitroanisole O -demethylating activity of CYP450 system, as a marker of functional impairment. Data obtained indicate that Cu2+ could both oxidize and bind to some amino acid residues of the CYP450 monooxygenase but not to its heme group. The differences observed between the effects of Cu2+ and Cu2+/ascorbate show that both mechanisms are involved in the catalytic activity inhibition of CYP450 system by copper ions. The significance of these findings on the pharmacokinetics and pharmacodynamics of drugs is discussed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Dichloroacetate- and trichloroacetate-induced phagocytic activation and production of oxidative stress in the hepatic tissues of mice after acute exposureJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2008Ezdihar A. Hassoun Abstract Dichoroacetate (DCA) and trichloroacetate (TCA) are by-products formed during chlorination of the drinking water and were found to be hepatotoxic and hepatocarcinogenic in rodents. In this study, the abilities of the compounds to induce oxidative stress and phagocytic activation have been studied in B6C3F1 mice. Groups of mice were administered 300 mg/kg of either DCA or TCA, p.o, and were sacrificed after 6 or 12 h. Peritoneal lavage cells (PLCs) were isolated and assayed for superoxide anion (SA) production, and hepatic tissues were assayed for the production of SA, lipid peroxidation (LP), and DNA-single strand breaks (SSBs). TCA resulted in significant production of SA in the PLCs, and in the production of SA, LP, and DNA-SSBs in the hepatic tissues, 12 h after dosing, as compared with the control. DCA administration, on the other hand, resulted in significant increases in the productions of LP and DNA-SSBs in the hepatic tissues at both time points, and in SA production in PLCs and hepatic tissues, 6 h after dosing. However, DCA-induced increases in SA production in PLC and hepatic tissues declined at the 12-h time point, reaching control level in the hepatic tissues. These results may implicate the contribution of phagocytic activation to the induction of oxidative stress in the hepatic tissues and also the role of SA production in the induction of LP and/or DNA damage in those tissues, in response to the compounds. The results also suggest studying the involvement of these mechanisms in the long-term hepatotoxicity/hepatocarcinogencity of the compounds. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:27,34, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20210 [source] The immunomodulatory effects of levamisole on the nonspecific immune system of Atlantic salmon, Salmo salar L.JOURNAL OF FISH DISEASES, Issue 6 2000V L Findlay Sea water-adapted Atlantic salmon, Salmo salar L., were given a 2-h bath in a 2.5 mg L,1 levamisole (as levamisole hydrochloride) solution in fresh-water. Following bathing, the fish were held in full salinity sea water for 2 weeks before being subjected to a number of immunological assays. Heightened activity of the nonspecific defence system was demonstrated by increases in phagocytic index, phagocytic capacity and phagocytic activity, increased levels of the reactive oxygen intermediate, superoxide anion, and an increased lytic activity of both the mucus and the serum. These results indicate that levamisole is effective in augmenting parts of the nonspecific defence system of Atlantic salmon. This is the first record of the use and efficacy of levamisole as an immunomodulator in Atlantic salmon. [source] ANTIOXBDANT PROPERTIES OF OREGANO (ORIGANUM VULGARE) LEAF EXTRACTSJOURNAL OF FOOD BIOCHEMISTRY, Issue 6 2000GIOVANNA CERVATO ABSTRACT We tested the antioxidant properties of both aqueous and methanolic extracts of oregano (origanum vulgare) They proved to be effective in the inhibition of all phases of the peroxidative process: first neutralizing free radicals (superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl radical), then blocking peroxidation catalysis by iron (through iron-chelating and iron-oxidizing properties), and finally through interruption of lipid-radical chain reactions (chain-breaking activity). Their anti-glycosylation activity was also effective. The glycosylation oflipoproteins is directly related to their peroxidation. The amount of extract used in our experiments was obtained from 0.1,1 mg of dried leaves, amounts far less than those normally used in the Mediterranean diet. [source] Effects of areca nut extracts on the functions of human neutrophils in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2000Shan-Ling Hung Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils. Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner. At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye. However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction. Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE. Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used. Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs. In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils. This effect may contribute to a less efficient elimination of bacteria from the periodontal environment. Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products. [source] Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2004Jing Gao The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCI4)-induced acute liver damage and D-galactosamine (D-GaIN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7- and 2.0-fold) induced by CCI4 were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100 mg kg,1 TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9- and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GaIN were blocked by pre-treatment with 0.05, 0.1, 0.5 gL,1 TCCE. In addition, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited by 50,500 ,m ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500 ,m, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals. [source] Cimetidine: antioxidant and metal-binding propertiesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2002Zaynab Lambat ABSTRACT Cimetidine is one of the most potent H2 receptor antagonists for inhibiting excessive histamine-induced acid secretion and is currently used worldwide to treat peptic ulcers. In this study, levels of free radicals were assessed and the ability of cimetidine to act as an antioxidant was determined using nitroblue-tetrazolium assay and lipid peroxidation assays. Free radical generation in the brain is promoted by the presence of iron, as occurs in the Fenton reaction. The results show that cimetidine reduces the generation of superoxide anion formed in the nitroblue-tetrazolium assay. In addition, cimetidine (1 mm) is able to reduce the iron-induced rise in lipid peroxidation in rat brain homogenates. Electrochemistry, UV/Vis spectroscopy and HPLC experiments show metal-ligand interactions between cimetidine and transition metals. The results imply that cimetidine provides a neuroprotective effect by binding to iron and copper, thus making them unavailable for free radical production. [source] Reactivity of C4-indolyl substituted 1,4-dihydropyridines toward superoxide anion (O2,) in dimethylsulfoxideJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6 2009Ricardo Salazar Abstract Reactivity of two new C4-indolyl substituted 1,4-dihydropyridines (1,4-DHPs) toward superoxide anion (O2,) in dimethylsulfoxide (DMSO) is reported. Reactivity was followed by electrochemical and spectroscopic techniques. Gas chromatography-mass spectrometry (GC,MS) was used to identify the final products of the reaction. C4 indolyl-substituted-1,4-DHPs reacted toward O2, at significant rates, according to the calculated kinetic rate constants. Results are compared with 4-phenyl-DHP and the commercial 1,4-DHPs, nimodipine, nisoldipine, and amlodipine. Indolyl-substituted 1,4-DHPs were more reactive than the commercial derivatives. The direct participation of proton of the 1-position of the secondary amine in the quenching of O2, was demonstrated. Copyright © 2008 John Wiley & Sons, Ltd. [source] Melatonin prevents endotoxin-induced circulatory failure in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2001Chin-Chen Wu The pineal secretory product melatonin was found to exert protective effects in septic shock. In a host infected by bacterial lipopolysaccharide (LPS), the expression and release of proinflammatory tumor necrosis factor-, (TNF-,) is rapidly increased, suggesting that TNF-, is associated with the etiology of endotoxic shock. Recent reports show that the expression of NO synthase (NOS) II and the production of superoxide anion ( in aortae. In addition, the infiltration of polymorphonuclear neutrophils into the liver from the surviving LPS mice treated with melatonin was reduced. Thus, our results support the clinical use of melatonin in endotoxemia. [source] Protective effects of melatonin in ischemic brain injuryJOURNAL OF PINEAL RESEARCH, Issue 4 2000Salvatore Cuzzocrea Recent studies have demonstrated that melatonin is a scavenger of oxyradicals and peroxynitrite and an inhibitor of nitric oxide (NO) production. NO, peroxynitrite (formed from NO and superoxide anion), and poly (ADP-Ribose) synthetase (PARS) have been implicated as mediators of neuronal damage following focal ischemia. In the present study, we have investigated the effects of melatonin treatment in Mongolian gerbils subjected to cerebral ischemia. Treatment of gerbils with melatonin (10 mg kg,1, 30 min before reperfusion and 1, 2, and 6 hr after reperfusion) reduced the formation of post-ischemic brain edema, evaluated by water content. Melatonin also attenuated the increase in the brain levels malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischemia. Positive staining for nitrotyrosine was found in the hippocampus of Mongolian gerbils subjected to cerebral ischemia. Hippocampus tissue sections, from Mongolian gerbils subjected to cerebral ischemia, also showed positive staining for PARS. The degrees of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received melatonin. Melatonin treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CA-1 showed a reduction of neuronal loss in animals that received melatonin. These results show that melatonin improves brain injury induced by transient cerebral ischemia. [source] | ||||||||||||||||||||||||||||||||||||||||