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Sample records for acid abts radical

  1. The Scavenging of DPPH, Galvinoxyl and ABTS Radicals by Imine Analogs of Resveratrol

    PubMed Central

    Kotora, Peter; Šeršeň, František; Filo, Juraj; Loos, Dušan; Gregáň, Juraj; Gregáň, Fridrich

    2016-01-01

    Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin produced by plants. Resveratrol is known for its anti-cancer, antiviral and antioxidant properties. We prepared imine analogs of resveratrol ((hydroxyphenyliminomethyl)phenols) and tested their antioxidant activity. All prepared resveratrol analogs were able to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR) and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The antioxidant activity efficiency correlated with the number and position of hydroxyl groups. The most effective antioxidants were resveratrol analogs containing three hydroxyl groups in the benzylidene part of their molecules. These results provide new insights into the relationship between the chemical structure and biological activity of resveratrol analogs. PMID:26805801

  2. Synthesis, crystal structure, ABTS radical-scavenging activity, antimicrobial and docking studies of some novel quinoline derivatives

    NASA Astrophysics Data System (ADS)

    Tabassum, Sumaiya; Suresha Kumara, T. H.; Jasinski, Jerry P.; Millikan, Sean P.; Yathirajan, H. S.; Sujan Ganapathy, P. S.; Sowmya, H. B. V.; More, Sunil S.; Nagendrappa, Gopalpur; Kaur, Manpreet; Jose, Gilish

    2014-07-01

    In this study, a series of nine novel 2-chloroquinolin-3-yl ester derivatives have been synthesized via a two-step protocol from 2-chloroquinoline-3-carbaldehyde. The structures of all these compounds were confirmed by spectral data. The single crystal X-ray structure of two derivatives, (2-chloroquinolin-3-yl)methyl acetate [6a] and (2-chloro-6-methylquinolin-3-yl)methyl acetate [6e] have also been determined. The synthesized compounds were further evaluated for their ABTS radical-scavenging activity and antimicrobial activities. Amongst all the tested compounds, 6a exhibited maximum scavenging activity with ABTS. Concerning antibacterial and antifungal activities, compound (2-chloro-6-methoxyquinolin-3-yl)methyl 2,4-dichlorobenzoate [6i] was found to be the most active in the series against B. subtilis, S. aureus, E. coli, K. pneumonia, C. albicans and A. niger species. The structure-antimicrobial activity relationship of these derivatives were studied using Autodock.

  3. Population pharmacokinetics and exposure-uric acid analyses after single and multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers.

    PubMed

    An, Guohua; Liu, Wei; Duan, W Rachel; Nothaft, Wolfram; Awni, Walid; Dutta, Sandeep

    2015-03-01

    ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT-639 after single- (up to 170 mg) and multiple doses (up to 160 mg BID) were evaluated in healthy volunteers in a randomized, double-blinded, placebo-controlled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic profiles in human. Results from assessment of the routine laboratory variables showed an unexpected statistically significant and clinically relevant decrease in blood uric acid with the increase in ABT-639 dose, which is possibly due to inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were constructed to characterize the relationship between ABT-639 exposure and uric acid response. The final model was a mechanism-based indirect response pharmacodynamic model with the stimulation of uric acid elimination by ABT-639. The model estimated K in values in males and females were 10.2 and 7.13 μmol/h, respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that can produce 50% stimulation in uric acid elimination was estimated to be 8,070 ng/mL. Based on the final model, further simulations were conducted to predict the effect of ABT-639 on uric acid in gout patients. The simulation results indicated that, if the urate-lowering response to ABT-639 in gout patients is similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would be expected to provide clinically meaningful lowering of blood uric acid levels below the 380 μmol/L solubility limit of monosodium urate. PMID:25567367

  4. Cytochrome c catalyses the formation of pentyl radical and octanoic acid radical from linoleic acid hydroperoxide.

    PubMed Central

    Iwahashi, Hideo; Nishizaki, Koji; Takagi, Ichiro

    2002-01-01

    A reaction of 13-hydroperoxide octadecadienoic acid (13-HPODE) with cytochrome c was analysed using ESR, HPLC-ESR and HPLC-ESR-MS by the combined use of the spin-trapping technique. The ESR, HPLC-ESR and HPLC-ESR-MS analyses showed that cytochrome c catalyses formation of pentyl and octanoic acid radicals from 13-HPODE. On the other hand, only the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone/octanoic acid radical adduct was detected in the elution profile of HPLC-ESR for a mixture of 13-HPODE with haematin, indicating that haematin catalyses the formation of octanoic acid radical. In addition, the reaction of 13-HPODE with cytochrome c was inhibited by chlorogenic acid, caffeic acid and ferulic acid via two possible mechanisms, i.e. reducing cytochrome c (chlorogenic acid and caffeic acid) and scavenging the radical intermediates (chlorogenic acid, caffeic acid and ferulic acid). PMID:11742529

  5. Antioxidant components of Viburnum opulus L. determined by on-line HPLC-UV-ABTS radical scavenging and LC-UV-ESI-MS methods.

    PubMed

    Karaçelik, Ayça Aktaş; Küçük, Murat; İskefiyeli, Zeynep; Aydemir, Sezgin; De Smet, Seppe; Miserez, Bram; Sandra, Patrick

    2015-05-15

    Antioxidant activity of the juice and seed and skin extracts prepared with methanol, acetonitrile, and water of Viburnum opulus L. grown in Eastern Black Sea Region were studied with an on-line HPLC-ABTS method and off-line antioxidant methods, among which a linear positive correlation was observed. The fruit extracts were analysed with the HPLC-UV method optimised with 14 standard phenolics. Identification of the phenolic components in the juice was made using an HPLC-UV-ESI-MS method. Nineteen phenolic compounds in juice were identified by comparing the retention times and mass spectra with those of the standards and the phenolics reported in the literature. The major peaks in the juice belonged to coumaroyl-quinic acid, chlorogenic acid, procyanidin B2, and procyanidin trimer. Quite different antioxidant composition profiles were obtained from the extracts with the solvents of different polarities. The antioxidant activities of the seed extracts were higher than those of the skin extracts in general. PMID:25577058

  6. Hydroxyl radical formation during peroxynitrous acid decomposition

    SciTech Connect

    Coddington, J.W.; Hurst, J.K.; Lymar, S.V.

    1999-03-24

    Yields of O{sub 2} formed during decomposition of peroxynitrous acid (ONOOH) under widely varying medium conditions are compared to predictions based upon the assumption that the reaction involves formation of discrete {sm{underscore}bullet}OH and {sm{underscore}bullet}NO{sub 2} radicals as oxidizing intermediates. The kinetic model used includes all reactions of {sm{underscore}bullet}OH, {sm{underscore}bullet}O{sub 2}{sup {minus}}, and reactive nitrogen species known to be important under the prevailing conditions; because the rate constants for all of these reactions have been independently measured, the calculations contain no adjustable fitting parameters. The model quantitatively accounts for (1) the complex pH dependence of the O{sub 2} yields and (2) the unusual effects of NO{sub 2} {sup {minus}}, which inhibits O{sub 2} formation in neutral, but not alkaline, solutions and also reverses inhibition by organic {sm{underscore}bullet}OH scavengers in alkaline media. Other observations, including quenching of O{sub 2} yields by ferrocyanide and bicarbonate, the pressure dependence of the decomposition rate, and the reported dynamic behavior for O{sub 2} generation in the presence of H{sub 2}O{sub 2}, also appear to be in accord with the suggested mechanism. Overall, the close correspondence between observed and calculated O{sub 2} yields provides strong support for decomposition via homolysis of the ONOOH peroxo bond.

  7. Free radicals. XXIII. Reaction of triphenylimidazolyl with CH acids

    SciTech Connect

    Tanaseichuk, B.S.; Belozerov, A.I.; Sanaeva, E.P.; Butin, K.P.

    1986-01-10

    The triphenylimidazolyl radical is capable of dehydrogenating ..beta..-dicarbonyl compounds which are characterized by a high content of the enolic form. The dehydrogenation rate increases with increase in the pK/sub a/ value of the enol. The formation of short-lived radicals during the dehydrogenation of CH acids by triphenylimidazolyl was confirmed by their capture by a spin trap (2,4,6-tribromo-nitrosobenzene). The diphenylaminyl radical also dehydrogenates nonenolizing CH acids with a sufficiently acid CH bond.

  8. Practical Radical Cyclizations with Arylboronic Acids and Trifluoroborates

    PubMed Central

    Lockner, Jonathan W.; Dixon, Darryl D.; Risgaard, Rune; Baran, Phil S.

    2011-01-01

    Practical radical cyclizations using organoboronic acids and trifluoroborates take place in water, open to air, and in a scalable fashion employing catalytic silver nitrate and stoichiometric potassium persulfate. Both Pschorr-type cyclizations and tandem radical cyclization/trap cascades are described, illustrating the utility of these mild conditions for the generation of polycyclic scaffolds. PMID:21923108

  9. Structural Insights into 2,2′-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS)-Mediated Degradation of Reactive Blue 21 by Engineered Cyathus bulleri Laccase and Characterization of Degradation Products

    PubMed Central

    Kenzom, T.; Srivastava, P.

    2014-01-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)]. This laccase was engineered to degrade effectively reactive blue 21 (RB21), a phthalocyanine dye reported to be decolorized only by peroxidases. The 816-bp segment (toward the C terminus) of the lcc gene was subjected to random mutagenesis and enzyme variants (Lcc35, Lcc61, and Lcc62) were selected based on increased ABTS oxidizing ability. Around 78 to 95% decolorization of RB21 was observed with the ABTS-supplemented Lcc variants in 30 min. Analysis of the degradation products by mass spectrometry indicated the formation of several low-molecular-weight compounds. Mapping the mutations on the modeled structure implicated residues both near and far from the T1 Cu site that affected the catalytic efficiency of the mutant enzymes on ABTS and, in turn, the rate of oxidation of RB21. Several inactive clones were also mapped. The importance of geometry as well as electronic changes on the reactivity of laccases was indicated. PMID:25261507

  10. In Vitro Antioxidant-Activity Evaluation of Gallic-Acid-Grafted Chitosan Conjugate Synthesized by Free-Radical-Induced Grafting Method.

    PubMed

    Hu, Qiaobin; Wang, Taoran; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

    2016-07-27

    The major objective of this work was to develop a green and facile process to prepare gallic acid-chitosan conjugate and comprehensively evaluate the physicochemical properties and biological activities of an as-prepared water-soluble chitosan derivative. A free-radical-induced grafting approach using an ascorbic acid-hydrogen peroxide redox pair was adopted. The obtained conjugate was characterized by Fourier transform infrared spectroscopy, UV-vis, X-ray diffraction, and pKa analysis. The antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulphonic acid (ABTS), reducing power, and oxygen-radical antioxidant-capacity assays. The results showed that the mass ratio of gallic acid to chitosan played a vital role in determining the grafting degree and ζ potential of the conjugates, with the ratio of 0.5:1 being the optimal ratio that resulted in the highest grafting degree. The antioxidant assays demonstrated that conjugation significantly improved the antioxidant activities, being dramatically higher than that of free chitosan. It was notable that the DPPH- and ABTS-scavenging activities of conjugate at 0.4 mg/mL reached the same level as the free gallic acid at the equivalent concentration. Our study demonstrated a green and facile synthesis approach to preparing a novel water-soluble chitosan derivative that may have promising potentials in the food industry. PMID:27379913

  11. Radical scavenging activity and cytotoxicity of ferulic acid.

    PubMed

    Ogiwara, Takako; Satoh, Kazue; Kadoma, Yoshinori; Murakami, Yukio; Unten, Senwa; Atsumi, Toshiko; Sakagami, Hiroshi; Fujisawa, Seiichiro

    2002-01-01

    Ferulic acid and eugenol were examined for their superoxide (O2-), hydroxyl radical (.OH) and nitric oxide (NO)-scavenging ability, using ESR spectroscopy with spin trap agents DMPO and carboxy-PTIO/NOC-7. Ferulic acid more efficiently scavenged .OH and NO than eugenol. The O2- scavenging activity of ferulic acid was comparable with that of eugenol. Ferulic acid significantly reduced the NO production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like cells (Raw 264.7 cells) compared to eugenol. The cytotoxic activity of ferulic acid against Raw 264.7 cells was comparable with that against human submandibular gland carcinoma (HSG) cells and the cytotoxicity of ferulic acid was about 10-fold smaller than that of eugenol. The stoichiometric factor (n) (number of moles of peroxy radical trapped by moles of the relevant phenol) of ferulic acid and eugenol was investigated, using the induction period methods of the methyl methacrylate polymerization system. The n-value of ferulic acid (1.5) was higher than that of eugenol (1.0) and was similar to that of 2, 6-di-t-butyl-4-methylphenol (BHT). Ferulic acid as well as eugenol may produce a dimer during the induction period due to an n-value less than 2. These results suggested that ferulic acid may be useful for preventing cell damage perhaps caused by O2-, and in particular by .OH and NO, in living systems. PMID:12529986

  12. Generation of hydroxyl radicals from metal-loaded humic acids

    SciTech Connect

    Paciolla, M.D.; Jansen, S.A.; Davies, G.

    1999-06-01

    Humic acids (HAs) are naturally occurring biopolymers that are ubiquitous in the environment. They are most commonly found in the soil, drinking water, and a variety of plants. Pharmacological and therapeutic studies involving humic acids have been reported to some extent. However, when certain transition metals are bound to humic acids, e.g., iron and copper, they can be harmful to biological organisms. For this study, humic acids were extracted from German, Irish, and New Hampshire soils that were selectively chosen because of their reich abundance in humic material. Each sample was treated at room temperature with 0.1 M ferric and cupric solutions for 48 h. The amount of iron and copper adsorbed by humic acid was accurately quantitated using atomic absorption spectroscopy. The authors further demonstrate that these metal-loaded humic acids can produce deleterious oxidizing species such as the hydroxyl radical (HO*) through the metal-driven Fenton reaction. Electron paramagnetic resonance (EPR) employing spin trapping techniques with 5,5-dimethylpyrroline N-oxide (DMPO) is used to confirm the generation of hydroxyl radicals. The DMPO-OH adduct with hyperfine splitting constants A{sub N} = A{sub H} = 14.9 G is observed upon the addition of exogenous hydrogen peroxide. The concentration of hydroxyl radical was determined using 4-hydroxytempo (TEMPO-OH) as a spin standard. The presence of another oxidizing species, Fe{double_bond}O{sup 2+}, is also proposed in the absence of hydrogen peroxide.

  13. Application of Controlled Radical Polymerization for Nucleic Acid Delivery

    PubMed Central

    CHU, DAVID S.H.; SCHELLINGER, JOAN G.; SHI, JULIE; CONVERTINE, ANTHONY J.; STAYTON, PATRICK S.; PUN, SUZIE H.

    2012-01-01

    CONSPECTUS Nucleic acid-based therapeutics can potentially address otherwise untreatable genetic disorders and have significant potential for a wide range of diseases. Therapeutic gene delivery can restore protein function by replacing defunct genes to restore cellular health while RNA interference (RNAi) can mask mutated and harmful genes. Cationic polymers have been extensively studied for nucleic acid delivery applications due to their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, but toxicity and particle stability have limited their clinical applications. The advent of controlled radical polymerization has improved the quality, control and reproducibility of synthesized materials. Controlled radical polymerization yields well-defined, narrowly disperse materials of designable architectures and molecular weight, allowing study of the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity for improved design of next-generation vectors. Robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) have been used to engineer materials that specifically enhance extracellular stability, cellular specificity, and decrease toxicity. This Account reviews findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. In addition, polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release are also discussed. Finally, promising materials with in vivo applications ranging from pulmonary gene delivery to DNA vaccines are described. PMID:22242774

  14. Unexpectedly high indoor hydroxyl radical concentrations associated with nitrous acid.

    PubMed

    Gómez Alvarez, Elena; Amedro, Damien; Afif, Charbel; Gligorovski, Sasho; Schoemaecker, Coralie; Schoemacker, Coralie; Fittschen, Christa; Doussin, Jean-Francois; Wortham, Henri

    2013-08-13

    The hydroxyl (OH) radical is the most important oxidant in the atmosphere since it controls its self-oxidizing capacity. The main sources of OH radicals are the photolysis of ozone and the photolysis of nitrous acid (HONO). Due to the attenuation of solar radiation in the indoor environment, the possibility of OH formation through photolytic pathways indoors has been ignored up to now. In the indoor air, the ozonolysis of alkenes has been suggested as an alternative route of OH formation. Models and indirect measurements performed up to now according to this hypothesis suggest concentrations of OH radicals on the order of 10(4)-10(5) molecules per cubic centimeter. Here, we present direct measurements of significant amounts of OH radicals of up to 1.8⋅10(6) molecules per cubic centimeter during an experimental campaign carried out in a school classroom in Marseille. This concentration is on the same order of magnitude of outdoor OH levels in the urban scenario. We also show that photolysis of HONO is an important source of OH radicals indoors under certain conditions (i.e., direct solar irradiation inside the room). Additionally, the OH concentrations were found to follow a linear dependence with the product J(HONO)⋅[HONO]. This was also supported by using a simple quasiphotostationary state model on the OH radical budget. These findings force a change in our understanding of indoor air quality because the reactivity linked to OH would involve formation of secondary species through chemical reactions that are potentially more hazardous than the primary pollutants in the indoor air. PMID:23898188

  15. Unexpectedly high indoor hydroxyl radical concentrations associated with nitrous acid

    PubMed Central

    Gómez Alvarez, Elena; Amedro, Damien; Afif, Charbel; Gligorovski, Sasho; Schoemaecker, Coralie; Fittschen, Christa; Doussin, Jean-Francois; Wortham, Henri

    2013-01-01

    The hydroxyl (OH) radical is the most important oxidant in the atmosphere since it controls its self-oxidizing capacity. The main sources of OH radicals are the photolysis of ozone and the photolysis of nitrous acid (HONO). Due to the attenuation of solar radiation in the indoor environment, the possibility of OH formation through photolytic pathways indoors has been ignored up to now. In the indoor air, the ozonolysis of alkenes has been suggested as an alternative route of OH formation. Models and indirect measurements performed up to now according to this hypothesis suggest concentrations of OH radicals on the order of 104–105 molecules per cubic centimeter. Here, we present direct measurements of significant amounts of OH radicals of up to 1.8⋅106 molecules per cubic centimeter during an experimental campaign carried out in a school classroom in Marseille. This concentration is on the same order of magnitude of outdoor OH levels in the urban scenario. We also show that photolysis of HONO is an important source of OH radicals indoors under certain conditions (i.e., direct solar irradiation inside the room). Additionally, the OH concentrations were found to follow a linear dependence with the product J(HONO)⋅[HONO]. This was also supported by using a simple quasiphotostationary state model on the OH radical budget. These findings force a change in our understanding of indoor air quality because the reactivity linked to OH would involve formation of secondary species through chemical reactions that are potentially more hazardous than the primary pollutants in the indoor air. PMID:23898188

  16. Pulse radiolytic study of the acid dissociation of OH protons in radicals related to salicylic acid

    SciTech Connect

    Sun, Q.; Schuler, R.H.

    1987-08-13

    The deprotonation of carboxylated benzosemiquinone radicals prepared by pulse radiolytic oxidation of dihydroxybenzoic acids has been examined by time-resolved absorption spectrophotometry. The pK/sub a/ for dissociation of the OH proton in 3-carboxyl-1,4-benzosemiquinone is found to be 6.47 or 2.4 units higher than that in the unsubstituted radical. This pK/sub a/ is, however, well below that of the OH proton in salicyclic acid (13.6) so that hydrogen bonding is appreciably decreased by the delocalization of the unpaired spin in this radical. Protonation of the basic form of the radical occurs at the diffusion-controlled rate. The rate constant for deprotonation by OH/sup -/ is relatively low, 4.7 X 10/sup 7/ M/sup -1/ s/sup -1/, so that reaction with base becomes important only above pH 10. As a result this radical provides an excellent system for studying acid-base equilibration processes in near neutral solutions. Azide ion is shown to be an efficient catalyst which allows the acid-base equilibrium to be examined on the 10-..mu..s time scale. Deprotonation is also catalyzed by the dihydroxybenzoic acid used as the radical source. Analogous studies on 4-carboxy-1,3-benzosemiquinone give the pK/sub a/ as 7.9. In spite of this high pK/sub a/, which indicates the rate constant for spontaneous dissociation of this radical to be > 10/sup 3/ s/sup -1/, the rate constant for deprotonation by OH/sup -/, 4.9 X 10/sup 8/ M/sup -1/ s/sup -1/, is considerably higher than in the case of 3-carboxy-1,4-benzosemiquinone.

  17. Atom Transfer Radical Polymerization of Methacrylic Acid: A Won Challenge.

    PubMed

    Fantin, Marco; Isse, Abdirisak A; Venzo, Alfonso; Gennaro, Armando; Matyjaszewski, Krzysztof

    2016-06-15

    Polymerization of acidic monomers is one of the biggest challenges for atom transfer radical polymerization (ATRP). An intramolecular cyclization reaction leading to the loss of the C-X chain-end functionality was found to be the main reason for the partial termination of the growing polymer chains. Three approaches were used to overcome this problem: using Cl as the chain-end halogen, lowering the pH (to 0.9), and increasing polymerization rate. Methacrylic acid (MAA) was polymerized by both electrochemically mediated ATRP and supplemental activator and reducing agent ATRP up to high conversion (>90%), in t ≤ 4 h at 25 °C, using inexpensive and nontoxic reagents (NaCl, diluted HCl, water). Control over molecular weight (MW) dispersity was satisfactory, and MWs were in agreement with theoretical values. The "livingness" of the process was confirmed by an electrochemical switch, used to repeatedly and periodically deactivate/reactivate growing chains. PMID:27244091

  18. Hydroxyl radical substitution in halogenated carbonyls: oxalic acid formation.

    PubMed

    Christiansen, Carrie J; Dalal, Shakeel S; Francisco, Joseph S; Mebel, Alexander M; Gaffney, Jeffrey S

    2010-03-01

    An ab initio study of OH radical substitution reactions in halogenated carbonyls is conducted. Hydroxyl radical substitution into oxalyl dichloride [ClC(O)C(O)Cl] and oxalyl dibromide [BrC(O)C(O)Br], resulting in the formation of oxalic acid, is presented. Analogous substitution reactions in formyl chloride [ClCH(O)], acetyl chloride [ClC(O)CH(3)], formyl bromide [BrCH(O)], and acetyl bromide [BrC(O)CH(3)] are considered. Energetics of competing hydrogen abstraction reactions for all applicable species are computed for comparison. Geometry optimizations and frequency computations are performed using the second-order Møller-Plesset perturbation theory (MP2) and the 6-31G(d) basis set for all minimum species and transition states. Single point energy computations are performed using fourth-order Møller-Plesset perturbation theory (MP4) and coupled cluster theory [CCSD(T)]. Potential energy surfaces, including activation energies and enthalpies, are determined from the computations. These potential energy surfaces show that OH substitution into ClC(O)C(O)Cl and BrC(O)C(O)Br, resulting in the formation of oxalic acid and other minor products, is energetically favorable. Energetics of analogous reactions with ClCH(O), BrCH(O), ClC(O)CH(3), and BrC(O)CH(3) are also computed. PMID:20131850

  19. Kinetics of the reaction of hydroxyl radicals with nitric acid

    NASA Technical Reports Server (NTRS)

    Margitan, J. J.; Watson, R. T.

    1982-01-01

    An extensive study was made of the reaction of hydroxyl radicals with nitric acid in a laser photolysis-resonance fluorescence system. A 266 nm laser was used to photolyze HNO3 in the temperature range 225-415 K at pressures of 20-300 torr. A temperature dependence was detected below room temperature, with a leveling off at 298 K and a wide spread in the rate constants. A pressure dependence was observed over the entire range and was more pronounced at lower temperatures. The results are noted to be in agreement with those of previous investigations. However, the wide range of rate constants are suggested to be a problem for stratospheric HO(x) modeling for anthropogenic effects. No explanation could be given of the varying results obtained by other investigators regarding the kinetics of the reactions.

  20. Characterization of the hyperline of D1/D0 conical intersections between the maleic acid and fumaric acid anion radicals

    NASA Astrophysics Data System (ADS)

    Takahashi, Ohgi; Sumita, Masato

    2004-10-01

    The cation and anion radicals of symmetrical 1,2-disubstituted ethylenes are expected to have a symmetry-allowed conical intersection (CI) between the ground doublet state (D0) and the lowest excited doublet state (D1) near a 90°-twisted geometry. By the complete active space self-consistent field method, we characterized the hyperline formed by D1/D0 CIs between the anion radicals of maleic acid (cis) and fumaric acid (trans). An implication of the results for the known one-way cis→trans photoisomerization of the maleic acid anion radical and other related ion radicals is presented.

  1. Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide.

    PubMed Central

    Rota, C; Barr, D P; Martin, M V; Guengerich, F P; Tomasi, A; Mason, R P

    1997-01-01

    The ESR spin-trapping technique was employed to investigate the reaction of rabbit cytochrome P-450 1A2 (P450) with linoleic acid hydroperoxide. This system was compared with chemical systems where FeSO4 or FeCl3 was used in place of P450. The spin trap 5, 5'-dimethyl-1-pyrroline N-oxide (DMPO) was employed to detect and identify radical species. The DMPO adducts of hydroxyl, O2-., peroxyl, methyl and acyl radicals were detected in the P450 system. The reaction did not require NADPH-cytochrome P-450 reductase or NADPH. The same DMPO-radical adducts were detected in the FeSO4 system. Only DMPO-.OH radical adduct and carbon-centred radical adducts were detected in the FeCl3 system. Peroxyl radical production was completely O2-dependent. We propose that polyunsaturated fatty acids are initially reduced to form alkoxyl radicals, which then undergo intramolecular rearrangement to form epoxyalkyl radicals. Each epoxyalkyl radical reacts with O2, forming a peroxyl radical. Subsequent unimolecular decomposition of this peroxyl radical eliminates O2-. radical. PMID:9371716

  2. Thermal-induced conversion of maleic and fumaric acid anion radicals in poly(methyl methacrylate)

    SciTech Connect

    Torikai, A.; Fukumoto, M.

    1980-04-01

    Thermal-induced conversion of maleic and fumaric acid anion radicals produced by ..gamma.. irradiation at 77/sup 0/K in poly(methyl methacrylate) (PMMA) was studied by electron spin resonance (ESR) and optical absorption spectroscopic measurements. The ESR spectra of these acid anion radicals change into two-line spectra with a line separation of ca. 10 G by thermal annealing. This spectrum is assigned to a protonated radical of each acid anion radical. Anion radicals of the solutes are relatively stable below the ..gamma.. transition point of PMMA and the conversion reaction takes place near this point. This means that the molecular motion of matrix molecule affects the radical conversion reaction.

  3. Performance evaluation of TCP over ABT protocols

    NASA Astrophysics Data System (ADS)

    Ata, Shingo; Murata, Masayuki; Miyahara, Hideo

    1998-10-01

    ABT is promising for effectively transferring a highly bursty data traffic in ATM networks. Most of past studies focused on the data transfer capability of ABT within the ATM layer. In actual, however, we need to consider the upper layer transport protocol since the transport layer protocol also supports a network congestion control mechanism. One such example is TCP, which is now widely used in the Internet. In this paper, we evaluate the performance of TCP over ABT protocols. Simulation results show that the retransmission mechanism of ABT can effectively overlay the TCP congestion control mechanism so that TCP operates in a stable fashion and works well only as an error recovery mechanism.

  4. Antioxidant and radical-scavenging activities of Slovak honeys - An electron paramagnetic resonance study.

    PubMed

    Zalibera, Michal; Staško, Andrej; Šlebodová, Anna; Jančovičová, Viera; Čermáková, Tatiana; Brezová, Vlasta

    2008-09-15

    The antioxidant properties of 15 honey samples from different floral sources and various Slovak regions were investigated by means of electron paramagnetic resonance spectroscopy. Cation radical of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) diammonium salt), DPPH (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals generated by the photochemical decomposition of hydrogen peroxide were used as oxidants. The antioxidant activities found with ABTS(+), expressed as trolox equivalent antioxidant capacity (TEAC), ranged from 0.15 to 1.14mmolkg(-1), and those determined with DPPH, from 0.04 to 0.32mmolkg(-1). TEAC values correlated well with results found by elimination of DPPH, and both values revealed a linear relationship with the concentration of phenolics obtained with the Folin-Ciocalteu phenol test (expressed as gallic acid equivalents, GAE). The colour coordinates (CIE L(∗)a(∗)b(∗)), as well as reflectance spectra determined for original honeys using a white background, demonstrated that the colour difference (ΔE(∗)) and coordinate b(∗) interrelate with TEAC values. The radical-scavenging capacities (RSC) of the honey samples determined in the experiments with photochemically decomposed hydrogen peroxide, generating reactive OH radicals in the presence of spin trapping agent, differ from those found with ABTS(+) and DPPH. Here, probably, the reactive OH radicals, having higher redox potential, are scavenged by a variety of compounds not effective with ABTS(+) and DPPH (e.g., saccharides, proteins). PMID:26049247

  5. ABTS as an Electron Shuttle to Enhance the Oxidation Kinetics of Substituted Phenols by Aqueous Permanganate.

    PubMed

    Song, Yang; Jiang, Jin; Ma, Jun; Pang, Su-Yan; Liu, Yong-Ze; Yang, Yi; Luo, Cong-Wei; Zhang, Jian-Qiao; Gu, Jia; Qin, Wen

    2015-10-01

    In this study, it was, interestingly, found that 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate (ABTS), a widely used electron shuttle, could greatly accelerate the oxidation of substituted phenols by potassium permanganate (Mn(VII)) in aqueous solutions at pH 5-9. This was attributed to the fact that these substituted phenols could be readily oxidized by the stable radical cation (ABTS(•+)), which was quickly produced from the oxidation of ABTS by Mn(VII). The reaction of Mn(VII) with ABTS exhibited second-order kinetics, with stoichiometries of ∼5:1 at pH 5-6 and ∼3:1 at pH 7-9, and the rate constants varied negligibly from pH 5 to 9 (k = (9.44 ± 0.21) × 10(4) M(-1) s(-1)). Comparatively, the reaction of ABTS(•+) with phenol showed biphasic kinetics. The second-order rate constants for the reactions of ABTS(•+) with substituted phenols obtained in the initial phase were strongly affected by pH, and they were several orders of magnitude higher than those for the reactions of Mn(VII) with substituted phenols at each pH. Good Hammett-type correlations were found for the reactions of ABTS(•+) with undissociated (log(k) = 2.82-4.31σ) and dissociated phenols (log(k) = 7.29-5.90σ). The stoichiometries of (2.2 ± 0.06):1 (ABTS(•+) in excess) and (1.38 ± 0.18):1 (phenol in excess) were achieved in the reaction of ABTS(•+) with phenol, but they exhibited no pH dependency. PMID:26378975

  6. Reaction of oleic acid particles with NO3 radicals: Products, mechanism, and implications for radical-initiated organic aerosol oxidation.

    PubMed

    Docherty, Kenneth S; Ziemann, Paul J

    2006-03-16

    The heterogeneous reaction of liquid oleic acid aerosol particles with NO3 radicals in the presence of NO2, N2O5, and O2 was investigated in an environmental chamber using a combination of on-line and off-line mass spectrometric techniques. The results indicate that the major reaction products, which are all carboxylic acids, consist of hydroxy nitrates, carbonyl nitrates, dinitrates, hydroxydinitrates, and possibly more highly nitrated products. The key intermediate in the reaction is the nitrooxyalkylperoxy radical, which is formed by the addition of NO3 to the carbon-carbon double bond and subsequent addition of O2. The nitrooxyalkylperoxy radicals undergo self-reactions to form hydroxy nitrates and carbonyl nitrates, and may also react with NO2 to form nitrooxy peroxynitrates. The latter compounds are unstable and decompose to carbonyl nitrates and dinitrates. It is noteworthy that in this reaction nitrooxyalkoxy radicals appear not to be formed, as indicated by the absence of the expected products of decomposition or isomerization of these species. This is different from gas-phase alkene-NO3 reactions, in which a large fraction of the products are formed through these pathways. The results may indicate that, for liquid organic aerosol particles in low NOx environments, the major products of the radical-initiated oxidation (including by OH radicals) of unsaturated and saturated organic compounds will be substituted forms of the parent compound rather than smaller decomposition products. These compounds will remain in the particle and can potentially enhance particle hygroscopicity and the ability of particles to act as cloud condensation nuclei. PMID:16526637

  7. Evaluation of the Antiradical Properties of Phenolic Acids

    PubMed Central

    Koroleva, Olga; Torkova, Anna; Nikolaev, Ilya; Khrameeva, Ekaterina; Fedorova, Tatyana; Tsentalovich, Mikhail; Amarowicz, Ryszard

    2014-01-01

    Antioxidant capacity (AOC) against peroxyl radical and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical cation was measured for a series of p-hydroxybenzoic (HB) and p-hydroxycinnamic (HC) acids at different pH. Quantum-chemical computation was performed using Gaussian 3.0 software package to calculate the geometry and energy parameters of the same compounds. Significant correlations were revealed between AOC and a number of calculated parameters. The most significant AOC descriptors for the studied compounds against peroxyl radical were found to be HOMO energy, rigidity (η) and Mulliken charge on the carbon atom in m-position to the phenolic hydroxyl. The most significant descriptor of the antioxidant properties against the ABTS radical cation at pH 7.40 is electron transfer enthalpy from the phenolate ion. The mechanism of AOC realization has been proposed for HB and HC acids against both radicals. PMID:25229820

  8. Unprotected Amino Acids as Stable Radical Precursors for Heterocycle C-H Functionalization.

    PubMed

    Mai, Duy N; Baxter, Ryan D

    2016-08-01

    An efficient and general method for the C-H alkylation of heteroarenes using unprotected amino acids as stable alkyl radical precursors is reported. This one-pot procedure is performed open to air under aqueous conditions and is effective for several natural and unnatural amino acids. Heterocycles of varying structure are suitably functionalized, and reactivity trends reflect the nucleophilic character of the radical species generated. PMID:27452036

  9. Ascorbic acid metabolism in protection against free radicals: A radiation model

    SciTech Connect

    Rose, R.C. )

    1990-06-15

    The role of ascorbic acid in scavenging free radicals was evaluated in a model of mammalian colonic epithelium homogenized in physiologic buffer and exposed to ionizing radiation. Ascorbic acid interacts with hydroxyl free radicals, resulting in production of the ascorbate free radical (AFR). Colonic mucosa contains a soluble factor that is heat sensitive, PCA precipitable and is contained within 1,000 MW dialysis tubing; it uses GSH and cysteine to reduce AFR. The factor from rat colon is fractionated between 55 and 70% saturation with solid (NH4)2SO4; a 3-4 fold increase in enzyme activity was achieved. We suggest that the factor is a cytosolic enzyme appropriately referred to as soluble AFR-reductase. This information provides insight into the mechanism by which ascorbic acid protects against damage by hydroxyl free radicals.

  10. Acid Is Key to the Radical-Trapping Antioxidant Activity of Nitroxides.

    PubMed

    Haidasz, Evan A; Meng, Derek; Amorati, Riccardo; Baschieri, Andrea; Ingold, Keith U; Valgimigli, Luca; Pratt, Derek A

    2016-04-27

    Persistent dialkylnitroxides (e.g., 2,2,6,6-tetramethylpiperidin-1-oxyl, TEMPO) play a central role in the activity of hindered amine light stabilizers (HALS)-additives that inhibit the (photo)oxidative degradation of consumer and industrial products. The accepted mechanism of HALS comprises a catalytic cycle involving the rapid combination of a nitroxide with an alkyl radical to yield an alkoxyamine that subsequently reacts with a peroxyl radical to eventually re-form the nitroxide. Herein, we offer evidence in favor of an alternative reaction mechanism involving the acid-catalyzed reaction of a nitroxide with a peroxyl radical to yield an oxoammonium ion followed by electron transfer from an alkyl radical to the oxoammonium ion to re-form the nitroxide. In preliminary work, we showed that TEMPO reacts with peroxyl radicals at diffusion-controlled rates in the presence of acids. Now, we show that TEMPO can be regenerated from its oxoammonium ion by reaction with alkyl radicals. We have determined that this reaction, which has been proposed to be a key step in TEMPO-catalyzed synthetic transformations, occurs with k ∼ 1-3 × 10(10) M(-1) s(-1), thereby enabling it to compete with O2 for alkyl radicals. The addition of weak acids facilitates this reaction, whereas the addition of strong acids slows it by enabling back electron transfer. The chemistry is shown to occur in hydrocarbon autoxidations at elevated temperatures without added acid due to the in situ formation of carboxylic acids, accounting for the long-known catalytic radical-trapping antioxidant activity of TEMPO that prompted the development of HALS. PMID:27023326

  11. Enhancement of carboxylic acid degradation with sulfate radical generated by persulfate activation.

    PubMed

    Criquet, J; Nebout, P; Karpel Vel Leitner, N

    2010-01-01

    The aim of this work was to investigate the generation of sulfate radical for the removal of two carboxylic acids in aqueous solution: acetic and citric acids. From photochemical and radiolytic processes, kinetics of the degradation of these two carboxylic acids was studied as a function of the pH of the solution. It was shown that the maximum of acetic acid degradation occurred at pH 5. Above this pH, competitive reactions with the carbon mineralized inhibit the reaction of with the solute. In the case of citric acid, pH has only a little effect on the kinetic of citric acid degradation. The determination of mineralization yields shows several differences depending on carboxylic acids and pH. The degradation of both carboxylic acids was also studied in the radiolysis process whether with or without persulfate addition. A comparison of the processes of sulfate radical production is presented. PMID:20220244

  12. Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: mechanistic aspects and antioxidant activity.

    PubMed

    Joshi, Ravi; Kumar, Sudheer; Unnikrishnan, M; Mukherjee, T

    2005-11-01

    Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD). PMID:16298742

  13. E.S.R. of spin-trapped radicals in gamma-irradiated polycrystalline amino acids. Chromatographic separation of radicals.

    PubMed

    Makino, K; Riesz, P

    1982-06-01

    The free radicals produced by gamma-radiolysis of polycrystalline amino acids (L-valine, L-leucine, L-isoleucine and L-proline) at room temperature in the absence of air were investigated by spin trapping with 2-methyl-2-nitrosopropane (MNP). The spin adducts produced by dissolving the irradiated solids in aqueous MNP solutions were separated by high-performance liquid chromatography and then identified by e.s.r. Deamination (ring-opening reaction for L-proline) was observed for all amino acid. For L-valine and L-leucine, H-abstraction from the tertiary carbon in the side chains occurred. For isoleucine, H-abstractions from the alpha-carbon of the amino acid and from a non-terminal carbon in the side chain were found. PMID:6288602

  14. Interactive enhancements of ascorbic acid and iron in hydroxyl radical generation in quinone redox cycling.

    PubMed

    Li, Yi; Zhu, Tong; Zhao, Jincai; Xu, Bingye

    2012-09-18

    Quinones are toxicological substances in inhalable particulate matter (PM). The mechanisms by which quinones cause hazardous effects can be complex. Quinones are highly active redox molecules that can go through a redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species. Electron spin resonance spectra have been reported for semiquinone radicals in PM, indicating the importance of ascorbic acid and iron in quinone redox cycling. However, these findings are insufficient for understanding the toxicity associated with quinone exposure. Herein, we investigated the interactions among anthraquinone (AQ), ascorbic acid, and iron in hydroxyl radical (·OH) generation through the AQ redox cycling process in a physiological buffer. We measured ·OH concentration and analyzed the free radical process. Our results showed that AQ, ascorbic acid, and iron have synergistic effects on ·OH generation in quinone redox cycling; i.e., ascorbyl radical oxidized AQ to semiquinone radical and started the redox cycling, iron accelerated this oxidation and enhanced ·OH generation through Fenton reactions, while ascorbic acid and AQ could help iron to release from quartz surface and enhance its bioavailability. Our findings provide direct evidence for the redox cycling hypothesis about airborne particle surface quinone in lung fluid. PMID:22891791

  15. Radical C-H arylations of (hetero)arenes catalysed by gallic acid.

    PubMed

    Perretti, Marcelle D; Monzón, Diego M; Crisóstomo, Fernando P; Martín, Víctor S; Carrillo, Romen

    2016-07-12

    Gallic acid efficiently catalyses radical arylations in water-acetone at room temperature. This methodology proved to be versatile and scalable. Therefore, it constitutes a greener alternative to arylation. Moreover, considering that gallic acid is an abundant vegetable tannin, this work also unleashes an alternative method for the reutilisation of bio-wastes. PMID:26804947

  16. Antioxidant and radical scavenging properties of curcumin.

    PubMed

    Ak, Tuba; Gülçin, Ilhami

    2008-07-10

    Curcumin (diferuoyl methane) is a phenolic compound and a major component of Curcuma longa L. In the present paper, we determined the antioxidant activity of curcumin by employing various in vitro antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH*) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by the Fe(3+)-Fe(2+) transformation method, superoxide anion radical scavenging by the riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe(2+)) chelating activities. Curcumin inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 microg/mL concentration (20 mM). On the other hand, butylated hydroxyanisole (BHA, 123 mM), butylated hydroxytoluene (BHT, 102 mM), alpha-tocopherol (51 mM) and trolox (90 mM) as standard antioxidants indicated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 microg/mL concentration, respectively. In addition, curcumin had an effective DPPH* scavenging, ABTS*(+) scavenging, DMPD*(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, BHA, BHT, alpha-tocopherol and trolox, were used as the reference antioxidant and radical scavenger compounds. According to the present study, curcumin can be used in the pharmacological and food industry because of these properties. PMID:18547552

  17. Radical C-H alkylation of BODIPY dyes using potassium trifluoroborates or boronic acids.

    PubMed

    Verbelen, Bram; Cunha Dias Rezende, Lucas; Boodts, Stijn; Jacobs, Jeroen; Van Meervelt, Luc; Hofkens, Johan; Dehaen, Wim

    2015-09-01

    A one-step synthetic procedure for the radical CH alkylation of BODIPY dyes has been developed. This new reaction generates alkyl radicals through the oxidation of boronic acids or potassium trifluoroborates and allows the synthesis of mono-, di-, tri-, and tetraalkylated fluorophores in a good to excellent yield for a broad range of organoboron compounds. Using this protocol, multiple bulky alkyl groups can be introduced onto the BODIPY core thus creating solid-state emissive BODIPY dyes. PMID:26215785

  18. Radical Changes in Lewis Acid Catalysis: Matching Metal and Substrate.

    PubMed

    Bleith, Tim; Deng, Qing-Hai; Wadepohl, Hubert; Gade, Lutz H

    2016-06-27

    Whereas the stereochemical rigidity of the coordination sphere of boxmi/Cu(II) catalysts is key to achieving high enantioselectivity in the electrophilic alkylation of β-ketoesters, this pathway is outperformed by a radical process for the corresponding catalytic transformation of oxindoles, giving rise to racemic products. For the corresponding Zn(II) catalysts, the selectivity in the latter process is outstanding despite the greater plasticity of the coordination shell. This reaction was thus developed into a highly useful synthetic method, which enabled the conversion of wide range of substrates with high yields and enantioselectivities. PMID:27253736

  19. OH-radical induced degradation of hydroxybenzoic- and hydroxycinnamic acids and formation of aromatic products—A gamma radiolysis study

    NASA Astrophysics Data System (ADS)

    Krimmel, Birgit; Swoboda, Friederike; Solar, Sonja; Reznicek, Gottfried

    2010-12-01

    The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH 3 by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.

  20. Reactions of reducing and oxidizing radicals with caffeic acid:. a pulse radiolysis and theoretical study

    NASA Astrophysics Data System (ADS)

    Li, Xifeng; Cai, Zhongli; Katsumura, Yosuke; Wu, Guozhong; Muroya, Yusa

    2001-01-01

    Molecular calculations coupled with pulse radiolysis studies are performed to understand the reactions of radicals with caffeic acid. From molecular calculation, we find that e aq- and ·OH tend to form adducts with caffeic acid, while N 3rad tends to abstract H from 4-hydroxyl group in benzene ring, generating a semi-quinoid radical. Based on comparison of the heat of formation, the most favorable radical attack sites and the most stable radical structures are predicted. The calculation results suggest that the stability of the electron adducts radicals < ·OH adducts of caffeic ions, in good agreement with their experimental second-order decay rate constants (2 k=(1.1±0.2)×10 9, (6.0±0.4)×10 7 and (2.0±0.2)×10 7 M -1 s -1, respectively), determined by pulse radiolysis. Molecular calculations seem to be a powerful tool to predict the stability and structures of transient radicals.

  1. Kinetics and Products of Heterogeneous Oxidation of Oleic acid, Linoleic acid and Linolenic acid in Aerosol Particles by Hydroxyl radicals

    NASA Astrophysics Data System (ADS)

    Nah, T.; Leone, S. R.; Wilson, K. R.

    2010-12-01

    A significant mass fraction of atmospheric aerosols is composed of a variety of oxidized organic compounds with varying functional groups that may affect the rate at which they chemically age. Here we study the heterogeneous reaction of OH radicals with different sub-micron, alkenoic acid particles: Oleic acid (OA), Linoleic acid (LA), and Linolenic acid (LNA), in the presence of H2O2 and O2. This research explores how OH addition reactions initiate chain reactions that rapidly transform the chemical composition of an organic particle. Particles are chemically aged in a photochemical flow tube reactor where they are exposed to OH radicals (~ 1011 molecule cm-3 s) that are produced by the photolysis of H2O2 at 254 nm. The aerosols are then sized and their composition analyzed via Atmospheric Pressure Chemical Ionization (APCI). Detailed kinetic measurements show that the reactive uptake coefficient is larger than 1, indicating the presence of secondary chemistry occurring in the condensed phase. Reactive uptake coefficient is found to scale linearly with the number of double bonds present in the molecule. In addition, the reactive uptake coefficient is found to depend sensitively upon the concentrations of O2 in the photochemical flow tube reactor, indicating that O2 plays a role in secondary chemistry. In the absence of O2 the reactive uptake coefficient increases to ~ 8, 5 and 3 for LNA, LA, and OA, respectively. The reactive uptake coefficient approaches values of 6, 4 and 2 for LNA, LA, and OA respectively when 18% of the total nitrogen flow is replaced with O2. Mechanistic pathways and products will also be presented herein.

  2. Niobium Complexes As Lewis Acid and Radical Catalysts

    SciTech Connect

    Wayne Tikkanen

    2005-10-01

    The reaction of lithium pentaphenylcyclopentadiende (Li C{sub 5}Ph{sub 5}) with niobium pentachloride in dichloromethane or toluene produces insoluble red-orange solids whose C/H/Cl analyses are not consistent with C{sub 5}Ph{sub 5}NbCl{sub 4}. Addition of an acetonitrile solution of LiC{sub 5}Ph{sub 5} with NbCl{sub 5} gives C{sub 5}Ph{sub 5}NbCl{sub 4} observed as a transient product by NMR spectroscopy, which then abstracts H from the acetonitrile solvent to give HC{sub 5}Ph{sub 5} and presumably NbCl{sub 4}CH{sub 2}CN. Reversal of the order of addition gives the {center_dot}C{sub 5}Ph{sub 5} radical as characterized by MS and EPR spectroscopy. Attempts to prepare the trimethylsilyl derivative Me{sub 3}SiC{sub 5}Ph{sub 5} (a less reducing cyclopentadienyl group) were unsuccessful. Reaction was observed only in tetrahydrofuran, producing only Me{sub 3}SiO(CH{sub 2}){sub 4}C{sub 5}Ph{sub 4}(m-C{sub 6}H{sub 4}(CH3)) characterized by {sup 1}H, {sup 13}C NMR and mass spectroscopy. The trimethylsilyltetraphenylcyclopentadienyl derivative, Me{sub 3}Si(H)C{sub 5}Ph{sub 4}, was characterized by {sup 1}H, {sup 13}C NMR and mass spectroscopy. This compound reacts with NbCl{sub 5} to give HCl and ClSiMe{sub 3} and a mixture of HC{sub 5}Ph{sub 4}NbCl{sub 4} and Me{sub 3}SiC{sub 5}Ph{sub 4}NbCl{sub 4}.

  3. Reactions of clofibric acid with oxidative and reductive radicals-Products, mechanisms, efficiency and toxic effects

    NASA Astrophysics Data System (ADS)

    Csay, Tamás; Rácz, Gergely; Salik, Ádám; Takács, Erzsébet; Wojnárovits, László

    2014-09-01

    The degradation of clofibric acid induced by hydroxyl radical, hydrated electron and O2-•/HO2• reactive species was studied in aqueous solutions. Clofibric acid was decomposed more effectively by hydroxyl radical than by hydrated electron or O2-•/HO2•. Various hydroxylated, dechlorinated and fragmentation products have been identified and quantified. A new LC-MS method was developed based on 18O isotope labeling to follow the formation of hydroxylated derivatives of clofibric acid. Possible degradation pathways have been proposed. The overall degradation was monitored by determination of sum parameters like COD, TOC and AOX. It was found that the organic chlorine degrades very effectively prior to complete mineralization. After the treatment no toxic effect was found according to Vibrio fischeri tests. However, at early stages some of the reaction products were more harmful than clofibric acid.

  4. Enhancement of hydroxyl radical generation in the Fenton reaction by alpha-hydroxy acid.

    PubMed

    Ali, M A; Konishi, T

    1998-09-01

    The effect of various organic acids on hydroxyl radical (.OH) generation in the Fenton reaction were examined by the ESR spin trapping technique, where 5,5-dimethyl-1-pyroline-N-nitroxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN) were used as the spin trapping reagents. alpha-Hydroxy acids such as lactic acid, glycolic acid and 2-hydroxy isobutyric acid were found to markedly enhance .OH generation in the reaction. In contrast, beta-hydroxy acid, alpha-keto acid, esters of alpha-hydroxy acids, aldehydes and other straight chain organic acids had no such enhancing activity. alpha-Amino acids had also no enhancing effect. The results suggest that the alpha-hydroxy acid moiety is prerequisite for the enhancement of .OH generation in the Fenton reaction. Superoxide dismutase did not inhibit the enhancing effect of alpha-hydroxy acids whereas catalase completely inhibited the .OH generation. Thus, alpha-hydroxy acids directly enhanced the .OH generation via the Fenton reaction but not the Haber-Weiss reaction. Possible role of lactic acid manipulating .OH generation is discussed in relation to the ischemia-reperfusion cell damage. PMID:9784848

  5. Hypochlorous acid as a precursor of free radicals in living systems.

    PubMed

    Panasenko, O M; Gorudko, I V; Sokolov, A V

    2013-12-01

    Hypochlorous acid (HOCl) is produced in the human body by the family of mammalian heme peroxidases, mainly by myeloperoxidase, which is secreted by neutrophils and monocytes at sites of inflammation. This review discusses the reactions that occur between HOCl and the major classes of biologically important molecules (amino acids, proteins, nucleotides, nucleic acids, carbohydrates, lipids, and inorganic substances) to form free radicals. The generation of such free radical intermediates by HOCl and other reactive halogen species is accompanied by the development of halogenative stress, which causes a number of socially important diseases, such as cardiovascular, neurodegenerative, infectious, and other diseases usually associated with inflammatory response and characterized by the appearance of biomarkers of myeloperoxidase and halogenative stress. Investigations aimed at elucidating the mechanisms regulating the activity of enzyme systems that are responsible for the production of reactive halogen species are a crucial step in opening possibilities for control of the development of the body's inflammatory response. PMID:24490735

  6. Photolysis of nitrous acid as a primary source of OH radicals indoors

    NASA Astrophysics Data System (ADS)

    Gomez Alvarez, E.; Amedro, D.; Afif, C.; Gligorovski, S.; Schoemacker, C.; Fittschen, C. M.; Doussin, J.; Wortham, H.

    2013-12-01

    Hydroxyl radical (OH) is the most important oxidant in the atmosphere controlling its self- oxidizing capacity. The main sources of OH radicals are the photolysis of ozone and the photolysis of nitrous acid (HONO). Due to the attenuation of solar radiation in the indoor environment, the possibility of OH formation through photolytic pathways indoors has been, up to now, ignored. We present the first direct measurement of OH radicals in the indoor environment. To the present moment, only indirect measurements based on the follow-up of different tracers or model studies had been carried out. The measurements were carried out between July, 19 and July, 30, 2011 in a classroom of 170 m3 with two large windows, oriented northwest. The effect of different concentrations of NO2 and RH were tested for their effect on the generation of HONO. In order to measure the generation of OH radicals under different light intensities, the experiments were performed at three different periods during the day, corresponding to different light intensity levels: 1) (11 a.m. to 15.00 p.m.), 2) (15.00 p.m. to 19.00 p.m.) and 3) (21.00 p.m. to 00:30 a.m.). A pool of state-of-the-art analytical instrumentation was deployed to tackle the objectives set. We measured OH radical concentrations of up to 1.8 106 cm-3 in the indoor environment (Gomez Alvarez et al., 2013). We also show that photolysis is an important source of OH radicals indoors under certain conditions, i.e. direct solar irradiation inside the room. HONO was the most probable precursor, considering the different sources leading to OH formation by photolysis. Additionally, the OH concentrations were found to follow a linear dependence with J(HONO) [HONO]. This was also supported by employing a simple quasi-photostationary state model (PSS) on the OH radical budget. These findings force a change in our understanding of indoor air quality as the reactivity linked to OH would involve formation of secondary species through chemical

  7. Sub-millitesla magnetic field effects on the recombination reaction of flavin and ascorbic acid radicals.

    PubMed

    Evans, Emrys W; Kattnig, Daniel R; Henbest, Kevin B; Hore, P J; Mackenzie, Stuart R; Timmel, Christiane R

    2016-08-28

    Even though the interaction of a <1 mT magnetic field with an electron spin is less than a millionth of the thermal energy at room temperature (kBT), it still can have a profound effect on the quantum yields of radical pair reactions. We present a study of the effects of sub-millitesla magnetic fields on the photoreaction of flavin mononucleotide with ascorbic acid. Direct control of the reaction pathway is achieved by varying the rate of electron transfer from ascorbic acid to the photo-excited flavin. At pH 7.0, we verify the theoretical prediction that, apart from a sign change, the form of the magnetic field effect is independent of the initial spin configuration of the radical pair. The data agree well with model calculations based on a Green's function approach that allows multinuclear spin systems to be treated including the diffusive motion of the radicals, their spin-selective recombination reactions, and the effects of the inter-radical exchange interaction. The protonation states of the radicals are uniquely determined from the form of the magnetic field-dependence. At pH 3.0, the effects of two chemically distinct radical pair complexes combine to produce a pronounced response to ∼500 μT magnetic fields. These findings are relevant to the magnetic responses of cryptochromes (flavin-containing proteins proposed as magnetoreceptors in birds) and may aid the evaluation of effects of weak magnetic fields on other biologically relevant electron transfer processes. PMID:27586950

  8. Development of an HPLC post-column antioxidant assay for Solidago canadensis radical scavengers.

    PubMed

    Marksa, Mindaugas; Radušienė, Jolita; Jakštas, Valdas; Ivanauskas, Liudas; Marksienė, Rūta

    2016-01-01

    The aim of this work was to modify and validate the post-column high-performance liquid chromatography (HPLC)-ABTS and DPPH methods for evaluating the antioxidant activity of the methanolic extracts of Solidago canadensis (Canadian goldenrod) leaves and flowers. Separation of the analytes was performed via the HPLC-PDA method on a YMC analytical column using a gradient elution program. Three compounds with antioxidant properties - chlorogenic acid, rutin and isoquercitrin - and two unidentified antioxidants were established. The research showed that the coil temperature regimes and loop length combinations influence the optimised post-column assay method for detecting the antioxidant activity of goldenrod radical scavengers. Investigations established that the temperature in the reaction coil was a substantial factor contributing to the signal strength of the analytes after reacting with the DPPH and ABTS radicals. PMID:25835071

  9. Formation of stable radicals in catechin/nitrous acid systems: participation of dinitrosocatechin.

    PubMed

    Morina, Filis; Takahama, Umeo; Mojović, Miloš; Popović-Bijelić, Ana; Veljović-Jovanović, Sonja

    2016-03-01

    Catechins are transformed into dinitrosocatechins (diNOcats) and then oxidized to the quinones by salivary nitrite under conditions simulating the stomach. This manuscript deals with formation of stable radicals in the NO group of diNOcat during nitrite-induced oxidation of (+)-catechin and diNOcat at pH 2. We postulated two mechanisms for the stable radical formation; one is nitrous acid-induced oxidation of diNOcat in the A-ring, and the other intermolecular charge transfer from the A-ring of diNOcat and/or diNOcat quinone to the quinone moiety of the B-ring of diNOcat quinone. In addition, an unstable phenoxyl radical, which might be transformed into quinone, was also produced, accompanying the formation of the stable radical on the NO group. Taking the above results into account, we mainly focus on the adverse effects of the radicals and quinone, which may be produced from (+)-catechin in the stomach under the conditions of high salivary nitrite concentrations. PMID:26471661

  10. Free Radicals, Salicylic Acid and Mycotoxins in Asparagus After Inoculation with Fusarium proliferatum and F. oxysporum.

    PubMed

    Dobosz, Bernadeta; Drzewiecka, Kinga; Waskiewicz, Agnieszka; Irzykowska, Lidia; Bocianowski, Jan; Karolewski, Zbigniew; Kostecki, Marian; Kruczynski, Zdzislaw; Krzyminiewski, Ryszard; Weber, Zbigniew; Golinski, Piotr

    2011-09-01

    Electron paramagnetic resonance was used to monitor free radicals and paramagnetic species like Fe, Mn, Cu generation, stability and status in Asparagus officinalis infected by common pathogens Fusarium proliferatum and F. oxysporum. Occurrence of F. proliferatum and F. oxysporum, level of free radicals and other paramagnetic species, as well as salicylic acid and mycotoxins content in roots and stems of seedlings were estimated on the second and fourth week after inoculation. In the first term free and total salicylic acid contents were related to free radicals level in stem (P = 0.010 and P = 0.033, respectively). Concentration of Fe(3+) ions in porphyrin complexes (g = 2.3, g = 2.9) was related to the species of pathogen. There was no significant difference between Mn(2+) concentrations in stem samples; however, the level of free radicals in samples inoculated with F. proliferatum was significantly higher when compared to F. oxysporum. PMID:21957331

  11. Radical scavenging ability of gallic acid toward OH and OOH radicals. Reaction mechanism and rate constants from the density functional theory.

    PubMed

    Marino, Tiziana; Galano, Annia; Russo, Nino

    2014-09-01

    Gallic acid is a ubiquitous compound, widely distributed in the vegetal kingdom and frequently found in the human diet. In the present work, its primary antioxidant activity has been investigated using the density functional theory (DFT), and the quantum mechanics-based test for overall free radical scavenging activity (QM-ORSA) protocol. It was found that gallic acid is a better antioxidant than the reference compound, Trolox, regardless of the polarity of the environment. In addition, gallic acid is predicted to be among the best peroxyl radical scavengers identified so far in nonpolar (lipid) media. This compound is capable of scavenging hydroxyl radicals at diffusion-limited rates, and hydroperoxyl radicals with rate constants in the order of 10(5) M(-1) s(-1). The deprotonation of gallic acid, in aqueous solution, is predicted to increase the protective action of this compound against oxidative stress. Gallic acid was also identified as a versatile scavenger, capable of rapidly deactivating a wide variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) via electron transfer at physiological pH. PMID:25119432

  12. Free radical mediated formation of 3-monochloropropanediol (3-MCPD) fatty acid diesters.

    PubMed

    Zhang, Xiaowei; Gao, Boyan; Qin, Fang; Shi, Haiming; Jiang, Yuangrong; Xu, Xuebing; Yu, Liangli Lucy

    2013-03-13

    The present study was conducted to test the hypothesis that a free radical was formed and mediated the formation of 3-monochloropropanediol (3-MCPD) fatty acid diesters, a group of food contaminants, from diacylglycerols at high temperature under a low-moisture condition for the first time. The presence of free radicals in a vegetable oil kept at 120 °C for 20 min was demonstrated using an electron spin resonance (ESR) spectroscopy examination with 5,5-dimethylpyrroline-N-oxide (DMPO) as the spin trap agent. ESR investigation also showed an association between thermal treatment degree and the concentration of free radicals. A Fourier transform infrared spectroscopy (FT-IR) analysis of sn-1,2-stearoylglycerol (DSG) at 25 and 120 °C suggested the possible involvement of an ester carbonyl group in forming 3-MCPD diesters. On the basis of these results, a novel free radical mediated chemical mechanism was proposed for 3-MCPD diester formation. Furthermore, a quadrupole-time of flight (Q-TOF) MS/MS investigation was performed and detected the DMPO adducts with the cyclic acyloxonium free radical (CAFR) and its product MS ions, proving the presence of CAFR. Furthermore, the free radical mechanism was validated by the formation of 3-MCPD diesters through reacting DSG with a number of organic and inorganic chlorine sources including chlorine gas at 120 and 240 °C. The findings of this study might lead to the improvement of oil and food processing conditions to reduce the level of 3-MCPD diesters in foods and enhance food safety. PMID:23425600

  13. Lewis-Acid-Mediated Stereospecific Radical Polymerization of Acrylimides Bearing Chiral Oxazolidinones.

    PubMed

    Fujita, Takehiro; Yamago, Shigeru

    2015-12-14

    Lewis acid (MgBr2)-catalyzed radical polymerization of acrylimides bearing chiral oxazolidinones gave highly isotactic polyacrylimides with up to >99% meso tetrad (mmm) selectivity. Polymerization in the absence of Lewis acid gave atactic polymers with 80% racemo diad (r) selectivity; the selectivity was deliberately tuned from 80% r to >99% mmm by varying the polymerization conditions. The polyacrylimide was quantitatively converted to corresponding polyacrylates while preserving the stereoregularity, thus providing a general method for the synthesis of atactic to isotactic polyacrylates. PMID:26500040

  14. Oxygen dependency of one-electron reactions generating ascorbate radicals and hydrogen peroxide from ascorbic acid.

    PubMed

    Boatright, William L

    2016-04-01

    The effect of oxygen on the two separate one-electron reactions involved in the oxidation of ascorbic acid was investigated. The rate of ascorbate radical (Asc(-)) formation (and stability) was strongly dependent on the presence of oxygen. A product of ascorbic acid oxidation was measurable levels of hydrogen peroxide, as high as 32.5 μM from 100 μM ascorbic acid. Evidence for a feedback mechanism where hydrogen peroxide generated during the oxidation of ascorbic acid accelerates further oxidation of ascorbic acid is also presented. The second one-electron oxidation reaction of ascorbic acid leading to the disappearance of Asc(-) was also strongly inhibited in samples flushed with argon. In the range of 0.05-1.2 mM ascorbic acid, maximum levels of measurable hydrogen peroxide were achieved with an initial concentration of 0.2 mM ascorbic acid. Hydrogen peroxide generation was greatly diminished at ascorbic acid levels of 0.8 mM or above. PMID:26593628

  15. ACID GAS REMOVAL CHARACTERISTICS OF CORONA RADICAL SHOWER SYSTEM FOR A TREATMENT OF STATIONARY ENGINE FLUE GAS

    EPA Science Inventory

    Acid gas removal experiments are carried out in large bench scale corona radical shower reactor. A simulated engine flue gas is air mixed with NO, SO2 and CH4. Optimums for acid gas removal rate have been conducted in terms of the ammonia to acid gas molar ratio, the applied volt...

  16. [Inhibition of oxygen free radicals in potassium channels of cardiac myocytes and the action of salvianolic acid A].

    PubMed

    Bao, G

    1993-10-01

    By using the patch clamp technique, the effect of oxygen free radicals on the single potassium channels of cardiac papillary muscle cells were studied, as well as the action of salvianolic acid A. It was found that xanthane-xanthane oxidase generated oxygen free radicals could apparently inhibited the unitary currents of the single potassium channel activity. This inhibition was reversed by salvianolic acid A, which is an effective component extracted from Salvia miltiorrhiza. PMID:8168213

  17. Do stable nitroxide radicals catalyze or inhibit the degradation of hyaluronic acid?

    PubMed

    Lurie, Ziva; Offer, Tal; Russo, Angelo; Samuni, Amram; Nitzan, Dorrit

    2003-07-15

    Reactive oxygen-derived species and particularly OH radicals can degrade hyaluronic acid (HA), resulting in a loss of viscosity and a subsequent decrease in its effectiveness as a joint-lubricating agent. The production of OH in the vicinity of HA can be catalyzed by bound redox-active metals, which participate in the Haber-Weiss reaction. Damage to HA can also occur as a result of hypochlorite formed by myeloperoxidase (MPO). The protective reagents commonly used to inhibit oxidative stress-induced degradation of HA include antioxidative enzymes, such as SOD and catalase, chelators that coordinate metal ions rendering them redox-inactive, and scavengers of radicals, such as OH, as well as nonradical reactive species. In recent years, stable cyclic nitroxides have also been widely used as effective antioxidants. In many cases, nitroxide antioxidants operate catalytically and mediate their protective effect through an exchange between their oxidized and reduced forms. It was anticipated, therefore, that nitroxides would protect HA from oxidative degradation as well. On the other hand, nitroxides serve as catalysts in many oxidation reactions of alcohols, sugars and polysaccharides, including hyalouronan. Such opposite effects of nitroxides on oxidative degradation are particularly intriguing and the aim of the present study was to examine their effect on HA when subjected to diverse forms of oxidative stress. The results indicate that nitroxides protect HA from OH radicals generated enzymatically or radiolytically. The protective effect is attributable neither to the scavenging of OH nor to the oxidation of reduced metal, but to the reaction of nitroxides with secondary carbohydrate radicals-most likely peroxyl radicals. PMID:12853073

  18. The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein

    SciTech Connect

    Vogler, Meike; Dickens, David; Dyer, Martin J.S.; Owen, Andrew; Pirmohamed, Munir; Cohen, Gerald M.

    2011-05-06

    Highlights: {yields} The BCL2-inhibitor ABT-263 is a substrate for P-glycoprotein. {yields} Apoptosis is inhibited by P-glycoprotein expression. {yields} Overexpression of P-glycoprotein may contribute to resistance to ABT-263 or ABT-737. -- Abstract: Inhibition of BCL2 proteins is one of the most promising new approaches to targeted cancer therapy resulting in the induction of apoptosis. Amongst the most specific BCL2-inhibitors identified are ABT-737 and ABT-263. However, targeted therapy is often only effective for a limited amount of time because of the occurrence of drug resistance. In this study, the interaction of BCL2-inhibitors with the drug efflux transporter P-glycoprotein was investigated. Using {sup 3}H labelled ABT-263, we found that cells with high P-glycoprotein activity accumulated less drug. In addition, cells with increased P-glycoprotein expression were more resistant to apoptosis induced by either ABT-737 or ABT-263. Addition of tariquidar or verapamil sensitized the cells to BCL2-inhibitor treatment, resulting in higher apoptosis. Our data suggest that the BCL2-inhibitors ABT-737 and ABT-263 are substrates for P-glycoprotein. Over-expression of P-glycoprotein may be, at least partly, responsible for resistance to these BCL2-inhibitors.

  19. Performance and penetration of laccase and ABTS inks on various printing substrates.

    PubMed

    Matilainen, Katriina; Hämäläinen, Tiina; Savolainen, Anne; Sipiläinen-Malm, Thea; Peltonen, Jouko; Erho, Tomi; Smolander, Maria

    2012-02-01

    Introduction of an enzyme and a colour-forming reagent into paper enables the development of an authenticity indicator. The purpose of this work was to study the performance of Trametes versicolor laccase, TvL, and ABTS, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt, in various printing substrates when printed with inkjet. The printing substrates included pre-coated mechanical paper additionally coated with PVA, silica and latex. The focus was on the bioanalytical performance and ink penetration. The setting of the printed TvL and ABTS ink was studied visually, with optical and confocal microscopy and with a so-called tape laminating technique. Technical properties of the printing substrates and effect of the surface chemistry were discussed and related to the bioanalytical properties. TvL activity persisted well during the printing. The best colour response was attained using the PVA-coated base paper. The film-forming ability of the PVA was found to be the main contributor to the colour reaction. The uniform, dense and non-porous PVA layer retains the ABTS and TVL molecules on top of the printing substrate. The high local ink concentration on the PVA coating layer combined with the absorptive paper substrate suggests that the PVA film acts as a filtering layer which retains TvL and ABTS molecules in the coating layer but allows most of the ink solvents to penetrate into the paper structure. TvL and ABTS molecules are also trapped in the PVA polymer network due to swelling effect of water. Electrostatic attractions between the PVA and ABTS and TvL molecules do not contribute to the colour reaction. PMID:22051108

  20. Spectroscopic studies on the antioxidant activity of p-coumaric acid.

    PubMed

    Kiliç, Ismail; Yeşiloğlu, Yeşim

    2013-11-01

    p-coumaric acid (4-hydroxycinnamic acid), a phenolic acid, is a hydroxyl derivative of cinnamic acid. It decreases low density lipoprotein (LDL) peroxidation and reduces the risk of stomach cancer. In vitro radical scavenging and antioxidant capacity of p-coumaric acid were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe(2+)) chelating activity and ferric ions (Fe(3+)) reducing ability. p-Coumaric acid inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45μg/mL concentration. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and ascorbic acid displayed 66.8%, 69.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, p-coumaric acid had an effective DPPH scavenging, ABTS(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that p-coumaric acid can be used in the pharmacological and food industry because of these properties. PMID:23892112

  1. Kinetic Reaction Mechanism of Sinapic Acid Scavenging NO2 and OH Radicals: A Theoretical Study.

    PubMed

    Lu, Yang; Wang, AiHua; Shi, Peng; Zhang, Hui; Li, ZeSheng

    2016-01-01

    The mechanism and kinetics underlying reactions between the naturally-occurring antioxidant sinapic acid (SA) and the very damaging ·NO2 and ·OH were investigated through the density functional theory (DFT). Two most possible reaction mechanisms were studied: hydrogen atom transfer (HAT) and radical adduct formation (RAF). Different reaction channels of neutral and anionic sinapic acid (SA-) scavenging radicals in both atmosphere and water medium were traced independently, and the thermodynamic and kinetic parameters were calculated. We find the most active site of SA/SA- scavenging ·NO2 and ·OH is the -OH group in benzene ring by HAT mechanism, while the RAF mechanism for SA/SA- scavenging ·NO2 seems thermodynamically unfavorable. In water phase, at 298 K, the total rate constants of SA eliminating ·NO2 and ·OH are 1.30×108 and 9.20×109 M-1 S-1 respectively, indicating that sinapic acid is an efficient scavenger for both ·NO2 and ·OH. PMID:27622460

  2. Comparison of a novel extraction-based colorimetric (ABTS) method with membrane introduction mass spectrometry (MIMS): trichloramine dynamics in pool water.

    PubMed

    Soltermann, Fabian; Widler, Tobias; Canonica, Silvio; von Gunten, Urs

    2014-07-01

    Trichloramine is a hazardous disinfection by-product, which is present in chlorinated swimming pools. Although it is primarily taken up by inhalation, the concentration in pool water is important to monitor pool water quality and to assess trichloramine mitigation strategies. To date, scarce data is available on trichloramine concentration in pool water due to the lack of a suitable and easily applicable analytical method. This study presents a novel low cost, colorimetric method which is easy to operate and suitable for on-site measurements of trichloramine concentrations ≥0.05 μM (≥0.01 mg L(-1) as Cl2). The analytical method (termed "extraction-based ABTS method") consists of, (i) trichloramine stripping from pool water samples, (ii) passing it through a solid phase filter, composed of silica gel impregnated with sulfamic acid to eliminate interferences and (iii) trichloramine reaction with the indicator 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) to produce the coloured ABTS(•-) radical, which is measured at λ = 405 nm to determine the trichloramine concentration in the pool water sample. A comparison of the extraction-based ABTS method with membrane introduction mass spectrometry (MIMS) for 28 pool samples revealed a good correlation of the two methods. The trichloramine concentration in pool samples is correlated to HOCl, which is the most important factor for its formation. Other parameters such as combined chlorine and pH play a minor role while no correlation between trichloramine and the urea or the TOC concentration was observed. On-site measurements with MIMS in a wading pool over 6 days with a time resolution of 1 h confirmed that trichloramine concentrations strongly responded to changes in free chlorine concentrations. A diurnal measurement of trichloramine with a time resolution of 20 min revealed that trichloramine concentrations reacted quickly and sensitively to the bather load and that urea is

  3. Antioxidant and Free Radical Scavenging Capacity of Seed and Shell Essential Oils Extracted from Abrus precatorius (L)

    PubMed Central

    Okoh, Sunday O.; Asekun, Olayinka T.; Familoni, Oluwole B.; Afolayan, Anthony J.

    2014-01-01

    Essential oils from plants have been proven safe as natural antioxidants, and few are already marketed as digestive enhancers as well as in prevention of several degenerative diseases. This study evaluated the antioxidant capacity of seed and shell essential oils of Abrus precatorius (L), a herb used for ethno-medicinal practices in Nigeria. The essential oils were obtained by hydro-distillation. The ability of the oils to act as hydrogen/electrons donor or scavenger of radicals were determined by in-vitro antioxidant assays using 2,2-diphenyl-2-picryl-hydrazyl free radical (DPPH.) scavenging; 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging; lipid peroxide and nitric oxide radicals scavenging assays. The IC50 of the seed and shell oils (2.10 mg/mL and 1.20 mg/mL respectively) showed that antioxidant activity is higher than that for the standard drugs (3.20 mg/mL and 3.40 mg/mL) for the nitric oxide scavenging assay. The lipid peroxidation radical activity of the oils were similar to vitamin C, weak DPPH and ABTS radical scavenging activities were discovered in comparison to vitamin C and rutin. Generally, in the four antioxidant assays, a significant correlation existed between concentrations of the oils and percentage inhibition of free radicals and lipid peroxidation. The composition of A. precatorius essential oils reported earlier may account for their antioxidant capacity. PMID:26784871

  4. Breaking the dogma: PCB-derived semiquinone free radicals do not form covalent adducts with DNA, GSH, and amino acids.

    PubMed

    Wangpradit, Orarat; Rahaman, Asif; Mariappan, S V Santhana; Buettner, Garry R; Robertson, Larry W; Luthe, Gregor

    2016-02-01

    Covalent bond formations of free radical metabolites with biomolecules like DNA and proteins are thought to constitute a major mechanism of toxicity and carcinogenesis. Glutathione (GSH) is generally accepted as a radical scavenger protecting the cell. In the present study, we investigated a semiquinone radical (SQ(●-)) metabolite of the semivolatile 4-chlorobiphenyl, using electron paramagnetic resonance spectroscopy, and oxygen consumption. Proton nuclear magnetic resonance ((1)H NMR) and liquid chromatography-mass spectrometry (LC-MS) were also employed to elucidate the radical interaction with DNA, amino acids, and GSH. We found that DNA and oligonucleotides stabilized SQ(●-) by electron delocalization in the π-stacking system, resulting in persistent radical intercalated, rather than forming a covalent bond with SQ(●-). This finding was strongly supported by the semiempirical calculation of the semioccupied molecular orbital and the linear combination of the atomic orbitals, indicating 9.8 kcal mol(-1) energy gain. The insertion of SQ(●-) into the DNA strand may result in DNA strand breaks and interruption of DNA replication process or even activate radical mediated secondary reactions. The presence of amino acids resulted in a decrease of the electron paramagnetic resonance (EPR) signal of SQ(●-) and correlated with their isoelectric points. The pH shifts the equilibrium of the dianions of hydroquinone and influenced indirectly the formation of SQ(●-). Similar findings were observed with GSH and Cys. GSH and Cys functioned as indirect radical scavengers; their activities depend on their chemical equilibria with the corresponding quinones, and their further reaction via Michael addition. The generally accepted role of GSH as radical scavenger in biological systems should be reconsidered based upon these findings, questioning the generally accepted view of radical interaction of semiquinones with biologically active compounds, like DNA, amino acids

  5. Reactivity of chlorine radical with submicron palmitic acid particles: kinetic measurements and products identification

    NASA Astrophysics Data System (ADS)

    Mendez, M.; Ciuraru, R.; Gosselin, S.; Batut, S.; Visez, N.; Petitprez, D.

    2013-06-01

    The heterogeneous reaction of Cl. radicals with sub-micron palmitic acid (PA) particles was studied in an aerosol flow tube in the presence or in the absence of O2. Fine particles were generated by homogeneous condensation of PA vapors and introduced in the reactor where chlorine atoms are produced by photolysis of Cl2 using UV lamps surrounding the reactor. The effective reactive uptake coefficient (γ) has been determined from the rate loss of PA measured by GC/MS analysis of reacted particles as a function of the chlorine exposure. In the absence of O2, γ = 14 ± 5 indicates efficient secondary chemistry involving Cl2. GC/MS analyses have shown the formation of monochlorinated and polychlorinated compounds in the oxidized particles. Although, the PA particles are solid, the complete mass can be consumed. In the presence of oxygen, the reaction is still dominated by secondary chemistry but the propagation chain length is smaller than in the absence of O2 which leads to an uptake coefficient γ = 3 ± 1. In the particulate phase, oxocarboxylic acids and dicarboxylic acids are identified by GC/MS. Formation of alcohols and monocarboxylic acids are also suspected. All these results show that solid organic particles could be efficiently oxidized by gas-phase radicals not only on their surface, but also in bulk by mechanisms which are still unclear. Furthermore the identified reaction products are explained by a chemical mechanism showing the pathway of the formation of more functionalized products. They help to understand the aging of primary tropospheric aerosol containing fatty acids.

  6. Reactivity of chlorine radical with submicron palmitic acid particles: kinetic measurements and product identification

    NASA Astrophysics Data System (ADS)

    Mendez, M.; Ciuraru, R.; Gosselin, S.; Batut, S.; Visez, N.; Petitprez, D.

    2013-12-01

    The heterogeneous reaction of Cl• radicals with submicron palmitic acid (PA) particles was studied in an aerosol flow tube in the presence or in the absence of O2. Fine particles were generated by homogeneous condensation of PA vapours and introduced into the reactor, where chlorine atoms were produced by photolysis of Cl2 using UV lamps surrounding the reactor. The effective reactive uptake coefficient (γ) has been determined from the rate loss of PA measured by gas chromatography-mass spectrometer (GC/MS) analysis of reacted particles as a function of the chlorine exposure. In the absence of O2, γ = 14 ± 5 indicates efficient secondary chemistry involving Cl2. GC/MS analysis has shown the formation of monochlorinated and polychlorinated compounds in the oxidized particles. Although the PA particles are solid, the complete mass can be consumed. In the presence of oxygen, the reaction is still dominated by secondary chemistry but the propagation chain length is smaller than in the absence of O2, which leads to an uptake coefficient γ = 3 ± 1. In the particulate phase, oxocarboxylic acids and dicarboxylic acids were identified by GC/MS. The formation of alcohols and monocarboxylic acids is also suspected. A reaction pathway for the main products and more functionalized species is proposed. All these results show that solid organic particles could be efficiently oxidized by gas-phase radicals not only on their surface but also in bulk by mechanisms which are still unclear. They help to understand the aging of primary tropospheric aerosol containing fatty acids.

  7. Oxidation of Fe III porphyrins by peroxyl radicals derived from 2-propanol and methanol. Evidence for acid-dependent and acid-independent pathways

    NASA Astrophysics Data System (ADS)

    Brault, D.; Neta, P.

    1985-11-01

    Iron(III) deuteroporphyrin dimethyl ester is oxidized to the radical cation form by the peroxyl radicals CH 2(OH)O 2- and (CH 3) 2C(OH)O 2- generated by pulse radiolysis of air saturated aqueous solutions of methanol and 2-propanol, respectively. Oxidation by CH 2(OH)O 2- radicals proceeds with k = 1×10 7 M -1 s -1 independent of pH. In contrast, the electron-transfer reaction of (CH 3) 2C(OH)O 2-1 is pH-dependent. A reaction scheme, which may apply to all peroxyl radicals depending on relative rate constants, is proposed. It involves the formation of an iron porphyrin peroxyl radical adduct that decays by acid-dependent and acid-independent routes.

  8. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    PubMed

    Genaro-Mattos, Thiago C; Maurício, Ângelo Q; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its beneficial effects

  9. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation—A Chemical Approach

    PubMed Central

    Genaro-Mattos, Thiago C.; Maurício, Ângelo Q.; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here—in association with its reported signaling effects—could be an explanation to its beneficial effects

  10. Radical production from photosensitization of imidazoles, benzophenone and 4-benzoylbenzoic acid

    NASA Astrophysics Data System (ADS)

    Corral Arroyo, Pablo; González, Laura; Steimer, Sarah; Volkamer, Rainer; George, Christian; Bartels-Rausch, Thorsten; Ammann, Markus

    2016-04-01

    Reactions promoted by light are key in atmospheric chemistry. Some of them occur in the condensed phase of aerosols which may contain light absorbing organic compounds that provoke photochemical reactions such as humic like material (GEORGE 2005). Our aim is to understand the role these reactions play in atmospheric photochemistry. This work explores the radical reactions initiated by UV light in mixtures of citric acid (CA) and imidazole-2-carboxaldehyde (IC), benzophenone and 4-Benzoylbenzoic acid (BBA) using NO as a probe molecule for HO2, by means of coated wall flow tube experiments. The loss of NO was measured by a chemiluminescence detector (CLD), also configured for the distinction of the products (HONO or NO2). The dependence of the NO loss on the initial NO concentration, the photosensitizer concentration in the film, relative humidity, light intensity, oxygen molar fraction were investigated as well as the HONO and NO2 yields. We found a clear correlation between the loss of NO above the film and the molar ratio of photosensitizer/CA, and also between the NO loss and the light intensity. The variation of the observed NO loss with oxygen corroborates a mechanism, in which the triplet excited state of the photosensitizer is reduced likely by the predominant donor in the system, citric acid, to a reduced ketyl radical. This reactive species is transferring an electron to molecular oxygen, which in turn leads to production of HO2 radicals, which are released to the gas phase. Therefore, in absence of gas phase oxidants, the loss of NO in the gas phase could be related to the production of HO2 radicals in the condensed phase. Relative humidity had a strong impact on the HO2 output, which shows a maximum value at intermediate humidity around 30%, likely due to different competing effects of dilution and reactant mobility. The observed NO2/HONO ratio was around 1.4 consistent with the secondary chemistry of HO2 in presence of NO in the gas phase, indicating no

  11. Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism

    SciTech Connect

    Radogna, F.; Sestili, P.; Martinelli, C.; Paolillo, M.; Paternoster, L.; Albertini, M.C.; Accorsi, A.; Gualandi, G.; Ghibelli, L.

    2009-07-15

    We have shown that melatonin immediately and transiently stimulates intracellular free radical production on a set of leukocytes, possibly as a consequence of calmodulin binding. We show here that melatonin-induced ROS are produced by lipoxygenase (LOX), since they are prevented by a set of LOX inhibitors, and are accompanied by increase of the 5-LOX product 5-HETE. LOX activation is accompanied by strong liberation of AA; inhibition of Ca{sup 2+}-independent, but not Ca{sup 2+}-dependent, phospholipase A2 (PLA2), prevents both melatonin-induced arachidonic acid and ROS production, whereas LOX inhibition only prevents ROS, indicating that PLA2 is upstream with respect to LOX, as occurs in many signaling pathways. Chlorpromazine, an inhibitor of melatonin-calmodulin interaction, inhibits both ROS and arachidonic acid production, thus possibly placing calmodulin at the origin of a melatonin-induced pro-radical pathway. Interestingly, it is known that Ca{sup 2+}-independent PLA2 binds to calmodulin: our results are compatible with PLA2 being liberated by melatonin from a steady-state calmodulin sequestration, thus initiating an arachidonate signal transduction. These results delineate a novel molecular pathway through which melatonin may participate to the inflammatory response.

  12. Hydrogen bonding in the hydroxysulfinyl radical-formic acid-water system: A theoretical study.

    PubMed

    Tušar, Simona; Lesar, Antonija

    2016-06-30

    Quantum chemical methods have been employed to evaluate the possible configurations of the 1:1 and 1:2 HOSO-formic acid complexes and 1:1:1 HOSO-formic acid-water complexes. The first type of complex involves two H bonds, while the other two types comprise three H bonds in a ring. The complexes are relatively stable, with CBS-QB3 computed binding energies of 14.3 kcal mol(-1) , 23.4 kcal mol(-1) , and 21.1 kcal mol(-1) for the lowest-energy structures of the 1:1, 1:2, and 1:1:1 complexes, respectively. Complex formations induce a large spectral red-shift and an enhancement of the IR intensity for the H-bonded OH stretching modes relative to those in the parent monomers. TDDFT calculations of the low-lying electronic excited states demonstrate that the complexes are photochemically quite stable in the troposphere. Small spectral shifts in comparison to the free HOSO radical suggest that the radical and the complexes would not be easily distinguishable using standard UV/vis absorption spectroscopy. © 2016 Wiley Periodicals, Inc. PMID:27074890

  13. Graphene Facilitated Removal of Labetalol in Laccase-ABTS System: Reaction Efficiency, Pathways and Mechanism

    PubMed Central

    Dong, Shipeng; Xiao, Huifang; Huang, Qingguo; Zhang, Jian; Mao, Liang; Gao, Shixiang

    2016-01-01

    The widespread occurrence of the beta-blocker labetalol causes environmental health concern. Enzymatic reactions are highly efficient and specific offering biochemical transformation of trace contaminants with short reaction time and little to none energy consumption. Our experiments indicate that labetalol can be effectively transformed by laccase-catalyzed reaction using 2, 2-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a mediator, while no significant removal of labetalol can be achieved in the absence of ABTS. A total of three products were identified. It is interesting that the presence of graphene greatly increased the reaction rate while not changed the products. In the presence of 100 μg/L graphene, the pseudo-first-order reaction rate constant was increased ~50 times. We found that the enhancement of graphene is probably attributed to the formation and releasing of ABTS2+ which has a much greater reactivity towards labetalol when graphene is present. This study provides fundamental information for laccase-ABTS mediated labetalol reactions and the effect of graphene, which could eventually lead to development of novel methods to control beta-blocker contamination. PMID:26891761

  14. Graphene Facilitated Removal of Labetalol in Laccase-ABTS System: Reaction Efficiency, Pathways and Mechanism

    NASA Astrophysics Data System (ADS)

    Dong, Shipeng; Xiao, Huifang; Huang, Qingguo; Zhang, Jian; Mao, Liang; Gao, Shixiang

    2016-02-01

    The widespread occurrence of the beta-blocker labetalol causes environmental health concern. Enzymatic reactions are highly efficient and specific offering biochemical transformation of trace contaminants with short reaction time and little to none energy consumption. Our experiments indicate that labetalol can be effectively transformed by laccase-catalyzed reaction using 2, 2-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a mediator, while no significant removal of labetalol can be achieved in the absence of ABTS. A total of three products were identified. It is interesting that the presence of graphene greatly increased the reaction rate while not changed the products. In the presence of 100 μg/L graphene, the pseudo-first-order reaction rate constant was increased ~50 times. We found that the enhancement of graphene is probably attributed to the formation and releasing of ABTS2+ which has a much greater reactivity towards labetalol when graphene is present. This study provides fundamental information for laccase-ABTS mediated labetalol reactions and the effect of graphene, which could eventually lead to development of novel methods to control beta-blocker contamination.

  15. Characterization of the hyperline of D{sub 1}/D{sub 0} conical intersections between the maleic acid and fumaric acid anion radicals

    SciTech Connect

    Takahashi, Ohgi; Sumita, Masato

    2004-10-08

    The cation and anion radicals of symmetrical 1,2-disubstituted ethylenes are expected to have a symmetry-allowed conical intersection (CI) between the ground doublet state (D{sub 0}) and the lowest excited doublet state (D{sub 1}) near a 90 deg.-twisted geometry. By the complete active space self-consistent field method, we characterized the hyperline formed by D{sub 1}/D{sub 0} CIs between the anion radicals of maleic acid (cis) and fumaric acid (trans). An implication of the results for the known one-way cis{yields}trans photoisomerization of the maleic acid anion radical and other related ion radicals is presented.

  16. Synthesis of dimeric phenol derivatives and determination of in vitro antioxidant and radical scavenging activities.

    PubMed

    Güllçin, Ilhami; Daştan, Arif

    2007-12-01

    In this study, di(2,6-dimethylphenol) (Di-DMP), di(2,6-diisopropylphenol) (Di-DIP, dipropofol) and di(2,6-di-t-butylphenol) (Di-DTP) were synthesized by the reaction of monomeric phenol derivatives with catalytic CuCl(OH). TMEDA and Na2S2O4. Their antioxidant capacity and radical scavenging activity were examined using different in vitro methodologies such as 1,1-diphenyl-2-picryl-hydrazyl (DPPH*) free radical scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, total antioxidant activity by ferric thiocyanate, total reducing power by potassium ferricyanide reduction method, superoxide anion radical scavenging, hydrogen peroxide scavenging and ferrous ions chelating activities. PMID:18237020

  17. Identification of the radicals formed in the reactions of some endogenous photosensitizers with oleic acid under the UVA irradiation.

    PubMed

    Mori, Hiroko; Iwahashi, Hideo

    2012-11-01

    Electron spin resonance measurements were performed for the reactions of some endogenous photosensitizers (flavin mononucleotide or flavin adenine dinucleotide or folic acid or β-nicotinamide adenine dinucleotide or β-nicotinamide adenine dinucleotide phosphate or pyridoxal-5'-phosphate or urocanic acid) with oleic acid under the ultraviolet light A irradiation using α-(4-pyridyl-1-oxide)-N-tert-butylnitrone as a spin trap reagent. Of the endogenous photosensitizers, prominent electron spin resonance signals (α(N) = 1.58 mT and α(H)β = 0.26 mT) were observed for the reaction mixture of flavin mononucleotide (or flavin adenine dinucleotide or folic acid), suggesting that radical species form in the reaction mixtures. Singlet oxygen seems to participate in the formation of the radicals because the electron spin resonance peak heights increased for the reactions in D(2)O to a great extent. A high performance liquid chromatography-electron spin resonance-mass spectrometry was employed to identify the radicals formed in the reactions of the endogenous photosensitizers (flavin mononucleotide or flavin adenine dinucleotide or folic acid) with oleic acid under the ultraviolet light A irradiation. The high performance liquid chromatography-electron spin resonance-mass spectrometry analyses showed that 7-carboxyheptyl and 1-(3-carboxypropyl)-4-hydroxybutyl radicals form in the reaction mixture of flavin mononucleotide (or flavin adenine dinucleotide or folic acid). PMID:23170043

  18. Phytic acid suppresses ischemia-induced hydroxyl radical generation in rat myocardium.

    PubMed

    Obata, Toshio; Nakashima, Michiko

    2016-03-01

    The present study examined whether ischemia-reperfusion-induced hydroxyl radical (·OH) generation was attenuated by myo-inositol hexaphosphoric acid (phytic acid). A flexibly mounted microdialysis technique was used to detect the generation of ·OH in in vivo rat hearts. To measure the level of ·OH, sodium salicylate in Ringer's solution (0.5mM or 0.5 nmol/μl/min) was infused directly through a microdialysis probe to detect the generation of ·OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). To confirm the generation of ·OH by Fenton-type reaction, iron(II) was infused through a microdialysis probe. A positive linear correlation between iron(II) and the formation of 2,3-DHBA (R(2)=0.983) was observed. However, the level of 2,3-DHBA in norepinephrine (100 μM) plus phytic acid (100 μM) treated group were significantly lower than those observed in norepinephrine-only-treated group (n=6, *p<0.05). To examine the effect of phytic acid on ischemia-reperfusion-induced ·OH generation, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with phytic acid. These results suggest that phytic acid is associated with antioxidant effect due to the suppression of iron-induced ·OH generation. PMID:26724394

  19. Radical scavenging activity and composition of raspberry (Rubus idaeus) leaves from different locations in Lithuania.

    PubMed

    Venskutonis, P R; Dvaranauskaite, A; Labokas, J

    2007-02-01

    Raspberry (Rubus idaeus) leaves, collected in different locations of Lithuania were extracted with ethanol and the extracts were tested for their antioxidant activity (AA) by using ABTS(.)(+) decolourisation and DPPH(.) scavenging methods. All extracts were active, with radical scavenging capacity at the used concentrations from 20.5 to 82.5% in DPPH(.) reaction system and from 8.0 to 42.7% in ABTS(.)(+) reaction. The total amount of phenolic compounds in the leaves varied from 4.8 to 12.0 mg of gallic acid equivalents (GAE) in 1 g of plant extract. Quercetin glucuronide, quercetin-3-O-glucoside and rutin were identified in the extracts. PMID:17215088

  20. Spectroscopic studies on the antioxidant activity of ellagic acid.

    PubMed

    Kilic, Ismail; Yeşiloğlu, Yeşim; Bayrak, Yüksel

    2014-09-15

    Ellagic acid (EA, C14H6O8) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anticarcinogenesis and anti-oxidation properties. In vitro radical scavenging and antioxidant capacity of EA were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. EA inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), α-tocopherol and ascorbic acid displayed 69.8%, 66.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, EA had an effective DPPH• scavenging, ABTS+ scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that EA can be used in the pharmacological, food industry and medicine because of these properties. PMID:24813273

  1. Nitrous acid (HONO) during polar spring in Barrow, Alaska: A net source of OH radicals?

    NASA Astrophysics Data System (ADS)

    Villena, G.; Wiesen, P.; Cantrell, C. A.; Flocke, F.; Fried, A.; Hall, S. R.; Hornbrook, R. S.; Knapp, D.; Kosciuch, E.; Mauldin, R. L., III; McGrath, J. A.; Montzka, D.; Richter, D.; Ullmann, K.; Walega, J.; Weibring, P.; Weinheimer, A.; Staebler, R. M.; Liao, J.; Huey, L. G.; Kleffmann, J.

    2011-07-01

    HONO was measured by a LOPAP instrument (LOng Path Absorption Photometer) for one month during the OASIS spring 2009 campaign in Barrow, Alaska. HONO concentrations between ≤ 0.4 pptv (DL) and ˜500 pptv were measured. The very high concentrations observed on several days were caused by local direct emissions and were highly correlated with the NOx and CO data. When only "clean days" were considered, average HONO concentrations varied between ≤ 0.4 - 10 pptv. Average HONO/NOx and HONO/NOy ratios of ˜6% and ˜1% were observed, respectively, in good agreement with other remote LOPAP measurement data, but lower than measured in most other polar regions by other methods. The strong correlation between sharp peaks of OH and HONO during daytime, which was not observed for any other measured radical precursor, suggested that HONO photolysis was a major source of OH radicals in Barrow. This was supported by calculated net OH radical production by HONO and O3 photolysis for which the contribution of O3 (2%) could be neglected compared to that of HONO (98%). A net extra HONO/OH source necessary to explain elevated HONO levels during daytime of up to 90 pptv/h was determined, which was highly correlated with the actinic flux. Accordingly, a photochemical HONO source is proposed here, in good agreement with recent studies. From the higher correlation of the net HONO source with ? and [NO2] compared to ? and [NO3-], photosensitized conversion of NO2 on humic acid containing snow surfaces may be a more likely source of HONO in the polar atmosphere of Barrow than nitrate photolysis.

  2. A combined theoretical and experimental study on the oxidation of fulvic acid by the sulfate radical anion.

    PubMed

    Gara, Pedro M David; Bosio, Gabriela N; Gonzalez, Mónica C; Russo, Nino; Del Carmen Michelini, Maria; Diez, Reinaldo Pis; Mártire, Daniel O

    2009-07-01

    The kinetics of the reaction of sulfate radicals with the IHSS Waskish peat fulvic acid in water was investigated in the temperature range from 289.2 to 305.2 K. The proposed mechanism considers the reversible binding of the sulfate radicals by the fulvic acid. The kinetic analysis of the data allows the determination of the thermodynamic parameters DeltaG degrees = -10.2 kcal mol(-1), DeltaH degrees = -16 kcal mol(-1) and DeltaS degrees = -20.3 cal K(-1) mol(-1) for the reversible association at 298.2 K. Theoretical (DFT) calculations performed with the Buffle model of the fulvic acids support the formation of H-bonded adducts between the inorganic radicals and the humic substances. The experimental enthalpy change compares well with the theoretical values found for some of the investigated adducts. PMID:19582275

  3. Effect of UV-C irradiation and low temperature storage on bioactive compounds, antioxidant enzymes and radical scavenging activity of papaya fruit.

    PubMed

    Rivera-Pastrana, Dulce M; Gardea, Alfonso A; Yahia, Elhadi M; Martínez-Téllez, Miguel A; González-Aguilar, Gustavo A

    2014-12-01

    Mature green 'Maradol' papaya fruits were exposed to ultraviolet (UV)-C irradiation (1.48 kJ·m(-2)) and stored at 5 or 14 °C. Changes in total phenols, total flavonoids, enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), as well as the scavenging activity against 2,2-diphenyl-1picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals were investigated in peel and flesh tissues at 0, 5, 10 and 15 days of storage. UV-C irradiation increased significantly (P < 0.05) the flavonoid content (2.5 and 26 %) and ABTS radical scavenging activity (5.7 and 6 %) in flesh and peel at 14 °C respectively; and CAT activity (16.7 %) in flesh at 5 °C. Flavonoid contents, CAT and SOD activities were positively affected under low storage temperature (5 °C). DPPH and ABTS radical scavenging activities increased in both control and UV-C treated papaya peel during storage at 5 °C. UV-C irradiation effect on radical scavenging of papaya peel could be attributed to increased flavonoid content. Papaya antioxidant system was activated by UV-C and cold storage by increasing phenolic content and antioxidant enzymatic activities as a defense response against oxidative-stress. PMID:25477649

  4. DDQ-promoted dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones by a radical ion mechanism.

    PubMed

    Ding, Ye; Huang, Zhangjian; Yin, Jian; Lai, Yisheng; Zhang, Shibo; Zhang, Zhiguo; Fang, Lei; Peng, Sixun; Zhang, Yihua

    2011-09-01

    A novel and facile DDQ-mediated dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones is described. The formation of lactones proceeds by a radical ion mechanism, which has been established by DPPH˙-mediated chemical identification, ESR spectroscopy and an enol intermediate trapping. PMID:21766102

  5. A novel method to measure both the reductive and the radical scavenging activity in a linoleic acid model system.

    PubMed

    Lindenmeier, Michael; Burkon, Alexander; Somoza, Veronika

    2007-12-01

    The aim of this study was to develop a combined method for measuring the total antioxidant activity, the reductive and the radical scavenging activity. Linoleic acid was used as the substrate for an iron-initiated lipid peroxidation to measure the total antioxidant activity. In addition, methyl esters of linoleic acid hydroperoxides were used as substrates to measure the reductive antioxidant activity. The radical scavenging antioxidant activity was calculated by subtracting the reductive antioxidative activity from the total antioxidative activity. As representative examples, the antioxidants alpha-tocopherol, ascorbic acid, trans-resveratrol and L-glutathione as well as commonly used food additives such as 2(3)-tert-butyl-4-hydroxyanisole (BHA) and 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT) were analyzed. The results for the novel antioxidation test showed that alpha-tocopherol, BHA and BHT are primarily acting as radical scavengers, whereas ascorbic acid and L-glutathione show a strong reductive capacity. As linoleic acid as well as its hydroperoxides both are present in foods and in the organism, the test presented here can be considered representative of radical reactions occurring in food matrixes and in vivo. Further experiments are required to document the comprehensive applicability in foods and in vivo. PMID:17680718

  6. Study of radical pairs generated by photoreduction of anthraquinone-2,6-disulfonic acid with thymine by Fourier transform electron paramagnetic resonance

    NASA Astrophysics Data System (ADS)

    Geimer, J.; Beckert, D.

    1998-05-01

    Using laser photolysis at 308 nm and FT-EPR, the triplet sensitized electron transfer from thymine to 9,10-anthraquinone-2,6-disulfonate in aqueous solution was studied. The anthraquinone radical anion and the deprotonated thymine-1-yl radical are spin-polarized by the CIDEP triplet mechanism and radical pair mechanism. The structure of the anthraquinone radical anion is strongly influenced by the pH of the solution. In weak acidic solution the radical anion dominates whereas the p K of the radical protonation was determined to be 3.2. The deprotonated thymine-1-yl radical shows two different radical pair polarization patterns which are distinguished by the phase of the polarization. This unusual behavior can be attributed to two different states in the primary radical pair.

  7. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

    PubMed Central

    Yildirim, Emre; Connor, David A.; Gould, Thomas J.

    2015-01-01

    Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

  8. Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level

    PubMed Central

    Joung, Kyoung-Woon; Choi, Seong-Soo; Kong, Yu-Gyeong; Yu, Jihion; Lim, Jinwook; Hwang, Jai-Hyun; Kim, Young-Kug

    2015-01-01

    Background: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy. Methods: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses. Results: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy. Conclusions: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy. PMID:26283877

  9. Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia.

    PubMed

    Honore, Prisca; Chandran, Prasant; Hernandez, Gricelda; Gauvin, Donna M; Mikusa, Joseph P; Zhong, Chengmin; Joshi, Shailen K; Ghilardi, Joseph R; Sevcik, Molly A; Fryer, Ryan M; Segreti, Jason A; Banfor, Patricia N; Marsh, Kennan; Neelands, Torben; Bayburt, Erol; Daanen, Jerome F; Gomtsyan, Arthur; Lee, Chih-Hung; Kort, Michael E; Reilly, Regina M; Surowy, Carol S; Kym, Philip R; Mantyh, Patrick W; Sullivan, James P; Jarvis, Michael F; Faltynek, Connie R

    2009-03-01

    Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel that functions as an integrator of multiple pain stimuli including heat, acid, capsaicin and a variety of putative endogenous lipid ligands. TRPV1 antagonists have been shown to decrease inflammatory pain in animal models and to produce limited hyperthermia at analgesic doses. Here, we report that ABT-102, which is a potent and selective TRPV1 antagonist, is effective in blocking nociception in rodent models of inflammatory, post-operative, osteoarthritic, and bone cancer pain. ABT-102 decreased both spontaneous pain behaviors and those evoked by thermal and mechanical stimuli in these models. Moreover, we have found that repeated administration of ABT-102 for 5-12 days increased its analgesic activity in models of post-operative, osteoarthritic, and bone cancer pain without an associated accumulation of ABT-102 concentration in plasma or brain. Similar effects were also observed with a structurally distinct TRPV1 antagonist, A-993610. Although a single dose of ABT-102 produced a self-limiting increase in core body temperature that remained in the normal range, the hyperthermic effects of ABT-102 effectively tolerated following twice-daily dosing for 2 days. Therefore, the present data demonstrate that, following repeated administration, the analgesic activity of TRPV1 receptor antagonists is enhanced, while the associated hyperthermic effects are attenuated. The analgesic efficacy of ABT-102 supports its advancement into clinical studies. PMID:19135797

  10. Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT-107 attenuates the reinstatement of nicotine-seeking behavior in rats.

    PubMed

    Lee, Alycia M; Arreola, Adrian C; Kimmey, Blake A; Schmidt, Heath D

    2014-11-01

    Current smoking cessation pharmacotherapies have modest efficacy, and most smokers relapse within the first few days after a quit attempt. Nicotine withdrawal-induced craving and cognitive impairments predict smoking relapse during abstinence and suggest that cognitive-enhancing drugs may prevent relapse. ABT-089 and ABT-107 are subtype-selective nAChR agonists that improve cognitive performance in laboratory animals. However, there are no studies examining the effects of ABT-089 and ABT-107 on nicotine self-administration and the reinstatement of nicotine-seeking behavior, an animal model of relapse in human smokers. The goal of the present study was to determine the effects of the α4β2*/α6β2* nAChR agonist ABT-089 and the α7 nAChR agonist ABT-107 on nicotine taking and seeking in rats. The effects of acute ABT-089 and ABT-107 pretreatment on nicotine self-administration and reinstatement were tested in male Sprague Dawley rats. Parallel studies of ABT-089 and ABT-107 on sucrose self-administration and reinstatement were tested in separate groups of rats to determine if the effects of these drug treatments generalized to other reinforced behaviors. Nicotine and sucrose self-administration behaviors were not altered following acute administration of ABT-089 (0, 0.12, 1.2 and 12.0mg/kg) or ABT-107 (0, 0.03 and 0.3mg/kg). In contrast, both ABT-089 and ABT-107 pretreatment dose-dependently attenuated nicotine reinstatement. These effects were reinforcer-specific as no effects of ABT-089 or ABT-107 pretreatment on sucrose seeking were noted. Taken together, these findings suggest that ABT-089 and ABT-107 do not affect nicotine consumption, but may reduce the likelihood that a smoking lapse will lead to relapse. PMID:25128791

  11. [Acidity and interaction with superoxide anion radical of echinochrome and its structural analogs].

    PubMed

    Lebedev, A V; Ivanova, M V; Krasnovid, N I; Kol'tsova, E A

    1999-01-01

    Weak acid properties, autoxidation and interaction of natural polyhydroxy1,4-naphthoquinones (PHNQ) with superoxide anion-radical (O2-.) were studied by methods of potentiometric titration, polarography, and UV- and visible spectrophotometry. Sea urchin pigments 3-acetyl-2,6,7-trihydroxynaphthazarin (spinochrome C), 2,3,6,7-trihydroxynaphthazarin (spinochrome D), 2,3,6,7-trihydroxynaphthazarin (spinochrome E), 6-ethyl-2,3,7-trihydroxynaphthazarin (echinochrome A), synthetic 2,3-dihydroxy-6,7-dimethylnaphthazarin and 6-ethyl-2,3,7-trimethoxynaphthazarin (trimethoxyechinochrome A) were tested. Determined dissociation constants (pKi) were in the range of pH 5.3-8.5 (40% ethanol solvent). PHNQ autoxidation observrd in basic pH were inhibited by superoxide dismutase. Xanthine and xanthine oxidase was applied for O2-. generation. Interaction with O2-. led to sufficient time-dependent changing in spectra of echinochrome A, spinochromes D and E. There was weak O2-. influence on spinochrome C spectrum and no changing in trimethoxyechinochrome A spectrum. The spectra, that were transforming during time of reaction, contained pronounced isobestic point. It means formation the single reaction product. We proposed formation of 1,2,3,4-tetraketones from 2,3,5,8-tetrahydroxy-1,4-naphthoquinones (echinochrome A, spinochromes D and E) due to O2-.-induced oxidation of their OH-groups in 2 and 3 positions. Reaction constants were determined by competition method using nitro blue tetrazolium (NBT). The reaction constants were about 10(4)-10(5) M-1s-1. They were decreased in the order: echinochrome A > spinochrome D > spinochrome C > NBT > trimethoxyechinochrome A. Thus, we concluded that some of the natural PGNQ, containing hydroxyl groups in 2nd and 3rd positions, could operate as powerful superoxide anion-radical scavengers. PMID:10378300

  12. Radical prostatectomy

    MedlinePlus

    Prostatectomy - radical; Radical retropubic prostatectomy; Radical perineal prostatectomy; Laparoscopic radical prostatectomy; LRP; Robotic-assisted laparoscopic prostatectomy; RALP; Pelvic lymphadenectomy; ...

  13. On the Origin of the Methyl Radical Loss from Deprotonated Ferulic and Isoferulic Acids: Electronic Excitation of a Transient Structure

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoping; Li, Fei; Lv, Huiqing; Wu, Yanqing; Bian, Gaofeng; Jiang, Kezhi

    2013-06-01

    Formation of radical fragments from even-electron ions is an exception to the "even-electron rule". In this work, ferulic acid (FA) and isoferulic acid (IFA) were used as the model compounds to probe the fragmentation mechanisms and the isomeric effects on homolytic cleavage. Elimination of methyl radical and CO2 are the two competing reactions observed in the CID-MS of [FA - H]- and [IFA - H]-, of which losing methyl radical violates the "even-electron rule". The relative intensity of their product ions is significantly different, and thereby the two isomeric compounds can be differentiated by tandem MS. Theoretical calculations indicate that both the singlet-triplet gap and the excitation energy decrease in the transient structures, as the breaking C-O bond is lengthened. The methyl radical elimination has been rationalized as the intramolecular electronic excitation of a transient structure with an elongating C-O bond. The potential energy diagrams, completed by the addition of the energy barrier of the radical elimination, have provided a reasonable explanation of the different CID-MS behaviors of [FA - H]- and [IFA - H]-.

  14. On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.

    PubMed

    Lugo-Huitrón, R; Blanco-Ayala, T; Ugalde-Muñiz, P; Carrillo-Mora, P; Pedraza-Chaverrí, J; Silva-Adaya, D; Maldonado, P D; Torres, I; Pinzón, E; Ortiz-Islas, E; López, T; García, E; Pineda, B; Torres-Ramos, M; Santamaría, A; La Cruz, V Pérez-De

    2011-01-01

    Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 μM) were tested in cerebellum and forebrain homogenates exposed to 5 μM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 μM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 μM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 μM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 μM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA

  15. Radical scavenging and antioxidant activities of essential oil components--an experimental and computational investigation.

    PubMed

    Sharopov, Farukh S; Wink, Michael; Setzer, William N

    2015-01-01

    The antioxidant activities of eighteen different essential oil components have been determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation assay, and the ferric reducing antioxidant power (FRAP) assay. The phenolic compounds, carvacrol, thymol, and eugenol, showed the best antioxidant activities, while camphor, menthol, and menthone were the least active. The structural and electronic properties of the essential oil components were assessed using density functional theory (DFT) at the B3LYP/6-311++G** level. Correlations between calculated electronic properties and antioxidant activities were generally poor, but bond-dissociation energies (BDEs) seem to correlate with DPPH radical-scavenging activities, and the ferric reducing antioxidant power (FRAP) assay correlated with vertical ionization potentials calculated at the Hartree-Fock/6-311++G** level. PMID:25920239

  16. Red-Light Initiated Decomposition of α-Hydroxy Methylperoxy Radical in the Presence of Organic and Inorganic Acids: Implications for the HOx Formation in the Lower Stratosphere.

    PubMed

    Kumar, Manoj; Francisco, Joseph S

    2016-05-01

    Theoretical calculations have been carried out to investigate the gas-phase decomposition of α-hydroxy methylperoxy (HOCH2(OO)) radical in the absence and presence of formic acid, acetic acid, nitric acid, and sulfuric acid. The HOCH2(OO) radical decomposition represents a new source of the HOx radical in troposphere. The results suggest that sulfuric acid will be more effective than other acids in catalyzing the peroxy radical decomposition. However, the significant stability of prereaction and postreaction complexes in all the bimolecular reactions implies a new photomechanism for the acid-mediated decomposition of the HOCH2(OO) radical that involves the visible or near IR overtone excitation of the OH stretching modes or electronic excitation of the O-O peroxy moiety in the acid-bound radical. This new overtone or electronic excitation-based photomechanism for the peroxy radical decomposition may provide useful insight into the missing photolytic source of the HOx at high solar zenith angles corresponding to the dawn or dusk photochemistry. PMID:27070960

  17. Characterization of a Cross-Linked Protein-Nucleic Acid Substrate Radical in the Reaction Catalyzed by RlmN

    SciTech Connect

    Silakov, Alexey; Grove, Tyler L.; Radle, Matthew I.; Bauerle, Matthew R.; Green, Michael T.; Rosenzweig, Amy C.; Boal, Amie K.; Booker, Squire J.

    2014-08-14

    RlmN and Cfr are methyltransferases/methylsynthases that belong to the radical S-adenosylmethionine superfamily of enzymes. RlmN catalyzes C2 methylation of adenosine 2503 (A2503) of 23S rRNA, while Cfr catalyzes C8 methylation of the exact same nucleotide, and will subsequently catalyze C2 methylation if the site is unmethylated. A key feature of the unusual mechanisms of catalysis proposed for these enzymes is the attack of a methylene radical, derived from a methylcysteine residue, onto the carbon center undergoing methylation to generate a paramagnetic protein–nucleic acid cross-linked species. This species has been thoroughly characterized during Cfr-dependent C8 methylation, but does not accumulate to detectible levels in RlmN-dependent C2 methylation. Herein, we show that inactive C118S/A variants of RlmN accumulate a substrate-derived paramagnetic species. Characterization of this species by electron paramagnetic resonance spectroscopy in concert with strategic isotopic labeling shows that the radical is delocalized throughout the adenine ring of A2503, although predominant spin density is on N1 and N3. Moreover, 13C hyperfine interactions between the radical and the methylene carbon of the formerly [methyl-13C]Cys355 residue show that the radical species exists in a covalent cross-link between the protein and the nucleic acid substrate. X-ray structures of RlmN C118A show that, in the presence of SAM, the substitution does not alter the active site structure compared to that of the wild-type enzyme. Together, these findings have new mechanistic implications for the role(s) of C118 and its counterpart in Cfr (C105) in catalysis, and suggest involvement of the residue in resolution of the cross-linked species via a radical mediated process

  18. Characterization of a Cross-Linked Protein–Nucleic Acid Substrate Radical in the Reaction Catalyzed by RlmN

    PubMed Central

    2015-01-01

    RlmN and Cfr are methyltransferases/methylsynthases that belong to the radical S-adenosylmethionine superfamily of enzymes. RlmN catalyzes C2 methylation of adenosine 2503 (A2503) of 23S rRNA, while Cfr catalyzes C8 methylation of the exact same nucleotide, and will subsequently catalyze C2 methylation if the site is unmethylated. A key feature of the unusual mechanisms of catalysis proposed for these enzymes is the attack of a methylene radical, derived from a methylcysteine residue, onto the carbon center undergoing methylation to generate a paramagnetic protein–nucleic acid cross-linked species. This species has been thoroughly characterized during Cfr-dependent C8 methylation, but does not accumulate to detectible levels in RlmN-dependent C2 methylation. Herein, we show that inactive C118S/A variants of RlmN accumulate a substrate-derived paramagnetic species. Characterization of this species by electron paramagnetic resonance spectroscopy in concert with strategic isotopic labeling shows that the radical is delocalized throughout the adenine ring of A2503, although predominant spin density is on N1 and N3. Moreover, 13C hyperfine interactions between the radical and the methylene carbon of the formerly [methyl-13C]Cys355 residue show that the radical species exists in a covalent cross-link between the protein and the nucleic acid substrate. X-ray structures of RlmN C118A show that, in the presence of SAM, the substitution does not alter the active site structure compared to that of the wild-type enzyme. Together, these findings have new mechanistic implications for the role(s) of C118 and its counterpart in Cfr (C105) in catalysis, and suggest involvement of the residue in resolution of the cross-linked species via a radical mediated process. PMID:24806349

  19. Probing the Influence of Protecting Groups on the Anomeric Equilibrium in Sialic Acid Glycosides with the Persistent Radical Effect

    PubMed Central

    2015-01-01

    A method for the investigation of the influence of protecting groups on the anomeric equilibrium in the sialic acid glycosides has been developed on the basis of the equilibration of O-sialyl hydroxylamines by reversible homolytic scission of the glycosidic bond following the dictates of the Fischer–Ingold persistent radical effect. It is found that a trans-fused 4O,5N-oxazolidinone group stabilizes the equatorial glycoside, i.e., reduces the anomeric effect, when compared to the 4O,5N-diacetyl protected systems. This effect is discussed in terms of the powerful electron-withdrawing nature of the oxazolidinone system, which in turn is a function of its strong dipole moment in the mean plane of the pyranose ring system. The new equilibration method displays a small solvent effect and is most pronounced in less polar media consistent with the anomeric effect in general. The unusual (for anomeric radicals) poor kinetic selectivity of anomeric sialyl radicals is discussed in terms of the planar π-type structure of these radicals and of competing 1,3-diaxial interactions in the diastereomeric transition states for trapping on the α- and β-faces of the radical. PMID:24606062

  20. Addition and elimination kinetics in OH radical induced oxidation of phenol and cresols in acidic and alkaline solutions

    NASA Astrophysics Data System (ADS)

    Roder, M.; Wojnárovits, L.; Földiák, G.; Emmi, S. S.; Beggiato, G.; D'Angelantonio, M.

    1999-05-01

    The rates of the two consecutive reactions, OH radical addition and H 2O/OH - elimination, were studied by pulse radiolysis in highly acidic (pH=1.3-1.9) and alkaline (pH≈11) solutions, respectively, for phenol and for the three cresol isomers. The rate coefficient of the addition as measured by the build-up of phenoxyl radical absorbance and by a competitive method is the same (1.4±0.1)×10 10 mol -1 dm 3 s -1 both in acidic and alkaline solution. The rate coefficient of the H 2O elimination in acidic solution is (1.6±0.2)×10 6 s -1, whereas the coefficient of the OH - elimination in alkaline solutions is 6-8 times higher. The kinetics of the phenoxyl radical formation was described by the two-exponential equation of the consecutive reactions: the first exponential is related to the pseudo-first-order addition, while the second to the elimination reaction. No considerable structure dependence was found in the rate coefficients, indicating that the methyl substitutent in these highly acidic or alkaline solutions influences neither the addition nor the elimination rate.

  1. The antioxidant activities of seasonings used in Asian cooking. Powerful antioxidant activity of dark soy sauce revealed using the ABTS assay.

    PubMed

    Long, L H; Kwee, D C; Halliwell, B

    2000-02-01

    Scavenging of the ABTS (2,2'-azinobis[3-ethylbenzothiazoline-6-sulphonate])-derived nitrogen-centred radical cation (ABTS*+) was used to compare the total antioxidant activities of several seasonings used in Asian cooking. The results were expressed as Trolox equivalent antioxidant capacity (TEAC). The TEAC activities of dark soy sauces were found to be exceptionally high. In evaluating the TEAC of commercial products, attention must be paid to the addition of preservatives by manufacturers to the seasonings tested. Sodium benzoate (a preservative added to several seasonings) did not react significantly with ABTS*+, but the sulphite content of certain white wines may have led to an over-estimation of their TEAC. PMID:10653488

  2. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity. PMID:25948326

  3. Towards fuel cell membranes with improved lifetime: Aquivion® Perfluorosulfonic Acid membranes containing immobilized radical scavengers

    NASA Astrophysics Data System (ADS)

    D'Urso, C.; Oldani, C.; Baglio, V.; Merlo, L.; Aricò, A. S.

    2014-12-01

    A facile synthesis, based on a wet impregnation technique and a thermal treatment, of a novel silica-supported cerium-oxide-based radical scavenger bearing sulfonic acid functionalities is presented. This material is loaded as a filler in ePTFE reinforced membranes (called R79-02S) prepared starting from Aquivion® Perfluoro-Sulfonic Acid (PFSA) dispersions. The aim is to mitigate the peroxy radicals attack to the polymeric membrane under fuel cell operating conditions. These membranes show much longer (7 times more) life-time in Accelerated Stress Tests (AST) and reduced fluoride release (about one half) in Fenton's tests than the radical scavenger-free membrane without any loss in electrochemical performance. Scavenger-free Aquivion® PFSA-based membrane durability is about 200 h in AST whereas the same membrane containing the newly developed radical scavenger exceeds 1400 h. These results confirm the stability of the modified membranes and the excellent activity of the composite scavenger in mitigating the polymer electrolyte degradation.

  4. Effects of precursor concentration and acidic sulfate in aqueous glyoxal-OH radical oxidation and implications for secondary organic aerosol.

    PubMed

    Tan, Yi; Perri, Mark J; Seitzinger, Sybil P; Turpin, Barbara J

    2009-11-01

    Previous experiments demonstrated that aqueous OH radical oxidation of glyoxal yields low-volatility compounds. When this chemistry takes place in clouds and fogs, followed by droplet evaporation (or if it occurs in aerosol water), the products are expected to remain partially in the particle phase, forming secondary organic aerosol (SOA). Acidic sulfate exists ubiquitously in atmospheric water and has been shown to enhance SOA formation through aerosol phase reactions. In this work, we investigate how starting concentrations of glyoxal (30-3000 microM) and the presence of acidic sulfate (0-840 microM) affect product formation in the aqueous reaction between glyoxal and OH radical. The oxalic acid yield decreased with increasing precursor concentrations, and the presence of sulfuric acid did not alter oxalic acid concentrations significantly. A dilute aqueous chemistry model successfully reproduced oxalic acid concentrations, when the experiment was performed at cloud-relevant concentrations (glyoxal <300 microM), but predictions deviated from measurements at increasing concentrations. Results elucidate similarities and differences in aqueous glyoxal chemistry in clouds and in wet aerosols. They validate for the first time the accuracy of model predictions at cloud-relevant concentrations. These results suggest that cloud processing of glyoxal could be an important source of SOA. PMID:19924930

  5. Potential role of stabilized Criegee radicals in sulfuric acid production in a high biogenic VOC environment.

    PubMed

    Kim, Saewung; Guenther, Alex; Lefer, Barry; Flynn, James; Griffin, Robert; Rutter, Andrew P; Gong, Longwen; Cevik, Basak Karakurt

    2015-03-17

    We present field observations made in June 2011 downwind of Dallas-Fort Worth, TX, and evaluate the role of stabilized Criegee radicals (sCIs) in gaseous sulfuric acid (H2SO4) production. Zero-dimensional model calculations show that sCI from biogenic volatile organic compounds composed the majority of the sCIs. The main uncertainty associated with an evaluation of H2SO4 production from the sCI reaction channel is the lack of experimentally determined reaction rates for sCIs formed from isoprene ozonolysis with SO2 along with systematic discrepancies in experimentally derived reaction rates between other sCIs and SO2 and water vapor. In general, the maximum of H2SO4 production from the sCI channel is found in the late afternoon as ozone increases toward the late afternoon. The sCI channel, however, contributes minor H2SO4 production compared with the conventional OH channel in the mid-day. Finally, the production and the loss rates of H2SO4 are compared. The application of the recommended mass accommodation coefficient causes significant overestimation of H2SO4 loss rates compared with H2SO4 production rates. However, the application of a lower experimental value for the mass accommodation coefficient provides good agreement between the loss and production rates of H2SO4. The results suggest that the recommended coefficient for the H2O surface may not be suitable for this relatively dry environment. PMID:25700170

  6. Association of Fatty Acid Synthase Polymorphisms and Expression with Outcomes after Radical Prostatectomy

    PubMed Central

    Cheng, Jinrong; Ondracek, Rochelle Payne; Mehedint, Diana C.; Kasza, Karin A.; Xu, Bo; Gill, Simpal; Azabdaftari, Gissou; Yao, Song; Morrison, Carl D.; Mohler, James L.; Marshall, James R.

    2016-01-01

    Fatty acid synthase (FASN), selectively overexpressed in prostate cancer cells, has been described as linked to the aggressiveness of prostate cancer (PCa). Constitutional genetic variation of the FASN gene and the expression levels of FASN protein in cancer cells could thus be expected to predict outcome after radical prostatectomy (RP). This study evaluates the associations of malignant tissue status, neoadjuvant androgen deprivation treatment (NADT) and single nucleotide polymorphisms of FASN with FASN protein expression in prostate tissue. The study then examines the associations of FASN single nucleotide polymorphisms (SNPs) and gene expression with 3 measures of post-prostatectomy outcome. Seven tagging FASN SNPs were genotyped in 659 European American men who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2005. FASN protein expression was assessed using immunohistochemistry. The patients were followed for an average of 6.9 years (range: 0.1 to 20.6 years). Outcome was assessed using 3 endpoints: biochemical failure, treatment failure and development of distant metastatic PCa. Cox proportional hazards analyses were used to evaluate the associations of the tagging SNPs and FASN expression with these endpoints. Bivariate associations with outcomes were considered; the associations also were controlled for known aggressiveness indicators. Overall, no SNPs were associated with any known aggressiveness indicators. FASN staining intensity was stronger in malignant than in benign tissue, and neoadjuvant androgen deprivation therapy (NADT) was associated with decreased FASN staining in both benign and malignant tissue. The relationships of FASN SNPs and staining intensity with outcome were less clear. One SNP, rs4246444, showed a weak association with outcome. FASN staining intensity also showed a weak and seemingly contradictory relationship with outcome. Additional study with longer follow-up and populations that include more metastatic

  7. Screening for antioxidants in complex matrices using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection.

    PubMed

    McDermott, Geoffrey P; Conlan, Xavier A; Noonan, Laura K; Costin, Jason W; Mnatsakanyan, Mariam; Shalliker, R Andrew; Barnett, Neil W; Francis, Paul S

    2011-01-17

    The use of high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection to screen for antioxidants in complex plant-derived samples was evaluated in comparison with two conventional post-column radical scavenging assays (2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(+))). In this approach, acidic potassium permanganate can react with readily oxidisable compounds (potential antioxidants), post-column, to produce chemiluminescence. Using flow injection analysis, experimental parameters that afforded the most suitable permanganate chemiluminescence signal for a range of known antioxidants were studied in a univariate approach. Optimum conditions were found to be: 1×10(-3)M potassium permanganate solution containing 1% (w/v) sodium polyphosphates adjusted to pH 2 with sulphuric acid, delivered at a flow rate of 2.5 mL min(-1) per line. Further investigations showed some differences in detection selectivity between HPLC with the optimised post-column permanganate chemiluminescence detection and DPPH and ABTS(+) assays towards antioxidant standards. However, permanganate chemiluminescence detection was more sensitive. Moreover, screening for antioxidants in green tea, cranberry juice and thyme using potassium permanganate chemiluminescence offers several advantages over the traditional DPPH and ABTS(+) assays, such as faster reagent preparation and superior stability; simpler post-column reaction manifold; and greater compatibility with fast chromatographic separations using monolithic columns. PMID:21167995

  8. Interactions between carnosine and captopril on free radical scavenging activity and angiotensin-converting enzyme activity in vitro.

    PubMed

    Nakagawa, Kazuo; Ueno, Akemi; Nishikawa, Yukari

    2006-01-01

    Interactions between carnosine (beta-alanyl-L-histidine), being plentiful in skeletal muscles and neuronal tissues, and captopril, a widely used angiotensin-converting enzyme (ACE) inhibitor, were examined concerning free radical scavenging activity and ACE activity in vitro. Not only captopril, but also carnosine, at concentrations less than those ordinarily found in muscles and neuronal tissues, significantly scavenged 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS) radical cations, and inhibited ACE activity. Cupric ions reversed the ABTS scavenging activity of carnosine and captopril, whereas cupric ions strengthened the inhibitory action of carnosine on ACE activity. In contrast, cupric ions antagonized the inhibition of ACE activity induced by ethylenediaminetetraacetic acid, indicating that the inhibitory effect of carnosine on ACE activity is not related to the chelating action of carnosine. On the other hand, carnosine and captopril synergistically enhanced the free radical scavenging activity, but not the inhibitory effect on the ACE activity. These data suggest that carnosine in its concurrent use with captopril could act as a beneficial free radical scavenger, with less danger of overdose, in the inhibition of ACE activity. PMID:16394648

  9. Mechanisms of hydroxyl radical production from abiotic oxidation of pyrite under acidic conditions

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Yuan, Songhu; Liao, Peng

    2016-01-01

    Hydroxyl radicals (radOH) produced from pyrite oxidation by O2 have been recognized, but mechanisms regarding the production under anoxic and oxic conditions are not well understood. In this study, the mechanisms of radOH production from pyrite oxidation under anoxic and oxic conditions were explored using benzoic acid (BA) as an radOH probe. Batch experiments were conducted at pH 2.6 to explore radOH production under anoxic and oxic conditions. The cumulative radOH concentrations produced under anoxic and oxic conditions increased linearly to 7.5 and 52.2 μM, respectively within 10 h at 10 g/L pyrite. Under anoxic conditions, radOH was produced from the oxidation of H2O on the sulfur-deficient sites on pyrite surface, showing an increased production with the increase of pyrite surface exposure due to oxidation. Under oxic conditions, the formation of radOH proceeds predominantly via the two-electron reduction of O2 on pyrite surface along with a minor contribution from the oxidation of H2O on surface sulfur-defects and the reactions of Fe2+/sulfur intermediates with O2. For both O2 reduction and H2O oxidation on the surface sulfur-defects, H2O2 was the predominant intermediate, which subsequently transformed to radOH through Fenton mechanism. The radOH produced had a significant impact on the transformation of contaminants in the environment. Anoxic pyrite suspensions oxidized 13.9% As(III) (C0 = 6.67 μM) and 17.6% sulfanilamide (C0 = 2.91 μM) within 10 h at pH 2.6 and 10 g/L pyrite, while oxic pyrite suspensions improved the oxidation percentages to 55.4% for As(III) and 51.9% for sulfanilamide. The ratios of anoxic to oxic oxidation are consistent with the relative contribution of surface sulfur-defects to radOH production. However, Fe2+ produced from pyrite oxidation competed with the contaminants for radOH, which is of particular significance with the increase of time in a static environment. We conclude that radOH can be produced from abiotic oxidation of

  10. Studies on the photolytic breakdown of hydroperoxides and peroxidized fatty acids by using electron spin resonance spectroscopy. Spin trapping of alkoxyl and peroxyl radicals in organic solvents.

    PubMed Central

    Davies, M J; Slater, T F

    1986-01-01

    Spin trapping using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been used to detect and distinguish between the carbon-centred, alkoxyl, and peroxyl radicals produced during the photolytic decomposition of hydroperoxides. Photolysis of tert-butyl and cumene hydroperoxides, and peroxidized fatty acids, in toluene, with low levels of u.v. light, is shown to lead to the initial production of alkoxyl radicals by homolysis of the oxygen-oxygen bond. Subsequent reaction of these radicals with excess hydroperoxide leads, by hydrogen abstraction, to the production of peroxyl radicals that can be detected as their corresponding adducts with the spin trap. Subsequent breakdown of these adducts produces alkoxyl radicals and a further species that is believed to be the oxidized spin-trap radical 5,5-dimethyl-1-pyrrolidone-2-oxyl. No evidence was obtained at low hydroperoxide concentrations, with either the cumene or lipid alkoxyl radicals, for the occurrence of beta-scission reactions; the production of low levels of carbon-centred radicals is believed to be due to the alternative reactions of hydrogen abstraction, ring closure, and/or 1,2 hydrogen shifts. Analogous experiments with 3,3,5,5-tetramethyl-1-pyrroline N-oxide (TMPO) led only to the trapping of alkoxyl radicals with no evidence for peroxyl radical adducts, this is presumably due to a decreased rate of radical addition because of increased steric hindrance. PMID:3030287

  11. Comparison of antioxidant effectiveness of lipoic acid and dihydrolipoic acid.

    PubMed

    Zhao, Feng; Liu, Zai-Qun

    2011-01-01

    The abilities of dihydrolipoic acid (DHLA) to scavenge peroxynitrite (ONOO(-) ), galvinoxyl radical, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS(+•) ), and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) were higher than those of lipoic acid (LA). The effectiveness of DHLA to protect methyl linoleate against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation was about 2.2-fold higher than that of LA, and DHLA can retard the autoxidation of linoleic acid (LH) in the β-carotene-bleaching test. DHLA can also trap ∼0.6 radicals in AAPH-induced oxidation of LH. Moreover, DHLA can scavenge ∼2.0 radicals in AAPH-induced oxidation of DNA and AAPH-induced hemolysis of erythrocytes, whereas LA can scavenge ∼1.5 radicals at the same experimental conditions. DHLA can protect erythrocytes against hemin-induced hemolysis, but accelerate the degradation of DNA in the presence of Cu(2+) . Therefore, the antioxidant capacity of -SH in DHLA is higher than S-S in LA. PMID:21812071

  12. The Rate of Decolorization of a Radical Ion Reagent Was Used to Determine the Phenolic Content of Various Food Extracts

    PubMed Central

    Bradley, Arthur

    2013-01-01

    Polyphenols are among the most valuable and widely studied food components. In the laboratory, they are readily extractable with aqueous alcohol. An aliquot rapidly decolorizes a measured portion of ABTS, a stable deep blue radical ion. The semilog plot of light absorption versus time is typically a straight line, and an immediately evident slope provides rapid classification in terms of gallic acid equivalents. Experimental data are presented to show general agreement with the literature. The disproportionate concentration of antioxidant in the skins and peels of fruits, vegetables, and nuts is given special attention. PMID:24282411

  13. ABT-controllable laser hyperthermia of biological objects

    NASA Astrophysics Data System (ADS)

    Krotov, Eugene V.; Yakovlev, Ivan V.; Zhadobov, Maxim; Reyman, Alexander M.

    2002-05-01

    The results of experimentally investigated laser heating of optically absorbing inhomogeneities inside the biological objects accompanied with monitoring of internal temperature by acoustical brightness thermometry (ABT) have been presented. One of the urgent problems of modern medicine is to provide organism safety during photodynamic therapy of various neoplasms including malignant ones. In the case when neoplasm differs from normal tissue mainly in optical absorption it seems to be effective to use laser heating for this purpose. In our experiments we used the NIR emission of CW and pulse-periodic Nd:YAG lasers (1064 nm) as well as CW semiconductor laser (800 nm) for heating of tissue- simulating phantom. Optically transparent gelatine with absorbing inhomogeneity inside was used as a phantom. Internal temperature was measured non-invasively by means of multi-channel ABT after long heating of an object by laser radiation. Temperature was also measured independently by contact electronic thermometer. The results of experiments demonstrated high efficiency of ABT application for internal temperature monitoring during PDT and other hyperthermia procedures. Besides that laser radiation can be used for backlighting followed by ABT investigation of internal structure of temperature distribution inside biological tissues. This work was supported by Russian Foundation for Basic Research (Projects # 00-02-16600; 01-02-06417; 01-02- 17645) and 6th competition-expertise of young scientists of Russian Academy of Sciences (Project #399).

  14. Targeted acylation for all the hydroxyls of (+)-catechin and evaluation of their individual contribution to radical scavenging activity.

    PubMed

    Hong, Shan; Liu, Songbai

    2016-04-15

    The reactivity profile of all the hydroxyl groups in (+)-catechin towards acylation and their respective contribution to radical scavenging activity were systematically explored in this work. Selective acylation of the hydroxyls on different rings was carried out employing either a basic or acidic activation strategy. Monoacylation of B ring was achieved effectively with the aid of dimethyltin dichloride. Monoacylation of A ring was accomplished by sequential protection and deprotection of B and C rings. Based on specific acylation of all the individual hydroxyls of (+)-catechins, the structure radical scavenging activity relationship of each hydroxyl of (+)-catechin was established. It was demonstrated that the vicinal phenolic hydroxyls on B ring played the most important role in the ABTS radical scavenging activity and those on A and C rings made a much smaller contribution. This study has laid solid groundwork for further modification of the catechins and improvement of their properties. PMID:26616969

  15. Influence of fatty acid on lipase-catalyzed synthesis of ascorbyl esters and their free radical scavenging capacity.

    PubMed

    Stojanović, Marija; Carević, Milica; Mihailović, Mladen; Veličković, Dušan; Dimitrijević, Aleksandra; Milosavić, Nenad; Bezbradica, Dejan

    2015-01-01

    Fatty acid (FA) ascorbyl esters are recently emerging food, cosmetic, and pharmaceutical additives, which can be prepared in an eco-friendly way by using lipases as catalysts. Because they are amphiphilic molecules, which possess high free radical scavenging capacity, they can be applied as liposoluble antioxidants as well as emulsifiers and biosurfactants. In this study, the influence of a wide range of acyl donors on ester yield in lipase-catalyzed synthesis and ester antioxidant activity was examined. Among saturated acyl donors, higher yields and antioxidant activities of esters were achieved when short-chain FAs were used. Oleic acid gave the highest yield overall and its ester exhibited a high antioxidant activity. Optimization of experimental factors showed that the highest conversion (60.5%) in acetone was achieved with 5 g L(-1) of lipase, 50 mM of vitamin C, 10-fold molar excess of oleic acid, and 0.7 mL L(-1) of initial water. Obtained results showed that even short- and medium-chain ascorbyl esters could be synthesized with high yields and retained (or even exceeded) free radical scavenging capacity of l-ascorbic acid, indicating prospects of broadening their application in emulsions and liposomes. PMID:25224149

  16. Radical formation in the FMN-photosensitized reactions of unsaturated fatty acids bearing double bonds at different positions.

    PubMed

    Nishihama, Nao; Iwahashi, Hideo

    2016-08-15

    -carboxybutyl, 7-carboxyheptyl and 9-carboxynonyl radicals formed in the control reaction mixtures of (z)-6-octadecenoic acid, (z)-9-octadecenoic acid {or (z, z)-9,12-octadecadienoic acid} and (z)-11-octadecenoic acid, respectively. The 4-carboxybutyl, 7-carboxyheptyl and 9-carboxynonyl radicals are all generated through β-scission of alkoxy radicals formed on carboxyl ends of the double bonds of the unsaturated fatty acids. Thus, we could reveal reactive sites of unsaturated fatty acids in the photosensitized reaction of flavin mononucleotide with unsaturated fatty acids bearing a double bond at different positions. PMID:27372435

  17. Antioxidant capacity of hydrolyzed animal by-products and relation to amino acid composition and peptide size distribution.

    PubMed

    Damgaard, Trine; Lametsch, René; Otte, Jeanette

    2015-10-01

    The antioxidative capacity of six different tissue hydrolysates (porcine colon, heart and neck and bovine lung, kidney and pancreas) were tested by three different assays monitoring iron chelation, ABTS radical scavenging and inhibition of lipid oxidation in emulsions, respectively. The hydrolysates were also investigated with respect to amino acid composition and peptide size distribution. The hydrolysates contained peptides ranging from 20 kDa to below 100 Da with a predominance of peptides with low molecular weight (53.8 to 89.0 % below 3 kDa). All hydrolysates exhibited antioxidant activity as assessed with all three methods; inhibition of lipid oxidation ranging from 72 to 88 % (at a final protein concentration of 7 mg/mL), iron chelation capacity from 23 to 63 % (at 1.1 mg/mL), and ABTS radical scavenging from 38 to 50 % (at 10 μg /mL). The antioxidant activity did not correlate with the proportion of low molecular weight peptides in the hydrolysed tissues, but with the content of specific amino acid residues. The ABTS radical scavenging capacity of the tissues was found to correlate with the content of Trp, Tyr, Met and Arg, whereas the ability to inhibit the oxidation of lineoleic acid correlated with the content of Glu and His. The chosen animal by-products thus represent a natural source of antioxidants with potential for food application. PMID:26396396

  18. DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic arsenics, are strongly enhanced by superoxide anion radicals.

    PubMed

    Rin, K; Kawaguchi, K; Yamanaka, K; Tezuka, M; Oku, N; Okada, S

    1995-01-01

    We previously reported that dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induced DNA single-strand breaks (ssb) both in vivo and in cultured alveolar type II (L-132) cells in vitro, possibly via the production of dimethylarsenic peroxyl radicals. Here, the interaction of superoxide anion radicals (O2-) in the induction of ssb in L-132 cells was investigated using paraquat, an O2(-)-producing agent. A significant enhancement of ssb formation was observed in the DMAA-exposed cells when coexposed to paraquat. This enhancement occurred even when post-exposed to DMAA after washing, suggesting that the DMAA exposure caused some modification of DNA such as DNA-adducts, which was recognized by active oxygens to form ssb. An experiment with UV-irradiation, which was likely to induce ssb at the modified region, supported the possibility of DNA modification by DMAA exposure. An ESR study indicated that O2- produced by paraquat in DMAA-exposed cells was more consumed than in non-exposed cells, assumingly through the reaction with the dimethylarsenic-modified region of DNA. The species of active oxygens were estimated by using diethyldithiocarbamate, aminotriazole, diethylmaleate, hydrogen peroxide (H2O2), gamma-irradiation and ethanol. O2- but neither H2O2 nor hydroxyl radicals was very likely to contribute to the ssb-enhancing action of paraquat. PMID:7735248

  19. Sulfate radical-induced degradation of Acid Orange 7 by a new magnetic composite catalyzed peroxymonosulfate oxidation process.

    PubMed

    Chen, Dan; Ma, Xiaolong; Zhou, Jizhi; Chen, Xi; Qian, Guangren

    2014-08-30

    We synthesized a novel magnetic composite, Fe3O4/Cu(Ni)Cr-LDH, as a heterogeneous catalyst for the degradation of organic dyes in the solution using sulfate radical-based advanced oxidation processes. The physicochemical properties of the composite synthesized via two-step microwave hydrothermal method were characterized by several techniques, such as X-ray diffraction (XRD), inductively coupled plasma (ICP), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The degradation tests were performed at 25°C with Acid Orange 7 (AO7) initial concentration of 25mg/L and AO7/peroxymonosulfate (PMS) molar ratio of 1:10, which showed that the complete degradation by Fe3O4/Cu1.5Ni0.5Cr-LDH could be achieved and the mineralization rate could reach 46%. PMS was activated by Cu (II) and Fe (II/III) of Fe3O4/Cu(Ni)Cr-LDH to generate sulfate radicals (SO4(-)). Subsequently, the organic functional groups of AO7 molecules were destroyed by sulfate radicals (SO4(-)), inducing the degradation of AO7. Moreover, the catalytic behavior of the catalysts could be reused five times. Therefore, our work suggested that the Fe3O4/Cu(Ni)Cr-LDH composite could be applied widely for the treatment of organic dyes in wastewater. PMID:25103453

  20. Interaction of gold nanoparticles with free radicals and their role in enhancing the scavenging activity of ascorbic acid.

    PubMed

    Razzaq, Humaira; Saira, Farhat; Yaqub, Azra; Qureshi, Rumana; Mumtaz, Misbah; Saleemi, Samia

    2016-08-01

    The present study investigates the interaction of citrate stabilized gold nanoparticles (12±1.5nm) (GNPs) with free radicals; 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable and electrochemically generated superoxide, O2(-). Different experiments were designed to understand the interaction between GNPs and DPPH by employing cyclic voltammetry, UV-vis spectroscopy and computational chemistry using 6-311G basis set. The increase in heterogeneous rate constant, ksh, of DPPH upon addition of GNPs pointed towards possible complex formation, DPPH-GNPs which were further explained by a model assuming surface adsorption of DPPH on GNPs. Further, the model was validated by studying interaction of GNPs with a biologically important free radical, O2(-). Exciting result in terms of disappearance of anodic peak after GNPs addition confirmed that gold nanoparticles interacted with stable as well as unstable free radicals. Also, the stoichiometry of the most stable complex GNP-DPPH was determined from UV-vis spectroscopy by applying Job's method. The GNP-DPPH complex was found to be active with 46.0% reduction of the IC50 value of standard antioxidant, ascorbic acid (AA), indicating its role in enhancing antioxidant activity. Hence, this study presents a simple and potential approach to enhance the efficiency of natural antioxidants without modifying their structure, or involving the complex functionalization of GNPs with antioxidants. PMID:27288656

  1. Spectroscopic studies on the antioxidant activity of p-coumaric acid

    NASA Astrophysics Data System (ADS)

    Kiliç, Ismail; Yeşiloğlu, Yeşim

    2013-11-01

    p-coumaric acid (4-hydroxycinnamic acid), a phenolic acid, is a hydroxyl derivative of cinnamic acid. It decreases low density lipoprotein (LDL) peroxidation and reduces the risk of stomach cancer. In vitro radical scavenging and antioxidant capacity of p-coumaric acid were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2‧-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. p-Coumaric acid inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and ascorbic acid displayed 66.8%, 69.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, p-coumaric acid had an effective DPPHrad scavenging, ABTSrad + scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that p-coumaric acid can be used in the pharmacological and food industry because of these properties.

  2. Combustion Processes as a Source of High Levels of Indoor Hydroxyl Radicals through the Photolysis of Nitrous Acid.

    PubMed

    Bartolomei, V; Gomez Alvarez, E; Wittmer, J; Tlili, S; Strekowski, R; Temime-Roussel, B; Quivet, E; Wortham, H; Zetzsch, C; Kleffmann, J; Gligorovski, S

    2015-06-01

    Hydroxyl radicals (OH) are known to control the oxidative capacity of the atmosphere but their influence on reactivity within indoor environments is believed to be of little importance. Atmospheric direct sources of OH include the photolysis of ozone and nitrous acid (HONO) and the ozonolysis of alkenes. It has been argued that the ultraviolet light fraction of the solar spectrum is largely attenuated within indoor environments, thus, limiting the extent of photolytic OH sources. Conversely, the ozonolysis of alkenes has been suggested as the main pathway of OH formation within indoor settings. According to this hypothesis the indoor OH radical concentrations span in the range of only 10(4) to 10(5) cm(-3). However, recent direct OH radical measurements within a school classroom yielded OH radical peak values at moderate light intensity measured at evenings of 1.8 × 10(6) cm(-3) that were attributed to the photolysis of HONO. In this work, we report results from chamber experiments irradiated with varying light intensities in order to mimic realistic indoor lighting conditions. The exhaust of a burning candle was introduced in the chamber as a typical indoor source causing a sharp peak of HONO, but also of nitrogen oxides (NOx). The photolysis of HONO yields peak OH concentration values, that for the range of indoors lightning conditions were estimated in the range 5.7 ×· 10(6) to 1.6 × 10(7) cm(-3). Excellent agreement exists between OH levels determined by a chemical clock and those calculated by a simple PSS model. These findings suggest that significant OH reactivity takes place at our dwellings and the consequences of this reactivity-that is, formation of secondary oxidants-ought to be studied hereafter. PMID:25942056

  3. Antioxidant activity and free radical-scavenging capacity of Gynura divaricata leaf extracts at different temperatures

    PubMed Central

    Wan, Chunpeng; Yu, Yanying; Zhou, Shouran; Liu, Wei; Tian, Shuge; Cao, Shuwen

    2011-01-01

    Background: Extraction temperature influences the total phenolic content (TPC), total flavonoid content (TFC) of medicinal plant extracts to a great extend. TPC and TFC are the principle activity constituents present in the plant. The effects of extraction temperature on TPC, TFC and free radical-scavenging capacity of Gynura divaricata leaf extracts are worth to study. Materials and Methods: Folin–Ciocalteu and aluminum chloride colorimetric assay were used to determine the TPC and TFC of Gynura divaricata leaf extracts at different temperatures. The antioxidant and free radical-scavenging activity were measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and phosphomolybdenum methods. Results: TPC and TFC were significantly elevated with increasing extraction temperature (from 40°C to 100°C). However, TPC and TFC were not significantly different (P > 0.05) at the extraction temperatures 90°C and 100°C. Also, the extracts obtained at a higher temperature exhibited a significant free radical-scavenging activity compared with extraction at lower temperatures (P < 0.05). The TPCs (13.95-36.68 mg gallic acid equivalent/g dry material) were highly correlated with DPPH (R2 = 0.9229), ABTS (R2 = 0.9951) free radical-scavenging capacity, and total antioxidant activity (R2 = 0.9872) evaluated by phosphomolybdenum method. Conclusion: The TPC and TFC of G. divaricata leaf was significantly influenced by the extraction temperatures, which were the main antioxidant constituents present in the G. divaricata plant. PMID:21472078

  4. Gram scale synthesis of the glucuronide metabolite of ABT-724.

    PubMed

    Engstrom, Kenneth M; Daanen, Jerome F; Wagaw, Seble; Stewart, Andrew O

    2006-10-27

    A gram scale synthesis of the glucuronide metabolite of ABT-724 is reported. Glycosidic coupling between a trichloroacetimidate glucuronyl donor and a Cbz-protected hydroxypyridylpiperazine glycosyl acceptor is the key step in the synthesis, since attempts to directly glucuronidate the aglycon, aglycon derivatives, and other truncated glycosyl acceptors were unsuccessful. The route was used to produce 2.1 g of metabolite in eight steps from 2-chloro-5-hydroxypyridine in 21% overall yield. PMID:17064008

  5. Mechanism of benzophenone ketyl radical formation in acid alcohols studied by pulse-radiolysis and rigid-matrix techniques. [Gamma rays

    SciTech Connect

    Hoshino, M.; Arai, S.; Imamura, M.; Ikehara, K.; Hama, Y.

    1980-10-02

    The mechanism of the benzophenone ketyl radical formation in acid methanol, ethanol, and 2-propanol was studied by using pulse-radiolysis and rigid-matrix techniques. When a 0.1 M ethanol solution of benzophenone containing hydrogen chloride (1.2 M) was irradiated at 77 K by ..gamma.. rays from /sup 60/Co, the absorption spectrum of the trapped intermediates was ascribed solely to benzophenone ketyl radicals. The pulse-radiolysis study of the solution at 100 K revealed that the ketyl radicals are produced by protonation of presolvated benzophenone anion radicals. At 153 K, the ketyl radicals were observed to be produced also by hydrogen-atom transfer from CH/sub 3/CHOH and CH/sub 3/CH(OH)CH/sub 3/ to benzophenone; the temperature dependence of the transfer rate constant was studied.

  6. Immobilized transition metal-based radical scavengers and their effect on durability of Aquivion® perfluorosulfonic acid membranes

    NASA Astrophysics Data System (ADS)

    D'Urso, C.; Oldani, C.; Baglio, V.; Merlo, L.; Aricò, A. S.

    2016-01-01

    A simple and broadly applicable preparation procedure to obtain silica-supported transition metal (namely Cr, Co and Mn)-based radical scavengers, containing sulfonic acid functionalities, is reported. These systems are widely characterised in terms of structure, bulk and surface composition and morphology by X-Ray Diffraction (XRD), X-Ray Fluorescence (XRF), X-Ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM). The scavenger material is loaded in ePTFE reinforced membranes prepared from Aquivion® perfluorosulfonic acid (PFSA) dispersions. All these composite membranes show longer lifetime in Accelerated Stress Tests (AST) and reduced fluoride release in Fenton's tests than the scavenger-free membranes without any loss in electrochemical performance. The Cr-scavenger-based polymer electrolyte shows a three-time larger stability than the pristine membrane.

  7. Tropospheric chemistry of natural hydrocarbons, aldehydes, and peroxy radicals: Their connections to sulfuric acid production and climate effects

    SciTech Connect

    Gaffney, J.S.; Marley, N.A.

    1993-05-01

    Recent work has shown that natural hydrocarbon emissions can significantly affect the levels of urban and regional tropospheric ozone. We report on the reactivities of these biogenic trace gases, particularly isoprene, focusing on their importance in the production of aldehydes and peroxy radicals, leading to increased levels of hydrogen over regional forests. Hydrogen peroxide can lead to the wet oxidation of sulfur dioxide to acidic sulfate in aerosols, fogs, and clouds. In turn, acidic sulfate can act to as a light scattering aerosol and a source of cloud condensation nuclei (CCN), potentially leading to global cooling. Aerosol sulfate and other dissolved organic and inorganic compounds can also play important roles as a greenhouse species in the lower troposphere.

  8. Reaction pathway of the degradation of the p-hydroxybenzoic acid by sulfate radical generated by ionizing radiations

    NASA Astrophysics Data System (ADS)

    Criquet, Justine; Leitner, Nathalie Karpel Vel

    2015-01-01

    The degradation of p-hydroxybenzoic acid (HBA) in aqueous solutions by ionizing radiation was studied. The phenolic pollutant was easily removed by the electron beam irradiation, as more than 80% of the initial 100 μM introduced was degraded for a dose of 600 Gy. It was shown that the addition of persulfate, producing the sulfate radical as additional reactive species, induced a change in the reaction pathway. LC-MS analyses were performed in order to identify the different by-products formed. In the absence of persulfate, the main by-product formed was 3,4-dihydroxybenzoic acid, while in presence of persulfate, 1,4-benzoquinone was detected and the hydroxylated by-products were not present. A reaction pathway of HBA degradation by hydroxyl and sulfate radicals was proposed from the identification of the chemical structure of the different by-products detected. The influences of pH and dissolved oxygen were also studied. A high decline of HBA degradation was observed at pH 11 compared to pH 4.5, this decrease was minimized in the presence of persulfate. The dissolved oxygen concentration was found to be a limiting parameter of HBA degradation, however an excess of dissolved oxygen in solution did not improve the degradation to a large extent.

  9. Absolute rate constants of alkoxyl radical reactions in aqueous solution. [Tert-butyl hydroperoxide

    SciTech Connect

    Erben-Russ, M.; Michel, C.; Bors, W.; Saran, M.

    1987-04-23

    The pulse radiolysis technique was used to generate the alkoxyl radical derived from tert-butyl hydroperoxide (/sup t/BuOOH) in aqueous solution. The reactions of this radical with 2,2'-azinobis(3-ethyl-6-benzothiazolinesulfonate) (ABTS) and promethazine were monitored by kinetic spectroscopy. The unimolecular decay rate constant of the tert-butoxyl radical (/sup t/BuO) was determined to be 1.4 x 10/sup 6/ s/sup -1/. On the basis of this value, the rate constants for /sup t/BuO attack on quercetin, crocin, crocetin, ascorbate, isoascorbate, trolox c, glutathione, thymidine, adenosine, guanosine, and unsaturated fatty acids were determined. In addition, the reaction of /sup t/BuO with the polyunsaturated fatty acids (PUFA) was observed by directly monitoring the formation of the fatty acid pentadienyl radicals. Interestingly, the attack of /sup t/BuO on PUFA was found to be faster by about one order of magnitude as compared to the same reaction in a nonpolar solvent.

  10. Interaction of aromatic alcohols, aldehydes and acids with α-hydroxyl-containing carbon-centered radicals: A steady state radiolysis study

    NASA Astrophysics Data System (ADS)

    Samovich, S. N.; Brinkevich, S. D.; Shadyro, O. I.

    2013-01-01

    Benzaldehyde and its derivatives efficaciously oxidize in aqueous solutions α-hydroxyl-containing carbon-centered radicals (α-HCR) of various structures, suppressing thereby the radical recombination and fragmentation reactions. The compounds containing cinnamic moieties are capable of adding α-hydroxyethyl radicals (α-HER) to the carbon-carbon double bonds conjugated with the aromatic system to form molecular products identifiable by mass spectrometry. On radiolysis of aqueous ethanol solutions, reduction of α-HER by aromatic alcohols and acids has been shown to proceed via formation of their adducts with hydrated electron species.

  11. Increased electrical output when a bacterial ABTS oxidizer is used in a microbial fuel cell.

    PubMed

    Hunter, William J; Manter, Daniel K

    2011-02-01

    Microbial fuel cells (MFCs) are a technology that provides electrical energy from the microbial oxidation of organic compounds. Most MFCs use oxygen as the oxidant in the cathode chamber. This study examined the formation in culture of an unidentified bacterial oxidant and investigated the performance of this oxidant in a two-chambered MFC with a proton exchange membrane and an uncoated carbon cathode. DNA, FAME profile and characterization studies identified the microorganism that produced the oxidant as Burkholderia cenocepacia. The oxidant was produced by log phase cells, oxidized the dye 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), had a mass below 1 kD, was heat stable (121°C) and was soluble in ethanol. In a MFC with a 1000 Ω load and ABTS as a mediator, the oxidizer increased cell voltage 11 times higher than atmospheric oxygen and 2.9 times higher than that observed with ferricyanide in the cathode chamber. No increase in cell voltage was observed when no mediator was present. Organisms that produce and release oxidizers into the media may prove useful as bio-cathodes by improving the electrical output of MFCs. PMID:20853166

  12. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals

    PubMed Central

    2010-01-01

    Background Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. Methods The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3) cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control) at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls). Results Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL). The extract reduced significantly (p < 0.05) apoptotic cell death due to DPPH and ABTS by 4 to 5-fold although the activity was less than vitamin C. Based on the DPPH assay, the radical scavenging activity of the extract was higher than phycocyanin and was at least 50% of vitamin C and vitamin E. Based on the ABTS assay, the antioxidant activity of the extract at 50 μmug/mL was as good as vitamin C and vitamin E. Conclusions The results showed that aqueous extract of Spirulina has a protective effect against apoptotic cell death due to free radicals

  13. Determination of Arrhenius and Thermodynamic Parameters for the Aqueous Reaction of the Hydroxyl Radical with Lactic Acid

    SciTech Connect

    Leigh R. Martin; Stephen P. Mezyk; Bruce J. Mincher

    2009-01-01

    Lactic acid is a major component of the TALSPEAK process planned for use in the separation of trivalent lanthanide and actinide elements. This acid acts both as a buffer, and also to protect the actinide complexant from radiolytic damage. However, there is little kinetic information on the reaction of water radiolysis species with lactic acid, particularly under the anticipated process conditions of aerated aqueous solution at pH~3, where oxidizing reactions are expected to dominate. Here we have determined temperature-dependent reaction rate constants for the reactions of the hydroxyl radical with lactic acid and the lactate ion. For lactic acid this rate constant is given by the equation: ln k1 = (23.85 ± 0.19) – (1120 ± 54) / T, corresponding to an activation energy of 9.31 ± 0.45 kJ mol-1 and a room temperature reaction rate constant of (5.24 ± 0.09) x 108 M-1 s-1 (24.0oC). For the lactate ion, the temperature-dependent rate constant is given by: ln k2 = (24.83 ± 0.14) – (1295 ± 42) / T, for an activation energy of 10.76 ± 0.35 kJ mol-1 and a room temperature value of (7.77 ± 0.11) x 108 M-1 s-1 (22.2oC). These kinetic data have been combined with autotitration measurements to determine the temperature-dependent behavior of the lactic acid pKa value, allowing thermodynamic parameters for the acid dissociation to be calculated as ?Hº = -10.75 ± 1.77 kJ mol-1, ?Sº = -103.9 ± 6.0 J K-1 mol-1 and ?Gº = 20.24 ± 2.52 kJ mol-1 at low ionic strength.

  14. Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls.

    PubMed

    Miro, P; Marin, M L; Miranda, M A

    2016-03-01

    The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH). The concept has been demonstrated using triplet carbonyls that can be efficiently generated upon selective UVA-excitation. Hydrogen atom transfer (HAT) from BSs to triplet benzophenone (BP) derivatives gave rise to radicals, ultimately leading to reduction of the BP chromophore with concomitant formation of the oxo-analogs of the corresponding BSs. The direct reactivity of triplet BP with BSs in the initial step was evaluated by determining the kinetic rate constants using laser flash photolysis (LFP). The BP triplet decay was monitored (λmax = 520 nm) upon addition of increasing BS concentrations, and the obtained rate constant values indicated a reactivity of the methine hydrogen atoms in the order of C-3 < C-12 < C-7. The steady-state kinetics of the overall process, monitored through the disappearance of the typical BP absorption band at 260 nm, was much faster under N2 than under O2, also supporting the role of the oxygen-quenchable triplet in the dehydrogenation process. Furthermore, irradiation of deaerated aqueous solutions of sodium cholate in the presence of KPMe provided the oxo-analogs, 3[O],7[O]-CA, 3[O]-CA and 7[O]-CA, arising from the HAT process. PMID:26833240

  15. Free radical grafting of gallic acid (GA) on cellulose nanocrystals (CNCS) and evaluation of antioxidant reinforced gellan gum films

    NASA Astrophysics Data System (ADS)

    Criado, P.; Fraschini, C.; Salmieri, S.; Becher, D.; Safrany, A.; Lacroix, M.

    2016-01-01

    Antiradical properties were introduced on cellulose nanocrystals (CNCs) by redox pair (RP) initiator and γ-radiation treatments. Different procedures were tested on CNC, first a 2 h reaction of hydrogen peroxide (H2O2)/ascorbic acid (AA) was performed on CNC solution. γ-Radiation treatment at 20 kGy dose was then applied and immediately after GA was reacted during 24 h with the pretreated CNCs, giving CNC-H2O2-AA-γ-GA. The formation of new carboxylic acids and carbonyl groups were characterized by FT-IR at 1650 and 1730 cm-1 respectively. Carboxylic acid functionalities were also analyzed by conductometric titration where an increase from 49 to 134 mmol COOH kg-1 was found from native to irradiated CNCs. A similar increase in the carboxylic acid content (132 mmol kg-1) was observed for CNC-H2O2-AA-γ-GA, showing the highest radical scavenging properties (8 mM Trolox eq/mg CNC). Thermogravimetric analysis confirmed the structural changes onto CNC. Film packaging containing 20% of CNC-H2O2-AA-γ-GA was then added to a gellan-based film packaging. A significant improvement (p<0.05) of the tensile strength (TS), the tensile modulus (TM) and the elongation at break (EB) and water vapor permeability reduction was observed when CNC-H2O2-AA-γ-GA was added to the film packaging formulation.

  16. [Therapeutic evaluation of the polylactic acid gel (PLA-G) used for preventing skin flap adhesion in modified radical mastectomy].

    PubMed

    Chen, Guojing; Liu, Tao

    2013-12-01

    The present preliminary study was to observe the feasibility of the use of polylactic acid gel (PLA-G) in modified radical mastectomy and the ability of the PLA-G in the prevention of flap adhesion after operation. Sixty-eight patients were diagnosed with breast cancer, and received modified radical mastectomy from Jan. 2004 to Dec. 2006. The patients were divided randomly into a treatment group and a control group (with 34 cases each). The PLA-G was used under the surface of the auxiliary operative wound in the treatment group, and nothing was used in the control group. The wound healing, the wound complication, the amount of drainage solution, the indwelling time of the drainage tube and the auxiliary skin adhesion were evaluated after operation in both groups. There were no statistical difference on wound healing between the first intension (29:27) and the second intention (5:7), and the wound dehiscence after taking the stitches out (0:0) between the two intensions, the hematoma (0:1) and the effusion of the wound (5:6), and the flap necrosis (1:2) between two groups. There were also no statistical difference on the amount of drainage solution per day (6 +/- 3) and indwelling time of the drainage tube (6 +/- 4) after operation between the two groups (P > 0.5). After the operation, the case load with no flap adhesion in the treatment group was significant higher compared with the control group (22:8). The case load with complete acquired skin flap adhesion in the treatment group was visibly lower than in the control group (3:19), which proved that there was a significant statistical difference between the two groups (P < 0.05). This study suggested that the using of PLA-G in the breast cancer modified radical mastectomy could prevent skin flap adhesion without any harmful effects in the wound healing. PMID:24645611

  17. ABT-263 induces apoptosis and synergizes with chemotherapy by targeting stemness pathways in esophageal cancer.

    PubMed

    Chen, Qiongrong; Song, Shumei; Wei, Shaozhong; Liu, Bin; Honjo, Soichiro; Scott, Ailing; Jin, Jiankang; Ma, Lang; Zhu, Haitao; Skinner, Heath D; Johnson, Randy L; Ajani, Jaffer A

    2015-09-22

    Activation of cancer stem cell signaling is central to acquired resistance to therapy in esophageal cancer (EC). ABT-263, a potent Bcl-2 family inhibitor, is active against many tumor types. However, effect of ABT-263 on EC cells and their resistant counterparts are unknown. Here we report that ABT-263 inhibited cell proliferation and induced apoptosis in human EC cells and their chemo-resistant counterparts. The combination of ABT-263 with 5-FU had synergistic lethal effects and amplified apoptosis that does not depend fully on its inhibition of BCL-2 family proteins in EC cells. To further explore the novel mechanisms of ABT-263, proteomic array (RPPAs) were performed and gene set enriched analysis demonstrated that ABT-263 suppresses the expression of many oncogenes including genes that govern stemness pathways. Immunoblotting and immunofluorescence further confirmed reduction in protein expression and transcription in Wnt/β-catenin and YAP/SOX9 axes. Furthermore, ABT263 strongly suppresses cancer stem cell properties in EC cells and the combination of ABT-263 and 5-FU significantly reduced tumor growth in vivo and suppresses the expression of stemness genes. Thus, our findings demonstrated a novel mechanism of ABT-263 antitumor effect in EC and indicating that combination of ABT-263 with cytotoxic drugs is worthy of pursuit in patients with EC. PMID:26317542

  18. Radical polymerization of N-vinylpyrrolidone in the presence of syndiotactic poly(methacrylic acid) templates. [Gamma ray

    SciTech Connect

    Koetsier, D.W.; Tan, Y.Y.; Challa, G.

    1980-06-01

    Radical polymerization of N-vinylpyrrolidone along poly(methacrylic acid) templates of high syndiotactic content was followed dilatometrically in dimethylformamide, which was used as solvent. The effects of template concentration, template molar mass, and temperature on polymerization rate and average molar mass of the formed polyvinylpyrrolidone (PVP) were examined. Template concentrations were varied around the critical concentration for homogeneous segmental distribution, C. Below this concentration, template coils can act as separate microreactors wherein growing PVP radicals exhibit maximum rate enhancement, i.e., relative rate upsilon/sub R/ = upsilon/sub R max/. In the free solution, blank polymerization occurs, i.e., upsilon/sub R/ = 1. Consequently, upsilon/sub R/ can be approximated by the equation ..nu../sub R/ = phi..nu../sub R/max/ + (1 - phi), where phi represents the volume fraction occupied by template coils. The slight increase in ..nu../sub R/ and PVP molar mass with the template chain length is supposed to be caused by the influence of translational diffusion on the termination step. Over the investigated temperature range of 50 to 70/sup 0/C, the activation energy and entropy were almost identical for blank and template polymerization. An expected decrease of ..delta..E not equal to and ..delta..S not equal to in template systems is supposed to be compensated by the effects of desolvation of the template macromolecules during the propagation step.

  19. Radical Scavenging Activity of the Essential Oil of Silver Fir (Abies alba)

    PubMed Central

    Yang, Seun-Ah; Jeon, Sang-Kyung; Lee, Eun-Jung; Im, Nam-Kyung; Jhee, Kwang-Hwan; Lee, Sam-Pin; Lee, In-Seon

    2009-01-01

    The essential oil of silver fir (Abies alba) is known to help respiratory system and have easing and soothing effect for muscle. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities of silver fir (Abies alba) essential oil. The composition of the oil was analyzed by GC-MS and bornyl acetate (30.31%), camphene (19.81%), 3-carene (13.85%), tricyclene (12.90%), dl-limonene (7.50%), α-pinene (2.87%), caryophyllene (2.18%), β-phellandrene (2.13%), borneol (1.74%), bicyclo[2.2.1]hept-2-ene,2,3-dimethyl (1.64%) and α-terpinene (1.24%) were the major components in the oil. The results tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that the oil showed no cytotoxic effect, at concentrations of 1 and 5%, for as long as 24 and 3 h, respectively. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC50) against DPPH radicals (2.7 ± 0.63%) was lower than ABTS radicals (8.5 ± 0.27%). The antibacterial activity of the oil was also evaluated using disc diffusion method against Staphylococcus aureus, Streptococcus mutans, Listeria monocytogenes, Acinetobacter baumannii, Escherichia coli, and Vibrio parahaemolyticcus. The oil exhibited no antibacterial activity against all the bacterial strains tested except S. aureus of mild activity. PMID:19430614

  20. Radical Scavenging Activity of the Essential Oil of Silver Fir (Abies alba).

    PubMed

    Yang, Seun-Ah; Jeon, Sang-Kyung; Lee, Eun-Jung; Im, Nam-Kyung; Jhee, Kwang-Hwan; Lee, Sam-Pin; Lee, In-Seon

    2009-05-01

    The essential oil of silver fir (Abies alba) is known to help respiratory system and have easing and soothing effect for muscle. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities of silver fir (Abies alba) essential oil. The composition of the oil was analyzed by GC-MS and bornyl acetate (30.31%), camphene (19.81%), 3-carene (13.85%), tricyclene (12.90%), dl-limonene (7.50%), alpha-pinene (2.87%), caryophyllene (2.18%), beta-phellandrene (2.13%), borneol (1.74%), bicyclo[2.2.1]hept-2-ene,2,3-dimethyl (1.64%) and alpha-terpinene (1.24%) were the major components in the oil. The results tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that the oil showed no cytotoxic effect, at concentrations of 1 and 5%, for as long as 24 and 3 h, respectively. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC(50)) against DPPH radicals (2.7 +/- 0.63%) was lower than ABTS radicals (8.5 +/- 0.27%). The antibacterial activity of the oil was also evaluated using disc diffusion method against Staphylococcus aureus, Streptococcus mutans, Listeria monocytogenes, Acinetobacter baumannii, Escherichia coli, and Vibrio parahaemolyticcus. The oil exhibited no antibacterial activity against all the bacterial strains tested except S. aureus of mild activity. PMID:19430614

  1. Free Radical Reactions in Food.

    ERIC Educational Resources Information Center

    Taub, Irwin A.

    1984-01-01

    Discusses reactions of free radicals that determine the chemistry of many fresh, processed, and stored foods. Focuses on reactions involving ascorbic acid, myoglobin, and palmitate radicals as representative radicals derived from a vitamin, metallo-protein, and saturated lipid. Basic concepts related to free radical structure, formation, and…

  2. OH-Radical Oxidation of Surface-Active cis-Pinonic Acid at the Air-Water Interface.

    PubMed

    Enami, Shinichi; Sakamoto, Yosuke

    2016-05-26

    Gaseous biogenic volatile organic compounds (BVOCs) are immediately oxidized by gaseous oxidants to form BVOC-acids that rapidly condense onto aqueous aerosol phase and thus contribute to the growth of atmospheric particles. Because BVOC-acids are highly hydrophobic and hence surface-active in nature, it seems critical to study the oxidation by gaseous hydroxyl radical (·OH(g)) at the air-water interface. Here we report on the fast (≤10 μs) oxidation of aqueous cis-pinonic acid (C10H16O3, CPA, cis-pinonate anion's m/z = 183), a representative BVOC-acid, by ·OH(g) at the air-water interface for the first time. We find that cis-pinonate anion is more enriched at the air-water interface by ∼4 and ∼14 times than n-octanoate anion at 10 and 100 μM, respectively, as revealed by an interface-specific mass spectrometry of the equimolar mixture of microjets. Exposure of aqueous CPA microjets to ·OH(g) pulses from the 266 nm laser photolysis of O3(g)/O2(g)/H2O(g)/N2(g) mixtures yields pinonic peroxyl radicals (m/z = 214) that lead to the functionalization products carbonyls (m/z = 197), alcohols (m/z = 199), and pinonic hydroperoxides (m/z = 215) in addition to smaller-mass products including carbonyls (m/z = 155 and 157). We confirmed the formation of the corresponding alcohols, aldehydes, and hydroperoxides in experiments performed in D2O solvent. The analysis of total mass balance implies a significant amount (>70%) of products would be emitted into the gas-phase during the heterogeneous ·OH-oxidations. Our results suggest ·OH-oxidations of amphiphilic BVOC-acids at the air-water interface may play a far more significant role in photochemical aging process of aqueous aerosols than previously assumed. PMID:27098046

  3. Products of the radical initiated oxidation of model solid and liquid organic acid particles in simulated "clean" and "polluted" environments.

    NASA Astrophysics Data System (ADS)

    Renbaum, L. H.; Smith, G. D.

    2009-05-01

    Using a flow tube reactor coupled to a chemical ionization mass spectrometer, the Cl-initiated oxidation of solid and supercooled liquid organic acid particles were investigated at 293 K. In creating aerosols of species which are able to be supercooled or solid at room temperature, it is possible to distinguish the effect of phase on particle reactivity and product formation. In a clean atmosphere, where there are negligible concentrations of NOx, the primary fate of peroxy radicals (formed from H-abstraction by Cl and OH radicals in the presence of O2) are their reactions to form ketone and alcohol products. These products are then able to undergo further oxidation to form multiply oxidized products. The formation of low-molecular weight volatile species may also be important in the oxidative aging of organic aerosols, however neither the mechanism of their formation nor their formation yields are well understood. We have shown that, for equivalent Cl exposures, more multiply-oxidized species as well as more low-molecular-weight species were created from the oxidation of solid particles than from liquid particles. The findings from these studies suggest that slower diffusion of the oxidation products in solid particles confines them to the surface where they continue to react with Cl radicals producing more-highly- functionalized products which may decompose more readily. By introducing nitric oxide to the flow tube reaction system, we show that in a polluted atmosphere, where NOx is present in significant concentrations, organic nitrate formation may become important on the surface of solid particles but not liquid particles as the RO2 are confined to the surface of solid particles (causing a enhanced localized concentration of RO2) where they may then react with ambient nitric oxide through the reaction RO2 + NO → RO2NO* → RONO2. These experiments of these model systems indicate that particle phase could be important in determining how organic aerosols

  4. Hydrogen bonding interaction between HO2 radical and selected organic acids, RCOOH (R = CH3, H, Cl and F)

    NASA Astrophysics Data System (ADS)

    Joshi, Ravi; Ghanty, Tapan K.

    2013-10-01

    A systematic study on the H-bonding interaction of hydroperoxyl radical with formic, acetic, chloroformic and fluoroformic acids has been carried out using B3LYP/6-311++G(2df,2p) and MP2/aug-cc-pVTZ methods. Several possible geometries have been considered, and the calculated global minima of RCOOH-HO2 have been found to be planar cyclic structure with two hydrogen bonds. A definite trend has been found between the electron donating character of the R group with calculated bond lengths, binding energies and vibrational frequencies. The most stable complex of RCOOH-HO2 with H2O has been found to be associated with a planar cyclic structure involving three hydrogen bonds.

  5. Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine.

    PubMed

    Heinecke, J W

    1997-01-01

    Many lines of evidence implicate oxidation of low density lipoprotein (LDL) in the pathogenesis of atherosclerosis, a chronic inflammatory disease. The physiologically relevant mechanisms have not been identified, but phagocytic white cells may play an important role because macrophage-rich lesions characterize the disorder. Recent studies have shown that myeloperoxidase, a heme enzyme secreted only by phagocytes, is present in human atherosclerotic tissue. The enzyme is a potent catalyst of LDL oxidation in vitro, it co-localizes with macrophages in lesions, and it generates products that are detectable in atherosclerotic plaque. These findings suggest that myeloperoxidase may promote LDL oxidation in the artery wall. This article reviews the enzyme's ability to generate a range of oxidants, including tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine. These products have the potential to damage host molecules as well as microbes, suggesting a mechanism that may contribute to atherosclerotic vascular disease. PMID:9259996

  6. Dipalmitoylphosphatidylcholine/linoleic acid mixed unilamellar vesicles as model membranes for studies on novel free-radical scavengers.

    PubMed

    Castelli, F; Trombetta, D; Tomaino, A; Bonina, F; Romeo, G; Uccella, N; Saija, A

    1997-04-01

    Large unilamellar vesicles (LUVs) are generally accepted to be a suitable model for peroxidation studies. In the present report, dipalmitoylphosphatidylcholine (DPPC)/linoleic acid-mixed LUVs were employed as model membranes to verify the inhibitory effect of tocopherol (an efficient representative antioxidant) against 2,2'-azobis(2-amidinopropane)hydrochloride-induced peroxidation (evaluated by monitoring conjugated diene accumulation). In this model, the appropriate experimental conditions (particularly, liposome composition and peroxidation temperature) were selected following characterization of bilayer physical state, and not only by evaluation of peroxidation rate. Thus, the experiments described provide a routine screening procedure that would be appropriate for assessing the activity profile of novel free-radical scavengers. PMID:9253749

  7. Influence of a Spirulina platensis biomass on the microflora of fermented ABT milks during storage (R1).

    PubMed

    Varga, L; Szigeti, J; Kovács, R; Földes, T; Buti, S

    2002-05-01

    The objective of this research was to investigate the effect of a cyanobacterial (Spirulina platensis) biomass on the microflora of a probiotic fermented dairy product during storage at two temperatures. Spirulina-enriched and control (plain) fermented acidophilus-bifidus-thermophilus (ABT) milks were produced using a fast fermentation starter culture (ABT-4) as the source of Lactobacillus acidophilus (A), bifidobacteria (B), and Streptococcus thermophilus (T). Incubation took 6 h at 40 degrees C. As for the cyanobacterial product, the S. platensis biomass was added to the process milk during stirring at pH 4.5 to 4.6. Thereafter, the ABT-type fermented milks were cooled to 25 degrees C in ice water, filled into sterile, tightly capped centrifuge tubes, further cooled at 4 degrees C for 24 h, and then stored either at 15 degrees C for 18 d or at 4 degrees C for 42 d. Microbiological analyses and acidity measurements were performed at regular intervals. Our results showed that the counts of the starter organisms were satisfactory during the entire storage period at both temperatures applied in this research. The S. platensis biomass had a beneficial effect on the survival of ABT starter bacteria regardless of storage temperature. Postacidification was observed at 15 degrees C, whereas pH remained stable during refrigerated storage at 4 degrees C. The abundance of bioactive substances in S. platensis is of great importance from a nutritional point of view because thus the cyanobacterial biomass provides a new opportunity for the manufacture of functional dairy foods. PMID:12086036

  8. The significance of electron spin resonance of the ascorbic acid radical in freeze dried human brain tumours and oedematous or normal periphery.

    PubMed Central

    Mueller, H. W.; Tannert, S.

    1986-01-01

    The ESR spectrum, attributed to the ascorbic acid (ascorbyl) radical and obtained by exposing freeze dried material to air, can not be used as proof for the occurrence of in vivo free radical reactions. Depending on the method of freeze drying, the content of blood or hemolyzed blood is the dominant factor in creating higher than normal ESR signals in brain or related tissue. These findings explain why the signal, though larger in many human brain tumours than in their surroundings, is not indicative of malignancy. No differences are seen between oedematous and normal tissue. The ascorbyl radical is definitely not stable in aqueous solution, which indicates that fresh tissue sections can also not be used to study in vivo radicals by ESR. PMID:3008800

  9. Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate.

    PubMed

    Yeh, Hui-Chun; Gerfen, Gary J; Wang, Jinn-Shyan; Tsai, Ah-Lim; Wang, Lee-Ho

    2009-02-10

    Prostacyclin synthase (PGIS) is a membrane-bound class III cytochrome P450 that catalyzes an isomerization of prostaglandin H(2), an endoperoxide, to prostacyclin. We report here the characterization of the PGIS intermediates in reactions with other peroxides, peracetic acid (PA), and iodosylbenzene. Rapid-scan stopped-flow experiments revealed an intermediate with an absorption spectrum similar to that of compound ES (Cpd ES), which is an oxo-ferryl (Fe(IV)O) plus a protein-derived radical. Cpd ES, formed upon reaction with PA, has an X-band (9 GHz) EPR signal of g = 2.0047 and a half-saturation power, P(1/2), of 0.73 mW. High-field (130 GHz) EPR reveals the presence of two species of tyrosyl radicals in Cpd ES with their g-tensor components (g(x), g(y), g(z)) of 2.00970, 2.00433, 2.00211 and 2.00700, 2.00433, 2.00211 at a 1:2 ratio, indicating that one is involved in hydrogen bonding and the other is not. The line width of the g = 2 signal becomes narrower, while its P(1/2) value becomes smaller as the reaction proceeds, indicating migration of the unpaired electron to an alternative site. The rate of electron migration ( approximately 0.2 s(-1)) is similar to that of heme bleaching, suggesting the migration is associated with the enzymatic inactivation. Moreover, a g = 6 signal that is presumably a high-spin ferric species emerges after the appearance of the amino acid radical and subsequently decays at a rate comparable to that of enzymatic inactivation. This loss of the g = 6 species thus likely indicates another pathway leading to enzymatic inactivation. The inactivation, however, was prevented by the exogenous reductant guaiacol. The studies of PGIS with PA described herein provide a mechanistic model of a peroxidase reaction catalyzed by the class III cytochromes P450. PMID:19187034

  10. Spectroscopic studies on the antioxidant activity of ellagic acid

    NASA Astrophysics Data System (ADS)

    Kilic, Ismail; Yeşiloğlu, Yeşim; Bayrak, Yüksel

    2014-09-01

    Ellagic acid (EA, C14H6O8) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anticarcinogenesis and anti-oxidation properties. In vitro radical scavenging and antioxidant capacity of EA were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2‧-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. EA inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), α-tocopherol and ascorbic acid displayed 69.8%, 66.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, EA had an effective DPPH• scavenging, ABTSrad + scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that EA can be used in the pharmacological, food industry and medicine because of these properties.

  11. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  12. Formulation design and evaluation of amorphous ABT-102 nanoparticles.

    PubMed

    Jog, Rajan; Kumar, Sumit; Shen, Jie; Jugade, Nital; Tan, David Cheng Thiam; Gokhale, Rajeev; Burgess, Diane J

    2016-02-10

    Amorphous nanoparticles are able to enhance the kinetic solubility and concomitant dissolution rates of BCS class II and BCS class II/IV molecules due to their characteristic increased supersaturation levels, smaller particle size and greater surface area. A DoE approach was applied to investigate formulation and spray drying process parameters for the preparation of spray dried amorphous ABT-102 nanoparticles. Stability studies were performed on the optimized formulations to monitor physical and chemical changes under different temperature and humidity conditions. SLS/soluplus and SLS/PVP K25 were the best stabilizer combinations. Trehalose was used to prevent nanoparticle aggregation during spray drying. Particle size distribution, moisture content, PXRD, PLM, FTIR and in vitro dissolution were utilized to characterize the spray dried nanoparticle formulations. The formulations prepared using soluplus showed enhanced dissolution rate compared to those prepared using PVP K25. Following three months storage, it was observed that the formulations stored at 4°C were stable in terms of particle size distribution, moisture content, and crystallinity, whereas those stored at 25°C/60%RH and 40°C/75%RH were unstable. A predictive model to prepare stable solid spray dried amorphous ABT-102 nanoparticles, incorporating both formulation and process parameters, was successfully developed using multiple linear regression analysis. PMID:26705150

  13. Non-extractable procyanidins and lignin are important factors in the bile acid binding and radical scavenging properties of cell wall material in some fruits.

    PubMed

    Hamauzu, Yasunori; Mizuno, Yukari

    2011-03-01

    The cell wall components and the food functions of alcohol-insoluble solids (AIS) of Chinese quince, quince, hawthorn, apple, pear and blueberry fruits were analyzed. Chinese quince contained characteristically high contents of cellulose, lignin, and non-extractable procyanidins (NEPCs). On the other hand, the quince AIS contained the highest proportion of NEPCs, the highest mean degree of polymerization (mDP), the strongest radical scavenging activity, and strong bile acid binding activity. In fruit AIS, the lignin and NEPC contents both showed positive correlations with the bile acid binding and radical scavenging activities. The value for mDP × NEPC content was a good index for the radical scavenging activity. The results suggest that highly polymerized NEPCs and lignin are important factors of cell wall components of fruits to having a high functionality, and Chinese quince and quince are interesting fruits from this view point. PMID:21243435

  14. Free radical oxidation of (E)-retinoic acid by prostaglandin H synthase.

    PubMed

    Samokyszyn, V M; Chen, T; Maddipati, K R; Franz, T J; Lehman, P A; Lloyd, R V

    1995-01-01

    Cooxidative metabolism of all-trans (E)-retinoic acid (RA) by prostaglandin H synthase was investigated employing ram seminal vesicle microsomes (RSVM) or purified, RSVM-derived enzyme. RA was shown to undergo hydroperoxide [H2O2 or 5-phenyl-4-penten-1-yl hydroperoxide (PPHP)]- or arachidonic acid-dependent cooxidation by microsomal prostaglandin H (PGH) synthase as evidenced by UV spectroscopic analysis of reaction mixtures. Cooxidation of RA by microsomal or purified PGH synthase, using PPHP as substrate, was characterized by uptake of dioxygen which was first order with respect to enzyme concentration. Dioxygen uptake was inhibited by the peroxidase reducing substrate 2-methoxyphenol. In addition, O2 uptake was inhibited by the spin trap nitrosobenzene. ESR spin trapping studies, using alpha-phenyl-N-tert-butylnitrone (PBN) as the spin trap, demonstrated the formation of RA-PBN adducts, characterized by hyperfine coupling constants of alpha H = 3.2 G and alpha N = 15.8 G. Reverse phase HPLC analysis of reaction mixtures demonstrated the formation of 4-hydroxy-RA, 5,6-epoxy-RA, 4-oxo-RA, (13Z)-retinoic acid, and other geometric isomers which were identified on the basis of cochromatography with synthetic standards, UV spectroscopy, and/or mass spectrometry. Mechanisms are proposed for the hydroperoxide-dependent, PGH synthase-catalyzed oxidation of RA that are consistent with these results. PMID:7548765

  15. The ratio of oleic-to-stearic acid in the prostate predicts biochemical failure after radical prostatectomy for localized prostate cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our study examined lifestyle-related factors that may influence the prognosis of clinically localized prostate cancer, we evaluated the relative impact of obesity and prostatic fatty acid concentrations at diagnosis on risk of biochemical failure following radical prostatectomy. Height and weight w...

  16. Progress in Understanding Algal Bloom-Mediated Fish Kills: The Role of Superoxide Radicals, Phycotoxins and Fatty Acids.

    PubMed

    Dorantes-Aranda, Juan José; Seger, Andreas; Mardones, Jorge I; Nichols, Peter D; Hallegraeff, Gustaaf M

    2015-01-01

    Quantification of the role of reactive oxygen species, phycotoxins and fatty acids in fish toxicity by harmful marine microalgae remains inconclusive. An in vitro fish gill (from rainbow trout Oncorhynchus mykiss) assay was used to simultaneously assess the effect in superoxide dismutase, catalase and lactate dehydrogenase enzymatic activities caused by seven species of ichthyotoxic microalgae (Chattonella marina, Fibrocapsa japonica, Heterosigma akashiwo, Karenia mikimotoi, Alexandrium catenella, Karlodinium veneficum, Prymnesium parvum). Quantification of superoxide production by these algae was also performed. The effect of purified phycotoxins and crude extracts was compared, and the effect of fatty acids is discussed. The raphidophyte Chattonella was the most ichthyotoxic (gill cell viability down to 35%) and also the major producer of superoxide radicals (14 pmol cell-1 hr-1) especially after cell lysis. The raphidophyte Heterosigma and dinoflagellate Alexandrium were the least toxic and had low superoxide production, except when A. catenella was lysed (5.6 pmol cell-1 hr-1). Catalase showed no changes in activity in all the treatments. Superoxide dismutase (SOD) and lactate dehydrogenase exhibited significant activity increases of ≤23% and 51.2% TCC (total cellular content), respectively, after exposure to C. marina, but SOD showed insignificant changes with remaining algal species. A strong relationship between gill cell viability and superoxide production or superoxide dismutase was not observed. Purified brevetoxins PbTx-2 and -3 (from Karenia brevis, LC50 of 22.1 versus 35.2 μg mL-1) and karlotoxin KmTx-2 (from Karlodinium; LC50 = 380 ng mL-1) could almost entirely account for the fish killing activity by those two dinoflagellates. However, the paralytic shellfish toxins (PST) GTX1&4, C1&C2, and STX did not account for Alexandrium ichthyotoxicity. Only aqueous extracts of Alexandrium were cytotoxic (≤65% decrease of viability), whereas crude

  17. Progress in Understanding Algal Bloom-Mediated Fish Kills: The Role of Superoxide Radicals, Phycotoxins and Fatty Acids

    PubMed Central

    Dorantes-Aranda, Juan José; Seger, Andreas; Mardones, Jorge I.; Nichols, Peter D.; Hallegraeff, Gustaaf M.

    2015-01-01

    Quantification of the role of reactive oxygen species, phycotoxins and fatty acids in fish toxicity by harmful marine microalgae remains inconclusive. An in vitro fish gill (from rainbow trout Oncorhynchus mykiss) assay was used to simultaneously assess the effect in superoxide dismutase, catalase and lactate dehydrogenase enzymatic activities caused by seven species of ichthyotoxic microalgae (Chattonella marina, Fibrocapsa japonica, Heterosigma akashiwo, Karenia mikimotoi, Alexandrium catenella, Karlodinium veneficum, Prymnesium parvum). Quantification of superoxide production by these algae was also performed. The effect of purified phycotoxins and crude extracts was compared, and the effect of fatty acids is discussed. The raphidophyte Chattonella was the most ichthyotoxic (gill cell viability down to 35%) and also the major producer of superoxide radicals (14 pmol cell-1 hr-1) especially after cell lysis. The raphidophyte Heterosigma and dinoflagellate Alexandrium were the least toxic and had low superoxide production, except when A. catenella was lysed (5.6 pmol cell-1 hr-1). Catalase showed no changes in activity in all the treatments. Superoxide dismutase (SOD) and lactate dehydrogenase exhibited significant activity increases of ≤23% and 51.2% TCC (total cellular content), respectively, after exposure to C. marina, but SOD showed insignificant changes with remaining algal species. A strong relationship between gill cell viability and superoxide production or superoxide dismutase was not observed. Purified brevetoxins PbTx-2 and -3 (from Karenia brevis, LC50 of 22.1 versus 35.2 μg mL-1) and karlotoxin KmTx-2 (from Karlodinium; LC50 = 380 ng mL-1) could almost entirely account for the fish killing activity by those two dinoflagellates. However, the paralytic shellfish toxins (PST) GTX1&4, C1&C2, and STX did not account for Alexandrium ichthyotoxicity. Only aqueous extracts of Alexandrium were cytotoxic (≤65% decrease of viability), whereas crude

  18. Syntheses, structural characterization, and DPPH radical scavenging activity of cocrystals of caffeine with 1- and 2-naphthoxyacetic acids

    NASA Astrophysics Data System (ADS)

    Suresh Kumar, G. S.; Seethalakshmi, P. G.; Sumathi, D.; Bhuvanesh, N.; Kumaresan, S.

    2013-03-01

    Caffeine:1-naphthoxyacetic acid [(caf)(1-naa)] and caffeine:2-naphthoxyacetic acid [(caf)(2-naa)] cocrystals have been synthesized and single crystals were grown by slow evaporation technique. The structures of the grown crystals were elucidated using single crystal X-ray diffraction analysis. Both the cocrystals belong to the monoclinic crystallographic system with space group P21/c, Z = 4, and α = γ = 90°, whereas β = 111.4244(18)° for [(caf)(1-naa)] and β = 109.281(6)° for [(caf)(2-naa)]. The crystal packing is predominantly stabilized by hydrogen bonding and π-π stacking interactions. The presence of unionized -COOH functional group in both the cocrystals was identified by FTIR spectral analysis. Thermal behavior and stability of both the cocrystals were studied by TGA/DTA analyses. Solvent-free formation of these cocrystals was confirmed by powder X-ray diffraction analyses. The theoretical energy of cocrystals showed that the formers have higher energy than cocrystals 1 and 2. DPPH radical scavenging activity of cocrystals 1 and 2 is slightly greater than the formers.

  19. α-Hydrogen Abstraction by •OH and •SH Radicals from Amino Acids and Their Peptide Derivatives.

    PubMed

    Chan, Bun; Karton, Amir; Easton, Christopher J; Radom, Leo

    2016-04-12

    We have used computational quantum chemistry to investigate the thermochemistry of α-hydrogen abstraction from the full set of amino acids normally found in proteins, as well as their peptide forms, by •OH and •SH radicals. These reactions, with their reasonable complexity in the electronic structure (at the α-carbon), are chosen as a consistent set of models for conducting a fairly robust assessment of theoretical procedures. Our benchmarking investigation shows that, in general, the performance for the various classes of theoretical methods improves in the order nonhybrid DFT → hybrid DFT → double-hybrid DFT → composite procedures. More specifically, we find that the DSD-PBE-P86 double-hybrid DFT procedure yields the best agreement with our high-level W1X-2 vibrationless barriers and reaction energies for this particular set of systems. A significant observation is that, when one considers relative instead of absolute values for the vibrationless barriers and reaction energies, even nonhybrid DFT procedures perform fairly well. To exploit this feature in a cost-effective manner, we have examined a number of multilayer schemes for the calculation of reaction energies and barriers for the abstraction reactions. We find that accurate values can be obtained when a "core" of glycine plus the abstracting radical is treated by DSD-PBE-P86, and the substituent effects are evaluated with M06-2X. Inspection of the set of calculated thermochemical data shows that the correlation between the free energy barriers and reaction free energies is strongest when the reactions are either endergonic or nearly thermoneutral. PMID:26950040

  20. Vinblastine rapidly induces NOXA and acutely sensitizes primary chronic lymphocytic leukemia cells to ABT-737

    PubMed Central

    Bates, Darcy J. P.; Danilov, Alexey V.; Lowrey, Christopher H.; Eastman, Alan

    2013-01-01

    Proteins of the BCL2 family provide a survival mechanism in many human malignancies including chronic lymphocytic leukemia (CLL). The BCL2 inhibitor ABT-263 (navitoclax) is active in clinical trials for lymphoid malignancies, yet resistance is expected based on preclinical models. We recently demonstrated that vinblastine can dramatically sensitize several leukemia cell lines to ABT-737 (the experimental congener of ABT-263). The goal of these experiments was to determine the impact of vinblastine on ABT-737 sensitivity in CLL cells isolated from peripheral blood and to define the underlying mechanism. Freshly isolated CLL cells from 35 patients, as well as normal lymphocytes and platelets, were incubated with various microtubule disrupting agents plus ABT-737 to assess sensitivity to the single agents and the combination. ABT-737 and vinblastine displayed a range of sensitivity as single agents, and vinblastine markedly sensitized all CLL samples to ABT-737 within 6 h. Vinblastine potently induced the pro-apoptotic protein PMAIP1 (NOXA) in both a time- and dose-dependent manner and this was required for the observed apoptosis. Combretastatin A4, which dissociates microtubules by binding a different site, had the same effect confirming that interaction of these agents with microtubules is the initial target. Similarly, vincristine and vinorelbine induced NOXA and enhanced CLL sensitivity to ABT-737. Furthermore, vinblastine plus ABT-737 overcame stroma-mediated resistance to ABT-737 alone. Apoptosis was induced with clinically achievable concentrations, with no additional toxicity to normal lymphocytes or platelets. These results suggest that vinca alkaloids may improve the clinical efficacy of ABT-263 in patients with CLL. PMID:23723123

  1. The action of peroxyl radicals, powerful deleterious reagents, explains why neither cholesterol nor saturated fatty acids cause atherogenesis and age-related diseases.

    PubMed

    Spiteller, Gerhard; Afzal, Mohammad

    2014-11-10

    Cells respond to alterations in their membrane structure by activating hydrolytic enzymes. Thus, polyunsaturated fatty acids (PUFAs) are liberated. Free PUFAs react with molecular oxygen to give lipid hydroperoxide molecules (LOOHs). In case of severe cell injury, this physiological reaction switches to the generation of lipid peroxide radicals (LOO(·)). These radicals can attack nearly all biomolecules such as lipids, carbohydrates, proteins, nucleic acids and enzymes, impairing their biological functions. Identical cell responses are triggered by manipulation of food, for example, heating/grilling and particularly homogenization, representing cell injury. Cholesterol as well as diets rich in saturated fat have been postulated to accelerate the risk of atherosclerosis while food rich in unsaturated fatty acids has been claimed to lower this risk. However, the fact is that LOO(·) radicals generated from PUFAs can oxidize cholesterol to toxic cholesterol oxides, simulating a reduction in cholesterol level. In this review it is shown how active LOO(·) radicals interact with biomolecules at a speed transcending usual molecule-molecule reactions by several orders of magnitude. Here, it is explained how functional groups are fundamentally transformed by an attack of LOO(·) with an obliteration of essential biomolecules leading to pathological conditions. A serious reconsideration of the health and diet guidelines is required. PMID:25318456

  2. Redox reactivity in propolis: direct detection of free radicals in basic medium and interaction with hemoglobin.

    PubMed

    Mot, Augustin-Catalin; Damian, Grigore; Sarbu, Costel; Silaghi-Dumitrescu, Radu

    2009-01-01

    Propolis is one of many natural products with known antioxidant properties. The present work aims to investigate the intimate molecular-level mechanisms of this antioxidant reactivity. Electron paramagnetic resonance (EPR)-detectable free radical signals are described here for the first time in propolis extracts. The shape of these signals and the conditions in which they were obtained, point to polyphenolic flavonoids as the sites of the radicals. An inverse correlation between antioxidant capacity and free radical signal intensity is shown. The free radical reactivity of propolis is also illustrated by the effect it exerts on the biologically-relevant peroxide reactivity of hemoglobin. A new test of antioxidant ability in natural extracts such as propolis is proposed, based on modulation of the ascorbate peroxidase activity of hemoglobin (HAPX). Results of this test correlate well with those obtained via traditional methods such as those based on DPPH (2,2-diphenyl-1-picrylhydrazyl), or on ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid). PMID:20003712

  3. 77 FR 68769 - Access to Confidential Business Information by Abt Associates, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... AGENCY Access to Confidential Business Information by Abt Associates, Inc. AGENCY: Environmental.... (Abt) of Cambridge, MA, to access information which has been submitted to EPA under section 8 of the... Confidential Business Information (CBI). DATES: Access to the confidential data occurred on or about October...

  4. 40 CFR 80.1270 - Who may generate benzene credits under the ABT program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Who may generate benzene credits under... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1270 Who may generate benzene credits under the ABT program?...

  5. 40 CFR 80.1270 - Who may generate benzene credits under the ABT program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Who may generate benzene credits under... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1270 Who may generate benzene credits under the ABT program?...

  6. 40 CFR 80.1270 - Who may generate benzene credits under the ABT program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Who may generate benzene credits under... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1270 Who may generate benzene credits under the ABT program?...

  7. 40 CFR 80.1270 - Who may generate benzene credits under the ABT program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Who may generate benzene credits under... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1270 Who may generate benzene credits under the ABT program?...

  8. 40 CFR 80.1270 - Who may generate benzene credits under the ABT program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Who may generate benzene credits under... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1270 Who may generate benzene credits under the ABT program?...

  9. Factors Influencing the ABT Phenomenon among Graduate Students in a Master Program in Mexico

    ERIC Educational Resources Information Center

    Gonzalez-Castillo, Vicente; Cisneros-Cohernour, Edith J.

    2007-01-01

    This paper presents the findings of a study examining the factors that influence the ABT phenomenon (all but thesis) among graduate students of a Master in Education program in the Southeast of Mexico. Findings of the study identified individual and organizational factors influencing ABT. The study allowed for a better understanding about how…

  10. A Metal and Base-Free Chemoselective Primary Amination of Boronic Acids Using Cyanamidyl/Arylcyanamidyl Radical as Aminating Species: Synthesis and Mechanistic Studies by Density Functional Theory.

    PubMed

    Chatterjee, Nachiketa; Arfeen, Minhajul; Bharatam, Prasad V; Goswami, Avijit

    2016-06-17

    An efficient, metal and base-free, chemoselective synthesis of aryl-, heteroaryl-, and alkyl primary amines from the corresponding boronic acids has been achieved at ambient temperature mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA) and N-bromosuccinimide (NBS) using cyanamidyl/arylcyanamidyl radicals as the aminating species. The primary amine compounds were initially obtained as their corresponding ammonium trifluoroacetate salts which, on treatment with aq NaOH, provide the free amines. Finally, the primary amines were isolated through column chromatography over silica-gel using hexane-EtOAc solvent system as the eluent. The reactions are sufficiently fast, completing within 1 h. Quantum chemical calculations in combination with experimental observations validate that the ipso amination of substituted boronic acids involves the formation of cyanamidyl/arylcyanamidyl radical, followed by regiospecific interaction of its nitrile-N center with boron atom of the boronic acids, leading to chemoselective primary amination. PMID:27182931

  11. Free radical derivatives formed from cyclooxygenase-catalyzed dihomo-γ-linolenic acid peroxidation can attenuate colon cancer cell growth and enhance 5-fluorouracil׳s cytotoxicity

    PubMed Central

    Xu, Yi; Qi, Jin; Yang, Xiaoyu; Wu, Erxi; Qian, Steven Y.

    2014-01-01

    Dihomo-γ-linolenic acid (DGLA) and its downstream fatty acid arachidonic acid (AA) are both nutritionally important ω–6 polyunsaturated fatty acids (ω–6s). Evidence shows that, via COX-mediated peroxidation, DGLA and its metabolites (1-series prostaglandins) are associated with anti-tumor activity, while AA and its metabolites (2-series prostaglandins) could be tightly implicated in various cancer diseases. However, it still remains a mystery why DGLA and AA possess contrasting bioactivities. Our previous studies showed that DGLA could go through an exclusive C-8 oxygenation pathway during COX-catalyzed lipid peroxidation in addition to a C-15 oxygenation pathway shared by both DGLA and AA, and that the exclusive C-8 oxygenation could lead to the production of distinct DGLA׳s free radical derivatives that may be correlated with DGLA׳s anti-proliferation activity. In the present work, we further investigate the anti-cancer effect of DGLA׳s free radical derivatives and their associated molecular mechanisms. Our study shows that the exclusive DGLA׳s free radical derivatives from C-8 oxygenation lead to cell growth inhibition, cell cycle arrest and apoptosis in the human colon cancer cell line HCA-7 colony 29, probably by up-regulating the cancer suppressor p53 and the cell cycle inhibitor p27. In addition, these exclusive radical derivatives were also able to enhance the efficacy of 5-Fluorouracil (5-FU), a widely used chemo-drug for colon cancer. For the first time, we show how DGLA׳s radical pathway and metabolites are associated with DGLA׳s anti-cancer activities and able to sensitize colon cancer cells to chemo-drugs such as 5-FU. Our findings could be used to guide future development of a combined chemotherapy and dietary care strategy for colon cancer treatment. PMID:25114837

  12. Self-catalyzed syntheses, structural characterization, DPPH radical scavenging-, cytotoxicity-, and DFT studies of phenoxyaliphatic acids of 1,8-dioxo-octahydroxanthene derivatives

    NASA Astrophysics Data System (ADS)

    Suresh Kumar, G. S.; Antony Muthu Prabhu, A.; Seethalashmi, P. G.; Bhuvanesh, N.; Kumaresan, S.

    2014-02-01

    One-pot, in-water syntheses of phenoxyaliphatic acids of 1,8-dioxo-octahydroxanthene derived from dimedone and formylphenoxyaliphatic acids are reported. Geometries of compounds 2b, 2c, and 5a have been examined crystallographically. The synthesized compounds showed better DPPH radical scavenging activity and cytotoxicity against A431 cancer cell line. The molecular properties of all synthesized xanthenes have been investigated using single crystal XRD and DFT method. Self-catalyzed Bronsted-Lowry acid catalytic behavior was also investigated by both experimental and theoretical methods.

  13. Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection

    PubMed Central

    O'Riordan, William D.; Asatryan, Armen; Freilich, Bradley L.; Box, Terry D.; Overcash, J. Scott; Lovell, Sandra; Ng, Teresa I.; Liu, Wei; Campbell, Andrew; Lin, Chih-Wei; Yao, Betty; Kort, Jens

    2015-01-01

    ABT-493 is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistance in vitro. In this open-label dose-ranging trial, antiviral activity and safety were assessed during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naive adults with HCV genotype 1 infection, with or without compensated cirrhosis. The presence of baseline resistance-associated variants (RAVs) was also evaluated. The mean maximal decreases in HCV RNA levels from baseline were approximately 4 log10 IU/ml for all ABT-493 doses ranging from 100 mg to 700 mg and for ABT-530 doses of ≥40 mg. There were no meaningful differences in viral load declines for patients with versus without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without RAVs. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have a slightly less robust viral load decline on day 3 of monotherapy. No serious or grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound. ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection, with or without compensated cirrhosis. Based on these results, phase II studies assessing the combination of these DAAs for the treatment of chronic HCV infection in patients with or without compensated cirrhosis have been initiated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01995071.) PMID:26711747

  14. Salivary thiocyanate/nitrite inhibits hydroxylation of 2-hydroxybenzoic acid induced by hydrogen peroxide/Fe(II) systems under acidic conditions: possibility of thiocyanate/nitrite-dependent scavenging of hydroxyl radical in the stomach.

    PubMed

    Takahama, Umeo; Oniki, Takayuki

    2004-11-18

    Formation of OH radicals in the stomach is possible by Fenton-type reactions, as gastric juice contains ascorbic acid (AA), iron ions and H2O2. An objective of the present study is to elucidate the effects of salivary SCN- and NO2- on the hydroxylation of salicylic acid which was induced by H2O2/Fe(II) and AA/H2O2/Fe(II) systems. Thiocyanate ion inhibited the hydroxylation of salicylic acid by the above systems in acidic buffer solutions and in acidified saliva. The inhibition by SCN- was deduced to be due to SCN- -dependent scavenging of OH radicals. Nitrite ion could enhance the SCN- -dependent inhibition of the hydroxylation induced by AA/H2O2/Fe(II) systems. The enhancement was suggested to be due to scavenging of OH radicals by NO which was formed by the reactions among AA, HNO2 and SCN- contained in the reaction mixture. The concentrations of SCN- and NO2-, which were effective for the inhibition, were in ranges of their normal salivary concentrations. These results suggest that salivary SCN- can cooperate with NO2- to protect stomach from OH radicals formed by AA/H2O2/Fe(II) systems under acidic conditions. PMID:15535976

  15. Kinetics of the competitive degradation of deoxyribose and other molecules by hydroxyl radicals produced by the Fenton reaction in the presence of ascorbic acid.

    PubMed

    Zhao, M J; Jung, L

    1995-09-01

    The competition method in which the Fenton reaction is employed as an .OH radical generator and deoxyribose as a detecting molecule, has been used to determine the rate constants for reactions of the .OH radical with its scavengers. Nonlinear competition plots were obtained for those scavengers which reacted with the Fenton reagents (Fe2+ or H2O2). Ascorbic acid is believed to overcome this problem. We have investigated the kinetics of deoxyribose degradation by .OH radicals generated by the Fenton reaction in the presence of ascorbic acid, and observed that the inclusion of ascorbic acid in the Fenton system greatly increased the rate of .OH radical generation. As a result, the interaction between some scavengers and the Fenton reagents became negligeable and linear competition plots of A degree/A vs scavenger concentrations were obtained. The effects of experimental conditions such as, the concentrations of ascorbic acid, deoxyribose, H2O2 and Fe(2+)-EDTA, the EDTA/Fe2+ ratio as well as the incubation time, on the deoxyribose degradation and the determination of the rate constant for mercaptoethanol chosen as a reference compound were studied. The small standard error, (6.76 +/- 0.21) x 10(9) M-1s-1, observed for the rate constant values for mercaptoethanol determined under 13 different experimental conditions, indicates the latter did not influence the rate constant determination. This is in fact assured by introducing a term, kx, into the kinetic equation. This term represents the rate of .OH reactions with other reagents such as ascorbic acid, Fe(2+)-EDTA, H2O2 etc. The agreement of the rate constants obtained in this work with that determined by pulse radiolysis techniques for cysteine, thiourea and many other scavengers, suggests that this simple competition method is applicable to a wide range of compounds, including those which react with the Fenton reagents and those whose solubility in water is low. PMID:7581818

  16. Formation of 7-carboxyheptyl radical induced by singlet oxygen in the reaction mixture of oleic acid, riboflavin and ferrous ion under the UVA irradiation.

    PubMed

    Mori, Hiroko; Iwahashi, Hideo

    2011-09-01

    Identification of the radicals was performed for the standard reaction mixtures, which contained 4.3 mM oleic acid, 25 µM riboflavin, 1 mM FeSO(4)(NH(4))(2)SO(4), 10 mM cholic acid, 40 mM phosphate buffer (pH 7.4) and 0.1 M α-(4-pyridyl-1-oxide)-N-tert-butylnitrone under the UVA irradiation (365 nm), using an electron spin resonance, an high performance liquid chromatography-electron spin resonance and an high performance liquid chromatography-electron spin resonance-mass spectrometry. The electron spin resonance and high performance liquid chromatography-electron spin resonance measurements of the standard reaction mixtures showed prominent signals (α(N) = 1.58 mT and α(H)β = 0.26 mT) and peaks 1 and 3 (retention times, 37.0 min and 49.0 min). Since the peak 3 was not observed for the standard reaction mixture without oleic acid, the radical of the peak 3 seems to be derived from oleic acid. Singlet oxygens seem to participate in the formation of the oleic acid-derived radicals because the peak height of the peak 3 observed in the standard reaction mixture of D(2)O increased to 308 ± 72% of the control. The high performance liquid chromatography-electron spin resonance-mass spectrometry analysis showed that 7-carboxyheptyl radical forms in the standard reaction mixture. PMID:21980232

  17. Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quantum Chemical Methods.

    PubMed

    Tutone, Marco; Lauria, Antonino; Almerico, Anna Maria

    2016-06-01

    Health benefits of dietary phytochemicals have been suggested in recent years. Among 1000s of different compounds, Betalains, which occur in vegetables of the Cariophyllalae order (cactus pear fruits and red beet), have been considered because of reducing power and potential to affect redox-modulated cellular processes. The antioxidant power of Betalains is strictly due to the dissociation rate of the acid moieties present in all the molecules of this family of phytochemicals. Experimentally, only the pK a values of betanin were determined. Recently, it was evidenced it was evidenced as the acid dissociation, at different environmental pHs, affects on its electron-donating capacity, and further on its free radical scavenging power. The identical correlation was studied on another Betalains family compound, Betalamic Acid. Experimental evidences showed that the free radical scavenging capacity of this compound drastically decreases at pH > 5, but pK a values were experimentally not measured. With the aim to justify the Betalamic Acid behavior as free radical scavenger, in this paper we tried to predict in silico the pK a values by means different approaches. Starting from the known experimental pK as of acid compounds, both phytochemicals and small organic, two empirical approaches and quantum-mechanical calculation were compared to give reliable prediction of the pK as of Betalamic Acid. Results by means these computational approaches are consistent with the experimental evidences. As shown herein, in silico, the totally dissociated species, at the experimental pH > 5 in solution, is predominant, exploiting the higher electron-donating capability (HOMO energy). Therefore, the computational estimated pK a values of Betalamic Acid resulted very reliable. PMID:26253717

  18. Preventive efficacy of hydroalcoholic extract of Cymbopogon citratus against radiation-induced DNA damage on V79 cells and free radical scavenging ability against radicals generated in vitro.

    PubMed

    Rao, B S S; Shanbhoge, R; Rao, B N; Adiga, S K; Upadhya, D; Aithal, B K; Kumar, M R S

    2009-04-01

    This study presents the findings of free radical scavenging and antigenotoxic effect of hydroalcoholic extract of Cymbopogon citratus (CCE). The CCE at a concentration of 60 microg/mL resulted in a significant scavenging ability of 2,2-diphenyl-2-picryl hydrazyl (DPPH; (85%), 2,2-azinobis (3-ethyl benzothiazoline-6-sulphonic acid) (ABTS; 77%), hydroxyl (70%), superoxide (76%), nitric oxide (78%) free radicals generated using in vitro and also a moderate anti-lipid peroxidative effect (57%). Further, the radiation-induced antigenotoxic potential of CCE was assessed in Chinese hamster lung fibroblast cells (V79) using micronucleus assay. The CCE resulted in a dose-dependent decrease in the yield of radiation-induced micronuclei, with a maximum effect at 125 microg/mL CCE for 1 h before 2 Gy of radiation. Similarly, there was a significant (P < 0.05-0.0001) decrease in percentage of micronuclei when V79 cells were treated with optimal dose of CCE (125 microg/mL) before exposure to different doses of gamma radiation, that is, 0.5-4 Gy, compared with radiation alone groups. The results of the micronucleus study indicated antigenotoxic effect demonstrating the radioprotective potential of CCE and, which may partly due to its and antioxidant capacity as it presented its ability to scavenge various free radicals in vitro and anti-lipid peroxidative potential. PMID:19734270

  19. DPPH radical scavenging activity of a mixture of fatty acids and peptide-containing compounds in a protein hydrolysate of Jatropha curcas seed cake.

    PubMed

    Phengnuam, Thanyarat; Goroncy, Alexander K; Rutherfurd, Shane M; Moughan, Paul J; Suntornsuk, Worapot

    2013-12-01

    Jatropha curcas, a tropical plant, has great potential commercial relevance as its seeds have high oil content. The seeds can be processed into high-quality biofuel producing seed cake as a byproduct. The seed cake, however, has not gotten much attention toward its potential usefulness. This work was aimed to determine the antioxidant activity of different fractions of a protein hydrolysate from J. curcas seed cake and to elucidate the molecular structures of the antioxidants. Seed cake was first processed into crude protein isolate and the protein was hydrolyzed by Neutrase. The hydrolysate obtained from 1 h of Neutrase hydrolysis showed the strongest antioxidant activity against DPPH radical (2,2-diphenyl-1-picrylhydrazyl). After a purification series of protein hydrolysate by liquid chromatography, chemicals acting as DPPH radical inhibitors were found to be a mixture of fatty acids, fatty acid derivatives, and a small amount of peptides characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. PMID:24191657

  20. Correlation of α-Lipoic Acid and S. Glutathione Level with Free Radical Excess in Tobacco Consumers

    PubMed Central

    Kaur, Manjinder; Suhalka, M.L.; Shrivastav, Chanchal

    2016-01-01

    Introduction Tobacco consumption is a serious health hazard and most important avoidable cause of death worldwide. Tobacco is recognized as lethal toxin, ripping off 7-11 minutes of human life with each cigarette through harmful compounds and inducing free radical synthesis and a high rate of lipid peroxidation. These free radicals are scavenged by the endogenous antioxidants viz. S. Glutathione (S.GSH) and S. α-Lipoic acid (S. α-LA), thus preventing the endothelial damage. Aim The present study was designed with an aim to find out the lipid peroxidative stress through S. Malondialdehyde (S.MDA) and its correlation with antioxidant levels like S. Glutathione (S. GSH) and S. α- Lipoic acid (S. α- LA) among tobacco users (in both smokers and chewers). Materials and Methods A case control cross-sectional study was carried out in the Department of Physiology among 200 subjects; aged 18-50 years of both sexes which were chosen randomly from institutional campus and healthy volunteers. The subjects were broadly divided into two groups (A & B); group A comprised of tobacco users (n=150) with history of smoking cigarette/biddies and chewing tobacco daily, for at least one year and group B had controls (non tobacco users) (n=50). S. MDA, S.GSH and S. α-LA levels were estimated by standardized methods. The data was analysed by unpaired student t-test and Pearson’s correlation coefficient (r) for finding the correlation between antioxidants and S.MDA in group-A and group-B. Results The present study reports the significantly higher (p<0.0001) levels of S.MDA and lower (p<0.0001) levels of S.GSH and S. α-LA in tobacco users as compared to nontobacco users. The observed value of S.MDA was (2.72±0.87, 1.39±0.47) nmol/ml, S. α-LA was (9.94±5.96, 14.24 ± 4.34) μg/ml and S.GSH was (23.24±7.04, 32.82±2.95) mg/dl respectively in group-A and group-B. A significant (p<0.01) strong negative correlation was observed between S. MDA and antioxidants (S.GSH and S.

  1. Isoquercitrin Esters with Mono- or Dicarboxylic Acids: Enzymatic Preparation and Properties.

    PubMed

    Vavříková, Eva; Langschwager, Fanny; Jezova-Kalachova, Lubica; Křenková, Alena; Mikulová, Barbora; Kuzma, Marek; Křen, Vladimír; Valentová, Kateřina

    2016-01-01

    A series of isoquercitrin (quercetin-3-O-β-d-glucopyranoside) esters with mono- or dicarboxylic acids was designed to modulate hydro- and lipophilicity and biological properties. Esterification of isoquercitrin was accomplished by direct chemoenzymatic reaction using Novozym 435 (lipase from Candida antarctica), which accepted C₅- to C12-dicarboxylic acids; the shorter ones, such as oxalic (C₂), malonic (C₃), succinic (C₄) and maleic (C₄) acids were not substrates of the lipase. Lipophilicity of monocarboxylic acid derivatives, measured as log P, increased with the chain length. Esters with glutaric and adipic acids exhibited hydrophilicity, and the dodecanedioic acid hemiester was more lipophilic. All derivatives were less able to reduce Folin-Ciocalteau reagent (FCR) and scavenge DPPH (1,1-diphenyl-2-picrylhydrazyl) than isoquercitrin; ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) radical-scavenging activity was comparable. Dodecanoate and palmitate were the least active in FCR and ABTS scavenging; dodecanoate and hemiglutarate were the strongest DPPH scavengers. In contrast, most derivatives were much better inhibitors of microsomal lipoperoxidation than isoquercitrin; butyrate and hexanoate were the most efficient. Anti-lipoperoxidant activity of monocarboxylic derivatives, except acetates, decreased with increasing aliphatic chain. The opposite trend was noted for dicarboxylic acid hemiesters, isoquercitrin hemidodecanedioate being the most active. Overall, IQ butyrate, hexanoate and hemidodecanedioate are the most promising candidates for further studies. PMID:27338349

  2. Isoquercitrin Esters with Mono- or Dicarboxylic Acids: Enzymatic Preparation and Properties

    PubMed Central

    Vavříková, Eva; Langschwager, Fanny; Jezova-Kalachova, Lubica; Křenková, Alena; Mikulová, Barbora; Kuzma, Marek; Křen, Vladimír; Valentová, Kateřina

    2016-01-01

    A series of isoquercitrin (quercetin-3-O-β-d-glucopyranoside) esters with mono- or dicarboxylic acids was designed to modulate hydro- and lipophilicity and biological properties. Esterification of isoquercitrin was accomplished by direct chemoenzymatic reaction using Novozym 435 (lipase from Candida antarctica), which accepted C5- to C12-dicarboxylic acids; the shorter ones, such as oxalic (C2), malonic (C3), succinic (C4) and maleic (C4) acids were not substrates of the lipase. Lipophilicity of monocarboxylic acid derivatives, measured as log P, increased with the chain length. Esters with glutaric and adipic acids exhibited hydrophilicity, and the dodecanedioic acid hemiester was more lipophilic. All derivatives were less able to reduce Folin–Ciocalteau reagent (FCR) and scavenge DPPH (1,1-diphenyl-2-picrylhydrazyl) than isoquercitrin; ABTS (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) radical-scavenging activity was comparable. Dodecanoate and palmitate were the least active in FCR and ABTS scavenging; dodecanoate and hemiglutarate were the strongest DPPH scavengers. In contrast, most derivatives were much better inhibitors of microsomal lipoperoxidation than isoquercitrin; butyrate and hexanoate were the most efficient. Anti-lipoperoxidant activity of monocarboxylic derivatives, except acetates, decreased with increasing aliphatic chain. The opposite trend was noted for dicarboxylic acid hemiesters, isoquercitrin hemidodecanedioate being the most active. Overall, IQ butyrate, hexanoate and hemidodecanedioate are the most promising candidates for further studies. PMID:27338349

  3. Radical scavenging potential of phenolics from Bryophyllum pinnatum (LAM.) OKEN.

    PubMed

    Gupta, Suneel; Banerjee, Rintu

    2011-01-01

    Optimization of the extraction process of phenolics from Bryophyllum pinnatum was carried out using response-surface methodology (RSM). The effect of different variables such as ratio of solvents, plant material/solvent ratio, extraction time, and temperature were investigated. An optimal phenolics yield of 7.952 mg/g gallic acid equivalence (GAE) was achieved at reduced levels of methanol/water ratio (1:1, v/v). During optimization, the product yield was enhanced by ∼2-fold at reduced extraction solvent (methanol/water) up to 37%. Validation of the RSM model for extraction of total phenolic content (TPC) was confirmed by high-performance liquid chromatography (HPLC) analysis. The obtained experimental values were in good agreement with the predicted values, thereby indicating the appropriateness of the model generated. Phenolic extracts from B. pinnatum were further examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods for determining the radical scavenging activities. EC(50) values of B. pinnatum extracts (BPEs) obtained by these methods were in accordance with the amount of phenolics present in the extract. Significant correlation was found between total phenolic content and antioxidant activities (p < 0.05). PMID:21660869

  4. Inhibition of the Conversion of 1-Aminocyclopropane-1-carboxylic Acid to Ethylene by Structural Analogs, Inhibitors of Electron Transfer, Uncouplers of Oxidative Phosphorylation, and Free Radical Scavengers 1

    PubMed Central

    Apelbaum, Akiva; Wang, Shiow Y.; Burgoon, Alan C.; Baker, James E.; Lieberman, Morris

    1981-01-01

    Cyclopropane carboxylic acid (CCA) at 1 to 5 millimolar, unlike related cyclopropane ring analogs of 1-aminocyclopropane-1-carboxylic acid (ACC) which were virtually ineffective, inhibited C2H4 production, and this inhibition was nullified by ACC. Inhibition by CCA is not competitive with ACC since there is a decline, rather than an increase, in native endogenous ACC in the presence of CCA. Similarly, short-chain organic acids from acetic to butyric acid and α-aminoisobutyric acid inhibited C2H4 production at 1 to 5 millimolar and lowered endogenous ACC levels. These inhibitions, like that of CCA, were overcome with ACC. Inhibitors of electron transfer and oxidative phosphorylation effectively inhibited ACC conversion to C2H4 in pea and apple tissues. The most potent inhibitors were 2,4-dinitrophenol (DNP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) which virtually eliminated ACC-stimulated C2H4 production in both tissues. Still other inhibitors of the conversion of ACC to C2H4 were putative free radical scavengers which reduced chemiluminescence in the free radical-activated luminol reaction. These inhibitor studies suggest the involvement of a free radical in the reaction sequence which converts ACC to C2H4. Additionally, the potent inhibition of this reaction by uncouplers of oxidative phosphorylation (DNP and CCCP) suggest the involvement of ATP or the necessity for an intact membrane for C2H4 production from ACC. In the latter case, CCCP may be acting as a proton ionophore to destroy the membrane integrity necessary for C2H4 production. PMID:16661637

  5. Assessing Supersaturation and Its Impact on In Vivo Bioavailability of a Low-Solubility Compound ABT-072 With a Dual pH, Two-Phase Dissolution Method.

    PubMed

    Shi, Yi; Erickson, Bryan; Jayasankar, Adivaraha; Lu, Liangjun; Marsh, Kennan; Menon, Rajeev; Gao, Ping

    2016-09-01

    ABT-072 is a candidate drug evaluated for treatment of hepatitis C virus. It is an acidic compound with extremely low intrinsic aqueous solubility. An in vitro dissolution-partition system, referred as biphasic test method, was used to characterize ABT-072 prototype formulations. This test used 2 aqueous dissolution media of pH 2 and 6.5 in a sequential manner to simulate the transition of drug in gastrointestinal tract. The biphasic test used in this work effectively differentiated various ABT-072 formulations derived from conventional and enabling technologies. In vitro profiles of these formulations indicate a complex interplay among the 3 competitive kinetic processes including dissolution, precipitation, and partition in the aqueous media. The relative amount of drug partitioned into the organic phase (i.e., octanol) from different formulations was found to be directly related to their in vivo exposures observed in both dogs and human subjects, respectively. An in vitro-in vivo relationship was obtained between ABT-072 concentrations in octanol at t = 2 h from these formulations and the relative bioavailabilities in dogs and human subjects. This work revealed the significance of polymeric precipitation inhibition by sustaining a supersaturated state of ABT-072 and its impact on in vivo exposure in human subjects. PMID:27321234

  6. Norcantharidin combined with ABT-737 for hepatocellular carcinoma: Therapeutic effects and molecular mechanisms

    PubMed Central

    Ren, Jing; Li, Gang; Zhao, Wen; Lin, Ling; Ye, Tao

    2016-01-01

    AIM: To study the therapeutic effect of norcantharidin (NCTD) combined with ABT-737 on hepatocellular carcinoma cells and the molecular mechanism. METHODS: Two hepatocellular carcinoma (HCC) cell lines, HepG2 and SMMC-7721, were selected. ABT-737 and NCTD were allocated into groups to be used alone or in combination. HepG2 and SMMC-7721 cells were cultured in vitro. Liver cancer cells in the logarithmic phase of growth were vaccinated and cultured to the cell wall stage; these cells were treated for 48 h with different concentrations of NCTD, or ABT-737, or NCTD combined with ABT-737. The cell proliferation inhibition rate was detected by methyl thiazolyl tetrazolium. The expression of Mcl in HCC cells was detected by Western Blotting, and the cells in each group after treatment had apoptosis detected by flow cytometry. The proliferation inhibition rate, the expression of Mcl-1 in cells and the apoptosis inducing effect of treatment were observed in each group, and the effect of NCTD on ABT-737 in the treatment of HCC and its mechanism of action were analyzed. RESULTS: As the concentration of NCTD increased, the cell proliferation inhibition rate gradually decreased; and the treatment effect of ABT-737 1-3 μm combined with NCTD on cell proliferation inhibition was stronger than that of ABT-737 alone. The difference was statistically significant (P < 0.05). In observing the expression of Mcl-1 in cells after the treatment of different concentrations of NCTD, this was partially inhibited after treatment with NCTD 15 μm, and the expression of Mcl-1 was almost undetectable after treatment with NCTD 30 μm and 60 μm. The effect on inducing apoptosis with the treatment of ABT-737 or NCTD alone for 48 h was lower than that of the control group. The difference was not statistically significant (P > 0.05). The effect on inducing apoptosis in HepG2 and SMMC-7721 cells with the treatment of ABT-737 combined with NCTD for 48 h was greater than that of ABT-737 or NCTD alone

  7. Application of Attenuated Total Reflectance-Fourier Transformed Infrared (ATR-FTIR) Spectroscopy To Determine the Chlorogenic Acid Isomer Profile and Antioxidant Capacity of Coffee Beans.

    PubMed

    Liang, Ningjian; Lu, Xiaonan; Hu, Yaxi; Kitts, David D

    2016-01-27

    The chlorogenic acid isomer profile and antioxidant activity of both green and roasted coffee beans are reported herein using ATR-FTIR spectroscopy combined with chemometric analyses. High-performance liquid chromatography (HPLC) quantified different chlorogenic acid isomer contents for reference, whereas ORAC, ABTS, and DPPH were used to determine the antioxidant activity of the same coffee bean extracts. FTIR spectral data and reference data of 42 coffee bean samples were processed to build optimized PLSR models, and 18 samples were used for external validation of constructed PLSR models. In total, six PLSR models were constructed for six chlorogenic acid isomers to predict content, with three PLSR models constructed to forecast the free radical scavenging activities, obtained using different chemical assays. In conclusion, FTIR spectroscopy, coupled with PLSR, serves as a reliable, nondestructive, and rapid analytical method to quantify chlorogenic acids and to assess different free radical-scavenging capacities in coffee beans. PMID:26725502

  8. Scavenger Activity Evaluation of the Clove Bud Essential Oil (Eugenia caryophyllus) and Eugenol Derivatives Employing ABTS+• Decolorization

    PubMed Central

    Merchán Arenas, Diego R.; Acevedo, Amner Muñoz; Vargas Méndez, Leonor Y.; Kouznetsov, Vladimir V.

    2011-01-01

    The essential oil (EO) of clove bud dried fruits from Eugenia caryophyllus was obtained by a conventional hydrodistillation process in an excellent yield (11.7 %). Its chemical composition was analyzed by GC-MS, identifying eugenol as a main constituent (60.5%). Four eugenol-like molecules, γ-diisoeugenol, hydroxymethyleugenol, dihydroeugenol and 1,3-dioxanylphenol, were synthesized using eugenol or isoeugenol as initial precursors under green chemistry protocols. To evaluate the possible antioxidant capacity of eugenol compounds including the clove bud EO, the Trolox® Equivalent Antioxidant Capacity value, obtained by the ABTS+• radical-cation discoloration method, was employed. The methodology was performed in a UV-Vis reader of 96-well microplates (dilution methodology), using well-known antioxidant agents (BHA, BHT and vitamin E) as reference compounds. It was found that the prepared eugenol derivatives had a more potent free radical scavenger activity than the reference compounds. In particular, the most active molecules, γ-diisoeugenol and 1,3-dioxanylphenol, were ca. 3-fold more potent than vitamin E. PMID:22145105

  9. Effects of roasting temperature and duration on fatty acid composition, phenolic composition, Maillard reaction degree and antioxidant attribute of almond (Prunus dulcis) kernel.

    PubMed

    Lin, Jau-Tien; Liu, Shih-Chun; Hu, Chao-Chin; Shyu, Yung-Shin; Hsu, Chia-Ying; Yang, Deng-Jye

    2016-01-01

    Roasting treatment increased levels of unsaturated fatty acids (linoleic, oleic and elaidic acids) as well as saturated fatty acids (palmitic and stearic acids) in almond (Prunus dulcis) kernel oils with temperature (150 or 180 °C) and duration (5, 10 or 20 min). Nonetheless, higher temperature (200 °C) and longer duration (10 or 20 min) roasting might result in breakdown of fatty acids especially for unsaturated fatty acids. Phenolic components (total phenols, flavonoids, condensed tannins and phenolic acids) of almond kernels substantially lost in the initial phase; afterward these components gradually increased with roasting temperature and duration. Similar results also observed for their antioxidant activities (scavenging DPPH and ABTS(+) radicals and ferric reducing power). The changes of phenolic acid and flavonoid compositions were also determined by HPLC. Maillard reaction products (estimated with non-enzymatic browning index) also increased with roasting temperature and duration; they might also contribute to enhancing the antioxidant attributes. PMID:26213005

  10. Acetylated Hyaluronic Acid: Enhanced Bioavailability and Biological Studies

    PubMed Central

    Saturnino, Carmela; Sinicropi, Maria Stefania; Puoci, Francesco

    2014-01-01

    Hyaluronic acid (HA), a macropolysaccharidic component of the extracellular matrix, is common to most species and it is found in many sites of the human body, including skin and soft tissue. Not only does HA play a variety of roles in physiologic and in pathologic events, but it also has been extensively employed in cosmetic and skin-care products as drug delivery agent or for several biomedical applications. The most important limitations of HA are due to its short half-life and quick degradation in vivo and its consequently poor bioavailability. In the aim to overcome these difficulties, HA is generally subjected to several chemical changes. In this paper we obtained an acetylated form of HA with increased bioavailability with respect to the HA free form. Furthermore, an improved radical scavenging and anti-inflammatory activity has been evidenced, respectively, on ABTS radical cation and murine monocyte/macrophage cell lines (J774.A1). PMID:25114930

  11. Free-radical scavenging and mitochondrial antioxidant activities of Reishi-Ganoderma lucidum (Curt: Fr) P. Karst and Arogyapacha-Trichopus zeylanicus Gaertn extracts.

    PubMed

    Cherian, Elizabeth; Sudheesh, Narayana P; Janardhanan, Kainoor K; Patani, George

    2009-01-01

    Endogenous damage to mitochondrial DNA by free radicals is believed to be a major contributory factor to aging. The current study examined the effects of the extracts of two important anti-fatigue and rejuvenating medicinal herbs Ganoderma lucidum and Trichopus zeylanicus for their free-radical scavenging property and for their effects on liver mitochondrial antioxidant activity in aged mice. Both extracts were administrated orally to aged BALB/c mice at doses of 50 and 250 mg/kg body weight for 15 days. Super oxide dismutase (SOD) and catalase (CAT) activity and levels of reduced glutathione (GSH) and lipid peroxidation as equivalents of malondialdehyde (MDA) formed were determined. Groups of young mice and aged mice (more than 15 months old) were taken as controls. Both G. lucidum and T. zeylanicus extracts increased antioxidant status in liver mitochondria of aged mice compared with the aged control. Higher levels of GSH, increased activity of SOD and CAT, and decreased level of MDA in both treated groups compared with the controls were evident. Both extracts possessed significant 2,2-diphenyl-1-picrylhydrazil (DPPH), 2, 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP). The DPPH, ABTS, and FRAP activities were higher in G. lucidum extract than in T. zeylanicus. G. lucidum extract also showed superoxide and hydroxyl radical scavenging activities. T. zeylanicus had significantly higher lipid peroxidation inhibiting activity than G. lucidum. Thus, we conclude that the antioxidative effect of the G. lucidum extract was higher than that of T. zeylanicus. Our findings suggest a potential therapeutic efficacy of G. lucidum extract to protect against aging and to a certain extent against age-related degenerative diseases. PMID:20214017

  12. Singlet oxygen quenching and radical scavenging capacities of structurally-related flavonoids present in Zuccagnia punctata Cav.

    PubMed

    Vieyra, Faustino E Morán; Boggetti, Héctor J; Zampini, Iris C; Ordoñez, Roxana M; Isla, María I; Alvarez, Rosa M S; De Rosso, Veridiana; Mercadante, Adriana Z; Borsarelli, Claudio D

    2009-06-01

    The singlet oxygen (1O2) quenching and free radical (DPPH(*), ABTS(* +) and O2(* -)) scavenging ability of three structurally-related flavonoids (7-hydroxyflavanone HF, 2',4'-dihydroxychalcone DHC and 3,7-dihydroxyflavone DHF) present in the Argentinean native shrub Zuccagnia punctata Cav. were studied in solution by combining electrochemical and kinetic measurements, mass spectroscopy, end-point antioxidant assays and computational calculations. The results showed that the antioxidant properties of these flavonoids depend on several factors, such as their electron- and hydrogen atom donor capacity, the ionization degree of the more acidic group, solvatation effects and electrostatic interactions with the oxidant species. The theoretical calculations for both the gas and solution phases at the B3LYP level of theory for the Osanger reaction field model agreed with the experimental findings, thus supporting the characterization of the antioxidant mechanism of the Z. punctata flavonoids. PMID:19431060

  13. In vitro antioxidant activities, free radical scavenging capacity, and tyrosinase inhibitory of flavonoid compounds and ferulic acid from Spiranthes sinensis (Pers.) Ames.

    PubMed

    Liang, Chung Pin; Chang, Chia Hao; Liang, Chien Cheng; Hung, Kuei Yu; Hsieh, Chang Wei

    2014-01-01

    In this study, ultrasound-assisted extraction (UAE) and other methods of extracting flavonoid compounds and ferulic acid (FA) from S. sinensis were investigated. Five different extraction methods, including water extraction (W), water extraction using UAE (W+U), 75% ethanol extraction (E), 75% ethanol extraction using UAE (E+U), and supercritical CO2 extraction (SFE) were applied in the extraction of bioactive compounds (flavonoids and ferulic acid) in order to compare their efficiency. The highest yield of flavonoids (4.28 mg/g) and ferulic acid (4.13 mg/g) content was detected in the E+U extract. Furthermore, S. sinensis extracts obtained by E+U show high antioxidant activity, and IC50 values of 0.47 mg/mL for DPPH radicals and 0.205 mg/mL for metal chelating activity. The total antioxidant assay shows superoxide radical scavenging capacity and in vitro mushroom tyrosinase inhibition in a dose-dependent manner, suggesting that E+U can be used for extraction of bioactive compounds from S. sinensis. PMID:24739930

  14. Chlorogenic acid, an antioxidant principle from the aerial parts ofArtemisia iwayomogi that acts on 1,1-diphenyl-2-picrylhydrazyl radical.

    PubMed

    Kim, S S; Lee, C K; Kang, S S; Jung, H A; Choi, J S

    1997-04-01

    The antioxidant activity ofArtemisia iwayomogi was determined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical The methanol extract ofA. iwayomogi showed strong antioxidant activity, and thus fractionated with several solvents. The antioxidant activity potential of the individual fraction was in the order of ethyl acetate>n-butanol>water>chloroform>n-hexane fraction. The ethyl acetate andn-butanol soluble fractions exhibiting strong antioxidant activity were further purified by repeated silica gel and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid was isolated as one of the active principles from then-butanol fraction, together with the inactive components, 1-octacosanol, scopoletin, scopolin, apigenin 7,4'-di-O-methylether luteolin 6,3'-di-O-methylether (jaceosidin), apigenin 7-methylether (genkwanin), 2,4-dihydroxy-6-methoxyacetophenone 4-O-beta-D-glucopyranoside and quebrachitol. The antioxidant activity of chlorogenic acid was comparable to that of L-ascorbic acid, which is a well known antioxidant. PMID:18975193

  15. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

    PubMed

    Comstock, G W; Alberg, A J; Huang, H Y; Wu, K; Burke, A E; Hoffman, S C; Norkus, E P; Gross, M; Cutler, R G; Morris, J S; Spate, V L; Helzlsouer, K J

    1997-11-01

    Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables. PMID:9367064

  16. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

    PubMed

    Comstock, George W; Alberg, Anthony J; Huang, Han-Yao; Wu, Kana; Burke, Alyce E; Hoffman, Sandra C; Norkus, Edward P; Gross, Myron; Cutler, Richard G; Morris, J Steven; Spate, Vickie L; Helzlsouer, Kathy J

    2008-10-01

    Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables. PMID:18820277

  17. Antipneumococcal Activity of ABT-773 Compared to Those of 10 Other Agents

    PubMed Central

    Davies, Todd A.; Ednie, Lois M.; Hoellman, Dianne M.; Pankuch, Glenn A.; Jacobs, Michael R.; Appelbaum, Peter C.

    2000-01-01

    MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC50s) and MIC90s were 0.016 to 0.03 and 0.125 μg/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC50, 0.06 μg/ml; MIC90, 0.125 μg/ml). Activities of pristinamycin (MIC90, 0.5 μg/ml) and vancomycin (MIC90, 0.25 μg/ml) were unaffected by macrolide or penicillin resistance, while β-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 μg/ml, while macrolide and azalide MICs were all ≥16.0 μg/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 μg/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or β-lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci. PMID:10858350

  18. A New Hyaluronic Acid Derivative Obtained from Atom Transfer Radical Polymerization as a siRNA Vector for CD44 Receptor Tumor Targeting.

    PubMed

    Palumbo, Fabio Salvatore; Bavuso Volpe, Antonella; Bongiovì, Flavia; Pitarresi, Giovanna; Giammona, Gaetano

    2015-11-01

    Two derivatives of hyaluronic acid (HA) have been synthesized by atom transfer radical polymerization (ATRP), starting from an ethylenediamino HA derivative (HA-EDA) and by using diethylaminoethyl methacrylate (DEAEMA) as a monomer for polymerization. Both samples, indicated as HA-EDA-pDEAEMA a and b, are able to condense siRNA, as determined by gel retardation assay and resulting complexes show a size and a zeta potential value dependent on polymerization number, as determined by dynamic light scattering measurements. In vitro studies performed on HCT 116 cell line, that over express CD44 receptor, demonstrate a receptor mediated uptake of complexes, regardless of their surface charge. PMID:26136372

  19. A 1H NMR Investigation of the Interaction between Phenolic Acids Found in Mango (Manguifera indica cv Ataulfo) and Papaya (Carica papaya cv Maradol) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) Free Radicals

    PubMed Central

    López-Martínez, Luis M.; Santacruz-Ortega, Hisila; Navarro, Rosa-Elena; Sotelo-Mundo, Rogerio R.; González-Aguilar, Gustavo A.

    2015-01-01

    The benefits of phenolic acids on human health are very often ascribed to their potential to counteract free radicals to provide antioxidant protection. This potential has been attributed to their acidic chemical structure, which possesses hydroxyl groups in different positions. Phenolic acids can interact between themselves and exhibit an additive, antagonistic or synergistic effect. In this paper, we used 1H NMR to analyze the interactions and mechanisms that are present in major phenolic acids found in mango (gallic, protocatechuic, chlorogenic and vanillic acids) and papaya (caffeic, ferulic and p-coumaric acids), and the DPPH radical was used to evaluate the effect of the antioxidant mixtures. The interactions were found to occur via hydrogen bonds between the -OH and -COOH groups. Moreover, the phenolic acids exhibit two types of mechanisms for the neutralization of the DPPH radical. According to the results, these two mechanisms are Hydrogen Atom Transfer (HAT) and Single Electron Transfer (SET). The ability of the phenolic acid to neutralize the DPPH radical decreases in the following order in mango: gallic > chlorogenic > protocatechuic > vanillic. Moreover, within the acids found in papaya, the order was as follows: caffeic > p-coumaric > ferulic. PMID:26559189

  20. Combination with vorinostat overcomes ABT-263 (navitoclax) resistance of small cell lung cancer.

    PubMed

    Nakajima, Wataru; Sharma, Kanika; Hicks, Mark A; Le, Ngoc; Brown, Rikiara; Krystal, Geoffrey W; Harada, Hisashi

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive tumor type with high mortality. One promising approach for SCLC treatment would be to utilize agents targeting molecular abnormalities regulating resistance to apoptosis. BH3 mimetic antagonists, such as ABT-737 and its orally available derivative ABT-263 (navitoclax) have been developed to block the function of pro-survival BCL-2 family members. The sensitivity of SCLC to these drugs varies over a broad range in vitro and in clinical trials. We have previously shown that the expression of Noxa, a BH3-only pro-apoptotic BCL-2 family protein, is a critical determinant of sensitivity to ABT-737. Thus, pharmacological up-regulation of Noxa could enhance cell death induced by the BH3 mimetics. We find that the combination of ABT-263 and a HDAC inhibitor, vorinostat, efficiently induces apoptosis in a variety of SCLC cell lines, including ABT-263 resistant cell lines. Cell death induced by combined treatment is Noxa- and/or BIM-dependent in some cell lines but in others appears to be mediated by down-regulation of BCL-XL and release of BAK from BCL-XL and MCL-1. These results suggest that combination of HDAC inhibitors and BCL-2 inhibitors could be an alternative and effective regimen for SCLC treatment. PMID:26575826

  1. ABT-627, an endothelin ET(A) receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain.

    PubMed

    Jarvis, M F; Wessale, J L; Zhu, C Z; Lynch, J J; Dayton, B D; Calzadilla, S V; Padley, R J; Opgenorth, T J; Kowaluk, E A

    2000-01-24

    Tactile allodynia, the enhanced perception of pain in response to normally non-painful stimulation, represents a common complication of diabetic neuropathy. The activation of endothelin ET(A) receptors has been implicated in diabetes-induced reductions in peripheral neurovascularization and concomitant endoneurial hypoxia. Endothelin receptor activation has also been shown to alter the peripheral and central processing of nociceptive information. The present study was conducted to evaluate the antinociceptive effects of the novel endothelin ET(A) receptor-selective antagonist, 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N, N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627), in the streptozotocin-induced diabetic rat model of neuropathic pain. Rats were injected with 75 mg/kg streptozotocin (i. p.), and drug effects were assessed 8-12 weeks following streptozotocin treatment to allow for stabilization of blood glucose levels (>/=240 mg/dl) and tactile allodynia thresholds (ABT-627 (1 and 10 mg/kg) was found to produce a dose-dependent increase in tactile allodynia thresholds. A significant antinociceptive effect (40-50% increase in tactile allodynia thresholds, P<0.05) was observed at the dose of 10 mg/kg, i.p., within 0.5-2-h post-dosing. The antinociceptive effects of ABT-627 (10 mg kg(-1) day(-1), p.o.) were maintained following chronic administration of the antagonist in drinking water for 7 days. In comparison, morphine administered acutely at a dose of 8 mg/kg, i.p., produced a significant 90% increase in streptozotocin-induced tactile allodynia thresholds. The endothelin ET(B) receptor-selective antagonist, 2R-(4-propoxyphenyl)-4S-(1, 3-benzodioxol-5-yl)-1-(N-(2, 6-diethylphenyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxy lic acid (A-192621; 20 mg/kg, i.p.), did not significantly alter tactile allodynia thresholds in streptozotocin-treated rats. Although combined i.p. administration

  2. Studies on the syntheses, structural characterization, antimicrobial-, and DPPH radical scavenging activity of the cocrystals caffeine:cinnamic acid and caffeine:eosin dihydrate

    NASA Astrophysics Data System (ADS)

    Suresh Kumar, G. S.; Seethalakshmi, P. G.; Bhuvanesh, N.; Kumaresan, S.

    2013-10-01

    Two organic cocrystals namely, caffeine:cinnamic acid [(caf)(ca)] (1) and caffeine:eosin dihydrate [(caf)(eos)]·2H2O (2) were synthesized and studied by FT-IR, TGA/DTA, and single crystal XRD. The crystal system of cocrystal 1 is triclinic with space group P-1 and Z = 2 and that of cocrystal 2 is monoclinic with space group P21/C and Z = 4. An imidazole-carboxylic acid synthon is observed in the cocrystal 1. The intermolecular hydrogen bond, O-H⋯N and π-π interactions play a major role in stabilizing 1 whereas the intermolecular hydrogen bonds, O-H⋯O, O-H⋯N, and intramolecular hydrogen bond, O-H⋯Br; along with π-π interactions together play a vital role in stabilizing the structure of 2. The antimicrobial- and DPPH radical scavenging activities of both the cocrystals were studied.

  3. Oxygen radicals and renal diseases.

    PubMed

    Klahr, S

    1997-01-01

    Reactive oxygen metabolites (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorous acid) are important mediators of renal damage in acute renal failure and glomerular and tubulointerstitial diseases. The role of these oxygen metabolites in the above entities is discussed, and the effects of antioxidants and scavengers of O2 radicals are considered. The role of oxygen radicals in the regulation of gene transcription is also considered. PMID:9387104

  4. Activities of ABT-773 against Listeria monocytogenes and Coryneform Bacteria of Clinical Interest

    PubMed Central

    Conejo, María del Carmen; Martínez-Martínez, Luis; Pascual, Álvaro; Suárez, Ana Isabel; Perea, Evelio J.

    2003-01-01

    The in vitro activities of ABT-773 were evaluated against 15 Listeria monocytogenes strains and 196 coryneform bacteria isolated from clinical samples. One hundred percent of the L. monocytogenes strains were inhibited by ≤0.015 μg of ABT-773/ml. MICs of ABT-773 (μg/ml) at which 50% of the isolates tested were inhibited (MIC50s) and MIC90s for other organisms were 0.125 and 0.5 (Corynebacterium amycolatum), 1 and >32 (Corynebacterium jeikeium), 0.03 and >32 (Corynebacterium minutissimum), >32 and >32 (Corynebacterium pseudodiphtheriticum and Corynebacterium urealyticum), 0.125 and >32 (Corynebacterium striatum), and 0.03 and 0.5 (Rhodococcus equi), respectively. PMID:12654678

  5. Activities of ABT-773 against Listeria monocytogenes and coryneform bacteria of clinical interest.

    PubMed

    Conejo, María del Carmen; Martínez-Martínez, Luis; Pascual, Alvaro; Suárez, Ana Isabel; Perea, Evelio J

    2003-04-01

    The in vitro activities of ABT-773 were evaluated against 15 Listeria monocytogenes strains and 196 coryneform bacteria isolated from clinical samples. One hundred percent of the L. monocytogenes strains were inhibited by ABT-773/ml. MICs of ABT-773 ( micro g/ml) at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s for other organisms were 0.125 and 0.5 (Corynebacterium amycolatum), 1 and >32 (Corynebacterium jeikeium), 0.03 and >32 (Corynebacterium minutissimum), >32 and >32 (Corynebacterium pseudodiphtheriticum and Corynebacterium urealyticum), 0.125 and >32 (Corynebacterium striatum), and 0.03 and 0.5 (Rhodococcus equi), respectively. PMID:12654678

  6. Radical scavenging activities of niacin-related compounds.

    PubMed

    Ogata, Shin; Takeuchi, Masayo; Teradaira, Shin; Yamamoto, Naokuni; Iwata, Keiko; Okumura, Katsuzumi; Taguchi, Hiroshi

    2002-03-01

    We investigated whether niacin-related compounds had radical-scavenging activity by electron spin resonance methods. Many compounds, but not trigonelline, had radical-scavenging activity against hydroxyl radicals. However, for the nitric oxide radical and 1,1-diphenyl-2-picrylhydrazyl radical, only nicotinic acid hydrazide and isonicotinic acid hydrazide had scavenging activities. These results suggest that the moiety of hydrazide might have an important role in scavenging abilities of various radicals. PMID:12005062

  7. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    SciTech Connect

    Shelton, Joseph W.; Waxweiler, Timothy V.; Landry, Jerome; Gao, Huiying; Xu, Yanbo; Wang, Lanfang; El-Rayes, Bassel; Shu, Hui-Kuo G.

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.

  8. Toxicological Evaluation of Emblica officinalis Fruit Extract and its Anti-inflammatory and Free Radical Scavenging Properties

    PubMed Central

    Middha, Sushil Kumar; Goyal, Arvind Kumar; Lokesh, Prakash; Yardi, Varsha; Mojamdar, Lavanya; Keni, Deepthi Sudhir; Babu, Dinesh; Usha, Talambedu

    2015-01-01

    Background: Emblica officinalis (Euphorbiaceae), popularly known as Indian gooseberry or “Amla” in India, is used in Ayurveda as “rejuvenating herb” since ancient times. Objective: This study was carried out to estimate toxicity, anti-inflammatory, and antioxidative activities of the methanolic extract of Emblica officinalis fruit (MEO) in an animal model. Materials and Methods: Antioxidative property of MEO was assessed by in vitro assays such as phosphomolybdenum assay (total antioxidant capacity), free radical scavenging assays 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis and 3-ethylbenzthiazoline-6-sulphonic acid (DPPH and ABTS method) and lipid peroxidation assay (LPO). The anti-inflammatory property was evaluated by carrageenan-induced acute inflammation in rats by measuring rat paw volume at different time intervals and toxicological analysis using mice. Results and Discussion: High performance liquid chromatography studies revealed the presence of gallic acid (2.10%), mucic acid (4.90%), ellagic acid (2.10%), quercetin (28.00%), rutin (3.89%), and β-glucogallin (1.46%). MEO showed highest antioxidant activities by using DPPH (17.33–89.00%), ABTS (23.03–94.16%), nitric oxide scavenging activity (12.94–70.16%), LPO (56.54%), and phosphomolybdenum assay (142 ± 6.09 μg/ml). The LD50 was found to be approximately 1125 mg/kg (p.o). High dose of MEO showed significant reduction (72.71%) in the inflammation after 4 h of treatment, which was comparable to diclofenac (10 mg/kg) (61.57%) treated group. Significant reduction (P < 0.05) in the inflammatory cytokine (interleukin-1β and tumor necrosis factor-α) markers were also observed (57.25% and 35.41%, respectively) in serum of MEO treated animals as compared to control. Conclusion: Taken together, phenolic compounds of MEO may serve as a potential herbal drug for amelioration of acute inflammation due to their modulatory action on free radicals. SUMMARY The methanolic extract of Emblica

  9. Radical Hysterectomy

    MedlinePlus

    ... the base of her partner’s penis during intercourse. Orgasm after radical hysterectomy Women who have had a ... the surgery will affect their ability to have orgasms. This has not been studied a great deal, ...

  10. Human Pluripotent Stem Cells and Derived Neuroprogenitors Display Differential Degrees of Susceptibility to BH3 Mimetics ABT-263, WEHI-539 and ABT-199

    PubMed Central

    Dimopoulos, Nicolás Alexis; Fernandez Espinosa, Damián Darío; Miriuka, Santiago Gabriel; Sevlever, Gustavo Emilio; Romorini, Leonardo; Scassa, María Elida

    2016-01-01

    Human embryonic stem cells (hESCs) are hypersensitive to genotoxic stress and display lower survival ability relative to their differentiated progeny. Herein, we attempted to investigate the source of this difference by comparing the DNA damage responses triggered by the topoisomerase I inhibitor camptothecin, in hESCs, human induced pluripotent stem cells (hiPSCs) and hESCs-derived neuroprogenitors (NP). We observed that upon camptothecin exposure pluripotent stem cells underwent apoptosis more swiftly and at a higher rate than differentiated cells. However, the cellular response encompassing ataxia-telangiectasia mutated kinase activation and p53 phosphorylation both on serine 15 as well as on serine 46 resulted very similar among the aforementioned cell types. Importantly, we observed that hESCs and hiPSCs express lower levels of the anti-apoptotic protein Bcl-2 than NP. To assess whether Bcl-2 abundance could account for this differential response we treated cells with ABT-263, WEHI-539 and ABT-199, small molecules that preferentially target the BH3-binding pocket of Bcl-xL and/or Bcl-2 and reduce their ability to sequester pro-apoptotic factors. We found that in the absence of stress stimuli, NP exhibited a higher sensitivity to ABT- 263 and WEHI-539 than hESCs and hiPSCs. Conversely, all tested cell types appeared to be highly resistant to the Bcl-2 specific inhibitor, ABT-199. However, in all cases we determined that ABT-263 or WEHI-539 treatment exacerbated camptothecin-induced apoptosis. Importantly, similar responses were observed after siRNA-mediated down-regulation of Bcl-xL or Bcl-2. Taken together, our results suggest that Bcl-xL contrary to Bcl-2 contributes to ensure cell survival and also functions as a primary suppressor of DNA double-strand brake induced apoptosis both in pluripotent and derived NP cells. The emerging knowledge of the relative dependence of pluripotent and progenitor cells on Bcl-2 and Bcl-xL activities may help to predict

  11. Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

    PubMed Central

    Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

    2014-01-01

    Objective(s): Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Conclusion: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID:25140204

  12. Antioxidant activities of rosemary (Rosmarinus Officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol.

    PubMed

    Erkan, Naciye; Ayranci, Guler; Ayranci, Erol

    2008-09-01

    Antioxidant activities of three pure compounds: carnosic acid, rosmarinic acid and sesamol, as well as two plant extracts: rosemary extract and blackseed essential oil, were examined by applying DPPH and ABTS(+) radical-scavenging assays and the ferric thiocyanate test. All three test methods proved that rosemary extract had a higher antioxidant activity than blackseed essential oil. The order of antioxidant activity of pure compounds showed variations in different tests. This was attributed to structural factors of individual compounds. Phenolic contents of blackseed essential oil and rosemary extract were also determined. Rosemary extract was found to have a higher phenolic content than blackseed essential oil. This fact was utilised in explaining the higher antioxidant activity of rosemary extract. PMID:26050168

  13. Impact of nitrous acid photolysis on the total hydroxyl radical budget during the Limitation of Oxidant Production/Pianura Padana Produzione di Ozono study in Milan

    NASA Astrophysics Data System (ADS)

    Alicke, B.; Platt, U.; Stutz, J.

    2002-11-01

    The photolysis of nitrous acid (HONO) in the early morning hours is believed to be a significant source of hydroxyl radicals (OH), the most important daytime oxidizing species. Although the importance of this mechanism has been recognized for many years, no accurate experimental quantification is available. Here we present measurements of HONO, NO2, SO2, O3 and HCHO by Differential Optical Absorption Spectroscopy (DOAS) during the Limitation of Oxidant Production/Pianura Padana Produzione di Ozono (LOOP/PIPAPO) study in May-June 1998 in Milan, Italy. The concentration of NO and J(NO2)/J(HONO) were simultaneously monitored by in situ monitors. The photolysis frequencies of HCHO and O3 were determined with a radiative transfer model. High nocturnal HONO mixing ratios of up to 4.4 ppb were regularly observed. Elevated daytime HONO levels during cloudy periods show that the formation of HONO proceeds after sunrise and therefore also represents a source of hydroxyl radicals throughout the day. Averaged over 24 hours, HCHO photolysis is the most important source of OH in Milan, followed by either ozone or HONO photolysis. Our observations indicate that on certain days the OH production from HONO can be even more important than that from ozone photolysis. The diurnal variation of the different OH formation mechanisms shows that HONO photolysis is by far the most important source in the early hours of the morning, and can be as large as and even surpass the total OH production at noon.

  14. Modulation of arachidonic acid metabolism by phenols: relation to positions of hydroxyl groups and peroxyl radical scavenging properties.

    PubMed

    Alanko, J; Riutta, A; Mucha, I; Vapaatalo, H; Metsä-Ketelä, T

    1993-01-01

    We have shown earlier that catecholamines have opposite regulative effects on prostaglandin (PG)E2 and leukotriene (LT)B4 formation with a receptor-independent mechanism in human polymorphonuclear leukocytes (PMNs) and whole blood. To shed further light on the mechanisms involved and structure-action relationship, we tested the effects of phenols (catechol, hydroquinone, phenol, and resorcinol) on the synthesis of PGE2 and LTB4 in human A23187-stimulated PMNs. To study the mechanism of how phenols influence PGE2 and LTB4 synthesis, their peroxyl radical-scavenging properties were analyzed. In general, low concentrations of phenols stimulated (catechol > hydroquinone > phenol) and high concentrations inhibited (resorcinol > catechol > hydroquinone > phenol) PGE2 formation. Resorcinol was different from the other phenols: It did not stimulate PGE2 synthesis at all, but it was effective inhibitor at high concentrations. Phenols had only an inhibitory effect on LTB4 formation (catechol = hydroquinone > phenol > resorcinol). The order of both stochiometric factors and reactivities of phenols for scavenging peroxyl radicals was catechol > hydroquinone > resorcinol > phenol. According to these results, phenols having hydroxyl groups in ortho- or paraposition have the greatest stimulative effect on PGE2 synthesis, the highest inhibitory action on LTB4 synthesis, and are good antioxidants. Resorcinol, having hydroxyl groups in the metaposition, behaves differently. It neither stimulates PGE2 nor inhibits LTB4 formation, but it is the most potent inhibitor of PGE2 formation. In spite of resorcinol's two hydroxyl groups, it mimics as an antioxidant phenol more than catechol and hydroquinone. PMID:8384148

  15. Nitrogen Oxides in the Nocturnal Boundary Layer: Chemistry of Nitrous Acid (HONO) and the Nitrate Radical (N03)

    SciTech Connect

    Jochen Stutz

    2005-05-24

    Summary Chemical processes occurring at night in the lowest part of the urban atmosphere, the so called nocturnal boundary layer (NBL), can influence the composition of the atmosphere during the night as well as the following day. They may impact the budgets of some of the most important pollutants, such as ozone and nitrogen oxides, as well as influence size and composition of particular matter. Few studies have thus far concentrated on the nocturnal chemistry of the urban NBL, most likely due to the strong influence of vertical transport and mixing, which requires the measurement of trace gas profiles instead of simple point observations. Motivated by our lack of observations and understanding of nocturnal chemistry, the focus of this project was the study of the vertical distribution of trace gases and the altitude dependence of nocturnal chemistry under polluted conditions through field observations and modeling studies. The analysis of three field experiments (TEXAQS, Houston, 2000; Phoenix Sunrise Ozone Experiment, 2001; NAPOX, Boston, 2002), two of which were performed in this project, showed that ozone concentrations typically increase with height in the lowest 150m, while NO2 typically decreases. NO3, the dominant nocturnal radical species, showed much higher concentrations in the upper part of the NBL, and was often not present at the ground. With the help of a one-dimensional chemical transport model, developed in this project, we found that the interaction of ground emissions of NOx and hydrocarbons, together with their vertical transport, is responsible for the vertical profiles. The dominant chemical reactions influencing ozone, NO2 and NO3 are the reaction of ozone and NO3 with freshly emitted NO. Sensitivity studies with our model showed that the magnitude of the trace gas gradients depend both on the emission rates and the vertical stability of the NBL. Observations and model analysis clearly show that nocturnal chemistry in urban areas is altitude

  16. Electron-transfer reaction of cinnamic acids and their methyl esters with the DPPH(*) radical in alcoholic solutions.

    PubMed

    Foti, Mario C; Daquino, Carmelo; Geraci, Corrada

    2004-04-01

    The kinetic behavior of cinnamic acids, their methyl esters, and two catechols 1-10 (ArOH) in the reaction with DPPH(*) in methanol and ethanol is not compatible with a reaction mechanism that involves hydrogen atom abstraction from the hydroxyl group of 1-10 by DPPH(*). The rate of this reaction at 25 degrees C is, in fact, comparatively fast despite that the phenolic OH group of ArOH is hydrogen bonded to solvent molecules. The observed rate constants (k(1)) relative to DPPH(*) + ArOH are 3-5 times larger for the methyl esters than for the corresponding free acids and, for the latter, decrease as their concentration is increased according to the relation k(1) = B/[ArOH](0)(m), where k(1) is given in units of M(-1) s(-1), m is ca. 0.5, and B ranges from 0.02 (p-coumaric acid) to ca. 3.48 (caffeic acid) in methanol and from 0.04 (p-coumaric acid) to ca. 13 (sinapic acid) in ethanol. Apparently, the reaction mechanism of DPPH(*) + ArOH involves a fast electron-transfer process from the phenoxide anion of 1-10 to DPPH(*). Kinetic analysis of the reaction sequence for the free acids leads to an expression for the observed rate constant, k(1), proportional to [ArOH](0)(-1/2) in excellent agreement with the experimental behavior of these phenols. The experimental results are also interpreted in terms of the influence that adventitious acids or bases present in the solvent may have. These impurities dramatically influence the ionization equilibrium of phenols and cause a reduction or an enhancement, respectively, of the measured rate constants. PMID:15049623

  17. Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC

    PubMed Central

    Gilormini, Marion; Malesys, Céline; Armandy, Emma; Manas, Patrick; Guy, Jean-Baptiste; Magné, Nicolas; Rodriguez-Lafrasse, Claire; Ardail, Dominique

    2016-01-01

    Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. HNSCC is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. The aim of this study was to evaluate combined effects of radiation and ABT-737, a BH3-mimetic molecule, in HNSCC. Although ABT-737, as a single agent, was largely ineffective at promoting HNSCC cell death, we found that combining ABT-737 and radiation induced strong synergistic apoptosis in HNSCC cell lines and delayed tumoral growth in vivo. Moreover, we demonstrated for the first time that ABT-737, alone or in combination with radiation, can efficiently eliminate cancer stem cells (CSCs). Altogether, our results indicate that therapy targeting anti-apoptotic Bcl-2 family members could be a highly effective potential adjuvant to radiotherapy capable of targeting CSCs in HNSCC and therefore overcoming cancer recurrence and metastasis. PMID:26934442

  18. 78 FR 29367 - Access to Confidential Business Information by ABT Associates, Incorporated; Perry Johnson...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ... Division (RCSD) as it conducts a study of the implementation of two currently used electronics recycling certification programs in the U.S.: The Responsible Recycling Practices (R2) and e-Stewards Standard for Responsible Recycling and Reuse of Electronic Equipment (e-Stewards). Contractor support from ABT will...

  19. Isolation of Lactic Acid Bacteria Showing Antioxidative and Probiotic Activities from Kimchi and Infant Feces.

    PubMed

    Ji, Keunho; Jang, Na Young; Kim, Young Tae

    2015-09-01

    The purpose of this study was to investigate lactic acid bacteria with antioxidative and probiotic activities isolated from Korean healthy infant feces and kimchi. Isolates A1, A2, S1, S2, and S3 were assigned to Lactobacillus sp. and isolates A3, A4, E1, E2, E3, and E4 were assigned to Leuconostoc sp. on the basis of their physiological properties and 16S ribosomal DNA sequence analysis. Most strains were confirmed as safe bioresources through nonhemolytic activities and non-production of harmful enzymes such as β-glucosidase, β- glucuronidase and tryptophanase. The 11 isolates showed different resistance to acid and bile acids. In addition, they exhibited antibacterial activity against foodborne bacteria, especially Bacillus cereus, Listeria monocytogenes, and Escherichia coli. Furthermore, all strains showed significantly high levels of hydrophobicity. The antioxidant effects of culture filtrates of the 11 strains included 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging capacity, 2.2'- azino-bis (2-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity, and superoxide dismutase activity. The results revealed that most of the culture filtrates have effective scavenging activity for DPPH and ABTS radicals. All strains appeared to have effective superoxide dismutase activity. In conclusion, the isolated strains A1, A3, S1, and S3 have significant probiotic activities applicable to the development of functional foods and health-related products. These strains might also contribute to preventing and controlling several diseases associated with oxidative stress, when used as probiotics. PMID:25951843

  20. THERMOCHEMISTRY OF HYDROCARBON RADICALS

    SciTech Connect

    Kent M. Ervin, Principal Investigator

    2004-08-17

    Gas phase negative ion chemistry methods are employed to determine enthalpies of formation of hydrocarbon radicals that are important in combustion processes and to investigate the dynamics of ion-molecule reactions. Using guided ion beam tandem mass spectrometry, we measure collisional threshold energies of endoergic proton transfer and hydrogen atom transfer reactions of hydrocarbon molecules with negative reagent ions. The measured reaction threshold energies for proton transfer yield the relative gas phase acidities. In an alternative methodology, competitive collision-induced dissociation of proton-bound ion-molecule complexes provides accurate gas phase acidities relative to a reference acid. Combined with the electron affinity of the R {center_dot} radical, the gas phase acidity yields the RH bond dissociation energy of the corresponding neutral molecule, or equivalently the enthalpy of formation of the R{center_dot} organic radical, using equation: D(R-H) = {Delta}{sub acid}H(RH) + EA(R) - IE(H). The threshold energy for hydrogen abstraction from a hydrocarbon molecule yields its hydrogen atom affinity relative to the reagent anion, providing the RH bond dissociation energy directly. Electronic structure calculations are used to evaluate the possibility of potential energy barriers or dynamical constrictions along the reaction path, and as input for RRKM and phase space theory calculations. In newer experiments, we have measured the product velocity distributions to obtain additional information on the energetics and dynamics of the reactions.

  1. Pulmonary delivery of a dopamine D-1 agonist, ABT-431, in dogs and humans.

    PubMed

    Zheng, Y; Marsh, K C; Bertz, R J; El-Shourbagy, T; Adjei, A L

    1999-11-30

    The purpose of this study was to evaluate the feasibility of intrapulmonary delivery of ABT-431, a selective D1 receptor agonist. Following intratracheal instillation of the drug solution, the lung bioavailability was found to be approximately 75% in dogs. An aerosol suspension formulation was then developed by dispersing the drug in tetrafluoroethane, HFC-134a, with the aid of poloxamer 124 and vitamin E. This ABT-431 MDI aerosol formulation showed about 40% of the particles emitted from the valve and actuator system to be under 5 microm in diameter. Also, the primary package (15 mL aluminum container, DF10/ACT-150 valve, and Micron-4-actuator with the orifice 0.4 mm) was satisfactory for accurate and reproducible dosimetry. Using tracheostomized beagle dogs, the C(max) following tracheal administration of 5 mg aerosolized ABT-431 was found to be 13.3+/-0.9 ng ml(-1) and the AUC(0-24) was estimated at 33.2+/-10.6 h ng ml(-1). The lung bioavailability of the aerosolized drug was 34% compared to intravenous injection in dogs. In humans, results from a single rising dose study demonstrated that rapid absorption of ABT-431 following oral inhalation administration resulted in a dose-dependent increase in the area under the plasma-time curve at dosage levels between 3.3 and 13.2 mg. There is a possibility of up to 25% absorption of the drug from human lung. Thus, pulmonary bioavailability of ABT-431 is significantly greater than that of oral administration. Also, these findings suggest that small and lipophilic compounds, especially with hepatic first pass effect, may be effectively delivered systemically using oral inhalation aerosols. PMID:10564839

  2. Madhucosides A and B, protobassic acid glycosides from Madhuca indica with inhibitory activity on free radical release from phagocytes.

    PubMed

    Pawar, Rahul S; Bhutani, K K

    2004-04-01

    The structures of madhucosides A (1) and B (2), isolated from the bark of Madhuca indica, were established as 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1--> 3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid and 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid, respectively. These two compounds showed significant inhibitory effects on both superoxide release from polymorphonuclear cells in a NBT reduction assay and hypochlorous acid generation from neutrophils assessed in a luminol-enhanced chemiluminescence assay. PMID:15104500

  3. Effects of Extraction and Processing Methods on Antioxidant Compound Contents and Radical Scavenging Activities of Laver (Porphyra tenera)

    PubMed Central

    Hwang, Eun-Sun; Thi, Nhuan Do

    2014-01-01

    Laver is one of the most consumed edible red algae seaweeds in the genus Porphyra. Laver is primarily prepared in the form of dried, roasted, and seasoned products. We investigated the total polyphenol and flavonoid contents of laver products, and evaluated the in vitro antioxidant properties of solvent extracts from commercially processed laver products. Significant differences in the concentration of phenolic compounds were found among differently processed laver. The total phenolic content for laver extracts ranged from 10.81 mg gallic acid equivalent (GAE)/g extract to 32.14 mg GAE/g extract, depending on extraction solvent and temperature. Laver extracts contained very few flavonoids (0.55 mg catechin equivalent/g extracts to 1.75 mg catechin equivalent/g extracts). 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), hydroxyl radical, and superoxide anion scavenging assays were used to determine the radical scavenging capacities of laver extracts. These assays revealed that the processing method and extraction condition affected the antioxidant potentials of laver. Antioxidant activity of dried laver, roasted laver, and seasoned laver increased in a concentration-dependent manner (100~1,000 μg/mL). The radical scavenging activities of 37°C and 100°C water extracts were lower than that of a 37°C 70% ethanol extract. The highest radical scavenging capacity was observed in the 37°C 70% ethanol extracts of dried laver, roasted laver, and seasoned laver. Overall, these results support that notion that laver contains bioactive compounds, such as polyphenols and flavonoids, which may have a positive effect on health. PMID:24772408

  4. The Effect of Methyl, Hydroxyl, and Ketone Functional Groups on the Heterogeneous Oxidation of Succinic Acid Aerosol by OH Radicals

    NASA Astrophysics Data System (ADS)

    Chan, M.; Zhang, H.; Wilson, K. R.

    2013-12-01

    The heterogeneous oxidation of atmospheric organic aerosols can influence their effects on climate, human health, and visibility. During oxidation, functionalization occurs when an oxygenated functional group is added to a molecule, leaving the carbon skeleton intact. Fragmentation involves carbon-carbon bond cleavage and produces two products with smaller carbon numbers than the parent compound. To gain better insights into how the molecular structure of more oxygenated organic compounds affects heterogeneous reactivity, succinic acid aerosols are photo-oxidized in an aerosol flow tube reactor, and the reaction products are analyzed using Direct Analysis in Real Time Mass Spectrometry for online chemical analysis. The effect of various functional groups (CH3, OH, C=O) along the carbon backbone on the heterogeneous reaction mechanisms are also investigated using model compounds. For this series of compounds, the formation of more oxygenated products through functionalization can be explained by well-known condensation-phase reactions such as Russell and Bennett and Summers. The number of fragmentation products is found to increase with the presence of OH and CH3 groups. This can be attributed to the increased number of tertiary carbons, enhancing the fragmentation after multiple oxidation steps. Smaller dicaids (oxalic acid and malonic acid) can be formed through the fragmentation processes in the heterogeneous oxidation of succinic acid. The effect of molecular structure on reaction kinetics, volatilization, and the relative importance of functionalization and fragmentation pathways will be discussed.

  5. Fluorinated amphiphilic amino acid derivatives as antioxidant carriers: a new class of protective agents.

    PubMed

    Ortial, Stéphanie; Durand, Grégory; Poeggeler, Burkhard; Polidori, Ange; Pappolla, Miguel A; Böker, Jutta; Hardeland, Rüdiger; Pucci, Bernard

    2006-05-01

    The use of classical antioxidants is limited by their low bioavailabilities, and therefore, high doses are usually required to display significant protective activity. In a recent article (J. Med. Chem. 2003, 46, 5230) we showed that the ability of the alpha-phenyl-N-tert-butylnitrone (PBN) to restore the viability of ATPase-deficient human skin fibroblasts was greatly enhanced by grafting it on a fluorinated amphiphilic carrier. With the aim of extending this concept to other antioxidants, we present here the design, the synthesis, and the physicochemical measurements of a new series of fluorinated amphiphilic antioxidant derivatives. The hydroxyl radical scavenging activity and the radical reducing potency of these newly designed compounds were respectively demonstrated in an ABTS competition and an ABTS(*+) reduction assay. We also showed that the protective effects of amphiphilic antioxidants derived from PBN, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) or lipoic acid (5-[1,2]-dithiolan-3-ylpentanoic acid) in primary cortical mixed cell cultures exposed to oxidotoxins are greatly improved compared to their parent compounds in the following rank-order: (1) PBN, (2) Trolox, and (3) lipoic acid. In contrast, the protective activity of indole-3-propionic acid was slightly decreased by grafting it on the amphiphilic carrier. Similar observations were made in in vivo experiments using aquatic invertebrate microorganisms, called rotifers, which were exposed to lethal concentrations of nonselective (H(2)O(2)) and mitochondria-selective (doxorubicin) oxidotoxins. The conclusion of these studies is that fluorinated amphiphilic PBN, Trolox, and lipoic acid derivatives exhibit very potent protective activities in in vitro and in vivo experiments. The findings demonstrated herein therefore strongly suggest that the amphiphilic character enhances the bioavailability of the antioxidants and allows for a selective targeting of mitochondria. PMID:16640342

  6. In Vitro Activity of ABT-773, a New Ketolide, against Recent Clinical Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

    PubMed Central

    Brueggemann, Angela B.; Doern, Gary V.; Huynh, Holly K.; Wingert, Elizabeth M.; Rhomberg, Paul R.

    2000-01-01

    The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae. ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin. PMID:10639382

  7. Effective sensitization of temozolomide by ABT-888 is lost with development of TMZ resistance in glioblastoma xenograft lines

    PubMed Central

    Clarke, Michelle J.; Mulligan, Evan A.; Grogan, Patrick T.; Mladek, Ann C.; Carlson, Brett L.; Schroeder, Mark A.; Curtin, Nicola J.; Lou, Zhenkun; Decker, Paul A.; Wu, Wenting; Plummer, E. Ruth; Sarkaria, Jann N.

    2009-01-01

    Resistance to temozolomide (TMZ) and radiotherapy (RT) is a major problem for patients with GBM but may be overcome using the PARP-inhibitor ABT-888. Using two primary GBM xenografts, the efficacy of ABT-888 combined with RT and/or TMZ was evaluated. Treatment with ABT-888 combined with TMZ resulted in significant survival prolongation (GBM12: 55.1%, p=0.005; GBM22: 54.4%, p=0.043). ABT-888 had no effect with RT alone, but significantly enhanced survival in GBM12 when combined with concurrent RT/TMZ. With multi-cycle therapy, ABT-888 further extended the survival benefit of TMZ in the inherently sensitive GBM12 and GBM22 xenograft lines. However, after in vivo selection for TMZ resistance, the derivative GBM12TMZ and GBM22TMZ lines were no longer sensitized by ABT-888 in combination with TMZ, and a similar lack of efficacy was observed in two other TMZ resistant tumor lines. Thus, the sensitizing effects of ABT-888 were limited to tumor lines that had not been previously exposed to TMZ, and these results suggest that patients with newly diagnosed GBM may be more likely to respond to combined TMZ/PARP inhibitor therapy than patients with recurrent disease. PMID:19174557

  8. Targeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia

    PubMed Central

    Lin, Kevin H.; Winter, Peter S.; Xie, Abigail; Roth, Cullen; Martz, Colin A.; Stein, Elizabeth M.; Anderson, Grace R.; Tingley, Jennifer P.; Wood, Kris C.

    2016-01-01

    ABT-199, a potent and selective small-molecule antagonist of BCL-2, is being clinically vetted as pharmacotherapy for the treatment of acute myeloid leukemia (AML). However, given that prolonged monotherapy tends to beget resistance, we sought to investigate the means by which resistance to ABT-199 might arise in AML and the extent to which those mechanisms might be preempted. Here we used a pathway-activating genetic screen to nominate MCL-1 and BCL-XL as potential nodes of resistance. We then characterized a panel of ABT-199-resistant myeloid leukemia cell lines derived through chronic exposure to ABT-199 and found that acquired drug resistance is indeed driven by the upregulation of MCL-1 and BCL-XL. By targeting MCL-1 and BCL-XL, resistant AML cell lines could be resensitized to ABT-199. Further, preemptively targeting MCL-1 and/or BCL-XL alongside administration of ABT-199 was capable of delaying or forestalling the acquisition of drug resistance. Collectively, these data suggest that in AML, (1) the selection of initial therapy dynamically templates the landscape of acquired resistance via modulation of MCL-1/BCL-XL and (2) appropriate selection of initial therapy may delay or altogether forestall the acquisition of resistance to ABT-199. PMID:27283158

  9. An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat.

    PubMed

    Otsuguro, Ken-ichi; Tomonari, Yuki; Otsuka, Saori; Yamaguchi, Soichiro; Kon, Yasuhiro; Ito, Shigeo

    2015-10-01

    Adenosine kinase (AK) inhibitor is a potential candidate for controlling pain, but some AK inhibitors have problems of adverse effects such as motor impairment. ABT-702, a non-nucleoside AK inhibitor, shows analgesic effect in animal models of pain. Here, we investigated the effects of ABT-702 on synaptic transmission via nociceptive and motor reflex pathways in the isolated spinal cord of neonatal rats. The release of adenosine from the spinal cord was measured by HPLC. ABT-702 inhibited slow ventral root potentials (sVRPs) in the nociceptive pathway more potently than monosynaptic reflex potentials (MSRs) in the motor reflex pathway. The inhibitory effects of ABT-702 were mimicked by exogenously applied adenosine, blocked by 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an adenosine A1 receptor antagonist, and augmented by EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an adenosine deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) inhibitors reversed the effects of ABT-702, but not those of adenosine. ABT-702 released adenosine from the spinal cord, an effect that was also reversed by ENT inhibitors. The ABT-702-facilitated release of adenosine by way of ENTs inhibits nociceptive pathways more potently than motor reflex pathways in the spinal cord via activation of A1 receptors. This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. PMID:26066576

  10. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1

    PubMed Central

    Yecies, Derek; Carlson, Nicole E.; Deng, Jing

    2010-01-01

    ABT-737 is a small-molecule antagonist of BCL-2 currently under evaluation in clinical trials in the oral form of ABT-263. We anticipate that acquired resistance to this promising drug will inevitably arise. To study potential mechanisms of resistance to ABT-737, we derived resistant lines from initially sensitive OCI-Ly1 and SU-DHL-4 lymphoma cell lines via long-term exposure. Resistance was based in the mitochondria and not due to an inability of the drug to bind BCL-2. Resistant cells had increased levels of BFL-1 and/or MCL-1 proteins, which are not targeted by ABT-737. Proapoptotic BIM was displaced from BCL-2 by ABT-737 in both parental and resistant cells, but in resistant cells, BIM was sequestered by the additional BFL-1 and/or MCL-1. Decreasing MCL-1 levels with flavopiridol, PHA 767491, or shRNA restored sensitivity to ABT-737 resistant cells. MCL-1 was up-regulated not by protein stabilization but rather by increased transcript levels. Surprisingly, in addition to stable increases in MCL-1 transcript and protein in resistant cells, there was a dynamic increase within hours after ABT-737 treatment. BFL-1 protein and transcript levels in resistant cells were similarly dynamically up-regulated. This dynamic increase suggests a novel mechanism whereby modulation of antiapoptotic protein function communicates with nuclear transcriptional machinery. PMID:20197552

  11. Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression

    PubMed Central

    Lutz, C; Mozaffari, M; Tosevski, V; Caj, M; Cippà, P; McRae, B L; Graff, C L; Rogler, G; Fried, M; Hausmann, M

    2015-01-01

    Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10tm1Cgn/J (IL-10−/−) weighing 25–30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4+CD44+CD62L+ central memory and CD8+, CD44+ CD62L− central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer’s patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim−/− and Il10−/− × Bim−/− impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD. PMID:25845418

  12. Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression.

    PubMed

    Lutz, C; Mozaffari, M; Tosevski, V; Caj, M; Cippà, P; McRae, B L; Graff, C L; Rogler, G; Fried, M; Hausmann, M

    2015-08-01

    Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) , CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer's patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-) (/) (-) and Il10(-) (/) (-) × Bim(-) (/) (-) impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD. PMID:25845418

  13. Radiosensitization of Pancreatic Cancer Cells In Vitro and In Vivo through Poly (ADP-ribose) Polymerase Inhibition with ABT-888

    PubMed Central

    Tuli, Richard; Surmak, Andrew J.; Reyes, Juvenal; Armour, Michael; Hacker-Prietz, Amy; Wong, John; DeWeese, Theodore L.; Herman, Joseph M.

    2014-01-01

    OBJECTIVES To determine whether poly (ADP-ribose) polymerase-1/2 (PARP-1/2) inhibition enhances radiation-induced cytotoxicity of pancreatic adenocarcinoma in vitro and in vivo, and the mechanism by which this occurs. Methods Pancreatic carcinoma cells were treated with ABT-888, radiation, or both. In vitro cell viability, apoptosis, and PARP activity were measured. Orthotopic xenografts were generated in athymic mice and treated with ABT-888 (25 mg/kg), radiation (5 Gy), both, or no treatment. Mice were monitored with bioluminescence imaging. RESULTS In vitro, treatment with ABT-888 and radiation led to higher rates of cell death after 8 days (P < .01). Co-treatment with 5 Gy and 1, 10 or 100 μmol/l of ABT-888 led to dose enhancement factors of 1.29, 1.41 and 2.36, respectively. Caspase activity was not significantly increased when treated with ABT-888 (10 μmol/l) alone (1.28-fold, P = .08), but became significant when radiation was added (2.03-fold, P < .01). PARP activity increased post-radiation and was abrogated following co-treatment with ABT-888. In vivo, treatment with ABT-888, radiation or both led to tumor growth inhibition (TGI) of 8, 30 and 39 days, and survival at 60 days of 0%, 0% and 40%, respectively. CONCLUSIONS ABT-888 with radiation significantly enhanced tumor response in vitro and in vivo. ABT-888 inhibited PAR protein polymerization resulting in dose-dependent feedback up-regulation of PARP and p-ATM suggesting increased DNA damage. This translated into enhancement in TGI and survival with radiation in vivo. In vitro PAR levels correlated with levels of tumor apoptosis suggesting potential as a predictive biomarker. These data are being used to support a Phase I study in locally advanced pancreatic cancer. PMID:24836647

  14. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

    PubMed Central

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

    2013-01-01

    Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

  15. Degradation of hyaluronic acid by photosensitized riboflavin in vitro. Modulation of the effect by transition metals, radical quenchers, and metal chelators.

    PubMed

    Frati, E; Khatib, A M; Front, P; Panasyuk, A; Aprile, F; Mitrovic, D R

    1997-01-01

    The effect of photoexcited riboflavin (RF) on the viscosity of hyaluronic acid (HA) solutions has been investigated. UV irradiation of RF causes under aerobic conditions fragmentation of HA and a decrease in the viscosity of its solutions. A decrease of HA viscosity occurs in PO(4)-buffered solutions and is accelerated by high pH, Fe2+ (but much less so by Fe3+), certain metal chelators, and horseradish peroxidase (HRP); it is partially inhibited by catalase and less so by superoxide dismutase (SOD). The reactivity of the system was completely blocked by Tris, ethanol, aspirin, d-manitol, dimethylthiourea (DMTU), dimethylsulfoxide (DMSO), and sodium azide. These results indicate that the most likely chemical species involved in the reaction is the hydroxyl radical. Singlet oxygen ((1)O(2)) generation is suggested by the ability of NaN3 and DMSO to completely inhibit the reactivity of the system. These two agents, however, may also interact with OH. radical, as well and suppress the reactivity of the system. H(2)O(2) and O(2).- seem also to be produced in significant amounts, because catalase and SOD partially block the reactivity of the system. The effect of HRP may be due to hydrogen subtraction from HA and H(2)O(2) reduction to water. Photoexcitation of RF may potentially occur in vitro and in vivo in the organs and tissues that are permeable to light, such as the eye or skin, and damage HA and other cell-matrix components causing inflammation and accelerating aging. PMID:9098086

  16. The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

    PubMed Central

    2011-01-01

    Background The primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts. Methods Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay). Results ABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain. Conclusions Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis

  17. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    SciTech Connect

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-07-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy.

  18. Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells

    PubMed Central

    ZHANG, HAIYANG; ZHONG, XIA; ZHANG, XIAO; SHANG, DEYA; ZHOU, YI; ZHANG, CHUNQING

    2016-01-01

    Gastric cancer is the second leading cause of cancer-associated mortality and is a frequently occurring cancer worldwide. Multiple drug resistance of gastric cancer cells leads to the poor prognosis. In addition, overexpression of anti-apoptotic protein B-cell lymphoma (Bcl)-2 have been demonstrated in various cancer cells and is closely associated with drug resistance and poor prognosis. Naringenin is a flavonoid that has antimutagenic and anticarcinogenic activities in numerous cancer types. In the present study, naringenin and a Bcl-2 inhibitor, ABT-737, were used to investigate their combinative anticancer effect in the SGC7901 gastric cancer cell line. The results revealed that naringenin and ABT-737 were able to inhibit SGC7901 cell growth and colony formation, alone or in combination. Furthermore, the combination of these drugs was found to further increase the cleavage of caspase-3 and poly ADP-ribose polymerase. Naringenin and ABT-737 also decreased Akt activation and increased p53 expression, suggesting the involvement of these pathways in the inhibition of gastric cell growth. PMID:26893664

  19. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.

    PubMed

    Chang, Jianhui; Wang, Yingying; Shao, Lijian; Laberge, Remi-Martin; Demaria, Marco; Campisi, Judith; Janakiraman, Krishnamurthy; Sharpless, Norman E; Ding, Sheng; Feng, Wei; Luo, Yi; Wang, Xiaoyan; Aykin-Burns, Nukhet; Krager, Kimberly; Ponnappan, Usha; Hauer-Jensen, Martin; Meng, Aimin; Zhou, Daohong

    2016-01-01

    Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI). Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a 'senolytic' pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type- and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents. PMID:26657143

  20. Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A.

    PubMed

    DeGoey, David A; Randolph, John T; Liu, Dachun; Pratt, John; Hutchins, Charles; Donner, Pamela; Krueger, A Chris; Matulenko, Mark; Patel, Sachin; Motter, Christopher E; Nelson, Lissa; Keddy, Ryan; Tufano, Michael; Caspi, Daniel D; Krishnan, Preethi; Mistry, Neeta; Koev, Gennadiy; Reisch, Thomas J; Mondal, Rubina; Pilot-Matias, Tami; Gao, Yi; Beno, David W A; Maring, Clarence J; Molla, Akhter; Dumas, Emily; Campbell, Andrew; Williams, Laura; Collins, Christine; Wagner, Rolf; Kati, Warren M

    2014-03-13

    We describe here N-phenylpyrrolidine-based inhibitors of HCV NS5A with excellent potency, metabolic stability, and pharmacokinetics. Compounds with 2S,5S stereochemistry at the pyrrolidine ring provided improved genotype 1 (GT1) potency compared to the 2R,5R analogues. Furthermore, the attachment of substituents at the 4-position of the central N-phenyl group resulted in compounds with improved potency. Substitution with tert-butyl, as in compound 38 (ABT-267), provided compounds with low-picomolar EC50 values and superior pharmacokinetics. It was discovered that compound 38 was a pan-genotypic HCV inhibitor, with an EC50 range of 1.7-19.3 pM against GT1a, -1b, -2a, -2b, -3a, -4a, and -5a and 366 pM against GT6a. Compound 38 decreased HCV RNA up to 3.10 log10 IU/mL during 3-day monotherapy in treatment-naive HCV GT1-infected subjects and is currently in phase 3 clinical trials in combination with an NS3 protease inhibitor with ritonavir (r) (ABT-450/r) and an NS5B non-nucleoside polymerase inhibitor (ABT-333), with and without ribavirin. PMID:24400777

  1. A phase I study of ABT-510 plus bevacizumab in advanced solid tumors

    PubMed Central

    Uronis, Hope E; Cushman, Stephanie M; Bendell, Johanna C; Blobe, Gerard C; Morse, Michael A; Nixon, Andrew B; Dellinger, Andrew; Starr, Mark D; Li, Haiyan; Meadows, Kellen; Gockerman, Jon; Pang, Herbert; Hurwitz, Herbert I

    2013-01-01

    Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Thirty-four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment-related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D-dimer, von Willebrand factor, placental growth factor, and stromal-derived factor 1 in response to treatment with the combination of bevacizumab and ABT-510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful. PMID:23930208

  2. A comparative study of the effects of ABT-418 and methylphenidate on spatial memory in an animal model of ADHD.

    PubMed

    Guo, Tianyou; Yang, Chuang; Guo, Lanting; Liu, Kezhi

    2012-10-18

    Impaired learning performance in scholastic settings is a characteristic of attention deficit hyperactivity disorder (ADHD). Our present study compares the effect of a nicotinic acetylcholine receptor (nAChR) agonist, ABT-418, and methylphenidate (MPH) on spatial memory in spontaneously hypertensive rats (SHRs), an animal model of ADHD. Neither chronic administration of ABT-418 nor MPH affected the learning performance during training in the Morris water maze. However, both compounds significantly improved memory. SHRs treated with a combination of the compounds did not perform better than either drug alone. Furthermore, the cortical α4 and β2 nAChR subunits and the hippocampal α4 subunit expression were significantly enhanced by ABT-418 treatments. Collectively, these results suggest that ABT-418 effectively improved spatial memory in an animal model of ADHD, providing a theoretical foundation for the use of a nAChR agonist in ADHD treatment. PMID:22985505

  3. Radical scavenging and cytochrome P450 3A4 inhibitory activity of bergaptol and geranylcoumarin from grapefruit.

    PubMed

    Girennavar, Basavaraj; Jayaprakasha, G K; Jadegoud, Y; Nagana Gowda, G A; Patil, Bhimanagouda S

    2007-06-01

    Grapefruit juice has been shown to increase the oral bioavailability of several clinically important drugs by inhibiting first pass metabolism. Several compounds in grapefruit juice have shown different biological activities. Unique among them are furocoumarins with potent inhibitory activity against cytochrome P450 enzymes. In the present study, two bioactive compounds were isolated from grapefruit juice and grapefruit peel oil. The purity of the isolated compounds has been analyzed by HPLC. Structures of the compounds were elucidated by extensive NMR and mass spectral studies and identified as bergaptol and geranylcoumarin. The isolated compounds were tested for their radical scavenging activity using 2,2'-azobis (3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazil (DPPH) methods at different concentrations. Bergaptol showed very good radical scavenging activity at all the tested concentrations. Furthermore, these compounds were evaluated for their inhibitory activity against CYP3A4 enzyme. Bergaptol and geranylcoumarin were found to be potent inhibitors of debenzylation activity of CYP3A4 enzyme with an IC(50) value of 24.92 and 42.93 microM, respectively. PMID:17400460

  4. Antioxidant activity and free radical scavenging capacity of phenolic extracts from Helicteres isora L. and Ceiba pentandra L.

    PubMed

    Loganayaki, Nataraj; Siddhuraju, Perumal; Manian, Sellamuthu

    2013-08-01

    In the present study, antioxidant activities of the phenolic extracts from H. isora fruits and C. pentandra seeds were investigated by employing established in vitro systems, which included reducing power, OH(●), DPPH(●), ABTS(●+), linoleic acid emulsion, metal chelation and antihemolytic activity. The extracts of C. pentandra contained relatively higher levels of total phenolics and flavonoids than those of H. isora. All the extracts showed dose dependent reducing power activity and moreover, they were well correlated with the total phenolic substances. A similar dose dependant trend has also been observed for hydroxyl radical scavenging activity and DPPH(●) radical scavenging activity. Further, addition of 250 μg of extracts to the reaction mixture produced 41.3-54.6% peroxidation inhibiting activity during 60 h of incubation. The potential of multiple antioxidant activity of samples can be further evidenced by inhibition of reactive oxygen mediated erythrocyte cell lysis and metal ion chelating activity. PMID:24425970

  5. Stability studies of ascorbic acid 2-glucoside in cosmetic lotion using surface response methodology.

    PubMed

    Huang, Wen-Ying; Lee, Pei-Chi; Huang, Ling-Kuei; Lu, Li-Ping; Liao, Wayne C

    2013-03-15

    Ascorbic acid 2-glucoside (AA-2G) has been widely used in cream and lotion types of cosmetic products. Thus, the degradation of AA-2G caused by the temperature change and pH variation was very critical for determining the bio-functionality of cosmetics. Response surface methodology (RSM) was introduced to study the influence of temperature and pH on the stability of AA-2G. The optimal condition of retaining AA-2G with the highest stability was determined to be 55.3°C and pH 6.4. The antioxidative activities of AA-2G including DPPH and ABTS free radical scavenging activities, metal chelating activity, and reducing ability were also determined. AA-2G was a good ascorbic acid derivative which could be used in cosmetic products as an active ingredient. PMID:23416010

  6. Development of 2-(Substituted Benzylamino)-4-Methyl-1, 3-Thiazole-5-Carboxylic Acid Derivatives as Xanthine Oxidase Inhibitors and Free Radical Scavengers.

    PubMed

    Ali, Md Rahmat; Kumar, Suresh; Afzal, Obaid; Shalmali, Nishtha; Sharma, Manju; Bawa, Sandhya

    2016-04-01

    A series of 2-(substituted benzylamino)-4-methylthiazole-5-carboxylic acid was designed and synthesized as structural analogue of febuxostat. A methylene amine spacer was incorporated between the phenyl ring and thiazole ring in contrast to febuxostat in which the phenyl ring was directly linked with the thiazole moiety. The purpose of incorporating methylene amine was to provide a heteroatom which is expected to favour hydrogen bonding within the active site residues of the enzyme xanthine oxidase. The structure of all the compounds was established by the combined use of FT-IR, NMR and MS spectral data. All the compounds were screened in vitro for their ability to inhibit the enzyme xanthine oxidase as per the reported procedure along with DPPH free radical scavenging assay. Compounds 5j, 5k and 5l demonstrated satisfactory potent xanthine oxidase inhibitory activities with IC50 values, 3.6, 8.1 and 9.9 μm, respectively, whereas compounds 5k, 5n and 5p demonstrated moderate antioxidant activities having IC50 15.3, 17.6 and 19.6 μm, respectively, along with xanthine oxidase inhibitory activity. Compound 5k showed moderate xanthine oxidase inhibitory activity as compared with febuxostat along with antioxidant activity. All the compounds were also studied for their binding affinity in active site of enzyme (PDB ID-1N5X). PMID:26575582

  7. Synthesis and Characterization of Surface Grafted Poly(N-isopropylacrylamide) and Poly(Carboxylic Acid)– Iron Particles via Atom Transfer Radical Polymerization for Biomedical Applications

    PubMed Central

    Sutrisno, Joko; Fuchs, Alan; Evrensel, Cahit

    2014-01-01

    This research relates to the preparation and characterization of surface grafted poly(N-isopropylacrylamide) and poly(carboxylic acid)–micron-size iron particles via atom transfer radical polymerization (ATRP). The surface grafted polymers–iron particles result in multifunctional materials which can be used in biomedical applications. The functionalities consist of cell targeting, imaging, drug delivery, and immunological response. The multifunctional materials are synthesized in two steps. First, surface grafting is used to place polymer molecules on the iron particles surface. The second step, is conjugation of the bio-molecules onto the polymer backbone. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy were used to confirm the presence of polymers on the iron particles. The thickness of the grafted polymers and glass transition temperature of the surface grafted polymers were determined by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The covalent bond between grafted polymers and iron particles caused higher glass transition temperature as compared with non-grafted polymers. The ability to target the bio-molecule and provide fluorescent imaging was simulated by conjugation of rat immunoglobulin and fluorescein isothiocyanate (FITC) labeled anti-rat. The fluorescence intensity was determined using flow cytometry and conjugated IgG-FITC anti-rat on iron particles which was imaged using a fluorescence microscopy. PMID:25382869

  8. Grafting of Poly(methyl methacrylate) Brushes from Magnetite Nanoparticles Using a Phosphonic Acid Based Initiator by Ambient Temperature Atom Transfer Radical Polymerization (ATATRP)

    PubMed Central

    2008-01-01

    Poly(methyl methacrylate) in the brush form is grown from the surface of magnetite nanoparticles by ambient temperature atom transfer radical polymerization (ATATRP) using a phosphonic acid based initiator. The surface initiator was prepared by the reaction of ethylene glycol with 2-bromoisobutyrl bromide, followed by the reaction with phosphorus oxychloride and hydrolysis. This initiator is anchored to magnetite nanoparticles via physisorption. The ATATRP of methyl methacrylate was carried out in the presence of CuBr/PMDETA complex, without a sacrificial initiator, and the grafting density is found to be as high as 0.90 molecules/nm2. The organic–inorganic hybrid material thus prepared shows exceptional stability in organic solvents unlike unfunctionalized magnetite nanoparticles which tend to flocculate. The polymer brushes of various number average molecular weights were prepared and the molecular weight was determined using size exclusion chromatography, after degrafting the polymer from the magnetite core. Thermogravimetric analysis, X-ray photoelectron spectra and diffused reflection FT-IR were used to confirm the grafting reaction.

  9. pH-responsive controlled-release fertilizer with water retention via atom transfer radical polymerization of acrylic acid on mussel-inspired initiator.

    PubMed

    Ma, Zhi-yuan; Jia, Xin; Zhang, Guo-xiang; Hu, Jia-mei; Zhang, Xiu-lan; Liu, Zhi-yong; Wang, He-yun; Zhou, Feng

    2013-06-12

    This work reports a polydopamine-graft-poly(acrylic acid) (Pdop-g-PAA)-coated controlled-release multi-element compound fertilizer with water-retention function by a combination of mussel-inspired chemistry and surface-initiated atom transfer radical polymerization (SI-ATRP) techniques for the first time. The morphology and composition of the products were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), gel permeation chromatography (GPC), and inductively coupled plasma (ICP) emission spectrometry. The results revealed that the stimuli-responsive layer formed by a Pdop inner layer and a PAA outer corona exhibit outstanding selective permeability to charged nutrients and the release rate of encapsulated elements can be tailored by the pH values. At low pH, the Pdop-g-PAA layer can reduce nutrient loss, and at high pH, the coating restrains transportation of negative nutrients but favors the release of cations. Moreover, PAA brushes provide good water-retention property. This Pdop-graft-polymer brushes coating will be effective and promising in the research and development of multi-functional controlled-release fertilizer. PMID:23692274

  10. Correlation of polyphenolic content with radical-scavenging capacity and anthelmintic effects of Rubus ulmifolius (Rosaceae) against Haemonchus contortus.

    PubMed

    Akkari, Hafidh; Hajaji, Soumaya; B'chir, Fatma; Rekik, Mourad; Gharbi, Mohamed

    2016-05-15

    Phenolic content, antioxidant and anthelmintic activities of herbal extracts are of particular interest to drug industry; plant extracts with significant anthelmintic activity have the potential to be used as alternatives to conventional chemical drugs. In the present study, Rubus ulmifolius fruit extracts obtained using solvents of increasing polarity (water, methanol, chloroform and hexane) were examined for their antioxidant and anthelmintic activities in correlation with their polyphenolic content. In vitro antioxidant activity of all extracts was carried out using free radical-scavenging activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethilenebenzotiazolin)-6-sulfonic acid (ABTS) radical cation. In vitro anthelmintic activities were investigated on the egg and adult worms of Haemonchus contortus from sheep in comparison to albendazole. Total polyphenol content of R. ulmifolius was higher in more polar extract, ranging from 64.5 in aqueous extract to 1.57mg gallic acid equivalents per gram of dry weight (GAE/g DW) in hexanic extract. Likewise, highest amounts of flavonoids and condensed tannins were found in aqueous extract (28.06mg QE/g and 7.42mg CE/g DW, respectively) compared to hexanic extract (0.71mg QE/g and 0.29mg CE/g DW, respectively) (p<0.05). Both DPPH and ABTS antioxidant assays showed that all tested extracts possess free radical scavenging activity, while the inhibitory concentration 50% (IC50) range values were similar for both assays (2.13-45.54μg/mL and 1.2-43.82μg/mL, respectively). All plant extracts showed ovicidal activity at all tested concentrations. Fruit methanolic (IC50=2.76mg/mL) and aqueous (IC50=2.08mg/mL) extracts showed higher inhibitory effects than chloroformic (IC50=7.62mg/mL) and hexanic (IC50=12.93mg/mL) extracts on egg hatching (p<0.05). There was a significant correlation of total polyphenol, flavonoids and tannins content with scavenging of either DPPH (r=0.722, 0.764 and 0.752, p<0

  11. ABT-724 alleviated hyperactivity and spatial learning impairment in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

    PubMed

    Yin, Ping; Cao, Ai-Hua; Yu, Lin; Guo, Liang-Jing; Sun, Ruo-Peng; Lei, Ge-Fei

    2014-09-19

    Dysfunction of dopamine D4 receptor (D4R) is linked to attention-deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive impairment. Here, we tested the possible therapeutic benefit of the D4R-selective agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724-treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were injected with saline. Then two cohorts of rats were tested in the open field and Làt maze that measured locomotion and non-selective attention (NSA), respectively. Another cohort of rats was subjected to water maze task for evaluation of spatial learning and memory. We found that control SHRs displayed hyperactivity as well as impaired NSA and spatial learning compared with normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used as a therapeutic intervention for ADHD patients during adolescence. PMID:25128216

  12. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia.

    PubMed

    Peirs, Sofie; Matthijssens, Filip; Goossens, Steven; Van de Walle, Inge; Ruggero, Katia; de Bock, Charles E; Degryse, Sandrine; Canté-Barrett, Kirsten; Briot, Delphine; Clappier, Emmanuelle; Lammens, Tim; De Moerloose, Barbara; Benoit, Yves; Poppe, Bruce; Meijerink, Jules P; Cools, Jan; Soulier, Jean; Rabbitts, Terence H; Taghon, Tom; Speleman, Frank; Van Vlierberghe, Pieter

    2014-12-11

    T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype of acute lymphoblastic leukemia (ALL) with gradually improved survival through introduction of intensified chemotherapy. However, therapy-resistant or refractory T-ALL remains a major clinical challenge. Here, we evaluated B-cell lymphoma (BCL)-2 inhibition by the BH3 mimetic ABT-199 as a new therapeutic strategy in human T-ALL. The T-ALL cell line LOUCY, which shows a transcriptional program related to immature T-ALL, exhibited high in vitro and in vivo sensitivity for ABT-199 in correspondence with high levels of BCL-2. In addition, ABT-199 showed synergistic therapeutic effects with different chemotherapeutic agents including doxorubicin, l-asparaginase, and dexamethasone. Furthermore, in vitro analysis of primary patient samples indicated that some immature, TLX3- or HOXA-positive primary T-ALLs are highly sensitive to BCL-2 inhibition, whereas TAL1 driven tumors mostly showed poor ABT-199 responses. Because BCL-2 shows high expression in early T-cell precursors and gradually decreases during normal T-cell differentiation, differences in ABT-199 sensitivity could partially be mediated by distinct stages of differentiation arrest between different molecular genetic subtypes of human T-ALL. In conclusion, our study highlights BCL-2 as an attractive molecular target in specific subtypes of human T-ALL that could be exploited by ABT-199. PMID:25301704

  13. Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo.

    PubMed

    Shen, Jie; Xu, Liang; Zhao, Qiong

    2016-05-13

    Here we explored the potential synergism between the novel Bcl-2 antagonist ABT-737 and the AKT inhibitor perifosine in lung cancer cells. Our in vitro results showed that perifosine and ABT-737 synergistically induced growth inhibition and apoptosis in both established (A549 and H460 lines) and patient-derived lung cancer cells. The combined activity was dramatically more potent than either single agent. For the molecular study, we showed that perifosine downregulated Mcl-1 expression, thus potentiating ABT-737 lethality against lung cancer cells. Exogenous over-expression of Mcl-1 remarkably attenuated perifosine plus ABT-737 combo-induced lung cancer cell apoptosis. In vivo, perifosine and ABT-737 co-administration strikingly inhibited A549 lung cancer xenograft growth in nude mice. The combined treatment in vivo was again superior than single treatment establishing a synergistic activity. Mcl-1 expression was also downregulated in combo-treated A549 tumors. The results of this preclinical study support the feasibility of further investigation of the perifosine plus ABT-737 regimen in future lung cancer clinical tests. PMID:27073162

  14. The ratio of Mcl-1 and Noxa determines ABT737 resistance in squamous cell carcinoma of the skin

    PubMed Central

    Geserick, P; Wang, J; Feoktistova, M; Leverkus, M

    2014-01-01

    Tumour progression and therapy resistance in squamous cell carcinoma of the skin (SCC) is strongly associated with resistance to intrinsic mitochondrial apoptosis. We thus investigated the role of various anti-apoptotic Bcl-2 proteins for apoptosis protection in SCC using the BH3 agonist ABT737 that can overcome multidomain Bcl-2 protein protection. Sensitive SCC cells underwent rapid loss of mitochondrial membrane potential (MMP), subsequent apoptosis concomitant with caspase-3 activation and an early release of mitochondria-derived cytochrome c and smac/DIABLO. In contrast, ABT737 resistance in subsets of SCC cells was not explained by XIAP, important for protection from DR-induced apoptosis in SCC. Of note, ABT737 did not prime SCC cells to DR-induced apoptosis. Interestingly, the ratio of Mcl-1 and Noxa determined sensitivity to ABT737: loss of Mcl-1 rendered resistant cells sensitive to ABT737, whereas loss of Noxa promoted resistance in sensitive cells. In line, suppression of Mcl-1 by the pan-Bcl-2 inhibitor Obatoclax or overexpression of Noxa rendered resistant SCC cells sensitive to BH3 mimetics. Our data indicate that targeting of the Mcl-1/Noxa axis is important to overcome resistance to mitochondrial apoptosis in SCC. Therefore, combination treatment of ABT737 or derivatives with Mcl-1 inhibitors, or inducers of Noxa, may represent a novel option of targeted therapy in metastatic SCC of the skin. PMID:25210795

  15. Oxidation of Gas-Phase SO2 on the Surfaces of Acidic Microdroplets: Implications for Sulfate and Sulfate Radical Anion Formation in the Atmospheric Liquid Phase.

    PubMed

    Hung, Hui-Ming; Hoffmann, Michael R

    2015-12-01

    The oxidation of SO2(g) on the interfacial layers of microdroplet surfaces was investigated using a spray-chamber reactor coupled to an electrospray ionization mass spectrometer. Four major ions, HSO3(-), SO3(•-), SO4(•-) and HSO4(-), were observed as the SO2(g)/N2(g) gas-mixture was passed through a suspended microdroplet flow, where the residence time in the dynamic reaction zone was limited to a few hundred microseconds. The relatively high signal intensities of SO3(•-), SO4(•-), and HSO4(-) compared to those of HSO3(-) as observed at pH < 3 without addition of oxidants other than oxygen suggests an efficient oxidation pathway via sulfite and sulfate radical anions on droplets possibly via the direct interfacial electron transfer from HSO3(-) to O2. The concentrations of HSO3(-) in the aqueous aerosol as a function of pH were controlled by the deprotonation of hydrated sulfur dioxide, SO2·H2O, which is also affected by the pH dependent uptake coefficient. When H2O2(g) was introduced into the spray chamber simultaneously with SO2(g), HSO3(-) is rapidly oxidized to form bisulfate in the pH range of 3 to 5. Conversion to sulfate was less at pH < 3 due to relatively low HSO3(-) concentration caused by the fast interfacial reactions. The rapid oxidation of SO2(g) on the acidic microdroplets was estimated as 1.5 × 10(6) [S(IV)] (M s(-1)) at pH ≤ 3. In the presence of acidic aerosols, this oxidation rate is approximately 2 orders of magnitude higher than the rate of oxidation with H2O2(g) at a typical atmospheric H2O2(g) concentration of 1 ppb. This finding highlights the relative importance of the acidic surfaces for SO2 oxidation in the atmosphere. Surface chemical reactions on aquated aerosol surfaces, as observed in this study, are overlooked in most atmospheric chemistry models. These reaction pathways may contribute to the rapid production of sulfate aerosols that is often observed in regions impacted by acidic haze aerosol such as Beijing and other

  16. Roaming Radicals

    NASA Astrophysics Data System (ADS)

    Bowman, Joel M.; Shepler, Benjamin C.

    2011-05-01

    Roaming is a recently verified unusual pathway to molecular products from unimolecular dissociation of an energized molecule. Here we present the evidence for this pathway for H2CO and CH3CHO. Theoretical analysis shows that this path visits the plateau region of the potential energy surface near dissociation to radical products. It is not clear whether roaming is a distinct isolated pathway, in addition to the conventional one via the well-known molecular saddle-point transition state. Evidence is presented to suggest that the two pathways may originate from a single, but highly complicated, dividing surface. Other examples of unusual reaction dynamics are also reviewed.

  17. Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression.

    PubMed

    Woo, S M; Min, K-J; Seo, B R; Nam, J-O; Choi, K S; Yoo, Y H; Kwon, T K

    2014-01-01

    Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one of the major compounds in coffee beans, has been reported to have anti-carcinogenic activity and tumor cell growth-inhibitory activity, and we examined whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in normal human skin fibroblast. Furthermore, combined treatment with cafestol and ABT-737 markedly reduced tumor growth compared with either drug alone in xenograft models. We found that cafestol inhibited Mcl-1 protein expression, which is important for ABT-737 resistance, through promotion of protein degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT-737. Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression. PMID:25375379

  18. Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751

    PubMed Central

    Innocenti, Federico; Ramírez, Jacqueline; Obel, Jennifer; Xiong, Julia; Mirkov, Snezana; Chiu, Yi-Lin; Katz, David A.; Carr, Robert A.; Zhang, Wei; Das, Soma; Adjei, Araba; Moyer, Ann M.; Chen, Pei Xian; Krivoshik, Andrew; Medina, Diane; Gordon, Gary B.; Ratain, Mark J.; Sahelijo, Leonardo; Weinshilboum, Richard M.; Fleming, Gini F.; Bhathena, Anahita

    2013-01-01

    Objective ABT-751, a novel orally available antitubulin agent, is mainly eliminated as inactive glucuronide (ABT-751G) and sulfate (ABT-751S) conjugates. We performed a pharmacogenetic investigation of ABT-751 pharmacokinetics using in-vitro data to guide the selection of genes for genotyping in a phase I trial of ABT-751. Methods UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes were screened for ABT-751 metabolite formation in vitro. Forty-seven cancer patients treated with ABT-751 were genotyped for 21 variants in these genes. Results UGT1A1, UGT1A4, UGT1A8, UGT2B7, and SULT1A1 were found to be involved in the formation of inactive ABT-751 glucuronide (ABT-751G) and sulfate (ABT-751S). SULT1A1 copy number (> 2) was associated with an average 34% increase in ABT-751 clearance (P= 0.044), an 18% reduction in ABT-751 AUC (P = 0.045), and a 50% increase in sulfation metabolic ratios (P=0.025). UGT1A8 rs6431558 was associated with a 28% increase in glucuronidation metabolic ratios (P =0.022), and UGT1A4*2 was associated with a 65% decrease in ABT-751 Ctrough (P = 0.009). Conclusion These results might represent the first example of a clinical pharmacokinetic effect of the SULT1A1 copy number variant on the clearance of a SULT1A1 substrate. A-priori selection of candidate genes guided by in-vitro metabolic screening enhanced our ability to identify genetic determinants of interpatient pharmacokinetic variability. PMID:23670235

  19. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized.

    PubMed

    van Delft, Mark F; Wei, Andrew H; Mason, Kylie D; Vandenberg, Cassandra J; Chen, Lin; Czabotar, Peter E; Willis, Simon N; Scott, Clare L; Day, Catherine L; Cory, Suzanne; Adams, Jerry M; Roberts, Andrew W; Huang, David C S

    2006-11-01

    Since apoptosis is impaired in malignant cells overexpressing prosurvival Bcl-2 proteins, drugs mimicking their natural antagonists, BH3-only proteins, might overcome chemoresistance. Of seven putative BH3 mimetics tested, only ABT-737 triggered Bax/Bak-mediated apoptosis. Despite its high affinity for Bcl-2, Bcl-x(L), and Bcl-w, many cell types proved refractory to ABT-737. We show that this resistance reflects ABT-737's inability to target another prosurvival relative, Mcl-1. Downregulation of Mcl-1 by several strategies conferred sensitivity to ABT-737. Furthermore, enforced Mcl-1 expression in a mouse lymphoma model conferred resistance. In contrast, cells overexpressing Bcl-2 remained highly sensitive to ABT-737. Hence, ABT-737 should prove efficacious in tumors with low Mcl-1 levels, or when combined with agents that inactivate Mcl-1, even to treat those tumors that overexpress Bcl-2. PMID:17097561

  20. A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats.

    PubMed

    Jarvis, Michael F; Scott, Victoria E; McGaraughty, Steve; Chu, Katharine L; Xu, Jun; Niforatos, Wende; Milicic, Ivan; Joshi, Shailen; Zhang, Qingwei; Xia, Zhiren

    2014-06-15

    Activation of T-type Ca²⁺ channels contributes to nociceptive signaling by facilitating action potential bursting and modulation of membrane potentials during periods of neuronal hyperexcitability. The role of T-type Ca²⁺ channels in chronic pain is supported by gene knockdown studies showing that decreased Ca(v)3.2 channel expression results in the loss of low voltage-activated (LVA) currents in dorsal root ganglion (DRG) neurons and attenuation of neuropathic pain in the chronic constriction injury (CCI) model. ABT-639 is a novel, peripherally acting, selective T-type Ca²⁺ channel blocker. ABT-639 blocks recombinant human T-type (Ca(v)3.2) Ca²⁺ channels in a voltage-dependent fashion (IC₅₀ = 2 μM) and attenuates LVA currents in rat DRG neurons (IC₅₀ = 8 μM). ABT-639 was significantly less active at other Ca²⁺ channels (e.g. Ca(v)1.2 and Ca(v)2.2) (IC₅₀ > 30 μM). ABT-639 has high oral bioavailability (%F = 73), low protein binding (88.9%) and a low brain:plasma ratio (0.05:1) in rodents. Following oral administration ABT-639 produced dose-dependent antinociception in a rat model of knee joint pain (ED₅₀ = 2 mg/kg, p.o.). ABT-639 (10-100 mg/kg, p.o.) also increased tactile allodynia thresholds in multiple models of neuropathic pain (e.g. spinal nerve ligation, CCI, and vincristine-induced). [corrected]. ABT-639 did not attenuate hyperalgesia in inflammatory pain models induced by complete Freund's adjuvant or carrageenan. At higher doses (e.g. 100-300 mg/kg) ABT-639 did not significantly alter hemodynamic or psychomotor function. The antinociceptive profile of ABT-639 provides novel insights into the role of peripheral T-type (Ca(v)3.2) channels in chronic pain states. PMID:24726441

  1. Protective effect of Pterostilbene against free radical mediated oxidative damage

    PubMed Central

    2013-01-01

    Background Pterostilbene, a methoxylated analog of Resveratrol, is gradually gaining more importance as a therapeutic drug owing to its higher lipophilicity, bioavailability and biological activity than Resveratrol. This study was undertaken to characterize its ability to scavenge free radicals such as superoxide, hydroxyl and hydrogen peroxide and to protect bio-molecules within a cell against oxidative insult. Methods Anti-oxidant activity of Pterostilbene was evaluated extensively by employing several in vitro radical scavenging/inhibiting assays and pulse radiolysis study. In addition, its ability to protect rat liver mitochondria against tertiary-butyl hydroperoxide (TBHP) and hydroxyl radical generated oxidative damage was determined by measuring the damage markers such as protein carbonyls, protein sulphydryls, lipid hydroperoxides, lipid peroxides and 8-hydroxy-2'-deoxyguanosine. Pterostilbene was also evaluated for its ability to inhibit •OH radical induced single strand breaks in pBR322 DNA. Result Pterostilbene exhibited strong anti-oxidant activity against various free radicals such as DPPH, ABTS, hydroxyl, superoxide and hydrogen peroxide in a concentration dependent manner. Pterostilbene conferred protection to proteins, lipids and DNA in isolated mitochondrial fractions against TBHP and hydroxyl radical induced oxidative damage. It also protected pBR322 DNA against oxidative assault. Conclusions Thus, present study provides an evidence for the strong anti-oxidant property of Pterostilbene, methoxylated analog of Resveratrol, thereby potentiating its role as an anti-oxidant. PMID:24070177

  2. Identification of a radical formed in the reaction mixtures of ram seminal vesicle microsomes with arachidonic Acid using high performance liquid chromatography-electron spin resonance spectrometry and high performance liquid chromatography-electron spin resonance-mass spectrometry.

    PubMed

    Minakata, Katsuyuki; Iwahashi, Hideo

    2010-03-01

    The reaction of ram seminal vesicle (RSV) microsomes with arachidonic acid (AA) was examined using electron spin resonance (ESR), high performance liquid chromatography-electron spin resonance spectrometry (HPLC-ESR), and high performance liquid chromatography-electron spin resonance-mass spectrometry (HPLC-ESR-MS) combined use of spin trapping technique. A prominent ESR spectrum (alpha(N) = 1.58 mT and alpha(H)beta = 0.26 mT) was observed in the complete reaction mixture of ram seminal vesicle microsomes with arachidonic acid containing 2.0 mg protein/ml ram seminal vesicle (RSV) microsomal suspension, 0.8 mM arachidonic acid, 0.1 M 4-POBN, and 24 mM tris/HCl buffer (pH 7.4). The ESR spectrum was hardly observed for the complete reaction mixture without the RSV microsomes. The formation of the radical appears to be catalyzed by the microsomal components. In the absence of AA, the intensity of the ESR signal decreased to 16 +/- 15% of the complete reaction mixture, suggesting that the radical is derived from AA. For the complete reaction mixture with boiled microsomes, the intensity of the ESR signal decreased to 49 +/- 4% of the complete reaction mixture. The intensity of the ESR signal of the complete reaction mixture with indomethacin decreased to 74 +/- 20% of the complete reaction mixture, suggesting that cyclooxygenese partly participates in the reaction. A peak was detected on the elution profile of HPLC-ESR analysis of the complete reaction mixture. To determine the structure of the peak, an HPLC-ESR-MS analysis was performed. The HPLC-ESR-MS analysis of the peak showed two prominent ions, m/z 266 and m/z 179, suggesting that the peak is a 4-POBN/pentyl radical adduct. An HPLC-ESR analysis of the authentic 4-POBN/pentyl radical adduct comfirmed the identification. PMID:20216946

  3. MEK Inhibition Enhances ABT-737-Induced Leukemia Cell Apoptosis via Prevention of ERK activated MCL-1 induction and Modulation of MCL-1/BIM Complex

    PubMed Central

    Konopleva, M; Milella, M; Ruvolo, P; Watts, JC; Ricciardi, MR; Korchin, B; Teresa, McQueen; Bornmann, William; Tsao, T; Bergamo, P; Mak, DH; Chen, W; McCubrey, J; Tafuri, A; Andreeff, M

    2013-01-01

    Recently, strategies for AML therapy have been developed that target anti-apoptotic BCL2 family members using BH3 mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-XL, ABT-737 poorly inhibits MCL-1. Here we report that, unexpectedly, ABT-737 induces activation of ERK and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737 –induced MCL-1 expression and when combined with ABT-737 resulted in potent synergistic killing of AML derived cell lines, primary AML blast and CD34+38−123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells. While control and CI-1040 treated mice exhibited progressive leukemia growth, ABT-737 and, to a significantly greater extent, ABT-737 + CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrate unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3 mimetic ABT-737 and MAPK signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces it’s expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML. PMID:22064351

  4. In vitro antioxidant assay of medium chain fatty acid rich rice bran oil in comparison to native rice bran oil.

    PubMed

    Sengupta, Avery; Ghosh, Mahua; Bhattacharyya, D K

    2015-08-01

    The study aimed to evaluate the in vitro antioxidant activity of medium chain fatty acid (MCFA) rich-rice bran oils in comparison with native rice bran oil. Different in vitro methods were used to evaluate the free radical scavenging activity, metal chelation activity, reducing acitivity, ABTS radical scavenging activity, thiobarbituric acid (TBA) value and so on at different concentrations of the oils such as 10-100 μg/mL. Inhibition of lipid peroxidation was evaluated measuring thiobarbituric acid responsive substance (TBARS) and conjugated diene formation. All the oils showed potent antioxidant activity at 100 μg/mL concentration. TBARS formation and conjugated diene formation was lower with MCFA rich oils i.e. the inhibition of lipid peroxidation was more in MCFA rich oils than original rice bran oil. Caprylic acid rich rice bran oil showed maximum antioxidant activity in comparison to capric- and lauric acid rich rice bran oils. Overall the MCFA rich rice bran oils showed to be more potent antioxidant than rice bran oil due to their lower unsaturated fatty acid content. PMID:26243941

  5. Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor.

    PubMed Central

    Markowitz, M; Mo, H; Kempf, D J; Norbeck, D W; Bhat, T N; Erickson, J W; Ho, D D

    1995-01-01

    Inhibitors of the human immunodeficiency virus protease represent a promising new class of antiretroviral drugs for the treatment of AIDS. We now report the in vitro selection of viral variants with decreased sensitivity to a symmetry-based protease inhibitor, ABT-538, currently being tested in clinical trials. Molecular characterization of the variants shows that an isoleucine-to-valine substitution at position 84 results in a substantial decrease in sensitivity to the drug. Moreover, an additional mutation at position 82, valine to phenylalanine, further decreases viral susceptibility to ABT-538. Three-dimensional analysis of the protease-drug complex provides a structural explanation for the relative drug resistance induced by these two mutations. These findings emphasize the importance of closely monitoring patients receiving ABT-538 for the emergence of viral resistance and provide information that may prove useful in designing the next generation of protease inhibitors. PMID:7815532

  6. Interactions between major chlorogenic acid isomers and chemical changes in coffee brew that affect antioxidant activities.

    PubMed

    Liang, Ningjian; Xue, Wei; Kennepohl, Pierre; Kitts, David D

    2016-12-15

    Coffee bean source and roasting conditions significantly (p<0.05) affected the content of chlorogenic acid (CGA) isomers, several indices of browning and subsequent antioxidant values. Principal component analysis was used to interpret the correlations between physiochemical and antioxidant parameters of coffee. CGA isomer content was positively correlated (p<0.001) to capacity of coffee to reduce nitric oxide and scavenge Frémy's salt. Indices of browning in roasted coffee were positively correlated (p<0.001) to ABTS and TEMPO radical scavenging capacity, respectively. Only the CGA content of coffee corresponded to intracellular antioxidant capacity measured in Caco-2 intestinal cells. This study concluded that the intracellular antioxidant capacity that best describes potential health benefits of coffee positively corresponds best with CGA content. PMID:27451179

  7. Antioxidant Activity and α-Glucosidase Inhibitory Activities of the Polycondensate of Catechin with Glyoxylic Acid

    PubMed Central

    Ma, Hanjun; Liu, Benguo

    2016-01-01

    In order to investigate polymeric flavonoids, the polycondensate of catechin with glyoxylic acid (PCG) was prepared and its chemically antioxidant, cellular antioxidant (CAA) and α-glucosidase inhibitory activities were evaluated. The DPPH and ABTS radical scavenging activities and antiproliferative effect of PCG were lower than those of catechin, while PCG had higher CAA activity than catechin. In addition, PCG had very high α-glucosidase inhibitory activities (IC50 value, 2.59 μg/mL) in comparison to catechin (IC50 value, 239.27 μg/mL). Inhibition kinetics suggested that both PCG and catechin demonstrated a mixture of noncompetitive and anticompetitive inhibition. The enhanced CAA and α-glucosidase inhibitor activities of PCG could be due to catechin polymerization enhancing the binding capacity to the cellular membrane and enzymes. PMID:26960205

  8. BCR signaling inhibitors differ in their ability to overcome Mcl-1-mediated resistance of CLL B cells to ABT-199.

    PubMed

    Bojarczuk, Kamil; Sasi, Binu K; Gobessi, Stefania; Innocenti, Idanna; Pozzato, Gabriele; Laurenti, Luca; Efremov, Dimitar G

    2016-06-23

    The Bcl-2 antagonist ABT-199 (venetoclax) has demonstrated promising clinical activity in patients with chronic lymphocytic leukemia (CLL). ABT-199 is strongly cytotoxic against unstimulated peripheral blood CLL cells in vitro but is much less effective against CLL cells that have received survival signals from the microenvironment. In particular, stimulation of CLL cells with CD40L results in substantial resistance mediated by induction of the antiapoptotic Bcl-2 family proteins Bcl-xL and Bfl-1. In this study, we investigated whether resistance to ABT-199 can be conferred by B-cell receptor (BCR) stimulation, which is another important survival signal from the leukemic microenvironment. We show that sustained BCR stimulation results in significant ABT-199 resistance, which correlates with induction of the antiapoptotic protein Mcl-1 and less consistently with downregulation of proapoptotic Bmf, Hrk, and BimEL A major role for Mcl-1 in conferring ABT-199 resistance is additionally supported by knockdown and enforced expression experiments with primary CLL cells. We further show that SYK, BTK, and phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitors significantly downregulate Mcl-1, but with different efficacy. Complete Mcl-1 downregulation was consistently achieved only with SYK inhibitors R406 and GS-9973 (entospletinib), whereas the BTK inhibitor ibrutinib and the PI3Kδ inhibitor idelalisib in more than half of the cases had only a partial effect. The greater ability of SYK inhibitors to downregulate Mcl-1 correlated with their greater capacity to block BCR-mediated inactivation of GSK-3, a major negative regulator of Mcl-1. The finding that BCR signaling inhibitors differ in their ability to target Mcl-1 is relevant for the design of clinical trials combining these agents with ABT-199. PMID:27095788

  9. MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA.

    PubMed

    Wei, Xinghua; Zhou, Ping; Lin, Xuanting; Lin, Yurong; Wu, Sifeng; Diao, Pengfei; Xie, Haiqing; Xie, Keji; Tang, Ping

    2014-10-01

    Patients undergoing androgen blockade therapy develop castration-resistant prostate cancer (CRPC), which is associated with Bcl-2 upregulation and results in disease progression and death. In recent years, promising therapeutic agents, such as the BH3-only mimetic ABT-263 and proteasome inhibitors, have been developed and widely evaluated against a broad spectrum of cancer types, including prostate cancer, alone or in combination with other chemotherapeutic agents. In this study, the antitumor efficacy of ABT-263 and MLN2238 were evaluated as single agents and in combination in four CRPC cell lines: PC3, C4-2B, C4-2, and DU145. The viability of the treated cells and markers of apoptosis were assayed. Protein-protein interactions were analyzed by co-immunoprecipitation in drug-treated cells. Lentivirus-mediated short hairpin RNA was used to knockdown Bax, Mcl-1, and NOXA expressions. We found that ABT-263 and MLN2238 alone exhibited a mild cytotoxicity, and in combination, they elicited a synergistic cytotoxic effect in CRPC cells. The cell apoptosis induced by the combination drug treatment was evidenced by enhanced caspase-3 and Poly (ADP-ribose) polymerase (PARP) cleavage, and annexin-V-positive staining was significantly depleted by Bax knockdown. MLN2238 treatment upregulated NOXA and Mcl-1 expression, leading NOXA/Mcl-1 complexes to disassociate Bak from its complexes with Mcl-1 and enhancing ABT263-triggered Bax activation. NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC. PMID:25027405

  10. Antioxidant activity of olive phenols and other dietary phenols in model gastric conditions: Scavenging of the free radical DPPH and inhibition of the haem-induced peroxidation of linoleic acid.

    PubMed

    Achat, Sabiha; Rakotomanomana, Njara; Madani, Khodir; Dangles, Olivier

    2016-12-15

    The antioxidant activity of dietary phenols in humans (direct reduction of radicals and other highly oxidizing species) could be largely restricted to fighting postprandial oxidative stress in the gastric compartment. Hence, the development of chemical tests simply modelling this situation is pertinent. In this work, the antioxidant properties of the olive phenols hydroxytyrosol and oleuropein are investigated in pH 5-6 micellar solutions through the reduction of the DPPH radical and the inhibition of the metmyoglobin-induced peroxidation of linoleic acid. In the first test, hydroxytyrosol and oleuropein proved as efficient as common polyphenols and their reactivity was only moderately affected by β-cyclodextrin and bovine serum albumin, taken as models of food macromolecules. In the second test, hydroxytyrosol and oleuropein by themselves came up as relatively weak inhibitors, despite their efficiency at reducing hypervalent haem iron. However, hydroxytyrosol was able to act in synergy with the typical chain-breaking antioxidant α-tocopherol. PMID:27451164

  11. Promising antioxidant and anticancer (human breast cancer) oxidovanadium(IV) complex of chlorogenic acid. Synthesis, characterization and spectroscopic examination on the transport mechanism with bovine serum albumin.

    PubMed

    Naso, Luciana G; Valcarcel, María; Roura-Ferrer, Meritxell; Kortazar, Danel; Salado, Clarisa; Lezama, Luis; Rojo, Teofilo; González-Baró, Ana C; Williams, Patricia A M; Ferrer, Evelina G

    2014-06-01

    A new chlorogenate oxidovanadium complex (Na[VO(chlorog)(H2O)3].4H2O) was synthesized by using Schlenk methodology in the course of a reaction at inert atmosphere in which deprotonated chlorogenic acid ligand binds to oxidovanadium(IV) in a reaction experiment controlled via EPR technique and based in a species distribution diagram. The compound was characterized by FTIR, EPR, UV-visible and diffuse reflectance spectroscopies and thermogravimetric, differential thermal and elemental analyses. The ligand and the complex were tested for their antioxidant effects on DPPH (1,1-diphenyl-2-picrylhydrazyl radical), ABTS(+) (radical cation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), O2(-), OH and ROO radicals and their cytotoxic activity on different cancer cell lines (SKBR3, T47D and MDAMB231) and primary human mammary epithelial cells. The complex behaved as good antioxidant agent with strongest inhibitory effects on O2(-), OH and ROO radicals and exhibited selective cytotoxicity against SKBR3 cancer cell line. Albumin interaction experiments denoted high affinity toward the complex and its calculated binding constant was indicative of a strong binding to the protein. Based on this study, it is hypothesized that Na[VO(chlorog)(H2O)3].4H2O would be a promising candidate for further evaluation as an antioxidant and anticancer agent. PMID:24681549

  12. Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.

    PubMed

    Rudek, Michelle A; Dasari, Arvind; Laheru, Daniel; He, Ping; Jin, Runyan; Walker, Rosalind; Taylor, Gretchen E; Jimeno, Antonio; Donehower, Ross C; Hidalgo, Manuel; Messersmith, Wells A; Purcell, W Thomas

    2016-08-01

    ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT-751 daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, and protein binding were explored. Twenty-four patients were treated over 5 dose levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically relevant alterations in ABT-751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer. PMID:26632033

  13. HETEROGENOUS PHOTOREACTION OF FORMALDEHYDE WITH HYDROXYL RADICALS

    EPA Science Inventory

    Atmospheric heterogeneous photoreactions occur between formaldehyde and hydroxyl radicals to produce formic acid. hese photoreactions not only occur in clouds, but also in other tropospheric hydrometeors such as precipitation and dew droplets. xperiments were performed by irradia...

  14. High-molar-mass hyaluronan behavior during testing its radical scavenging capacity in organic and aqueous media: effects of the presence of manganese(II) ions.

    PubMed

    Rapta, Peter; Valachová, Katarína; Gemeiner, Peter; Soltés, Ladislav

    2009-02-01

    This study compares the radical scavenging capacity of high-molar-mass hyaluronan (HA) using standardized methods applying 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and 2,2'-azinobis[3-ethylbenzthiazoline sulfonate] (ABTS) radical cations as oxidants. Additionally, spin-trapping technique combined with electron paramagnetic resonance (EPR) was used to evaluate the ability of HA to scavenge reactive radicals. The thermal decomposition of K2S2O8 in pure H2O or in a H2O/dimethyl sulfoxide (DMSO) mixture at 333 K was used as a source of reactive paramagnetic species. We found that HA does not exhibit radical-scavenging activity when DPPH radicals or ABTS(.+) radical cations are used as oxidant, but that HA is an effective radical scavenger at low concentrations, if the oxidation reactions are initiated by the decomposition of K2S2O8. At higher HA concentrations, a more complex behavior and prooxidant HA action was observed. The influence of Mn(II) ions on the reaction mechanisms of radical generation and termination in the K2S2O8/H2O/DMSO system in the presence of HA was studied in detail. PMID:19235158

  15. Fatty Acid and Essential Oil Compositions of Trifolium angustifolium var. angustifolium with Antioxidant, Anticholinesterase and Antimicrobial Activities

    PubMed Central

    Ertaş, Abdulselam; Boğa, Mehmet; Haşimi, Nesrin; Yılmaz, Mustafa Abdullah

    2015-01-01

    This study represents the first report on the chemical composition and biological activity of Trifolium angustifolium var. angustifolium. The major components of the essential oil were identified as hexatriacontene (23.0%), arachidic acid (15.5%) and α-selinene (10.0%). The main constituents of the fatty acid obtained from the petroleum ether extract were identified as palmitic acid (29.8%), linoleic acid (18.6%) and oleic acid (10.5%). In particular, the water extract exhibited higher activity than α-tocopherol and BHT, which were used as standards in the ABTS cation radical scavenging assay and indicated higher inhibitory effect against acetylcholinesterase enzyme than the reference compound, galanthamine but exhibited weak activity in β-carotene bleaching, DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays. The petroleum ether extract exhibited higher activity than α-tocopherol which was used as standard in the β-carotene bleaching method at concentration 100 μg/mL. The acetone extract exhibited higher activity than α-tocopherol which was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100 μg/mL concentration. The acetone and methanol extracts were active on all microorganisms tested with a small zone diameter indicating weak activity. PMID:25561929

  16. Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model

    PubMed Central

    Yang, Kwang Mo; Russell, James; Lupu, Mihaela E.; Cho, HyungJoon; Li, Xiao-Feng; Koutcher, Jason A.; Ling, C. Clifton

    2010-01-01

    The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone. PMID:19717985

  17. Theoretical chemical kinetic study of the H-atom abstraction reactions from aldehydes and acids by Ḣ atoms and ȮH, HȮ2, and ĊH3 radicals.

    PubMed

    Mendes, Jorge; Zhou, Chong-Wen; Curran, Henry J

    2014-12-26

    We have performed a systematic, theoretical chemical kinetic investigation of H atom abstraction by Ḣ atoms and ȮH, HȮ2, and ĊH3 radicals from aldehydes (methanal, ethanal, propanal, and isobutanal) and acids (methanoic acid, ethanoic acid, propanoic acid, and isobutanoic acid). The geometry optimizations and frequencies of all of the species in the reaction mechanisms of the title reactions were calculated using the MP2 method and the 6-311G(d,p) basis set. The one-dimensional hindered rotor treatment for reactants and transition states and the intrinsic reaction coordinate calculations were also determined at the MP2/6-311G(d,p) level of theory. For the reactions of methanal and methanoic acid with Ḣ atoms and ȮH, HȮ2, and ĊH3 radicals, the calculated relative electronic energies were obtained with the CCSD(T)/cc-pVXZ (where X = D, T, and Q) method and were extrapolated to the complete basis set limit. The electronic energies obtained with the CCSD(T)/cc-pVTZ method were benchmarked against the CCSD(T)/CBS energies and were found to be within 1 kcal mol(-1) of one another. Thus, the energies calculated using the less expensive CCSD(T)/cc-pVTZ method were used in all of the reaction mechanisms and in calculating our high-pressure limit rate constants for the title reactions. Rate constants were calculated using conventional transition state theory with an asymmetric Eckart tunneling correction, as implemented in Variflex. Herein, we report the individual and average rate constants, on a per H atom basis, and total rate constants in the temperature range 500-2000 K. We have compared some of our rate constant results to available experimental and theoretical data, and our results are generally in good agreement. PMID:25387985

  18. Single- and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT-116 (a TRPV1 antagonist) in dogs.

    PubMed

    Niyom, S; Mama, K R; Gustafson, D L; Rezende, M L

    2015-08-01

    Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5 μg·h/mL, T(max) of 3.7 h, and C(max) of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24-h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery in dogs. PMID:25376244

  19. Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry

    PubMed Central

    Clerc, Pascaline; Carey, Gregory B.; Mehrabian, Zara; Wei, Michael; Hwang, Hyehyun; Girnun, Geoffrey D.; Chen, Hegang; Martin, Stuart S.; Polster, Brian M.

    2012-01-01

    Cells that exhibit an absolute dependence on the anti-apoptotic BCL-2 protein for survival are termed “primed for death” and are killed by the BCL-2 antagonist ABT-737. Many cancers exhibit a primed phenotype, including some that are resistant to conventional chemotherapy due to high BCL-2 expression. We show here that 1) stable BCL-2 overexpression alone can induce a primed for death state and 2) that an ABT-737-induced loss of functional cytochrome c from the electron transport chain causes a reduction in maximal respiration that is readily detectable by microplate-based respirometry. Stable BCL-2 overexpression sensitized non-tumorigenic MCF10A mammary epithelial cells to ABT-737-induced caspase-dependent apoptosis. Mitochondria within permeabilized BCL-2 overexpressing cells were selectively vulnerable to ABT-737-induced cytochrome c release compared to those from control-transfected cells, consistent with a primed state. ABT-737 treatment caused a dose-dependent impairment of maximal O2 consumption in MCF10A BCL-2 overexpressing cells but not in control-transfected cells or in immortalized mouse embryonic fibroblasts lacking both BAX and BAK. This impairment was rescued by delivering exogenous cytochrome c to mitochondria via saponin-mediated plasma membrane permeabilization. An ABT-737-induced reduction in maximal O2 consumption was also detectable in SP53, JeKo-1, and WEHI-231 B-cell lymphoma cell lines, with sensitivity correlating with BCL-2:MCL-1 ratio and with susceptibility (SP53 and JeKo-1) or resistance (WEHI-231) to ABT-737-induced apoptosis. Multiplexing respirometry assays to ELISA-based determination of cytochrome c redistribution confirmed that respiratory inhibition was associated with cytochrome c release. In summary, cell-based respiration assays were able to rapidly identify a primed for death state in cells with either artificially overexpressed or high endogenous BCL-2. Rapid detection of a primed for death state in individual cancers

  20. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer.

    PubMed

    Faber, Anthony C; Farago, Anna F; Costa, Carlotta; Dastur, Anahita; Gomez-Caraballo, Maria; Robbins, Rebecca; Wagner, Bethany L; Rideout, William M; Jakubik, Charles T; Ham, Jungoh; Edelman, Elena J; Ebi, Hiromichi; Yeo, Alan T; Hata, Aaron N; Song, Youngchul; Patel, Neha U; March, Ryan J; Tam, Ah Ting; Milano, Randy J; Boisvert, Jessica L; Hicks, Mark A; Elmiligy, Sarah; Malstrom, Scott E; Rivera, Miguel N; Harada, Hisashi; Windle, Brad E; Ramaswamy, Sridhar; Benes, Cyril H; Jacks, Tyler; Engelman, Jeffrey A

    2015-03-17

    BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC. PMID:25737542

  1. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

    PubMed Central

    Faber, Anthony C.; Farago, Anna F.; Costa, Carlotta; Dastur, Anahita; Gomez-Caraballo, Maria; Robbins, Rebecca; Wagner, Bethany L.; Rideout, William M.; Jakubik, Charles T.; Ham, Jungoh; Edelman, Elena J.; Ebi, Hiromichi; Yeo, Alan T.; Hata, Aaron N.; Song, Youngchul; Patel, Neha U.; March, Ryan J.; Tam, Ah Ting; Milano, Randy J.; Boisvert, Jessica L.; Hicks, Mark A.; Elmiligy, Sarah; Malstrom, Scott E.; Rivera, Miguel N.; Harada, Hisashi; Windle, Brad E.; Ramaswamy, Sridhar; Benes, Cyril H.; Jacks, Tyler; Engelman, Jeffrey A.

    2015-01-01

    BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC. PMID:25737542

  2. Proteasomal Degradation of Mcl-1 by Maritoclax Induces Apoptosis and Enhances the Efficacy of ABT-737 in Melanoma Cells

    PubMed Central

    Doi, Kenichiro; Sharma, Arun K.; Wang, Hong-Gang; Amin, Shantu

    2013-01-01

    Background and purpose Metastatic melanoma remains one of the most invasive and highly drug resistant cancers. The over expression of anti-apoptotic protein Mcl-1 has been associated with inferior survival, poor prognosis and chemoresistance of malignant melanoma. A BH3 mimetic, ABT-737, has demonstrated efficacy in several forms of cancers. However, the efficacy of ABT-737 depends on Mcl-1. Because the over expression of Mcl-1 is frequently observed in melanoma, specifically targeting of Mcl-1 may overcome the resistance of ABT-737. In this study, we investigated the effects of Maritoclax, a novel Mcl-1-selective inhibitor, alone and in combination with ABT-737, on the survival of human melanoma cells. Experimental approach For cell viability assessment we performed MTT assay. Apoptosis was determined using western blot and flow cytometric analysis. Key results The treatment of Maritoclax reduced the cell viability of melanoma cells with an IC50 of between 2.2–5.0 µM. Further, treatment of melanoma cells with Maritoclax showed significant decrease in Mcl-1 expression. We found that Maritoclax was able to induce apoptosis in melanoma cells in a caspase-dependent manner. Moreover, Maritoclax induced Mcl-1 degradation via the proteasome system, which was associated with its pro-apoptotic activity. We also found that Maritoclax treatment increased mitochondrial translocation of Bim and Bmf. Importantly, Maritoclax markedly enhanced the efficacy of ABT-737 against melanoma cells in both two- and three-dimensional spheroids. Conclusions and implications Taken together, these results suggest that targeting of Mcl-1 by Maritoclax may represent a new therapeutic strategy for melanoma treatment that warrants further investigation as a single therapy or in combination with other agents such as Bcl-2 inhibitors. PMID:24223823

  3. Melanin and humic acid-like polymer complex from olive mill waste waters. Part I. Isolation and characterization.

    PubMed

    Khemakhem, Maissa; Papadimitriou, Vassiliki; Sotiroudis, Georgios; Zoumpoulakis, Panagiotis; Arbez-Gindre, Cécile; Bouzouita, Nabiha; Sotiroudis, Theodore G

    2016-07-15

    A water soluble humic acid and melanin-like polymer complex (OMWW-ASP) was isolated from olive mill waste waters (OMWW) by ammonium sulfate fractionation to be used as natural additive in food preparations. The dark polymer complex was further characterized by a variety of biochemical, physicochemical and spectroscopic techniques. OMWW-ASP is composed mainly of proteins associated with polyphenols and carbohydrates and the distribution of its relative molecular size was determined between about 5 and 190 kDa. SDS-PAGE shows the presence of a well separated protein band of 21.3 kDa and a low molecular weight peptide. The OMWW-ASP complex exhibits a monotonically increasing UV-Vis absorption spectrum and it contains stable radicals. Antioxidant activity measurements reveal the ability of the OMWW protein fraction to scavenge both the cationic 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)) radical, as well as the stable nitroxide free radical 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL). PMID:26948649

  4. Free radicals, antioxidants, and nutrition.

    PubMed

    Fang, Yun-Zhong; Yang, Sheng; Wu, Guoyao

    2002-10-01

    Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions. PMID:12361782

  5. Hydrogen bond network between amino acid radical intermediates on the proton-coupled electron transfer pathway of E. coli α2 ribonucleotide reductase.

    PubMed

    Nick, Thomas U; Lee, Wankyu; Kossmann, Simone; Neese, Frank; Stubbe, JoAnne; Bennati, Marina

    2015-01-14

    Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides in all organisms. In all Class Ia RNRs, initiation of nucleotide diphosphate (NDP) reduction requires a reversible oxidation over 35 Å by a tyrosyl radical (Y122•, Escherichia coli) in subunit β of a cysteine (C439) in the active site of subunit α. This radical transfer (RT) occurs by a specific pathway involving redox active tyrosines (Y122 ⇆ Y356 in β to Y731 ⇆ Y730 ⇆ C439 in α); each oxidation necessitates loss of a proton coupled to loss of an electron (PCET). To study these steps, 3-aminotyrosine was site-specifically incorporated in place of Y356-β, Y731- and Y730-α, and each protein was incubated with the appropriate second subunit β(α), CDP and effector ATP to trap an amino tyrosyl radical (NH2Y•) in the active α2β2 complex. High-frequency (263 GHz) pulse electron paramagnetic resonance (EPR) of the NH2Y•s reported the gx values with unprecedented resolution and revealed strong electrostatic effects caused by the protein environment. (2)H electron-nuclear double resonance (ENDOR) spectroscopy accompanied by quantum chemical calculations provided spectroscopic evidence for hydrogen bond interactions at the radical sites, i.e., two exchangeable H bonds to NH2Y730•, one to NH2Y731• and none to NH2Y356•. Similar experiments with double mutants α-NH2Y730/C439A and α-NH2Y731/Y730F allowed assignment of the H bonding partner(s) to a pathway residue(s) providing direct evidence for colinear PCET within α. The implications of these observations for the PCET process within α and at the interface are discussed. PMID:25516424

  6. Ferulic acid in combination with PARP inhibitor sensitizes breast cancer cells as chemotherapeutic strategy.

    PubMed

    Choi, Young Eun; Park, Eunmi

    2015-03-13

    Homologous-recombination (HR)-dependent repair defective cells are hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Combinations of defective HR pathway and PARP inhibitors have been an effective chemotherapeutic modality. We previously showed that knockdown of the WD40-repeat containing protein, Uaf1, causes an HR repair defect in mouse embryo fibroblast cells and therefore, increases sensitivity to PARP inhibitor, ABT-888. Similarly, here, we show that ferulic acid reduces HR repair, inhibits RAD 51 foci formation, and accumulates γ-H2AX in breast cancer cells. Moreover, ferulic acid, when combined with ABT-888, renders breast cancer cells become hypersensitive to ABT-888. Our study indicates that ferulic acid in combination with ABT-888 treatment may serve as an effective combination chemotherapeutic agent as a natural bioactive compound. PMID:25677620

  7. Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells

    PubMed Central

    ZHENG, RUINIAN; YOU, ZHIJIAN; JIA, JUN; LIN, SHUNHUAN; HAN, SHUAI; LIU, AIXUE; LONG, HUIDONG; WANG, SENMING

    2016-01-01

    At present, the therapeutic treatment strategies for patients with hepatocellular carcinoma (HCC) remain unsatisfactory, and novel methods are urgently required to treat this disease. Members of the B cell lymphoma (Bcl)-2 family are anti-apoptotic proteins, which are commonly expressed at high levels in certain HCC tissues and positively correlate with the treatment resistance of patients with HCC. ABT-737, an inhibitor of Bcl-2 anti-apoptotic proteins, has been demonstrated to exhibit potent antitumor effects in several types of tumor, including HCC. However, treatment with ABT-737 alone also activates certain pro-survival signaling pathways, which attenuate the antitumor validity of ABT-737. Curcumin, which is obtained from Curcuma longa, is also an antitumor potentiator in multiple types of cancer. In the present study, the synergistic effect of curcumin and ABT-737 on HCC cells was investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT-737 on HepG2 cells, which was partially dependent on the induction of apoptosis, according to western blot analysis and flow cytometric apoptosis analysis. In addition, the sustained activation of the ROS-ASK1-c-Jun N-terminal kinase pathway may be an important mediator of the synergistic effect of curcumin and ABT-737. Collectively, these results indicated that the combination of curcumin and ABT-737 can efficaciously induce the death of HCC cells, and may offer a potential treatment strategy for patients with HCC. PMID:26707143

  8. Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma

    PubMed Central

    Chiron, David; Touzeau, Cyrille; Maïga, Sophie; Moreau, Philippe; Pellat-Deceunynck, Catherine; Le Gouill, Steven; Amiot, Martine

    2015-01-01

    The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL + MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-xL up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors. PMID:25797245

  9. Radical prostatectomy - discharge

    MedlinePlus

    ... prostatectomy - discharge; Laparoscopic radical prostatectomy - discharge; LRP - discharge; Robotic-assisted laparoscopic prostatectomy - discharge ; RALP - discharge; Pelvic lymphadenectomy - ...

  10. Hydroxyl radical detection in vivo

    SciTech Connect

    Chevion, M.; Floyd, R.A.

    1986-05-01

    Hydroxyl radicals have been implicated as the actual species responsible for the deleterious effects of active oxygen in biology. However, in most cases, its presence has only been inferred by circumstantial evidence. Using electrochemical detection coupled to HPLC separation technique the authors can identify and quantitate (at sub-picomole level) the hydroxylated products of 3 aromatic compounds (phenol, salicylate, and 2-deoxy-guanosine) as a direct measure of hydroxyl radical formation. Firstly, the authors showed that mixing ascorbate with copper ions (in the absence of presence of a protein) yields catechols, dihydroxybenzoic acids and 8-OH-deoxy-guanosine (8-OHdG). This approach has been used to study the formation of OH in vivo. Human granulocytes stimulated with TPA showed that 8-OHdG was formed in the cellular DNA at high levels (one 8-OHdG/800 DNA bases). Unstimulated granulocytes contained 8-OHdG below detection level. Formation of 8-OHdG in the TPA-stimulated granulocytes DNA was decreased by the addition of SOD and catalase. Using salicylate as an in vivo scavenger of hydroxyl radicals the authors showed that the level of trapped-dihydroxybenzoic acids is increased approx.8 and approx.3 fold in the lungs and liver of paraquat-poisoned mice, respectively, as compared to normal animals. Similarly, the detected level of dihydroxybenzoic acids in the hearts of adriamycin-treated rats was increased over 100-fold as compared to the hearts of control animals.

  11. A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain.

    PubMed

    Rowbotham, Michael C; Duan, W Rachel; Thomas, James; Nothaft, Wolfram; Backonja, Misha-Miroslav

    2009-12-01

    ABT-594 is a neuronal nicotinic acetylcholine receptor (NNR) agonist that exhibits potent analgesic activity in preclinical models of acute, chronic, and neuropathic pain. The purpose of this phase 2, randomized, multicenter, double-blind, placebo-controlled study was to evaluate the safety and analgesic efficacy of ABT-594 in patients with diabetic peripheral neuropathic pain (DPNP). A total of 266 DPNP patients were randomized 1:1:1:1 to receive placebo, ABT-594 150 microg BID, ABT-594 225 microg BID, or ABT-594 300 microg BID. Patients were titrated to a fixed-dose of ABT-594 over 7 days and remained at this dose for another 6 weeks. Compared to placebo, all three ABT-594 treatment groups showed significantly greater decreases on the average diary-based 0-10 Pain Rating Scale (PRS) score from baseline to final evaluation, the primary efficacy measure (placebo, -1.1; 150 microg BID, -1.9; 225 microg BID, -1.9; 300 microg BID, -2.0). The proportion of patients achieving at least a 50% improvement in the average diary-based PRS was greater in all three ABT-594 treatment groups. However, adverse event (AE) dropout rates were significantly higher in all three ABT-594 treatment groups (28% for 150 microg BID, 46% for 225 microg BID, and 66% for 300 microg BID) than for the placebo group (9%). Consistent with the expected side-effect profile of NNR agonists, the most frequently reported AEs were nausea, dizziness, vomiting, abnormal dreams, and asthenia. This study establishes proof of concept for NNR agonists as a new class of compounds for treating neuropathic pain. PMID:19632048

  12. Sunlight and free radicals

    NASA Astrophysics Data System (ADS)

    Tidwell, Thomas

    2013-08-01

    Thomas Tidwell reflects on the overlooked -- but prescient -- proposal by the British chemists Arthur Downes and Thomas Blunt for photochemical free-radical formation, decades before Moses Gomberg launched the field of radical chemistry by preparing triphenylmethyl, the first stable organic radical.

  13. Prophylactic treatment with the BH3 mimetic ABT-737 impedes Myc-driven lymphomagenesis in mice.

    PubMed

    Kelly, P N; Grabow, S; Delbridge, A R D; Adams, J M; Strasser, A

    2013-01-01

    As many oncogenic changes, such as Myc overexpression, promote apoptosis, the survival of emerging neoplastic clones may often initially depend upon endogenous levels of particular pro-survival members of the Bcl-2 protein family. Pertinently, we recently showed that in lymphoma-prone Eμ-myc transgenic mice, which overexpress Myc in all B-lymphoid cells, endogenous Bcl-x(L) is critical for the survival, as well as the expansion of preneoplastic B-lymphoid cells and the development of malignant disease. This discovery raised the possibility that pharmacological blockade of Bcl-x(L) might impede Myc-driven lymphoma development. Indeed, we report here that treatment of preleukaemic Eμ-myc transgenic mice with the Bcl-2 homology (BH)3 mimetic drug ABT-737, which inhibits Bcl-x(L), as well as Bcl-2 and Bcl-w, augmented apoptosis of preneoplastic B-lymphoid cells, reduced their numbers and greatly prolonged lymphoma-free survival. These findings reveal that BH3 mimetic drugs may provide a prophylactic strategy to prevent the development of certain tumours, particularly those driven by deregulated Myc expression. Moreover, such treatment may help in the management of patients with hereditary cancer syndromes and perhaps also in the prevention of tumour relapses. PMID:22814621

  14. Bcl-2high mantle cell lymphoma cells are sensitized to acadesine with ABT-199

    PubMed Central

    Montraveta, Arnau; Xargay-Torrent, Sílvia; Rosich, Laia; López-Guerra, Mònica; Roldán, Jocabed; Rodríguez, Vanina; Lee-Vergés, Eriong; de Frías, Mercè; Campàs, Clara; Campo, Elias; Roué, Gaël; Colomer, Dolors

    2015-01-01

    Acadesine is a nucleoside analogue with known activity against B-cell malignancies. Herein, we showed that in mantle cell lymphoma (MCL) cells acadesine induced caspase-dependent apoptosis through turning on the mitochondrial apoptotic machinery. At the molecular level, the compound triggered the activation of the AMPK pathway, consequently modulating known downstream targets, such as mTOR and the cell motility-related vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation by acadesine was concomitant with a blockade of CXCL12-induced migration. The inhibition of the mTOR cascade by acadesine, committed MCL cells to enter in apoptosis by a translational downregulation of the antiapoptotic Mcl-1 protein. In contrast, Bcl-2 protein levels were unaffected by acadesine and MCL samples expressing high levels of Bcl-2 tended to have a reduced response to the drug. Targeting Bcl-2 with the selective BH3-mimetic agent ABT-199 sensitized Bcl-2 high MCL cells to acadesine. This effect was validated in vivo, where the combination of both agents displayed a more marked inhibition of tumor outgrowth than each drug alone. These findings support the notions that antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and that the combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. PMID:26110568

  15. Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737.

    PubMed

    Renault, Thibaud T; Teijido, Oscar; Missire, Florent; Ganesan, Yogesh Tengarai; Velours, Gisèle; Arokium, Hubert; Beaumatin, Florian; Llanos, Raul; Athané, Axel; Camougrand, Nadine; Priault, Muriel; Antonsson, Bruno; Dejean, Laurent M; Manon, Stéphen

    2015-07-01

    Bax cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis. Bcl-xL is an important regulator of this event and was recently shown to promote the retrotranslocation of mitochondrial Bax to the cytosol. The present study identifies a new aspect of the regulation of Bax localization by Bcl-xL: in addition to its role in Bax inhibition and retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL expression levels led to an increase of Bax mitochondrial content. This finding was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by retrotranslocation, as we observed that Bcl-xLΔC, which is unable to promote Bax retrotranslocation, was more efficient than the full-length protein in stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT-737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes mitochondria to permeabilization and cytochrome c release. PMID:25862283

  16. Solid state drug-polymer miscibility studies using the model drug ABT-102.

    PubMed

    Jog, Rajan; Gokhale, Rajeev; Burgess, Diane J

    2016-07-25

    Amorphous solid dispersions typically suffer storage stability issues due to: their amorphous nature, high drug loading, uneven drug:stabilizer ratio and plasticization effects as a result of hygroscopic excipients. An extensive solid state miscibility study was conducted to aid in understanding the mechanisms involved in drug/stabilizer interactions. ABT-102 (model drug) and nine different polymers with different molecular weights and viscosities were selected to investigate drug/polymer miscibility. Three different polymer:drug ratios (1:3, 1:1 and 3:1, w/w) were analyzed using: DSC, FTIR and PXRD. Three different techniques were used to prepare the amorphous solid dispersions: serial dilution, solvent evaporation and spray drying. Spray drying was the best method to obtain amorphous solid dispersions. However, under certain conditions amorphous formulations could be obtained using solvent evaporation. Melting point depression was used to calculate interaction parameters and free energy of mixing for the various drug polymer mixtures. The spray dried solid dispersions yielded a negative free energy of mixing which indicated strong drug-polymer miscibility compared to the solvent evaporation and serial dilution method. Soluplus was the best stabilizer compared to PVP and HPMC, which is probably a consequence of strong hydrogen bonding between the two CO moieties of soluplus and the drug NH moieities. PMID:27265312

  17. Competition of charge- versus radical-directed fragmentation of gas-phase protonated cysteine sulfinyl radicals.

    PubMed

    Love, Chasity B; Tan, Lei; Francisco, Joseph S; Xia, Yu

    2013-04-24

    The fragmentation behavior of various cysteine sulfinyl ions (intact, N-acetylated, and O-methylated), new members of the gas-phase amino acid radical ion family, was investigated by low-energy collision-induced dissociation (CID). The dominant fragmentation channel for the protonated cysteine sulfinyl radicals ((SO•)Cys) was the radical-directed Cα-Cβ homolytic cleavage, resulting in the formation of glycyl radical ions and loss of CH2SO. This channel, however, was not observed for protonated N-acetylated cysteine sulfinyl radicals (Ac-(SO•)Cys); instead, charge-directed H2O loss followed immediately by SH loss prevailed. Counterintuitively, the H2O loss did not derive from the carboxyl group but involved the sulfinyl oxygen, a proton, and a Cβ hydrogen atom. Theoretical calculations suggested that N-acetylation significantly increases the barrier (~14 kcal mol(-1)) for the radical-directed fragmentation channel because of its reduced capability to stabilize the thus-formed glycyl radical ions via the captodative effect. N-Acetylation also assists in moving the proton to the sulfinyl site, which reduces the barrier for H2O loss. Our studies demonstrate that for cysteine sulfinyl radical ions, the stability of the product ions (glycyl radical ions) and the location of the charge (proton) can significantly modulate the competition between radical- and charge-directed fragmentation. PMID:23527556

  18. Hydroxyl Radical Dosimetry for High Flux Hydroxyl Radical Protein Footprinting Applications Using a Simple Optical Detection Method.

    PubMed

    Xie, Boer; Sharp, Joshua S

    2015-11-01

    Hydroxyl radical protein footprinting (HRPF) by fast photochemical oxidation of proteins (FPOP) is a powerful benchtop tool used to probe protein structure, interactions, and conformational changes in solution. However, the reproducibility of all HRPF techniques is limited by the ability to deliver a defined concentration of hydroxyl radicals to the protein. This ability is impacted by both the amount of radical generated and the presence of radical scavengers in solution. In order to compare HRPF data from sample to sample, a hydroxyl radical dosimeter is needed that can measure the effective concentration of radical that is delivered to the protein, after accounting for both differences in hydroxyl radical generation and nonanalyte radical consumption. Here, we test three radical dosimeters (Alexa Fluor 488, terepthalic acid, and adenine) for their ability to quantitatively measure the effective radical dose under the high radical concentration conditions of FPOP. Adenine has a quantitative relationship between UV spectrophotometric response, effective hydroxyl radical dose delivered, and peptide and protein oxidation levels over the range of radical concentrations typically encountered in FPOP. The simplicity of an adenine-based dosimeter allows for convenient and flexible incorporation into FPOP applications, and the ability to accurately measure the delivered radical dose will enable reproducible and reliable FPOP across a variety of platforms and applications. PMID:26455423

  19. Characterization of pH-Responsive Hydrogels of Poly(Itaconic acid-g-Ethylene Glycol) Prepared by UV-Initiated Free Radical Polymerization as Biomaterials for Oral Delivery of Bioactive Agents

    PubMed Central

    Betancourt, Tania; Pardo, Juan; Soo, Ken; Peppas, Nicholas A.

    2009-01-01

    Effective oral delivery of proteins is impeded by steep pH gradients and proteolytic enzymes in the gastrointestinal tract, as well as low absorption of the proteins into the bloodstream due to their size, charge or solubility. In the present work, pH-responsive complexation hydrogels of poly(itaconic acid) with poly(ethylene glycol) grafts were synthesized for applications in oral drug delivery. These hydrogels were expected to be in collapsed configuration at low pH due to hydrogen bonding between poly(itaconic acid) carboxyl groups and poly(ethylene glycol), and to swell with increasing pH because of charge repulsion between deprotonated carboxylic acid groups. Hydrogels were prepared by UV-initiated free radical polymerization using tetraethylene glycol as the crosslinking agent and Irgacure® 2959 as the initiator. The effect of monomer ratios, crosslinking ratio and solvent amount on the properties of the hydrogels were investigated. The composition of the hydrogels was confirmed by FTIR. Equilibrium swelling studies in the pH range of 1.2 to 7 revealed that the extent of swelling increased with increasing pH up to a pH of about 6, when no further carboxylic acid deprotonation occurred. Studies in Caco-2 colorectal carcinoma cells confirmed the cytocompatibility of these materials at concentrations of up to 5 mg/ml. PMID:19536838

  20. Blockade of [11C](+)-PHNO binding in human subjects by the dopamine D3 receptor antagonist ABT-925.

    PubMed

    Graff-Guerrero, Ariel; Redden, Laura; Abi-Saab, Walid; Katz, David A; Houle, Sylvain; Barsoum, Penny; Bhathena, Anahita; Palaparthy, Ramesh; Saltarelli, Mario D; Kapur, Shitij

    2010-04-01

    Dopamine D3 receptors are preferentially localized in the limbic system and midbrain, and thus may be involved in the pathophysiology of neuropsychiatry disorders. [11C](+)-PHNO is the first preferential D3 receptor radioligand in humans, yet there are no blockade studies with a D3 receptor antagonist in humans. This study characterized the blockade of [11C](+)-PHNO binding by ABT-925, a D3 receptor antagonist, in healthy male subjects. Sixteen subjects underwent 2-3 positron emission tomography (PET) scans, at baseline and following one or two doses of ABT-925 ranging from 50 mg to 600 mg. Receptor occupancies were estimated for globus pallidus, substantia nigra, caudate, putamen, and ventral striatum. At the 600-mg dose (n=9), ABT-925 receptor occupancy (mean+/-s.d.) was higher in substantia nigra (75+/-10%) and globus pallidus (64+/-22%) than in ventral striatum (44+/-17%), caudate (40+/-18%) and putamen (38+/-17%) (ANOVA: F4,140=15.02, p<0.001). The fractions of [11C](+)-PHNO binding attributable to D3 receptors in D3 receptor-rich regions were 100% (substantia nigra) and 90% (globus pallidus), and in D2 receptor-rich regions were 55% (caudate) and 53% (putamen). The ED50 of ABT-925 was 4.37 microg/ml across regions. Our results demonstrate that [11C](+)-PHNO binding can be blocked by a D3 receptor antagonist and confirm preclinical findings that [11C](+)-PHNO signal in the substantia nigra and globus pallidus is mainly reflective of its binding to D3 receptors. Thus, [11C](+)-PHNO seems a suitable PET radiotracer to estimate D3 receptor occupancy in humans. PMID:19751545

  1. Analysis of B3LYP and MP2 conformational population distributions in trans-nicotine, acetylcholine, and ABT-594

    NASA Astrophysics Data System (ADS)

    Mora, M.; Castro, M. E.; Niño, A.; Melendez, F. J.; Muñoz-Caro, C.

    This work presents an analysis of the equivalence of MP2 and DFT (B3LYP functional) conformational populations. As a test case, we select three cholinergic agents (trans-nicotine, acetylcholine, and the nicotinic analgesic ABT-594), where the minima on the conformational energy hypersurfaces expand a large range of energies (˜0-30 kJ mol-1). From energetic and structural data obtained in vacuo at the MP2 and B3LYP/cc-pVDZ levels, we build conformational partition functions, including the effect of the conformational kinetic energy and the rotovibrational coupling. Our results at a physiological temperature (37°C) show qualitative agreement in all cases. Quantitative agreement, however, is only found for trans-nicotine and ABT-594. In the first case, energy minima differ by <0.2 kJ mol-1. Therefore, the equivalence of structural results translates in the equivalence of the conformational distribution. For ABT-594, the minima are separated by as much as 8.0 kJ mol-1, and the conformational energy determines the conformational distribution. In this case, the slight relative variation of conformational energy, between B3LYP and MP2, does not affect the population, since the secondary minima are high in energy and very low in population.

  2. OBATOCLAX and ABT-737 Induce ER Stress Responses in Human Melanoma Cells that Limit Induction of Apoptosis

    PubMed Central

    Wroblewski, David; Jiang, Chen Chen; Croft, Amanda; Farrelly, Margaret L.; Zhang, Xu Dong; Hersey, Peter

    2013-01-01

    Anti-apoptotic Bcl-2 family proteins, in particular, Mcl-1, are known to play a critical role in resistance of human melanoma cells to induction of apoptosis by endoplasmic reticulum stress and other agents. The present study examined whether the BH3 mimetics, Obatoclax and ABT-737, which inhibit multiple anti-apoptotic Bcl-2 family proteins, would overcome resistance to apoptosis. We report that both agents induced a strong unfolded protein response (UPR) and that RNAi knockdown of UPR signalling proteins ATF6, IRE1α and XBP-1 inhibited Mcl-1 upregulation and increased sensitivity to the agents. These results demonstrate that inhibition of anti-apoptotic Bcl-2 proteins by Obatoclax and ABT-737 appears to elicit a protective feedback response in melanoma cells, by upregulation of Mcl-1 via induction of the UPR. We also report that Obatoclax, but not ABT-737, strongly induces autophagy, which appears to play a role in determining melanoma sensitivity to the agents. PMID:24367627

  3. Effect of Base Stacking on the Acid-Base Properties of the Adenine Cation Radical [A•+] in Solution: ESR and DFT Studies

    PubMed Central

    Adhikary, Amitava; Kumar, Anil; Khanduri, Deepti

    2015-01-01

    In this study, the acid–base properties of the adenine cation radical are investigated by means of experiment and theory. Adenine cation radical (A•+) is produced by one-electron oxidation of dAdo and of the stacked DNA-oligomer (dA)6 by Cl2•− in aqueous glass (7.5 M LiCl in H2O and in D2O) and investigated by ESR spectroscopy. Theoretical calculations and deuterium substitution at C8–H and N6–H in dAdo aid in our assignments of structure. We find the pKa value of A•+ in this system to be ca. 8 at 150 K in seeming contradiction to the accepted value of ≤ 1 at ambient temperature. However, upon thermal annealing to ≥160 K, complete deprotonation of A•+ occurs in dAdo in these glassy systems even at pH ca. 3. A•+ found in (dA)6 at 150 K also deprotonates on thermal annealing. The stability of A•+ at 150 K in these systems is attributed to charge delocalization between stacked bases. Theoretical calculations at various levels (DFT B3LYP/6-31G*, MPWB95, and HF-MP2) predict binding energies for the adenine stacked dimer cation radical of 12 to 16 kcal/mol. Further DFT B3LYP/6-31G* calculations predict that, in aqueous solution, monomeric A•+ should deprotonate spontaneously (a predicted pKa of ca. −0.3 for A•+). However, the charge resonance stabilized dimer AA•+ is predicted to result in a significant barrier to deprotonation and a calculated pKa of ca. 7 for the AA•+ dimer which is 7 pH units higher than the monomer. These theoretical and experimental results suggest that A•+ isolated in solution and A•+ in adenine stacks have highly differing acid–base properties resulting from the stabilization induced by hole delocalization within adenine stacks. PMID:18611019

  4. Antioxidant potential and radical scavenging effects of various extracts from Abutilon indicum and Abutilon muticum.

    PubMed

    Yasmin, Sammia; Kashmiri, Muhammad Akram; Asghar, Muhammad Nadeem; Ahmad, Mushtaq; Mohy-ud-Din, Ayesha

    2010-03-01

    Abutilon indicum L. (Malvaceae) and Abutilon muticum DC. (Malvaceae) are traditional medicinal herbs used for analgesic, anthelmintic, hepatoprotective, and hypoglycemic properties. These effects may be correlated with the presence of antioxidant compounds. Extracts in organic solvents from the aerial parts and roots of both species were prepared and evaluated for their total antioxidant capacity (TAC), total phenolic content, and total flavonoid content. The Trolox equivalent antioxidant capacity (TEAC) of all the extracts of both plants was found, employing ABTS and FRAP assays. TEAC values ranged from 3.019 to 10.5 muM for n-hexane and butanol fractions of Abutilon indicum and from 2.247 to 14.208 muM for n-hexane and butanol fractions of Abutilon muticum, respectively, using the ABTS assay. The FRAP assay showed reducing powers of the fractions in the order of butanol > ethyl acetate > chloroform > n-hexane and butanol > chloroform > hexane > ethyl acetate for Abutilon indicum and Abutilon muticum, respectively. EC(50) and T(EC50) values for the extracts of both plants were determined using the DPPH free radical assay. The reaction kinetics with this free radical indicated the presence of both slow reacting and fast reacting antioxidant components in the extracts of both plants. The antioxidant/radical scavenging capacity of the extracts was found to be a dose-dependent activity. The results obtained in the present study indicate that both Abutilon species are potential sources of natural antioxidants. PMID:20645814

  5. In Vitro Activities of ABT-773, a New Ketolide, against Aerobic and Anaerobic Pathogens Isolated from Antral Sinus Puncture Specimens from Patients with Sinusitis

    PubMed Central

    Goldstein, Ellie J. C.; Conrads, Georg; Citron, Diane M.; Merriam, C. Vreni; Warren, Yumi; Tyrrell, Kerin

    2001-01-01

    The comparative in vitro activities of ABT-773 against 207 aerobic and 162 anaerobic antral sinus puncture isolates showed that erythromycin-resistant pneumococcal strains were susceptible to ABT-773 (≤0.125 μg/ml); the MIC at which 90% of the isolates tested were inhibited for Haemophilus influenzae and other Haemophilus spp. was 4 μg/ml; and all Moraxella spp. and beta-lactamase-producing Prevotella species strains were inhibited by ≤0.125 μg/ml. Among the anaerobes tested, only fusobacteria (45%) required ≥4 μg of ABT-773/ml for inhibition. ABT-773 may offer a therapeutic alternative for sinus infections. PMID:11451698

  6. Contemporary Radical Prostatectomy

    PubMed Central

    Fu, Qiang; Moul, Judd W.; Sun, Leon

    2011-01-01

    Purpose. Patients diagnosed with clinically localized prostate cancer have more surgical treatment options than in the past. This paper focuses on the procedures' oncological or functional outcomes and perioperative morbidities of radical retropubic prostatectomy, radical perineal prostatectomy, and robotic-assisted laparoscopic radical prostatectomy. Materials and Methods. A MEDLINE/PubMed search of the literature on radical prostatectomy and other new management options was performed. Results. Compared to the open procedures, robotic-assisted radical prostatectomy has no confirmed significant difference in most literatures besides less blood loss and blood transfusion. Nerve sparing is a safe means of preserving potency on well-selected patients undergoing radical prostatectomy. Positive surgical margin rates of radical prostatectomy affect the recurrence and survival of prostate cancer. The urinary and sexual function outcomes have been vastly improved. Neoadjuvant treatment only affects the rate of positive surgical margin. Adjuvant therapy can delay and reduce the risk of recurrence and improve the survival of the high risk prostate cancer. Conclusions. For the majority of patients with organ-confined prostate cancer, radical prostatectomy remains a most effective approach. Radical perineal prostatectomy remains a viable approach for patients with morbid obesity, prior pelvic surgery, or prior pelvic radiation. Robot-assisted laparoscopic prostatectomy (RALP) has become popular among surgeons but has not yet become the firmly established standard of care. Long-term data have confirmed the efficacy of radical retropubic prostatectomy with disease control rates and cancer-specific survival rates. PMID:22110994

  7. Identification of predictive factors of response to the BH3-mimetic molecule ABT-737: an ex vivo experiment in human serous ovarian carcinoma.

    PubMed

    Lheureux, Stéphanie; N'Diaye, Monique; Blanc-Fournier, Cécile; Dugué, Audrey Emmanuelle; Clarisse, Bénédicte; Dutoit, Soizic; Giffard, Florence; Abeilard, Edwige; Briand, Mélanie; Labiche, Alexandre; Grellard, Jean-Michel; Crouet, Hubert; Martin, Sandrine; Joly, Florence; Poulain, Laurent

    2015-03-01

    Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naïve and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737). PMID:25066666

  8. What do preschoolers know about alcohol? Evidence from the electronic Appropriate Beverage Task (eABT).

    PubMed

    Kuntsche, Emmanuel; Le Mével, Lydie; Zucker, Robert A

    2016-10-01

    While much is known about alcohol use in adolescence and beyond, factors leading to such behaviors are rooted much earlier in life. To investigate what preschoolers (aged three to six) know about alcohol and adult alcohol use, we developed an electronic version (eABT) of the Appropriate Beverage Task (Zucker, Kincaid, Fitzgerald, & Bingham, 1995). Drawings of adults and children in 11 everyday scenarios and 12 photos of different beverages were shown on a touchscreen computer to 301 three- to six-year-olds (49.5% girls) from 37 preschools and seven nurseries in French-speaking Switzerland. First, the children assigned a beverage to each individual in each drawing, and then were asked if the beverage contained alcohol and if they knew its name. The results revealed that 68.1% correctly classified beer, white wine, red wine and champagne as alcoholic beverages, while 46.4% knew the beverages by name, compared to 83.2% and 73.1% for non-alcoholic beverages. Alcoholic beverages were assigned more often to men (42.2%) than to women (28.7%) or to children (12.7%), and more often to adults at a party (39.4%) than to those playing outdoors (34.7%). In conclusion, children as young as three often have some beverage-specific knowledge. From the age of four onwards, they begin to know that alcoholic beverages contain alcohol. Children aged six and over tend to have some knowledge of adult drinking norms, i.e. who is drinking and in what circumstances. PMID:27240210

  9. Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin

    PubMed Central

    Li, Geqiang; Miskimen, Kristy L.; Wang, Zhengqi; Xie, Xiu Yan; Tse, William; Gouilleux, Fabrice; Moriggl, Richard; Bunting, Kevin D.

    2010-01-01

    Signal transducer and activator of transcription-5 (STAT5) is a critical transcription factor for normal hematopoiesis and its sustained activation is associated with hematologic malignancy. A persistently active mutant of STAT5 (STAT5aS711F) associates with Grb2 associated binding protein 2 (Gab2) in myeloid leukemias and promotes growth in vitro through AKT activation. Here we have retrovirally transduced wild-type or Gab2−/− mouse bone marrow cells expressing STAT5aS711F and transplanted into irradiated recipient mice to test an in vivo myeloproliferative disease (MPD) model. To target Gab2-independent AKT/mTOR activation, wild-type mice were treated separately with rapamycin. In either case, mice lacking Gab2 or treated with rapamycin displayed attenuated myeloid hyperplasia and modestly improved survival, but the effects were not cytotoxic and were reversible. To improve upon this approach, in vitro targeting of STAT5-mediated AKT/mTOR using rapamycin was combined with inhibition of the STAT5 direct target genes bcl-2 and bcl-XL using ABT-737. Striking synergy with both drugs was observed in mouse BaF3 cells expressing STAT5aS711F, TEL-JAK2, or BCR-ABL and in the relatively single agent-resistant human BCR-ABL positive K562 cell line. Therefore, targeting distinct STAT5 mediated survival signals, e.g. bcl-2/bcl-XL and AKT/mTOR may be an effective therapeutic approach for human myeloproliferative neoplasms. PMID:20535152

  10. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

    PubMed Central

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-01-01

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions. PMID:26927160

  11. Assessment of the Polyphenolic Content, Free Radical Scavenging, Anti-inflammatory, and Antimicrobial Activities of Acetone and Aqueous Extracts of Lippia javanica (Burm.F.) Spreng

    PubMed Central

    Asowata-Ayodele, Abiola M.; Otunola, Gloria A.; Afolayan, Anthony J.

    2016-01-01

    polyphenolic content and biological activities of the spice plant, Lippia javanica from South Africa was evaluatedSignificantly high polyphenolic content and free radical scavenging activities were observed for both extractsModerate antimicrobial action, concentration-dependent inhibition of protein denaturation and membrane haemolysis were also observed. Abbreviations used: AA: ascorbic acid, ABTS: 2,2’azino-bis (3-ethylbenthiazoline-6-sulfonic acid), BHT: Butylated hydroxytoluene, DPPH: 1,1-Diphenyl-2-picryl-hydrazyl, NBT: 2,2’-di-pnitrophenyl-5,5’-diphenyl-(3,3’-dimethoxy-4,4’-diphenylene)- ditetrazolium chloride, PMS: Potassium metabisulfite, ROS: Reactive oxygen species, TBA: Thiobarbituric acid, TCA: Trichloroacetic acid. PMID:27563225

  12. Radicalization and Radical Catalysis of Biomass Sugars: Insights from First-principles Studies

    NASA Astrophysics Data System (ADS)

    Yang, Gang; Zhu, Chang; Zou, Xianli; Zhou, Lijun

    2016-07-01

    Ab initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites, and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes, and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars, and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Brønsted acids, and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions.

  13. Radicalization and Radical Catalysis of Biomass Sugars: Insights from First-principles Studies.

    PubMed

    Yang, Gang; Zhu, Chang; Zou, Xianli; Zhou, Lijun

    2016-01-01

    Ab initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites, and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes, and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars, and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Brønsted acids, and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions. PMID:27405843

  14. Radicalization and Radical Catalysis of Biomass Sugars: Insights from First-principles Studies

    PubMed Central

    Yang, Gang; Zhu, Chang; Zou, Xianli; Zhou, Lijun

    2016-01-01

    Ab initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites, and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes, and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars, and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Brønsted acids, and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions. PMID:27405843

  15. Optimization of Ultrasonic-Assisted Extraction and Radical-Scavenging Capacity of Phenols and Flavonoids from Clerodendrum cyrtophyllum Turcz Leaves

    PubMed Central

    Zhou, Jing; Zheng, Xiaoxue; Yang, Qi; Liang, Zhenyi; Li, Donghai; Yang, Xiaobo; Xu, Jing

    2013-01-01

    Ultrasonic-assisted extraction (UAE) was developed to extract phenolic and flavonoid antioxidants from Clerodendrum cyrtophyllum Turcz leaves. The optimal experimental parameters for antioxidant extraction from C. cyrtophyllum leaves were measured using single-factor experimentation combined with response surface methodology (RSM). Total phenolic content (TPC) and total flavonoid content (TFC) assays were used to quantify antioxidant compounds. Next, antioxidant radical scavenging capacity was measured using 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′ -azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radicals. Optimized extraction conditions for UAE from C. cyrtophyllum leaves were as follows: 60.9% ethanol, 85.4 min, and 63.3°C for maximal TPC extraction (16.8±0.2 mg GAE/g DW); 67.7% ethanol, 82.9 min, and 63.0°C for maximal TFC extraction (49.3±0.4 mg RT/g DW); 48.8% ethanol, 85.1 min, and 63.9°C for maximal DPPH radical-scavenging capacity (86.8±0.2%); and 50.6% ethanol, 81.3 min, and 63.4°C for maximal ABTS radical-scavenging capacity (92.9±0.5%). Ethanol concentration was the most important factor in the extraction process. Our work offers optimal extraction conditions for C. cyrtophyllum as a potential source of natural antioxidants. PMID:23874607

  16. Cethromycin: A-195773, A-195773-0, A-1957730, Abbott-195773, ABT 773.

    PubMed

    2007-01-01

    Cethromycin [ABT 773, A-195773, Abbott-195773, A-1957730, A-195773-0] is a once-daily ketolide antibiotic that originated from Abbott Laboratories' research into next-generation compounds to the macrolide antibacterial, clarithromycin. The aim of the research programme was to maintain the positive attributes of clarithromycin and to add the property of efficacy against macrolide-resistant organisms. Cethromycin acts by binding to the 23S molecule of the 50S ribosomal subunit. Advanced Life Sciences is conducting multinational, pivotal phase III trials of cethromycin for the treatment of mild-to-moderate community-acquired pneumonia, phase II/III trials for treatment of acute bacterial sinusitis, as well as preclinical trials for the treatment of anthrax. Advanced Life Sciences plans to advance discussions with prospective commercialisation partners for cethromycin during 2006. Abbott Laboratories and Taisho Pharmaceutical entered a collaboration to develop and commercialise new macrolide antibacterials in October 1997. Each company brought its existing macrolides into the collaboration and both companies were to jointly develop novel new macrolides. Abbott was to have exclusive marketing, manfacturing and supply rights worldwide (except in Japan) to any compounds resulting from this collaboration. Taisho was to receive royalties on Abbott's sales in consideration of granted rights. In Japan, the two companies were to co-market any resulting macrolide antibacterials. This agreement extended to the development of cethromycin; however, the agreement was suspended in April 2004 and appears to have been terminated. Abbott exclusively licensed cethromycin to Advanced Life Sciences worldwide excluding Japan in December 2004. Advanced Life Sciences initiated commercial manufacturing agreements for cethromycin with DSM and Cardinal Health in May 2006. In March 2006, Advanced Life Sciences completed private placement of $US36 million from which the net proceeds will be used

  17. Reassessing Radical Pedagogy.

    ERIC Educational Resources Information Center

    Sweet, Stephen

    1998-01-01

    Responds to comments about, and critiques of, his own article on radical pedagogy. Outlines major points of contention raised by other commentators and responds to them, including matters of definition, power relations in the classroom, and tempering radical theory with pragmatism. (DSK)

  18. [Alchemists' humid radical].

    PubMed

    Lafont, Olivier

    2007-01-01

    The term radical has been used by chemists since the beginnings and even when they still were alchemists. The term "humid radical" is present in numerous alchemists' texts. It was used to represent a kind of "humid", which was considered as different from what is nowadays called "humid", but was a sort of principle necessary for life. PMID:17575839

  19. Chemical composition, fatty acid content and antioxidant potential of meat from goats supplemented with Moringa (Moringa oleifera) leaves, sunflower cake and grass hay.

    PubMed

    Qwele, K; Hugo, A; Oyedemi, S O; Moyo, B; Masika, P J; Muchenje, V

    2013-03-01

    The present study determined the chemical composition, fatty acid (FA) content and antioxidant capacity of meat from goats supplemented with Moringa oleifera leaves (MOL) or sunflower cake (SC) or grass hay (GH). The meat from goat supplemented with MOL had higher concentrations of total phenolic content (10.62±0.27 mg tannic acid equivalent E/g). The MOL significantly scavenged 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic-acid (ABTS) radical to 93.51±0.19% (93.51±0.19%) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical to 58.95±0.3% than other supplements. The antioxidative effect of MOL supplemented meat on catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and lipid oxidation (LO) was significantly (P<0.05) higher than other meat from goat feed on grass hay or those supplemented with sunflower seed cake. The present study indicated that the anti-oxidative potential of MOL may play a role in improving meat quality (chemical composition, colour and lipid stability). PMID:23273450

  20. Impact of Altitudes and Habitats on Valerenic Acid, Total Phenolics, Flavonoids, Tannins, and Antioxidant Activity of Valeriana jatamansi.

    PubMed

    Jugran, Arun K; Bahukhandi, Amit; Dhyani, Praveen; Bhatt, Indra D; Rawal, Ranbeer S; Nandi, Shyamal K

    2016-07-01

    The changes in total phenolics, flavonoids, tannins, valerenic acid, and antioxidant activity were assessed in 25 populations of Valeriana jatamansi sampled from 1200 to 2775 m asl and four habitat types of Uttarakhand, West Himalaya. Significant (p < 0.05) variations in total phenolics, flavonoids, valerenic acid, and antioxidant activity in aerial and root portions and across the populations were observed. Antioxidant activity measured by three in vitro antioxidant assays, i.e., 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic) (ABTS) radical scavenging, 2,2'-diphenyl-1-picryylhydrazyl (DPPH) free radical scavenging, and ferric-reducing antioxidant power (FRAP) assays, showed significant (p < 0.05) differences across the populations. However, no clear pattern was found in phytochemicals across the altitudinal range. Among habitat types, (pine, oak, mixed forest, and grassy land), variation in phytochemical content and antioxidant activity were observed. Equal class ranking, neighbor-joining cluster analysis, and principal component analysis (PCA) identified Talwari, Jaberkhet, Manjkhali, and Khirshu populations as promising sources with higher phytochemicals and antioxidant activity. The results recommended that the identified populations with higher value of phytochemicals and antioxidants can be utilized for mass multiplication and breeding program to meet the domestic as well as commercial demand. PMID:26971960

  1. Contribution of cytochrome P450 and UDT-glucuronosyltransferase to the metabolism of drugs containing carboxylic acid groups: risk assessment of acylglucuronides using human hepatocytes.

    PubMed

    Jinno, Norimasa; Tagashira, Mizuka; Tsurui, Kazuyuki; Yamada, Shizuo

    2014-08-01

    1. In order to evaluate the inhibition activity of 1-aminobenzotriazole (ABT) and (-)-borneol (borneol) against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), the substrates of these metabolic enzymes were incubated with ABT and borneol in human hepatocytes. We found that 3 mM ABT and 300 μM borneol were the most suitable experimental levels to specifically inhibit CYP and UGT. 2. Montelukast, mefenamic acid, flufenamic acid, diclofenac, tienilic acid, gemfibrozil, ibufenac and repaglinide were markedly metabolized in human hepatocytes, and the metabolism of gemfibrozil, mefenamic acid and flufenamic acid was inhibited by borneol. With regard to repaglinide, montelukast, diclofenac and tienilic acid, metabolism was inhibited by ABT. Ibufenac was partly inhibited by both inhibitors. Zomepirac, tolmetin, ibuprofen, indomethacin and levofloxacin were moderately metabolized by human hepatocytes, and the metabolism of zomepirac, ibuprofen and indomethacin was equally inhibited by both ABT and borneol. The metabolism of tolmetin was strongly inhibited by ABT, and was also inhibited weakly by borneol. Residual drugs, telmisartan, valsartan, furosemide, naproxen and probenecid were scarcely metabolized. 3. Although we attempted to predict the toxicological risks of drugs containing carboxylic groups from the combination chemical stability and CLint via UGT, the results indicated that this combination was not sufficient and that clinical daily dose is important. PMID:24575896

  2. Decay Mechanism of NO3(•) Radical in Highly Concentrated Nitrate and Nitric Acidic Solutions in the Absence and Presence of Hydrazine.

    PubMed

    Garaix, Guillaume; Horne, Gregory P; Venault, Laurent; Moisy, Philippe; Pimblott, Simon M; Marignier, Jean Louis; Mostafavi, Mehran

    2016-06-01

    The decay mechanism of NO3(•) has been determined through a combination of experiment and calculation for 7 mol dm(-3) solutions of deaerated aqueous LiNO3 and HNO3, in the absence and presence of hydrazine (N2H4, N2H5(+), and N2H6(2+)). In the absence of hydrazine, the predominant NO3(•) decay pathways are strongly dependent upon the pH of the solution. For neat, neutral pH LiNO3 solutions (7 mol dm(-3)), NO3(•) produced by the pulse is fully consumed within 160 μs by OH(•) (37%), H2O (29%), NO2(-) (17%), and NO2 (17%). For acidic HNO3 solutions (7 mol dm(-3)), radiolytically produced NO3(•) is predominantly consumed within 1 ms by HNO2 (15%) and NO2 (80%). Intervening formulations exhibit the mechanistic transition from neat LiNO3 to neat HNO3. In highly acidic nitric acid solution, hydrazine exists mainly as N2H5(+) and N2H6(2+), both of which rapidly consume NO3(•) in addition to other decay mechanisms, with rate constants of 2.9 (±0.9) × 10(7) and 1.3 (±0.3) × 10(6) dm(3) mol(-1) s(-1), respectively. PMID:27171587

  3. Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice.

    PubMed

    Kakkola, L; Denisova, O V; Tynell, J; Viiliäinen, J; Ysenbaert, T; Matos, R C; Nagaraj, A; Ohman, T; Kuivanen, S; Paavilainen, H; Feng, L; Yadav, B; Julkunen, I; Vapalahti, O; Hukkanen, V; Stenman, J; Aittokallio, T; Verschuren, E W; Ojala, P M; Nyman, T; Saelens, X; Dzeyk, K; Kainov, D E

    2013-01-01

    ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections. PMID:23887633

  4. BMX acts downstream of PI3K to promote colorectal cancer cell survival and pathway inhibition sensitizes to the BH3 mimetic ABT-737.

    PubMed

    Potter, Danielle S; Kelly, Paul; Denneny, Olive; Juvin, Veronique; Stephens, Len R; Dive, Caroline; Morrow, Christopher J

    2014-02-01

    Evasion of apoptosis is a hallmark of cancer, and reversing this process by inhibition of survival signaling pathways is a potential therapeutic strategy. Phosphoinositide 3-kinase (PI3K) signaling can promote cell survival and is upregulated in solid tumor types, including colorectal cancer (CRC), although these effects are context dependent. The role of PI3K in tumorigenesis combined with their amenability to specific inhibition makes them attractive drug targets. However, we observed that inhibition of PI3K in HCT116, DLD-1, and SW620 CRC cells did not induce apoptotic cell death. Moreover, these cells were relatively resistant to the Bcl-2 homology domain 3 (BH3) mimetic ABT-737, which directly targets the Bcl-2 family of apoptosis regulators. To test the hypothesis that PI3K inhibition lowers the apoptotic threshold without causing apoptosis per se, PI3K inhibitors were combined with ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis by 2.3- to 4.5-fold and reduced expression levels of MCL-1, the resistance biomarker for ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis a further 1.4- to 2.4-fold in CRC cells with small interfering RNA-depleted MCL-1, indicative of additional sensitizing mechanisms. The observation that ABT-737-induced apoptosis was unaffected by inhibition of PI3K downstream effectors AKT and mTOR, implicated a novel PI3K-dependant pathway. To elucidate this, an RNA interference (RNAi) screen of potential downstream effectors of PI3K signaling was conducted, which demonstrated that knockdown of the TEC kinase BMX sensitized to ABT-737. This suggests that BMX is an antiapoptotic downstream effector of PI3K, independent of AKT. PMID:24709422

  5. ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys.

    PubMed

    Decker, M W; Bannon, A W; Curzon, P; Gunther, K L; Brioni, J D; Holladay, M W; Lin, N H; Li, Y; Daanen, J F; Buccafusco, J J; Prendergast, M A; Jackson, W J; Arneric, S P

    1997-10-01

    ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride], a novel ligand at neuronal nicotinic acetylcholine receptors with reduced adverse effects and improved oral bioavailability relative to (-)-nicotine, was tested in a variety of cognitive tests in rats and monkeys. Administered acutely, ABT-089 only marginally improved the spatial discrimination water maze performance of septal-lesioned rats. However, more robust improvement (45% error reduction on the last training day) was observed when ABT-089 was administered continuously via subcutaneous osmotic pumps (minimum effective dose: 1.3 micromol/kg/day). Continuous infusion of (-)-nicotine produced comparable improvement in the spatial discrimination water maze performance of septal-lesioned rats, but a 40-fold higher dose of (-)-nicotine was required (62 micromol/kg/day). Continuous infusion of ABT-089 to aged rats enhanced spatial learning in a standard Morris water maze, as indexed by spatial bias exhibited during a probe trial conducted after 4 days of training, but not when they were subsequently trained in a two-platform spatial discrimination water maze. The compound induced a small impairment in young rats on the standard water maze, but not on the two-platform task. A probe trial conducted after additional training in the standard water maze revealed no age or drug effects. ABT-089 did not affect performance of either the aged or young rats during inhibitory (passive) avoidance training. Also, continuous infusion of ABT-089 did not affect responses to acoustic startle or prepulse inhibition of acoustic startle in young, aged or septal-lesioned rats and did not affect locomotor activity in either sham-lesioned or septal-lesioned rats. In monkeys, acute administration of ABT-089 modestly improved the delayed matching-to-sample performance of mature, adult monkeys and more robustly improved performance in aged monkeys. Improved performance in the aged monkeys was restricted to the longest

  6. A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain

    PubMed Central

    Ziegler, Dan; Duan, W. Rachel; An, Guohua; Thomas, James W.; Nothaft, Wolfram

    2015-01-01

    Abstract T-type Cav3.2 calcium channels represent a novel target for neuropathic pain modulation. Preclinical studies with ABT-639, a peripherally acting highly selective T-type Cav3.2 calcium channel blocker, showed dose-dependent reduction of pain in multiple pain models. ABT-639 also demonstrated an acceptable safety profile at single- and multiple-dose levels evaluated in a clinical phase 1 study in healthy volunteers. The primary objective of this phase 2, multicenter, randomized, double-blind, placebo-controlled, and active-controlled study was to compare the analgesic efficacy and safety of ABT-639 with placebo in the treatment of diabetic neuropathic pain. Pregabalin, an approved treatment for painful diabetic neuropathy, was included as a positive control. A total of 194 patients were randomized and treated for 6 weeks; 62 patients received ABT-639 (100 mg twice daily), 70 patients received pregabalin (150 mg twice daily), and 62 patients received placebo. When assessing the mean changes from baseline in patient-recorded pain scores at the end of week 6, there was no significant difference observed for ABT-639 compared with placebo (−2.28 vs −2.36; P = 0.582). Pregabalin treatment resulted in a transient improvement in pain compared with placebo, which did not persist throughout the study. There were no significant safety issues identified with ABT-639. A majority of adverse events were considered mild to moderate in intensity. In conclusion, treatment with the highly selective T-type Cav3.2 calcium channel blocker ABT-639 100 mg twice daily for 6 weeks showed no safety signals that would preclude further investigation but did not reduce neuropathic pain in patients with diabetes (ClinicalTrials.gov identifier: NCT01345045). PMID:26067585

  7. In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107: preclinical considerations in Alzheimer's disease.

    PubMed

    Bitner, R Scott; Bunnelle, William H; Decker, Michael W; Drescher, Karla U; Kohlhaas, Kathy L; Markosyan, Stella; Marsh, Kennan C; Nikkel, Arthur L; Browman, Kaitlin; Radek, Rich; Anderson, David J; Buccafusco, Jerry; Gopalakrishnan, Murali

    2010-09-01

    We previously reported that alpha7 nicotinic acetylcholine receptor (nAChR) agonism produces efficacy in preclinical cognition models correlating with activation of cognitive and neuroprotective signaling pathways associated with Alzheimer's disease (AD) pathology. In the present studies, the selective and potent alpha7 nAChR agonist 5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole (ABT-107) was evaluated in behavioral assays representing distinct cognitive domains. Studies were also conducted to address potential issues that may be associated with the clinical development of an alpha7 nAChR agonist. Specifically, ABT-107 improved cognition in monkey delayed matching to sample, rat social recognition, and mouse two-trial inhibitory avoidance, and continued to improve cognitive performance at injection times when exposure levels continued to decline. Rats concurrently infused with ABT-107 and donepezil at steady-state levels consistent with clinical exposure showed improved short-term recognition memory. Compared with nicotine, ABT-107 did not produce behavioral sensitization in rats or exhibit psychomotor stimulant activity in mice. Repeated (3 days) daily dosing of ABT-107 increased extracellular cortical acetylcholine in rats, whereas acute administration increased cortical extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation in mice, neurochemical and biochemical events germane to cognitive function. ABT-107 increased cortical phosphorylation of the inhibitory residue (Ser9) of glycogen synthase kinase-3, a primary tau kinase associated with AD pathology. In addition, continuous infusion of ABT-107 in tau/amyloid precursor protein transgenic AD mice reduced spinal tau hyperphosphorylation. These findings show that targeting alpha7 nAChRs may have potential utility for symptomatic alleviation and slowing of disease progression in the treatment AD, and expand the understanding of the potential

  8. A Randomized Trial of the Efficacy and Safety of the H3 Antagonist ABT-288 in Cognitive Impairment Associated With Schizophrenia

    PubMed Central

    Haig, George M.; Bain, Earle; Robieson, Weining; Othman, Ahmed A.; Baker, Jeffrey; Lenz, Robert A.

    2014-01-01

    Introduction: ABT-288 is a highly potent histamine-3 receptor antagonist that has demonstrated pro-cognitive effects in preclinical models relevant to schizophrenia. This study evaluated the efficacy and safety of two doses of ABT-288 in the treatment of cognitive impairment associated with schizophrenia. Methods: A randomized, double-blind, placebo-controlled, parallel-group 12-week study was conducted at 23 centers in the United States. Clinically stable subjects with schizophrenia were randomized in an equal ratio to ABT-288 10mg, ABT-288 25mg, or placebo once daily while continuing their antipsychotic regimen. The primary efficacy measure was the change from baseline to day 84 evaluation on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) composite score vs placebo. Secondary measures included cognitive functioning and psychiatric scales. Safety assessments and sparse pharmacokinetic sampling were also conducted. Results: A total of 214 subjects were randomized. The mean baseline MCCB composite score was 28.4. Approximately 80% of subjects completed the study. The MCCB composite score mean change from baseline to day 84 was numerically worse for both the 10mg (1.90, P = .618) and 25mg (0.64, P = .946) doses of ABT-288 vs placebo (2.19). Results from the secondary measures were consistent with the primary analysis. Subjects’ schizophrenia symptoms remained stable throughout the study as evidenced by stable Positive and Negative Syndrome Scale scores. Overall, study medication was tolerated; however, an increased incidence of psychosis-related and sleep-related adverse events was associated with ABT-288. Discussion: Neither dose of ABT-288 resulted in cognitive improvement in clinically stable adults with schizophrenia. PMID:24516190

  9. Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice

    PubMed Central

    Kakkola, L; Denisova, O V; Tynell, J; Viiliäinen, J; Ysenbaert, T; Matos, R C; Nagaraj, A; Öhman, T; Kuivanen, S; Paavilainen, H; Feng, L; Yadav, B; Julkunen, I; Vapalahti, O; Hukkanen, V; Stenman, J; Aittokallio, T; Verschuren, E W; Ojala, P M; Nyman, T; Saelens, X; Dzeyk, K; Kainov, D E

    2013-01-01

    ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections. PMID:23887633

  10. Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity.

    PubMed

    Bak, Jia; Kim, Hee Jung; Kim, Seong Yun; Choi, Yun-Sik

    2016-05-01

    Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD. PMID:27162482

  11. Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity

    PubMed Central

    Bak, Jia; Kim, Hee Jung; Kim, Seong Yun

    2016-01-01

    Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD. PMID:27162482

  12. Release properties of tannic acid from hydrogen bond driven antioxidative cellulose nanofibrous films.

    PubMed

    Zhou, Bin; Hu, Xiaoqian; Zhu, Jinjin; Wang, Zhenzhen; Wang, Xichang; Wang, Mingfu

    2016-10-01

    Layer-by-layer (LBL) assembled films have been exploited for surface-mediated bioactive compound delivery. Here, an antioxidative hydrogen-bonded multilayer electrospun nanofibrous film was fabricated from tannic acid (TA), acting as a polyphenolic antioxidant, and poly(ethylene glycol) (PEG) via layer-by-layer assembly. It overcame the burst release behavior of nanofibrous carrier, due to the reversible/dynamic nature of hydrogen bond, which was responded to external stimuli. The PEG/TA nanofibrous films disassembled gradually and released TA to the media, when soaked in aqueous solutions. The release rate of TA increased with increasing bilayer number, pH and temperature, but decreased with enhancing ionic strength. The surface morphology of the nanofibrous mats was observed by scanning electron microscopy (SEM). The following antioxidant activity assay revealed that it could scavenge DPPH free radicals and ABTS(+) cation radicals, a major biological activity of polyphenols. This technology can be used to fabricate other phenolic-containing slowly releasing antioxidative nanofibrous films. PMID:27234492

  13. Protection of free radical-induced cytotoxicity by 2-O-α-D-glucopyranosyl-L-ascorbic acid in human dermal fibroblasts.

    PubMed

    Hanada, Yukako; Iomori, Atsuko; Ishii, Rie; Gohda, Eiichi; Tai, Akihiro

    2014-01-01

    The stable ascorbic acid (AA) derivative, 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G), exhibits vitamin C activity after enzymatic hydrolysis to AA. The biological activity of AA-2G per se has not been studied in detail, although AA-2G has been noted as a stable source for AA supply. The protective effect of AA-2G against the oxidative cell death of human dermal fibroblasts induced by incubating with 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) for 24 h was investigated in this study. AA-2G showed a significant protective effect against the oxidative stress in a concentration-dependent manner. AA-2G did not exert a protective effect during the initial 12 h of incubation, but had a significant protective effect in the later part of the incubation period. Experiments using a α-glucosidase inhibitor and comparative experiments using a stereoisomer of AA-2G confirmed that AA-2G had a protective effect against AAPH-induced cytotoxicity without being converted to AA. Our results provide an insight into the efficacy of AA-2G as a biologically interesting antioxidant and suggest the practical use of AA-2G even before being converted into AA as a beneficial antioxidant. PMID:25036685

  14. Radical chemistry of artemisinin

    NASA Astrophysics Data System (ADS)

    Denisov, Evgenii T.; Solodova, S. L.; Denisova, Taisa G.

    2010-12-01

    The review summarizes physicochemical characteristics of the natural sesquiterpene peroxide artemisinin. The kinetic schemes of transformations of artemisinin radicals under anaerobic conditions are presented and analyzed. The sequence of radical reactions of artemisinin in the presence of oxygen is considered in detail. Special emphasis is given to the intramolecular chain oxidation resulting in the transformation of artemisinin into polyatomic hydroperoxide. The kinetic characteristics of elementary reaction steps involving alkyl, alkoxyl, and peroxyl radicals generated from artemisinin are discussed. The results of testing of artemisinin and its derivatives for the antimalarial activity and the scheme of the biochemical synthesis of artemisinin in nature are considered.

  15. Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

    PubMed Central

    Chen, Jing; Guo, Jiawei; Chen, Zhi; Wang, Jieqiong; Liu, Mingyao; Pang, Xiufeng

    2016-01-01

    Gastric cancer, highly dependent on tumor angiogenesis, causes uncontrolled lethality, in part due to chemoresistance. Here, we demonstrate that linifanib (ABT-869), a novel multi-targeted receptor tyrosine kinase inhibitor, markedly augments cytotoxicity of chemotherapies in human gastric cancer. ABT-869 and chemotherapeutic agents exhibited a strong synergy to inhibit the viability of several gastric cancer cell lines, with combination index values ranging from 0.017 to 0.589. Additionally, the combination of ABT-869 and chemotherapeutic agents led to remarkable suppression of vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo. Importantly, in a preclinical gastric cancer xenograft mouse model, drug co-treatments led to increased mouse survival as well as a synergistic reduction in tumor size and the inhibition of tumor angiogenesis. Mechanistic studies further revealed that all of the co-treatments containing ABT-869 resulted in decreased activation of the VEGF receptor, the epidermal growth factor receptor and the insulin growth factor receptor. Inhibition of these receptor tyrosine kinases consequently attenuated the activation of the downstream AKT/mTOR signaling pathway both in cultured gastric cancer cells and in gastric cancer xenografts. Collectively, our findings suggest that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. PMID:27387652

  16. Antimicrobial, free radical scavenging activities and catalytic oxidation of benzyl alcohol by nano-silver synthesized from the leaf extract of Aristolochia indica L.: a promenade towards sustainability

    NASA Astrophysics Data System (ADS)

    Shanmugam, C.; Sivasubramanian, G.; Parthasarathi, Bera; Baskaran, K.; Balachander, R.; Parameswaran, V. R.

    2015-07-01

    Silver nanoparticles (Ag-NPs) were synthesized from aqueous silver nitrate through a simple route using the leaf extract of Aristolochia indica L. (LAIL) which acted as a reducing as well as capping agent. X-ray diffraction confirmed that the synthesized silver particles have a face centred cubic structure. EDS predicted the presence of elemental silver. The SEM images showed the synthesis of spherically mono-dispersed particles, with nano dimensions accounted by the TEM images. Infra-red spectrum adopted to the different organic functionalities present at the surface of the particles. TGA indicated an overall 11 % weight loss up to 1000 °C, suggesting desorption of biomolecules from the surface. X-ray photoelectron spectroscopy (XPS) analysis revealed the presence of metallic silver nanoparticles. The prepared material was utilized as catalyst in the oxidation of benzyl alcohol with molecular oxygen as the oxidant in methanol, under ambient conditions of temperature and pressure. Also Ag-NPs showed good to moderate anti-microbial activity employing the Agar disc diffusion method against various strains using Ciprofloxacin and Fluconazole as standard. Free radical scavenging activity of the nanoparticles were observed by modified 1,1-diphynyl-2-picrylhydrazyl, DPPH and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS in vitro assays. The work presented here demonstrates the adaptability of the synthesized Ag-NPs in participating as a disinfectant agent, free radical scavenger and an effective oxidation catalyst. The basic premise of attaining sustainability through the green synthesis of smart multifaceted materials has been consciously addressed.

  17. Antimicrobial, free radical scavenging activities and catalytic oxidation of benzyl alcohol by nano-silver synthesized from the leaf extract of Aristolochia indica L.: a promenade towards sustainability

    NASA Astrophysics Data System (ADS)

    Shanmugam, C.; Sivasubramanian, G.; Parthasarathi, Bera; Baskaran, K.; Balachander, R.; Parameswaran, V. R.

    2016-06-01

    Silver nanoparticles (Ag-NPs) were synthesized from aqueous silver nitrate through a simple route using the leaf extract of Aristolochia indica L. (LAIL) which acted as a reducing as well as capping agent. X-ray diffraction confirmed that the synthesized silver particles have a face centred cubic structure. EDS predicted the presence of elemental silver. The SEM images showed the synthesis of spherically mono-dispersed particles, with nano dimensions accounted by the TEM images. Infra-red spectrum adopted to the different organic functionalities present at the surface of the particles. TGA indicated an overall 11 % weight loss up to 1000 °C, suggesting desorption of biomolecules from the surface. X-ray photoelectron spectroscopy (XPS) analysis revealed the presence of metallic silver nanoparticles. The prepared material was utilized as catalyst in the oxidation of benzyl alcohol with molecular oxygen as the oxidant in methanol, under ambient conditions of temperature and pressure. Also Ag-NPs showed good to moderate anti-microbial activity employing the Agar disc diffusion method against various strains using Ciprofloxacin and Fluconazole as standard. Free radical scavenging activity of the nanoparticles were observed by modified 1,1-diphynyl-2-picrylhydrazyl, DPPH and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS in vitro assays. The work presented here demonstrates the adaptability of the synthesized Ag-NPs in participating as a disinfectant agent, free radical scavenger and an effective oxidation catalyst. The basic premise of attaining sustainability through the green synthesis of smart multifaceted materials has been consciously addressed.

  18. Free radicals and activated oxygen.

    PubMed

    Famaey, J P

    1982-01-01

    Superoxide anion (0(-2)), hydrogen peroxide (H2O2) and hydroxyl radical (OH.) are products of the biological reduction of 0(2). They are very reactive and poorly tolerated within living systems and enzymes that catalytically scavenge these products have been evolved as defense mechanisms. These include superoxide dismutases (SOD), catalase and peroxidases. Large amounts of O-2 are produced by different enzymatic and non enzymatic biological processes. Large amounts of activated oxygens are produced by phagocytosing cells such as macrophages and polymorphonuclear cells. This production is associated with the bactericidal actions of these cells but it also largely contributes to exacerbate and sustain the inflammation where these cells congregate. The arachidonic acid pathway triggered by the inflammatory stimuli is also a source for these oxidizing radicals. The production of activated oxygens has been associated with the normal aging process but also with various toxic reactions (e.g. the toxicity of the herbicide paraquat, of the ionizing radiations, of certain antibiotics such as streptonigrin, etc. . . .). O-2 induces the depolymerization of hyaluronic acid which lends viscosity and lubricating properties to synovial fluids. SOD possess antiinflammatory properties and a bovine SOD, orgotein, has now been largely investigated by intramuscular and intraarticular injections in the treatment of rheumatic diseases. Various antiinflammatory compounds (e.g. the salicylates) are able either to inhibit the production of these oxygen radicals or to scavenge them which seems of importance for their antiinflammatory properties. Singlet oxygen, another activated oxygen, might also play a role in the inflammatory process. PMID:6295769

  19. BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition.

    PubMed

    Yang, Lifeng; Wan, Juefeng; Xiao, Sheng; Barkhouse, Darryll; Zhu, Ji; Li, Guichao; Lu, Bo; Zhang, Zhen

    2016-01-01

    The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer. PMID:27429848

  20. BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition

    PubMed Central

    Yang, Lifeng; Wan, Juefeng; Xiao, Sheng; Barkhouse, Darryll; Zhu, Ji; Li, Guichao; Lu, Bo; Zhang, Zhen

    2016-01-01

    The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer. PMID:27429848

  1. Determination of the antioxidant capacity of culinary herbs subjected to various cooking and storage processes using the ABTS(*+) radical cation assay.

    PubMed

    Chohan, Magali; Forster-Wilkins, Gary; Opara, Elizabeth I

    2008-06-01

    Culinary herbs have the potential to be a significant source of antioxidants in the diet. However, many culinary herbs are cooked or undergo some other form of processing before they are consumed as part of a meal and such factors may affect their significance as a source of dietary antioxidants. Thus, the impact of cooking (simmering, microwaving, stewing, stir frying and grilling) and storage (vinegar maceration, cold maceration and freezing) on the antioxidant capacity of common culinary herbs was investigated. Extracts of cinnamon, cloves, fennel, ginger, lavender, parsley, rose, rosemary, sage and thyme were prepared pre and post cooking or storage and their antioxidant capacities determined using the Trolox equivalent antioxidant capacity assay (TEAC). Simmering, soup making and stewing significantly increased antioxidant capacity, whilst grilling and stir frying decreased it. Both freezing herbs at -20 degrees C and cold maceration had preservative effects on antioxidant capacity. Herbs in cold vinegar macerations for 1 week showed a decrease in antioxidant capacity compared to the control extracts. These results indicate that the potential of culinary herbs to be significant contributors to dietary antioxidant intake is significantly affected by both cooking and storage. PMID:18224444

  2. Gallic Acid Ameliorates Cyclophosphamide-Induced Neurotoxicity in Wistar Rats Through Free Radical Scavenging Activity and Improvement in Antioxidant Defense System.

    PubMed

    Oyagbemi, Ademola Adetokunbo; Omobowale, Temidayo Olutayo; Saba, Adebowale Bernard; Olowu, Ebunoluwa Racheal; Dada, Racheal Omolola; Akinrinde, Akinleye Stephen

    2016-07-01

    Cyclophosphamide (CPA) is a widely used anticancer chemotherapeutic agent and its toxicity has been associated with its toxic metabolites phosphormide mustard. Therefore, the ameliorative effect of Gallic acid against neurotoxicity was examined in this study. Sixty rats were grouped into 10 rats per group. Group 1 received saline orally. Group 2 received CPA at 100 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 were treated with Gallic acid (GA) at 60 and 120 mg/kg body weight only for 10 days and also received a single dose of CPA (100 mg/kg) intraperitoneally on day 1, respectively. Rats in groups 5 and 6 received GA at 60 and 120 mg/kg body weight only for 10 days. Groups 3, 4, 5, and 6 received GA orally. The cerebellar and cerebral malondialdehyde (MDA) contents and hydrogen peroxide generation were significantly (p < .05) elevated. The cerebellar and cerebral catalase (CAT), superoxide dismutase and glutathione-S-transferase (GST) activities were significantly (p < .05) reduced in CPA treated group. The activity of glutathione peroxidase (GPx) was significantly increased in rats that were treatment with CPA. Also, nitrite content was significantly elevated in the brain of rats that received the toxic dose of CPA. All these findings suggest that treatment with GA (60 and 120 mg/kg) ameliorated the neurotoxicity induced by CPA via reduction of oxidative stress and increase in antioxidant defense system. Combining all, chemotherapeutic agents with structure/function similar to GA could be of potential benefit to the pharmaceutical industries as an adjuvant in chemotherapy with little or no side effects. PMID:26716793

  3. Hydroxyl radical oxidation of feruloylated arabinoxylan.

    PubMed

    Bagdi, Attila; Tömösközi, Sándor; Nyström, Laura

    2016-11-01

    Feruloylated arabinoxylan (AX) has a unique capacity to form covalent gels in the presence of certain oxidizing agents. The present study demonstrates that hydroxyl radical oxidation does not provoke ferulic acid dimerization and thus oxidative gelation. We studied the hydroxyl radical mediated oxidation of an alkali-extracted AX preparation (purity: 92g/100g dry matter) that showed gel-forming capability upon peroxidase/hydrogen peroxide treatment. Hydroxyl radicals were produced with ascorbate-driven Fenton reaction and the radical formation was monitored with electron paramagnetic resonance, using a POBN/EtOH spin trapping system. Oxidation was carried out at different catalytic concentrations of iron (50 and 100μM) and at different temperatures (20°C, 50°C, and 80°C). It was demonstrated that hydroxyl radical oxidation does not provoke gel formation, but viscosity decrease in AX solution, which suggests polymer degradation. Furthermore, it was demonstrated that hydroxyl radical formation in AX solution can be initiated merely by increasing temperature. PMID:27516272

  4. Hydroxyl radicals in indoor environments

    NASA Astrophysics Data System (ADS)

    Sarwar, Golam; Corsi, Richard; Kimura, Yosuke; Allen, David; Weschler, Charles J.

    Indoor hydroxyl radical concentrations were estimated using a new indoor air quality model which employs the SAPRC-99 atmospheric chemistry model to simulate indoor homogenous reactions. Model results indicate that typical indoor hydroxyl radical concentrations are lower than typical outdoor summertime urban hydroxyl radical levels of 5-10×10 6 molecules cm -3; however, indoor levels can be similar to or greater than typical nighttime outdoor hydroxyl radical levels of approximately 5×10 4 molecules cm -3. Effects of selected parameters on indoor hydroxyl radical concentrations are presented herein. Indoor hydroxyl radical concentrations are predicted to increase non-linearly with increasing outdoor ozone concentrations, indoor alkene emission rates, and air exchange rates. Indoor hydroxyl radical concentrations decrease with increasing outdoor nitric oxide concentrations. Indoor temperature and indoor light intensity have moderate impacts on indoor hydroxyl radical concentrations. Outdoor hydroxyl radical concentrations, outdoor nitrate (NO 3rad ) radical concentrations, outdoor hydroperoxy radical concentrations, and hydroxyl radical removal by indoor surfaces are predicted to have no appreciable impact on indoor hydroxyl radical concentrations. Production of hydroxyl radicals in indoor environments appears to be controlled primarily by reactions of alkenes with ozone, and nitric oxide with hydroperoxy radical. Estimated indoor hydroxyl radical levels may potentially affect indoor air quality. Two examples are presented in which reactions of d-limonene and α-pinene with indoor hydroxyl radicals produce aldehydes, which may be of greater concern than the original compounds.

  5. Effect of Dietary Supplementation of the Combination of Gallic and Linoleic Acid in Thigh Meat of Broilers

    PubMed Central

    Lee, Kyung Haeng; Jung, Samooel; Kim, Hyun Joo; Kim, Il Suk; Lee, Jun Heon; Jo, Cheorun

    2012-01-01

    This study was performed to investigate the combined effect of dietary supplementation of gallic and linoleic acid (GL) on the antioxidative effect and quality of thigh meat from broilers. Broilers received 3 dietary treatments: i) commercial finisher diet (control), ii) 0.5% GL (gallic:linoleic acid = 1 M:1 M), and iii) 1.0% GL during the 22 to 36 d. The pH value of broiler thigh meat was increased by GL supplementation. Water holding capacity of the thigh meat was enhanced by the 1.0% dietary GL supplementation. Antioxidative effect (total phenolic content, DPPH radical scavenging activity, ABTS+ reducing activity, reducing power, and TBARS value) in the thigh from the broilers improved significantly with 1.0% GL. Linoleic acid and docosahexaenoic acids were higher in the broilers fed both levels of dietary GL. However, volatile basic nitrogen content and microbiological quality was not shown to be different between control and treated group. Results indicate that 1.0% dietary supplementation of GL can improve the antioxidant activity of broiler thigh meat and may enhance the meat quality. PMID:25049528

  6. A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of α4β2 Agonist ABT-894 in Adults with ADHD

    PubMed Central

    Bain, Earle E; Robieson, Weining; Pritchett, Yili; Garimella, Tushar; Abi-Saab, Walid; Apostol, George; McGough, James J; Saltarelli, Mario D

    2013-01-01

    Dysregulation of the neuronal nicotinic acetylcholine receptor (NNR) system has been implicated in attention-deficit/hyperactivity disorder (ADHD), and nicotinic agonists improve attention across preclinical species and humans. Hence, a randomized, double-blind, placebo-controlled, crossover study was designed to determine the safety and efficacy of a novel α4β2 NNR agonist (ABT-894 (3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane)) in adults with ADHD. Participants (N=243) were randomized to one of four dose regimens of ABT-894 (1, 2, and 4 mg once daily (QD)) or 4 mg twice daily (BID) or the active comparator atomoxetine (40 mg BID) vs placebo for 28 days. Following a 2-week washout period, participants crossed over to the alternative treatment condition (active or placebo) for an additional 28 days. Primary efficacy was based on an investigator-rated Conners' Adult ADHD Rating Scale (CAARS:Inv) Total score at the end of each 4-week treatment period. Additional secondary outcome measures were assessed. A total of 238 patients were assessed for safety end points, 236 patients were included in the intent-to-treat data set, and 196 were included in the completers data set, which was the prespecified, primary data set for efficacy. Both the 4 mg BID ABT-894 and atomoxetine groups demonstrated significant improvement on the primary outcome compared with placebo. Several secondary outcome measures were also significantly improved with 4 mg BID ABT-894. Overall, ABT-894 was well tolerated at all dose levels. These results provide initial proof of concept for the use of α4β2 agonists in the treatment of adults with ADHD. Further investigation of ABT-894, including higher doses, is therefore warranted. PMID:23032073

  7. Surface-Deacetylated Chitin Nano-Fiber/Hyaluronic Acid Composites as Potential Antioxidative Compounds for Use in Extended-Release Matrix Tablets

    PubMed Central

    Anraku, Makoto; Tabuchi, Ryo; Ifuku, Shinsuke; Ishiguro, Takako; Iohara, Daisuke; Hirayama, Fumitoshi

    2015-01-01

    In this study, we examined a possible use of a surface-deacetylated chitin nano-fiber (SDCH-NF) and hyaluronic acid (HA) interpolymer complex (IPC) tablet as a potential antioxidative compound in extended-release matrix tablets. The antioxidant properties of untreated chitin (UCH), SDCH-NF, and HA were examined using N-centered radicals derived from 1,1′-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). SDCH-NF and HA had acceptable scavenging abilities and were relatively efficient radical scavengers, but UCH was much less effective. The results suggest that SDCH-NF and HA could serve as scavengers of compounds related to the development of oxidative stress. An SDCH-NF/HA IPC tablet was prepared and evaluated as an extended-release tablet matrix using famotidine (FMT) as a model drug. The release of FMT from the IPC tablet (DCF-NF:HA = 1:1) was slower than that from a SDCH-NF only tablet. Turbidity measurements and X-ray diffraction (XRD) data also indicated that the optimum complexation ratio for IPC between SDCH-NF/HA is 1/1, resulting in a good relationship between turbidity or XRD of the complex and the release ratio of FMT. These results suggest that an SDCH-NF/HA tablet has the potential for use in an extended-release IPC tablet with a high antioxidant activity. PMID:26501272

  8. Antioxidant Capacity and Radical Scavenging Effect of Polyphenol Rich Mallotus philippenensis Fruit Extract on Human Erythrocytes: An In Vitro Study

    PubMed Central

    Gautam, Manish Kumar; Sharma, Amit Kumar; Tripathi, Yamini B.; Goel, R. K.; Nath, Gopal

    2014-01-01

    Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines. PMID:25525615

  9. Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: an in vitro study.

    PubMed

    Gangwar, Mayank; Gautam, Manish Kumar; Sharma, Amit Kumar; Tripathi, Yamini B; Goel, R K; Nath, Gopal

    2014-01-01

    Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines. PMID:25525615

  10. Neurotoxins: Free Radical Mechanisms and Melatonin Protection

    PubMed Central

    Reiter, Russel J.; Manchester, Lucien C.; Tan, Dun-Xian

    2010-01-01

    Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier. PMID:21358970

  11. Hydroxyl radicals do not crosslink a DNA-lysozyme complex

    SciTech Connect

    Werbin, H.; Cheng, C.J.

    1985-12-01

    The ionic complex between lysozyme and either Escherichia coli DNA or pBR322 DNA was not crosslinked by two systems capable of producing nanomolar amounts of hydroxyl radicals, the oxidation of xanthine by xanthine oxidase and the iron catalyzed oxidation of ascorbic acid. Nor did effective crosslinking occur with micromolar quantities of hydroxyl radicals raised by the addition of adenosine nucleotides to ferrous iron and hydrogen peroxide. In this case, radical content was estimated by colorimetric analysis of formaldehyde following hydroxyl radical oxidation of dimethyl sulfoxide. Similar amounts of radicals generated by pulse radiolysis in a nitrous oxide atmosphere failed also to induce crosslinking. These findings do not support a role for hydroxy radicals in the N-acetoxy-2-acetylaminofluorene induced crosslinking of DNA to lysozyme proposed earlier.

  12. Chemistry of carotenoid neutral radicals.

    PubMed

    Ligia Focsan, A; Magyar, Adam; Kispert, Lowell D

    2015-04-15

    Proton loss from the carotenoid radical cations (Car(+)) to form neutral radicals (#Car) was investigated by numerous electrochemical, EPR, ENDOR and DFT studies described herein. The radical cation and neutral radicals were formed in solution electrochemically and stabilized on solid silica-alumina and MCM-41 matrices. Carotenoid neutral radicals were recently identified in Arabidopsis thaliana plant and photosystem II samples. Deprotonation at the terminal ends of a zeaxanthin radical cation could provide a secondary photoprotection pathway which involves quenching excited state chlorophyll by the long-lived zeaxanthin neutral radicals formed. PMID:25687648

  13. Monofluoroalkenylation of Dimethylamino Compounds through Radical-Radical Cross-Coupling.

    PubMed

    Xie, Jin; Yu, Jintao; Rudolph, Matthias; Rominger, Frank; Hashmi, A Stephen K

    2016-08-01

    An unprecedented and challenging radical-radical cross-coupling of α-aminoalkyl radicals with monofluoroalkenyl radicals derived from gem-difluoroalkenes was achieved. This first example of tandem C(sp(3) )-H and C(sp(2) )-F bond functionalization through visible-light photoredox catalysis offers a facile and flexible access to privileged tetrasubstituted monofluoroalkenes under very mild reaction conditions. The striking features of this redox-neutral method in terms of scope, functional-group tolerance, and regioselectivity are illustrated by the late-stage fluoroalkenylation of complex molecular architectures such as bioactive (+)-diltiazem, rosiglitazone, dihydroartemisinin, oleanic acid, and androsterone derivatives, which represent important new α-amino C-H monofluoroalkenylations. PMID:27351709

  14. Short communication: Viability of culture organisms in honey-enriched acidophilus-bifidus-thermophilus (ABT)-type fermented camel milk.

    PubMed

    Varga, L; Süle, J; Nagy, P

    2014-11-01

    The aim of this research was to monitor the survival during refrigerated storage of Lactobacillus acidophilus LA-5 (A), Bifidobacterium animalis ssp. lactis BB-12 (B), and Streptococcus thermophilus CHCC 742/2130 (T) in cultured dairy foods made from camel and, for comparison, cow milks supplemented with black locust (Robinia pseudoacacia L.) honey and fermented by an acidophilus-bifidus-thermophilus (ABT)-type culture. Two liters of dromedary camel milk and 2 L of cow milk were heated to 90 °C and held for 10 min, then cooled to 40 °C. One half of both types of milk was fortified with black locust honey at the rate of 5.0% (wt/vol), whereas the other half was devoid of honey and served as a control. The camel and cow milks with and without honey were subsequently inoculated with ABT-5 culture and were fermented at 37 °C until a pH value of 4.6 was reached. Thereafter, the probiotic fermented milks were cooled to 15 °C in ice water and were each separated into 18 fractions that were transferred in sterile, tightly capped centrifuge tubes. After 24 h of cooling at 8 °C (d 0), the samples were stored at refrigeration temperature (4 °C). Three tubes of all 4 products (i.e., fermented camel and cow milks with and without honey) were taken at each sampling time (i.e., following 0, 7, 14, 21, 28, and 35 d of storage), and the counts of characteristic microorganisms and those of certain spoilage microbes (yeasts, molds, coliforms, Escherichia coli) were enumerated. The entire experimental program was repeated twice. The results showed that addition of black locust honey at 5% to heat-treated camel and cow milks did not influence the growth and survival of starter streptococci during production and subsequent refrigerated storage of fermented ABT milks. In contrast, honey improved retention of viability of B. animalis ssp. lactis BB-12 in the camel milk-based product during storage at 4 °C up to 5 wk. No spoilage organisms were detected in any of the samples tested

  15. An exploratory study on the peroxyl-radical-scavenging activity of 2,6-dimethyl-5-hepten-2-ol and its heterocyclic analogues

    NASA Astrophysics Data System (ADS)

    Stobiecka, Agnieszka; Sikora, Magdalena; Bonikowski, Radosław; Kula, Józef

    2016-03-01

    The structural properties and radical scavenging activity of 2,6-dimethyl-5-hepten-2-ol (1) and its new heterocyclic analogues, i.e. 2-methyl-4-(5-methylfuran-2-yl)-butan-2-ol (2) and 2-methyl-4-(5-methylthiophen-2-yl)-butan-2-ol (3) and have been studied by using the experimental and theoretical methods for the first time. Activity of title compounds against the peroxyl radical was determined by using standard fluorimetric test, i.e. the Oxygen Radical Absorbance Capacity assay (ORACFL). Furthermore, the electron-donating ability of odorants has been evaluated by using colorimetric ABTS assay. According to the experimental results obtained from the ORACFL test 2,6-dimethyl-5-hepten-2-ol was characterized by the highest activity in comparison with the novel counterparts. Nevertheless, all investigated compounds exhibited pronounced anti-peroxyl radical activity comparable to that exerted by the one of the most prominent antioxidant among the monoterpene alcohols, i.e. by linalool. On the other hand, the title compounds exerted relatively low capacity to quench the radical cation of ABTS. Theoretical calculations based on the Density Functional Theory (DFT) method with the hybrid functional B3LYP were carried out in order to investigate selected structural and electronic properties including the geometrical parameters as well as the energy of frontier molecular orbitals of parent molecules and the resulting radicals. Furthermore, the possible mechanism of peroxyl-radical-scavenging has been determined by using the thermodynamic descriptors such as the bond dissociation enthalpies (BDEs) and ionization potentials (IPs). These theoretical data pointed out the relevance of HAT mechanism in the peroxyl-radical-scavenging exhibited by 2,6-dimethyl-5-hepten-2-ol and its new heterocyclic analogues in polar and non-polar medium.

  16. Resveratrol products resulting by free radical attack

    NASA Astrophysics Data System (ADS)

    Bader, Yvonne; Quint, R. M.; Getoff, Nikola

    2008-06-01

    Trans-resveratrol ( trans-3,4',5-trihydroxystilbene; RES), which is contained in red wine and many plants, is one of the most relevant and extensively investigated stilbenes with a broad spectrum of biological activities. Among other duties, RES has been reported to have anti-carcinogenetic activities, which could be attributed to its antioxidant properties. The degradation of RES was studied under various conditions. The products (aldehydes, carboxylic acids, etc.) generated from RES by the attack of free radicals were registered as a function of the radical concentration (absorbed radiation dose). Based on the obtained data it appears that the OH radicals are initiating the rather complicated process, which involves of the numerous consecutive reactions. A possible starting reaction mechanism is presented.

  17. Sources, sinks, and mechanisms of hydroxyl radical (•OH) photoproduction and consumption in authentic acidic continental cloud waters from Whiteface Mountain, New York: The role of the Fe(r) (r = II, III) photochemical cycle

    NASA Astrophysics Data System (ADS)

    Arakaki, Takemitsu; Faust, Bruce C.

    1998-02-01

    Hydroxyl radical (•OH) photoproduction in 25 authentic acidic (pH = 2.9-4.4) continental cloud waters from Whiteface Mountain, New York was quantified by phenol formed from the •OH-mediated oxidation of benzene (1.2 mM) that was added as an •OH scavenger. Based on the effect of added bisulfite (HSO3-/HOSO2-), an HOOH sink, the •OH photoproduction in these samples was apportioned into two categories: HOOH-dependent sources (dominant), and HOOH-independent sources (minor). On average only a small percentage (median = 9.4%, mean±standard deviation = 16±12%) of the HOOH-dependent •OH source is due to direct photolysis (313 nm) of HOOH. Nearly all of the HOOH-dependent •OH source is accounted for by an iron(II)-HOOH photo-Fenton reaction mechanism (Fe(II) + HOOH → Fe(III) + •OH + OH-) that is initiated by photoreduction of Fe(III) to Fe(II) in the presence of HOOH. A photostationary state is established, involving rapid photolysis of Fe(III) to form Fe(II), and rapid reoxidation of Fe(II) to Fe(III). Consequently, a new term is introduced, Fe(r) (r = II, III), to represent the family of labile Fe(III) and Fe(II) species whose rapid photoredox cycling drives the Fenton production of •OH. The Fe(r) photochemical cycle, which drives the aqueous phase photoformation of •OH, is analogous to the classical NOx photochemical cycle, which drives the gas phase formation of O3 and thus •OH. Based on the cloud waters studied here, the iron(II)-HOOH photo-Fenton reaction is a significant source of •OH to acidic continental cloud waters in comparison to gas-to-drop partitioning processes. Filtering (0.5 μm Teflon) cloud water samples had little effect on the •OH photoformation kinetics. Measured lifetimes of aqueous •OH ranged from 2.4 to 10.6 μs in these cloud waters, and decreased with increasing concentration of dissolved organic carbon. In acidic atmospheric water drops, the principal aqueous sinks for •OH will be reactions with dissolved organic

  18. Novel reactions of one-electron oxidized radicals of selenomethionine in comparison with methionine.

    PubMed

    Mishra, B; Sharma, A; Naumov, S; Priyadarsini, K I

    2009-05-28

    Pulse radiolysis studies on hydroxyl (*OH) radical reactions of selenomethionine (SeM), a selenium analogue of methionine, were carried out, and the resultant transient radical cations and their subsequent reactions have been reported. At pH<3, the >Se*-OH radical adducts produced on reaction of SeM with *OH radical were converted to selenium centered radical cations (Se*+M), which react with another molecule of SeM to form dimer radical cation M(Se therefore Se)M+. At pH 7, the >Se*-OH radical adducts were converted to a monomer radical of the type (Se therefore N)M+ that acquires intramolecular stability through interaction with the lone pair of the N atom and this radical is denoted as SeM*+. SeM*+ decayed by first order kinetics, and the reduction potential of the couple SeM*+/SeM was determined to be 1.21+/-0.05 V vs NHE at pH 7. SeM*+ oxidized ABTS2- and TMPD with rate constants of (2.5+/-0.1)x10(8) and (6.1+/-0.2)x10(8) M(-1) s(-1), respectively, and reacted with hydroxide ion with a rate constant of (3.8+/-0.9)x10(5) M(-1) s(-1). SeM*+ reacts with molecular oxygen, and the rate constant for this reaction was determined to be (4.3+/-0.2)x10(8) M(-1) s(-1); similar reaction with methionine could not be observed experimentally. Like methionine radical cations, SeM*+ undergoes decarboxylation, although with lesser yield, to produce reducing 3-methyl-selenopropyl amino radicals (referred as alpha-amino radicals). The formation of these radicals was confirmed both by the estimation of the liberated CO2 and by one-electron reduction of MV2+, thionine, and PNAP. These results have been supported by quantum chemical calculations. Implications of these results in the biological role of SeM have also been briefly discussed. PMID:19408939

  19. Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

    ERIC Educational Resources Information Center

    Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

    2011-01-01

    Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

  20. MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199

    PubMed Central

    Benito, Juliana M.; Godfrey, Laura; Kojima, Kensuke; Hogdal, Leah; Wunderlich, Mark; Geng, Huimin; Marzo, Isabel; Harutyunyan, Karine G.; Golfman, Leonard; North, Phillip; Kerry, Jon; Ballabio, Erica; Chonghaile, Triona Ní; Gonzalo, Oscar; Qiu, Yihua; Jeremias, Irmela; Debose, LaKiesha; O’Brien, Eric; Ma, Helen; Zhou, Ping; Jacamo, Rodrigo; Park, Eugene; Coombes, Kevin R.; Zhang, Nianxiang; Thomas, Deborah A.; O’Brien, Susan; Kantarjian, Hagop M.; Leverson, Joel D.; Kornblau, Steven M.; Andreeff, Michael; Müschen, Markus; Zweidler-McKay, Patrick A.; Mulloy, James C.; Letai, Anthony; Milne, Thomas A.; Konopleva, Marina

    2015-01-01

    Summary Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias. PMID:26711339

  1. MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199.

    PubMed

    Benito, Juliana M; Godfrey, Laura; Kojima, Kensuke; Hogdal, Leah; Wunderlich, Mark; Geng, Huimin; Marzo, Isabel; Harutyunyan, Karine G; Golfman, Leonard; North, Phillip; Kerry, Jon; Ballabio, Erica; Chonghaile, Triona Ní; Gonzalo, Oscar; Qiu, Yihua; Jeremias, Irmela; Debose, LaKiesha; O'Brien, Eric; Ma, Helen; Zhou, Ping; Jacamo, Rodrigo; Park, Eugene; Coombes, Kevin R; Zhang, Nianxiang; Thomas, Deborah A; O'Brien, Susan; Kantarjian, Hagop M; Leverson, Joel D; Kornblau, Steven M; Andreeff, Michael; Müschen, Markus; Zweidler-McKay, Patrick A; Mulloy, James C; Letai, Anthony; Milne, Thomas A; Konopleva, Marina

    2015-12-29

    Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias. PMID:26711339

  2. Comparative In Vitro Activities of ABT-773 against Aerobic and Anaerobic Pathogens Isolated from Skin and Soft-Tissue Animal and Human Bite Wound Infections

    PubMed Central

    Goldstein, Ellie J. C.; Citron, Diane M.; Merriam, C. Vreni; Warren, Yumi; Tyrrell, Kerin

    2000-01-01

    We studied the comparative in vitro activities of ABT-773, a new ketolide, against 268 aerobic and 148 anaerobic recent isolates from clinical bites using an agar dilution method and inocula of 104 CFU/spot for aerobes and 105 CFU for anaerobes. The following are the MIC ranges and MICs at which 90% of isolates are inhibited (MIC90s) of ABT-773 for various isolates, respectively: Pasteurella multocida and Pasteurella septica, 0.125 to 2 and 1 μg/ml; other Pasteurella species, 0.125 to 1 and 0.5 μg/ml; Corynebacterium spp., 0.015 to 0.06 and 0.015 μg/ml; Staphylococcus aureus, 0.03 to 0.06 and 0.06 μg/ml; coagulase-negative staphylococci, 0.015 to >32 and 32 μg/ml; streptococci, 0.015 to 0.03 and 0.03 μg/ml; Eikenella corrodens, 0.25 to 1 and 1 μg/ml; and Bergeyella zoohelcum, 0.03 to 0.25 and 0.06 μg/ml. For anaerobes the MIC ranges and MIC90s of ABT-773 were as follows, respectively: Prevotella heparinolytica, 0.06 to 0.125 and 0.125 μg/ml; Prevotella spp., 0.015 to 0.125 and 0.06 μg/ml; Porphyromonas spp., 0.015 to 0.03 and 0.015 μg/ml; Fusobacterium nucleatum, 0.5 to 8 and 8 μg/ml; other Fusobacterium spp., 0.015 to 8 and 0.5 μg/ml; Bacteroides tectum, 0.015 to 0.5 and 0.06 μg/ml; and Peptostreptococcus spp., 0.015 to 0.25 and 0.03 μg/ml. ABT-773 was more active than all macrolides tested against S. aureus, E. corrodens, and anaerobes, but all compounds were poorly active against F. nucleatum. The activity of ABT-773 was within 1 dilution of that of azithromycin against Pasteurella spp., and ABT-773 was four- to eightfold more active than clarithromycin against Pasteurella spp. ABT-773 may offer a therapeutic alternative for bite wound infections. PMID:10952607

  3. [Aging and free radicals].

    PubMed

    Manso, C

    1992-02-01

    Several theories on aging are presented. All of them give important contributions but none explains all the aspects of the problem. Oxygen radicals produced during cellular combustion contribute to aging through multiple cumulative microlesions throughout life. The importance of glucose is emphasized; it forms early and late Maillard compounds. Other causes of aging are discussed. PMID:1595373

  4. Radical School Reform.

    ERIC Educational Resources Information Center

    Gross, Beatrice, Ed.; Gross, Ronald, Ed.

    This book provides a comprehensive examination of the nature of the school crisis and the ways in which radical thinkers and educators are dealing with it. Excerpts from the writings of Jonathan Kozol, John Holt, Kenneth Clark, and others are concerned with the realities of education in ghettos and suburbs. Paul Goodman, Marshall McLuhan, Sylvia…

  5. Biocompatible and biodegradable poly(Tannic Acid) hydrogel with antimicrobial and antioxidant properties.

    PubMed

    Sahiner, Nurettin; Sagbas, Selin; Sahiner, Mehtap; Silan, Coskun; Aktas, Nahit; Turk, Mustafa

    2016-01-01

    A novel resourceful bulk poly(Tannic Acid) (p(TA)) hydrogel was prepared by crosslinking TA molecules with an epoxy crosslinker, trimethylolpropane triglycidyl ether (TMPGDE), in an autoclave at 90°C for 2h. The obtained p(TA) hydrogels were in disk form and have highly porous morphology. The swelling characteristics of p(TA) hydrogels were investigated in wound healing pH conditions of pH 5.4, 7.4, and 9 at 37.5°C, and the hydrogels showed good swelling and moisture content behavior. Especially, p(TA) hydrogels were found to be sensitive to pH 9 with 1669% maximum swelling. P(TA) hydrogels were completely degraded at pH 9 hydrolytically in 9 days. Total phenol contents and the effects of scavenging ABTS(+) radicals of degraded p(TA) hydrogels at pH 5.4, 7.4, and 9 were evaluated and calculated in terms of gallic acid equivalent and trolox equivalent antioxidant capacity, respectively, and found to be very effective. Moreover, degraded p(TA) hydrogels display strong antimicrobial behavior against gram positive Staphylococcus aureus, Bacillus subtilis, gram negative Pseudomonas aeruginosa bacteria strains and Candida albicans fungus strain. The WST-1 results indicated that bulk p(TA) hydrogels have no cyctotoxicity to the L929 fibroblast cell line in vitro. PMID:26526171

  6. Tyrosyl Radicals in Dehaloperoxidase

    PubMed Central

    Dumarieh, Rania; D'Antonio, Jennifer; Deliz-Liang, Alexandria; Smirnova, Tatyana; Svistunenko, Dimitri A.; Ghiladi, Reza A.

    2013-01-01

    Dehaloperoxidase (DHP) from Amphitrite ornata, having been shown to catalyze the hydrogen peroxide-dependent oxidation of trihalophenols to dihaloquinones, is the first oxygen binding globin that possesses a biologically relevant peroxidase activity. The catalytically competent species in DHP appears to be Compound ES, a reactive intermediate that contains both a ferryl heme and a tyrosyl radical. By simulating the EPR spectra of DHP activated by H2O2, Thompson et al. (Thompson, M. K., Franzen, S., Ghiladi, R. A., Reeder, B. J., and Svistunenko, D. A. (2010) J. Am. Chem. Soc. 132, 17501–17510) proposed that two different radicals, depending on the pH, are formed, one located on either Tyr-34 or Tyr-28 and the other on Tyr-38. To provide additional support for these simulation-based assignments and to deduce the role(s) that tyrosyl radicals play in DHP, stopped-flow UV-visible and rapid-freeze-quench EPR spectroscopic methods were employed to study radical formation in DHP when three tyrosine residues, Tyr-28, Tyr-34, and Tyr-38, were replaced either individually or in combination with phenylalanines. The results indicate that radicals form on all three tyrosines in DHP. Evidence for the formation of DHP Compound I in several tyrosine mutants was obtained. Variants that formed Compound I showed an increase in the catalytic rate for substrate oxidation but also an increase in heme bleaching, suggesting that the tyrosines are necessary for protecting the enzyme from oxidizing itself. This protective role of tyrosines is likely an evolutionary adaptation allowing DHP to avoid self-inflicted damage in the oxidative environment. PMID:24100039

  7. Sorafenib Sensitizes Glioma Cells to the BH3 Mimetic ABT-737 by Targeting MCL1 in a STAT3-Dependent Manner12

    PubMed Central

    Kiprianova, Irina; Remy, Janina; Milosch, Nelli; Mohrenz, Isabelle V.; Seifert, Volker; Aigner, Achim; Kögel, Donat

    2015-01-01

    The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is overactivated in malignant glioma and plays a key role in promoting cell survival, thereby increasing the acquired apoptosis resistance of these tumors. Here we investigated the STAT3/myeloid cell leukemia 1 (MCL1) signaling pathway as a target to overcome the resistance of glioma cells to the Bcl-2-inhibiting synthetic BH3 mimetic ABT-737. Stable lentiviral knockdown of MCL1 sensitized LN229 and U87 glioma cells to apoptotic cell death induced by single-agent treatment with ABT-737 which was associated with an early activation of DEVDase activity, cytochrome c release, and nuclear apoptosis. Similar sensitizing effects were observed when ABT-737 treatment was combined with the multikinase inhibitor sorafenib which effectively suppressed levels of phosphorylated STAT3 and MCL1 in MCL1-proficient LN229 and U87 glioma cells. In analogous fashion, these synergistic effects were observed when we combined ABT-737 with the STAT3 inhibitor WP-1066. Lentiviral knockdown of the activating transcription factor 5 combined with subsequent quantitative polymerase chain reaction analysis revealed that sorafenib-dependent suppression of MCL1 occurred at the transcriptional level but did not depend on activating transcription factor 5 which previously had been proposed to be essential for MCL1-dependent glioma cell survival. In contrast, the constitutively active STAT3 mutant STAT3-C was able to significantly enhance MCL1 levels under sorafenib treatment to retain cell survival. Collectively, these data demonstrate that sorafenib targets MCL1 in a STAT3-dependent manner, thereby sensitizing glioma cells to treatment with ABT-737. They also suggest that targeting STAT3 in combination with inducers of the intrinsic pathway of apoptosis may be a promising novel strategy for the treatment of malignant glioma. PMID:26297434

  8. Lipid modification processes induced by thiyl radicals

    NASA Astrophysics Data System (ADS)

    Mihaljević, Branka; Bujak, Ivana Tartaro

    2016-07-01

    Polyunsaturated fatty acid (PUFA) oxidation by thiyl radicals (RS•) is believed to be responsible for some of the biological radiation damage. At the same time, RS• can cause isomerization of PUFA double bonds with the formation of trans isomers. The aim of this study was to better understand the competition between lipid peroxidation and geometrical isomerization processes in biomimetic model system of linoleic acid in the presence of 2-mercaptoethanol using irradiation as a method for free radicals generation. In air-equilibrated conditions the propagation of lipid peroxidation was dominant up to the dose of 400 Gy, after which at higher doses up to 10 kGy the termination occurred with the predominance of geometrical isomerization. This study revealed that undesirable and permanent lipid modifications are possible at higher irradiation doses which should be considered in the planning of irradiation treatment of foods and feeds with high content of lipids and sulfur compounds.

  9. Ischemia, reperfusion and oxygen free radicals.

    PubMed

    Manso, C F

    1992-11-01

    Alterations which occur during ischemia are reviewed. They modify the metabolic status in such a way they prepare the cell to an anomalous response to reoxygenation. The consequence of this disturbance is the generation of oxygen free radicals through several mechanisms, including the mitochondrial oxidative phosphorylation, the arachidonic acid cascade, the activation of xanthine oxidase, activation of phagocytes, iron mobilization, etc. Reduced glutathione is exhausted, proteins are inactivated. Lipid peroxidation induces membrane breakdown and cellular death. PMID:1290647

  10. In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates.

    PubMed

    Romano, Beatriz; Plano, Daniel; Encío, Ignacio; Palop, Juan Antonio; Sanmartín, Carmen

    2015-04-15

    Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate. PMID:25792142

  11. Evaluation of Both Free Radical Scavenging Capacity and Antioxidative Damage Effect of Polydatin.

    PubMed

    Jin, Ju; Li, Yan; Zhang, Xiuli; Chen, Tongsheng; Wang, Yifei; Wang, Zhiping

    2016-01-01

    Cellular damage such as oxidation and lipid peroxidation, and DNA damage induced by free-radicals like reactive oxygen species, has been implicated in several diseases. Radicals generated by 2,2-azobis (2-amidino-propane) dihydrochloride (AAPH) are similar to physiologically active ones. In this study we found that polydatin, a resveratrol natural precursor derived from many sources, has the capacity of free radical scavenging and antioxidative damage. Using free radical scavenging assays, the IC50 values of polydatin were 19.25 and 5.29 μg/ml with the DPPH and the ABTS assay, respectively, and 0.125 mg ferrous sulfate/1 mg polydatin with the FRAP assay. With the AAPH-induced oxidative injury cell model assay, polydatin showed a strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicate that the antioxidant properties of polydatin have great potential for use as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetics and pharmaceutical preparations for the treatment of oxidative diseases. PMID:27526125

  12. Toward Radicalizing Community Service Learning

    ERIC Educational Resources Information Center

    Sheffield, Eric C.

    2015-01-01

    This article advocates a radicalized theoretical construction of community service learning. To accomplish this radicalization, I initially take up a discussion of traditional understandings of CSL rooted in pragmatic/progressive thought. I then suggest that this traditional structural foundation can be radicalized by incorporating Deborah…

  13. Free radical tissue damage: Protective role of antioxidant nutrients

    SciTech Connect

    Machling, L.J.; Bendich, A. )

    1987-12-01

    Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.

  14. Selective deposition of dietary α-Lipoic acid in mitochondrial fraction and its synergistic effect with α-Tocoperhol acetate on broiler meat oxidative stability

    PubMed Central

    2013-01-01

    The use of bioactive antioxidants in feed of broiler to mitigate reactive oxygen species (ROS) in biological systems is one of promising nutritional strategies. The aim of present study was to alleviate ROS production in mitochondrial fraction (MF) of meat by supplemented dietary antioxidant in feed of broiler. For this purpose, mitochondria specific antioxidant: α-lipoic acid (25 mg, 75 mg and 150 mg) with or without combination of α-tocopherol acetate (200 mg) used in normal and palm olein oxidized oil (4%) supplemented feed. One hundred and eighty one day old broiler birds were randomly divided into six treatments and provided the mentioned feed from third week. Feed intake, feed conversion ratio (FCR) remained statistically same in all groups while body weight decreased in supplemented groups accordingly at the end of study. The broiler meat MF antioxidant potential was significantly improved by feeding supplemented feed estimated as 1,1-di phenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, 2,2-azinobis-(3- ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and thiobarbituric acid reactive substances (TBARS). The maximum antioxidant activity was depicted in group fed on 150 mg/kg α-lipoic acid (ALA) and 200 mg/kg α-tocopherol acetate (ATA) (T4) in both breast and leg MF. Moreover, TBARS were higher in leg as compared to breast MF. Although, oxidized oil containing feed reduced the growth, lipid stability and antioxidant potential of MF whilst these traits were improved by receiving feed containing ALA and ATA. ALA and ATA showed higher deposition in T4 group while least in group received oxidized oil containing feed (T5). Positive correlation exists between DPPH free radical scavenging activity and the ABTS + reducing activity. In conclusion, ALA and ATA supplementation in feed had positive effect on antioxidant status of MF that consequently diminished the oxidative stress in polyunsaturated fatty acid enriched meat. PMID:23617815

  15. Selective deposition of dietary α-lipoic acid in mitochondrial fraction and its synergistic effect with α-tocoperhol acetate on broiler meat oxidative stability.

    PubMed

    Parveen, Rashida; Asghar, Ali; Anjum, Faqir M; Khan, Muhammad I; Arshad, Muhammad Sajid; Yasmeen, Ammara

    2013-01-01

    The use of bioactive antioxidants in feed of broiler to mitigate reactive oxygen species (ROS) in biological systems is one of promising nutritional strategies. The aim of present study was to alleviate ROS production in mitochondrial fraction (MF) of meat by supplemented dietary antioxidant in feed of broiler. For this purpose, mitochondria specific antioxidant: α-lipoic acid (25 mg, 75 mg and 150 mg) with or without combination of α-tocopherol acetate (200 mg) used in normal and palm olein oxidized oil (4%) supplemented feed. One hundred and eighty one day old broiler birds were randomly divided into six treatments and provided the mentioned feed from third week. Feed intake, feed conversion ratio (FCR) remained statistically same in all groups while body weight decreased in supplemented groups accordingly at the end of study. The broiler meat MF antioxidant potential was significantly improved by feeding supplemented feed estimated as 1,1-di phenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, 2,2-azinobis-(3- ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and thiobarbituric acid reactive substances (TBARS). The maximum antioxidant activity was depicted in group fed on 150 mg/kg α-lipoic acid (ALA) and 200 mg/kg α-tocopherol acetate (ATA) (T4) in both breast and leg MF. Moreover, TBARS were higher in leg as compared to breast MF. Although, oxidized oil containing feed reduced the growth, lipid stability and antioxidant potential of MF whilst these traits were improved by receiving feed containing ALA and ATA. ALA and ATA showed higher deposition in T4 group while least in group received oxidized oil containing feed (T5). Positive correlation exists between DPPH free radical scavenging activity and the ABTS + reducing activity. In conclusion, ALA and ATA supplementation in feed had positive effect on antioxidant status of MF that consequently diminished the oxidative stress in polyunsaturated fatty acid enriched meat. PMID:23617815

  16. Free radical explosive composition

    DOEpatents

    Walker, Franklin E.; Wasley, Richard J.

    1979-01-01

    An improved explosive composition is disclosed and comprises a major portion of an explosive having a detonation velocity between about 1500 and 10,000 meters per second and a minor amount of a getter additive comprising a compound or mixture of compounds capable of capturing or deactivating free radicals or ions under mechanical or electrical shock conditions and which is not an explosive. Exemplary getter additives are isocyanates, olefins and iodine.

  17. Impacts of an unknown daytime nitrous acid source on its daytime concentration and budget, as well as those of hydroxyl, hydroperoxyl, and organic peroxy radicals, in the coastal regions of China

    NASA Astrophysics Data System (ADS)

    Tang, Y.; An, J.; Wang, F.; Li, Y.; Qu, Y.; Chen, Y.; Lin, J.

    2015-01-01

    Many field experiments have found high nitrous acid (HONO) mixing ratios in both urban and rural areas during daytime, but these high daytime HONO mixing ratios cannot be explained well by gas-phase production, suggesting that an unknown daytime HONO source (Punknown) could exist. The formula Punknown ≈ 19.60 × NO2 × J(NO2) was obtained using observed data from 13 field experiments across the globe. The additional HONO sources (i.e. the Punknown, HONO emissions, and nighttime hydrolysis conversion of nitrogen dioxide (NO2) on aerosols) were coupled into the WRF-Chem model (Weather Research and Forecasting model coupled with Chemistry) to assess the Punknown impacts on the concentrations and budgets of HONO and peroxy (hydroxyl, hydroperoxyl, and organic peroxy) radicals (ROx) (= OH + HO2 + RO2) in the coastal regions of China. Results indicated that the additional HONO sources produced a significant improvement in HONO and OH simulations, particularly in the daytime. Elevated daytime-mean Punknown values were found in the coastal regions of China, with a maximum of 2.5 ppb h-1 in the Beijing-Tianjin-Hebei region. The Punknown produced a 60-250% increase of OH, HO2 and RO2 near the ground in the major cities of the coastal regions of China, and a 5-48% increase of OH, HO2 and RO2 in the daytime meridional-mean mixing ratios within 1000 m above the ground. When the additional HONO sources were included, the photolysis of HONO was dominated in the OH production rate in Beijing, Shanghai and Guangzhou before 10:00 LST with a maximum of 10.01 [7.26 due to the Punknown] ppb h-1 in Beijing, whereas the reaction of HO2 + NO (nitric oxide) was dominated after 10:00 LST with a maximum of 9.38 [7.23] ppb h-1 in Beijing. The whole ROx cycle was accelerated by the additional HONO sources, especially the Punknown. The OH production rate was enhanced by 0.67 [0.64] to 4.32 [3.86] ppb h-1 via the reaction of HO2 + NO, and by 0.85 [0.69] to 4.11 [3.61] ppb h-1 via the

  18. Free radical propulsion concept

    NASA Technical Reports Server (NTRS)

    Hawkins, C. E.; Nakanishi, S.

    1981-01-01

    The concept of a free radical propulsion system, utilizing the recombination energy of dissociated low molecular weight gases to produce thrust, is analyzed. The system, operating at a theoretical impulse with hydrogen, as high as 2200 seconds at high thrust to power ratio, is hypothesized to bridge the gap between chemical and electrostatic propulsion capabilities. A comparative methodology is outlined by which characteristics of chemical and electric propulsion for orbit raising mission can be investigated. It is noted that free radicals proposed in rockets previously met with difficulty and complexity in terms of storage requirements; the present study proposes to eliminate the storage requirements by using electric energy to achieve a continuous-flow product of free radicals which are recombined to produce a high velocity propellant. Microwave energy used to dissociate a continuously flowing gas is transferred to the propellant via three-body-recombination for conversion to propellant kinetic energy. Microwave plasma discharge was found in excess of 90 percent over a broad range of pressure in preliminary experiments, and microwave heating compared to electrothermal heating showed much higher temperatures in gasdynamic equations.

  19. Laparoscopic radical cystectomy

    PubMed Central

    Fergany, Amr

    2012-01-01

    Objective Laparoscopic radical cystectomy (LRC) has emerged as a minimally invasive alternative to open radical cystectomy (ORC). This review focuses on patient selection criteria, technical aspects and postoperative outcomes of LRC. Methods Material for the review was obtained by a PubMed search over the last 10 years, using the keywords ‘laparoscopic radical cystectomy’ and ‘laparoscopic bladder cancer’ in human subjects. Results Twenty-two publications selected for relevance and content were used for this review from the total search yield. The level of evidence was IIb and III. LRC results in comparable short- and intermediate-range oncological outcomes to ORC, with generally longer operative times but decreased blood loss, postoperative pain and hospital stay. Overall operative and postoperative morbidity are equivalent. Conclusion In experienced hands, LRC is an acceptable minimally invasive alternative to ORC in selected patients, with the main advantage of decreased blood loss and postoperative pain, as well as a shorter hospital stay and recovery. PMID:26558003

  20. Assessment of Free Radical Scavenging Activity of Dimethylglycine Sodium Salt and Its Role in Providing Protection against Lipopolysaccharide-Induced Oxidative Stress in Mice.

    PubMed

    Bai, Kaiwen; Xu, Wen; Zhang, Jingfei; Kou, Tao; Niu, Yu; Wan, Xiaoli; Zhang, Lili; Wang, Chao; Wang, Tian

    2016-01-01

    In the present study, the free radical scavenging activities (against 1,1-diphenyl-2-pierylhydrazy (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6- sulphonate) (ABTS+), Hydrogen peroxide (H2O2)) of dimethylglycine sodium salt (DMG-Na) were measured and compared with those of Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid), a commonly used antioxidant. The radical scavenging activities of DMG-Na were found to be the highest at 40 mg/ml. In Experiment 2, gastric intubation in mice with 12 mg DMG-Na/0.3 ml sterile saline solution significantly increased (P < 0.05) the body weight (BW) (28 d), organ proportion (liver and spleen), and antioxidant capacity in serum and the liver (Superoxide dismutase (SOD), Hydrogen peroxidase (CAT), Glutathione peroxidase (GPx), and Total antioxidant capacity (T-AOC)), and significantly decreased (P < 0.05) the activities of serum Glutamic-pyruvic transaminase (ALT) and Glutamic oxalacetic transaminase (AST) and Methane Dicarboxylic Aldehyde (MDA) contents in the serum and liver. Specifically, the effect of 12 mg DMG-Na/0.3 ml sterile saline solution, which showed the highest antioxidant capacity, was further studied using a mice model. In Experiment 3, the mice CL (CON+ lipopolysaccharide (LPS)) group showed a significant decrease (P < 0.05) in the serum ALT and AST content; hepatic mitochondrial antioxidant capacity (Manganese Superoxide dismutase (MnSOD), Glutathione reductase (GR), GPx, Glutathione (GSH)); MDA and Protein carbonyl (PC) content; Reactive oxygen species (ROS) level, Mitochondrial membrane potential (MMP) level, and expression of liver antioxidant genes (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase 1 (HO-1), Manganese superoxide dismutase (MnSOD), Glutathione peroxidase 1 (Gpx1), Sirtuin 1 (Sirt1)) relative to the mice CS (CON+ sterile saline) group. The DL (DMG+LPS) group showed a significant decrease (P < 0.05) in serum ALT and AST content, ROS level, and expression of liver

  1. Assessment of Free Radical Scavenging Activity of Dimethylglycine Sodium Salt and Its Role in Providing Protection against Lipopolysaccharide-Induced Oxidative Stress in Mice

    PubMed Central

    Zhang, Jingfei; Kou, Tao; Niu, Yu; Wan, Xiaoli; Zhang, Lili; Wang, Chao; Wang, Tian

    2016-01-01

    In the present study, the free radical scavenging activities (against 1,1-diphenyl-2-pierylhydrazy (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6- sulphonate) (ABTS+), Hydrogen peroxide (H2O2)) of dimethylglycine sodium salt (DMG-Na) were measured and compared with those of Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid), a commonly used antioxidant. The radical scavenging activities of DMG-Na were found to be the highest at 40 mg/ml. In Experiment 2, gastric intubation in mice with 12 mg DMG-Na/0.3 ml sterile saline solution significantly increased (P < 0.05) the body weight (BW) (28 d), organ proportion (liver and spleen), and antioxidant capacity in serum and the liver (Superoxide dismutase (SOD), Hydrogen peroxidase (CAT), Glutathione peroxidase (GPx), and Total antioxidant capacity (T-AOC)), and significantly decreased (P < 0.05) the activities of serum Glutamic-pyruvic transaminase (ALT) and Glutamic oxalacetic transaminase (AST) and Methane Dicarboxylic Aldehyde (MDA) contents in the serum and liver. Specifically, the effect of 12 mg DMG-Na/0.3 ml sterile saline solution, which showed the highest antioxidant capacity, was further studied using a mice model. In Experiment 3, the mice CL (CON+ lipopolysaccharide (LPS)) group showed a significant decrease (P < 0.05) in the serum ALT and AST content; hepatic mitochondrial antioxidant capacity (Manganese Superoxide dismutase (MnSOD), Glutathione reductase (GR), GPx, Glutathione (GSH)); MDA and Protein carbonyl (PC) content; Reactive oxygen species (ROS) level, Mitochondrial membrane potential (MMP) level, and expression of liver antioxidant genes (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase 1 (HO-1), Manganese superoxide dismutase (MnSOD), Glutathione peroxidase 1 (Gpx1), Sirtuin 1 (Sirt1)) relative to the mice CS (CON+ sterile saline) group. The DL (DMG+LPS) group showed a significant decrease (P < 0.05) in serum ALT and AST content, ROS level, and expression of liver

  2. Effects of radical scavengers on aqueous solutions exposed to heavy-ion irradiation using the liquid microjet technique

    NASA Astrophysics Data System (ADS)

    Nomura, Shinji; Tsuchida, Hidetsugu; Furuya, Ryousuke; Miyahara, Kento; Majima, Takuya; Itoh, Akio

    2015-12-01

    The effects of the radical scavenger ascorbic acid on water radiolysis are studied by fast heavy-ion irradiation of aqueous solutions of ascorbic acid, using the liquid microjet technique under vacuum. To understand the reaction mechanisms of hydroxyl radicals in aqueous solutions, we directly measure secondary ions emitted from solutions with different ascorbic acid concentrations. The yield of hydronium secondary ions is strongly influenced by the reaction between ascorbic acid and hydroxyl radicals. From analysis using a simple model considering chemical equilibria, we determine that the upper concentration limit of ascorbic acid with a radical scavenger effect is approximately 70 μM.

  3. The free radical scavenging and antioxidant activities of pod and seed extract of Clitoria fairchildiana (Howard)- an underutilized legume.

    PubMed

    Annegowda, H V; Bhat, Rajeev; Tze, Liong Min; Karim, A A; Mansor, S M

    2013-06-01

    We evaluated the phenolic content and antioxidant capacities of pod and seed extracts (in methanol, ethanol, and water) of an underutilized legume, Clitoria fairchildiana (Howard). The antioxidant capacity of the extracts was determined using the ferric reducing antioxidant potential assay, and the free radical-scavenging capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical-scavenging and ABTS assays. In addition, the total flavonoids, flavonols, and tannin contents were also determined. Overall, the methanol extracts of the pod contained high concentration of phenolics and showed high antioxidant capacities compared to seed extracts. In addition, a positive correlation was found between total phenol and tannin versus antioxidant capacity. Results of the present study indicate pods and seeds of C. fairchildiana to possess rich amount of natural antioxidants, and can be further explored for their possible use as a natural additive in food or in pharmaceutical industries. PMID:24425949

  4. Efficacy of carboplatin alone and in combination with ABT888 in intracranial murine models of BRCA-mutated and BRCA-wild-type triple negative breast cancer

    PubMed Central

    Karginova, Olga; Siegel, Marni B.; Van Swearingen, Amanda E. D.; Deal, Allison M.; Adamo, Barbara; Sambade, Maria J.; Bazyar, Soha; Nikolaishvili-Feinberg, Nana; Bash, Ryan; O’Neal, Sara; Sandison, Katie; Parker, Joel S.; Santos, Charlene; Darr, David; Zamboni, William; Lee, Yueh Z.; Miller, C. Ryan; Anders, Carey K.

    2015-01-01

    Patients with breast cancer brain metastases have extremely limited survival and no approved systemic therapeutics. Triple negative breast cancer (TNBC) commonly metastasizes to the brain and predicts poor prognosis. TNBC frequently harbors BRCA mutations translating to platinum sensitivity potentially augmented by additional suppression of DNA repair mechanisms through poly(ADP-ribose)polymerase (PARP) inhibition. We evaluated brain penetrance and efficacy of Carboplatin +/− the PARP inhibitor ABT888, and investigated gene expression changes in murine intracranial (IC) TNBC models stratified by BRCA and molecular subtype status. Athymic mice were inoculated intra-cerebrally with BRCA-mutant: SUM149 (basal), MDA-MB-436 (claudin-low), or BRCA-wild-type: MDA-MB-468 (basal), MDA-MB-231BR (claudin-low) TNBC cells and treated with PBS control (IP, weekly), Carboplatin (50mg/kg/week, IP), ABT888 (25mg/kg/day, OG), or their combination. DNA-damage (γ-H2AX), apoptosis (cleaved-Caspase-3(cC3)) and gene expression were measured in IC tumors. Carboplatin+/−ABT888 significantly improved survival in BRCA-mutant IC models compared to control, but did not improve survival in BRCA-wild-type IC models. Carboplatin+ABT888 revealed a modest survival advantage versus Carboplatin in BRCA-mutant models. ABT888 yielded a marginal survival benefit in the MDA-MB-436, but not in the SUM149 model. BRCA-mutant SUM149 expression of γ-H2AX and cC3 proteins was elevated in all treatment groups compared to Control, while BRCA-wild-type MDA-MB-468 cC3 expression did not increase with treatment. Carboplatin treatment induced common gene expression changes in BRCA-mutant models. Carboplatin+/−ABT888 penetrates the brain and improves survival in BRCA-mutant IC TNBC models with corresponding DNA damage and gene expression changes. Combination therapy represents a potential promising treatment strategy for patients with TNBC brain metastases warranting further clinical investigation. PMID

  5. Changes in free-radical scavenging ability of kombucha tea during fermentation.

    PubMed

    Jayabalan, R; Subathradevi, P; Marimuthu, S; Sathishkumar, M; Swaminathan, K

    2008-07-01

    Kombucha tea is a fermented tea beverage produced by fermenting sugared black tea with tea fungus (kombucha). Free-radical scavenging abilities of kombucha tea prepared from green tea (GTK), black tea (BTK) and tea waste material (TWK) along with pH, phenolic compounds and reducing power were investigated during fermentation period. Phenolic compounds, scavenging activity on DPPH radical, superoxide radical (xanthine-xanthine oxidase system) and inhibitory activity against hydroxyl radical mediated linoleic acid oxidation (ammonium thiocyanate assay) were increased during fermentation period, whereas pH, reducing power, hydroxyl radical scavenging ability (ascorbic acid-iron EDTA) and anti-lipid peroxidation ability (thiobarbituric assay) were decreased. From the present study, it is obvious that there might be some chances of structural modification of components in tea due to enzymes liberated by bacteria and yeast during kombucha fermentation which results in better scavenging performance on nitrogen and superoxide radicals, and poor scavenging performance on hydroxyl radicals. PMID:26054285

  6. Resonant cavity spectroscopy of radical species

    NASA Astrophysics Data System (ADS)

    Ritchie, Grant

    2015-04-01

    Photo-oxidation in the troposphere is highly complex, being initiated by short lived radical species, in the daytime dominated by the hydroxyl radical, OH, with contributions from Cl atoms, and at night by either NO3 radicals or ozone. Chemical oxidation cycles, which couple OH, HO2 and peroxy (RO2) radical species, remove primary emitted trace species which are harmful to humans or to the wider environment. However, many of the secondary products produced by atmospheric photo-oxidation are also directly harmful, for example O3, NO2, acidic and multifunctional species, many of which are of low volatility and are able to partition effectively to the condensed phase, creating secondary organic aerosol (SOA), which contributes a significant fraction of tropospheric aerosol, with associated impacts on climate and human health. The accuracy of atmospheric models to predict these impacts necessarily requires accurate knowledge of the chemical oxidative cycling. Two of the simplest intermediates are the hydroperoxy radical, HO2, and the smallest and dominant organic peroxy radical, CH3O2, formed directly by the reactions of OH with CO/O2 and CH4/O2, respectively, and indirectly following the oxidation of larger VOCs. OH, HO2 and RO2 (collectively known as ROx) are rapidly cycled, being at the centre of tropospheric oxidation, and hence are some of the best targets for models to compare with field data. The reaction of HO2 and RO2 with NO constitutes the only tropospheric in-situ source of O3. Despite their importance, neither HO2 nor CH3O2 is measured directly in the atmosphere. HO2 is only measured indirectly following its conversion to OH and CH3O2 is not measured at all. Typically only the sum of RO2 radicals is measured, making no distinction between different organic peroxy radicals. This contribution will detail recent studies using (i) optical feedback cavity enhanced absorption spectroscopy with both quantum and inter-band cascade lasers in the mid-IR, and (ii

  7. Acid-base equilibria involved in secondary reactions following the 4-carboxybenzophenone sensitized photooxidation of methionylglycine in aqueous solution. Spectral and time resolution of the decaying (S...N){sup +} radical cation

    SciTech Connect

    Hug, G.L.; Marciniak, B. |; Bobrowski, K. ||

    1996-09-05

    A radical cation with an intramolecular sulfur-nitrogen bond was formed in the photoinitiated transfer of an electron from the sulfur atom of the dipeptide Met-Gly to 4-carboxybenzophenone in its triplet state. The sulfur-nitrogen coupling involved two-center, three-electron bonds. The kinetics of the reactions of these radical cations, which were initiated by a laser flash, were followed over time. The principal method of implementing the spectral resolutions was accomplished through a multiple linear regression technique. This spectral analysis was repeated for numerous time windows during the lifetime of the transients` decays. The resulting concentrations of the transients were consistent with an independent factor analysis. It was found that the decay of the radical cations was multiexponential and that the decay varied with pH. A simplified reaction scheme was proposed whereby the absorbing radical cations can alternatively decay by an irreversible channel or react reversibly with OH{sup -}. Rate constants for the three elementary reactions of this scheme were determined from an analysis of the decay of the concentration of the radical cations. In addition, the equilibrium constant for the reversible reaction was determined by two separate procedures. 35 refs., 7 figs., 2 tabs.

  8. Navitoclax (ABT-263) and bendamustine ± rituximab induce enhanced killing of non-Hodgkin's lymphoma tumours in vivo

    PubMed Central

    Ackler, S; Mitten, MJ; Chen, J; Clarin, J; Foster, K; Jin, S; Phillips, DC; Schlessinger, S; Wang, B; Leverson, JD; Boghaert, ER

    2012-01-01

    BACKGROUND AND PURPOSE Bendamustine with or without rituximab provides an effective and more tolerable alternative to the polytherapy cyclophosphamide–doxorubicin–vincristine–prednisolone (CHOP) in the treatment of haematological tumours and is currently approved for the treatment of many haematological malignancies. Navitoclax (ABT-263) is a potent inhibitor of Bcl-2, Bcl-xL and Bcl-w, which has demonstrated efficacy in haematological tumours alone and in combination with other agents. This paper describes the in vivo efficacy of combining either bendamustine or bendamustine plus rituximab (BR) with navitoclax in xenograft models of non-Hodgkin's lymphoma EXPERIMENTAL APPROACH Activity was tested in xenograft models of diffuse large B-cell lymphoma (DoHH-2, SuDHL-4), mantle cell lymphoma (Granta 519) and Burkitt's lymphoma (RAMOS). Activity was also monitored in a systemic model of Granta 519. KEY RESULTS Navitoclax potentiated bendamustine activity in all cell lines tested. Bendamustine activated p53 in Granta 519 tumours, concurrent with activation of caspase 3. Navitoclax also improved responses to bendamustine-rituximab (BR) in a subset of tumours. CONCLUSIONS AND IMPLICATIONS Navitoclax in combination with bendamustine and BR is a viable combination strategy for use in the clinic and demonstrated superior efficacy compared with previously reported data for navitoclax plus CHOP and rituximab-CHOP. PMID:22624727

  9. PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression.

    PubMed

    Mariano, Germano; Ricciardi, Maria Rosaria; Trisciuoglio, Daniela; Zampieri, Michele; Ciccarone, Fabio; Guastafierro, Tiziana; Calabrese, Roberta; Valentini, Elisabetta; Tafuri, Agostino; Del Bufalo, Donatella; Caiafa, Paola; Reale, Anna

    2015-06-20

    To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADP-ribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating anti-apoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDA-MB-231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosis. PMID:25938539

  10. PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression

    PubMed Central

    Mariano, Germano; Ricciardi, Maria Rosaria; Trisciuoglio, Daniela; Zampieri, Michele; Ciccarone, Fabio; Guastafierro, Tiziana; Calabrese, Roberta; Valentini, Elisabetta; Tafuri, Agostino; Del Bufalo, Donatella; Caiafa, Paola; Reale, Anna

    2015-01-01

    To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADP-ribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating anti-apoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDA-MB-231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosis. PMID:25938539

  11. Radical production from photosensitization of imidazoles

    NASA Astrophysics Data System (ADS)

    Corral Arroyo, P.; Gonzalez, L.; Steimer, S.; Aellig, R.; Volkamer, R. M.; George, C.; Bartels-Rausch, T.; Ammann, M.

    2015-12-01

    Reactions promoted by light are key in atmospheric chemistry. Some of them occur in the condensed phase of aerosols containing light absorbing organic compounds (George et al., 2015). This work explores the radical reactions initiated by near-UV light in mixtures of citric acid (CA) and imidazole-2-carboxaldehyde (IC) using NO as a probe molecule for HO2, by means of coated wall flow tube experiments. Citric acid may act as H atom or electron donor in condensed phase radical cycles. IC may act as a photosensitizer. The loss of NO was measured by a chemiluminescence detector. The dependence of the NO loss on the NO concentration, the IC/CA ratio in the film, relative humidity, light intensity, oxygen molar fraction were investigated as well as the HONO and NO2 yields. We also added halide salts to investigate the effect of a competing electron donor in the system and the output of halogens to the gas phase. We found a correlation between the loss of NO above the film and the molar ratio of IC/CA and the light intensity. The variation of the NO loss with oxygen corroborates a mechanism, in which the triplet excited state of IC is reduced by citric acid, to a reduced ketyl radical that transfers an electron to molecular oxygen, which in turn leads to production of HO2 radicals. Therefore, the NO loss in the gas phase is related to the production of HO2 radicals. Relative humidity had a strong impact on the HO2 output, which shows a maximum production rate at around 30%. The addition of halide ions (X- = Cl-, Br-, I-) increases the HO2 output at low concentration and decrease it at higher concentration when X2- radical ions likely scavenge HO2. We could preliminarily quantify for the first time the contribution of these processes to the oxidative capacity in the atmosphere and conclude that their role is significant for aerosol aging and potentially a significant source of halogen compounds to the gas phase.

  12. Evaluation of free radical scavenging capacity and antioxidative damage effect of resveratrol-nanostructured lipid carriers

    NASA Astrophysics Data System (ADS)

    Jin, Ju; Shi, Fan; Li, Qiu-wen; Li, Pei-shan; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Cellular damage induced by free-radicals like reactive oxygen species has been implicated in several diseases. 2, 2-azobis(2-amidino-propane) dihydrochloride(AAPH) generates two potent ROS capable of inducing lipid peroxidation: alkoxy radical(RO-) and peroxy radical(ROO-). These radicals are similar to those that are physiologically active and thus might initiate a cascade of intracellular toxic events leading to oxidation, lipid peroxidation, DNA damage and subsequent cell death. Hence naturally anti-oxidant play a vital role in combating these conditions. In this study, resveratrol loaded nanostructured lipid carriers (Res-NLC) was prepared by hot melting and then high pressure homogenization technique. The effects of Res-NLC on free radical scavenging capacity and antioxidative damage is investigated. The particle size and zeta potential of Res-NLC were 139.3 ± 1.7 nm and -11.21 ± 0.41 mV, respectively. By free radical scavenging assays, the IC50 value of Res-NLC were 19.25, 5.29 μg/mL with DPPH, ABTS assay respectively, and 0.161 mg ferrous sulfate/1 mg Res-NLC with FRAP assay; and by AAPH-induced oxidative injury cell model assay, Res-NLC showed the strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicated that the antioxidant properties of Res-NLC hold great potential used as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetic and pharmaceutical preparations for the oxidative diseases treatment.

  13. Delivery of vanillin by poly(lactic-acid) nanoparticles: Development, characterization and in vitro evaluation of antioxidant activity.

    PubMed

    Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-05-01

    Poly(lactic acid) (PLA) nanoparticles containing vanillin were prepared using an emulsion-solvent evaporation technique and were characterized and assessed for their in vitro antioxidant potential. Physicochemical properties of the nanoparticles were characterized by size, polydispersity index, zeta potential, encapsulation efficiency and stability. Solid state and thermal properties were assessed using X-ray diffraction and differential scanning calorimetry, while in vitro drug release profile was also evaluated. Results showed PLA nanoparticles having a characteristic amorphous structure, sizes in the range of 240 nm with high homogeneity in size distribution, zeta potential of -22 mV and vanillin encapsulation efficiency of 41%. In vitro release study showed a slow and sustained release of vanillin governed by diffusion. Nanoparticles were stable over a period of three months. Antioxidant ability of the vanillin-loaded PLA nanoparticles in scavenging the radical 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was inferior to free vanillin and due to its prolonged release showed a profile that was both time and concentration dependent, while free vanillin showed concentration-dependent activity. The study concluded that PLA nanoparticles are potential carriers for vanillin delivery. PMID:26952391

  14. The Quality Changes of Postharvest Mulberry Fruit Treated by Chitosan-g-Caffeic Acid During Cold Storage.

    PubMed

    Yang, Caifeng; Han, Beibei; Zheng, Yu; Liu, Lili; Li, Changlong; Sheng, Sheng; Zhang, Jian; Wang, Jun; Wu, Fuan

    2016-04-01

    This study aimed to characterize the effects of chitosan-g-caffeic acid (CTS-g-CA) on improving the quality and extending the shelf life of postharvest mulberry fruit during storage at 4 °C for 18 d. CTS-g-CA was enzymatically synthesized using laccase from Pleurotus ostreatus as a catalyst. The synergistic effects of CTS-g-CA treatment on mulberry fruit were evaluated using a co-toxicity factor (cf). The results showed that the rotting rate of CTS-g-CA-treated fruit was 37.67% (compared with that of the control at 97.67%) on day 18. The weight loss and malondialdehyde (MDA) contents of the CTS-g-CA-treated mulberry fruit were significantly lower (P < 0.05) than those of the control, CA, CTS, and CA+CTS treatments. Moreover, the DPPH and ABTS radical scavenging activities of the CTS-g-CA treatment were both higher than those of the control. Furthermore, the CTS-g-CA treatment also maintained higher levels of main active substances, such as anthocyanins, ascorbic acid, polyphenols and flavones, in mulberry fruit than the other treatments. Therefore, CTS-g-CA could be used to improve the quality and extend the shelf life of postharvest mulberry fruit during cold storage. PMID:26992122

  15. A comparison of radical and non-radical conversion rates of SVOCs in the tropospheric condensed phase

    NASA Astrophysics Data System (ADS)

    Tilgner, Andreas; Herrmann, Hartmut

    2010-05-01

    can sometimes be partly competitive with radical oxidation reactions and might, to some extend, act as a non-oxidative pathway for less volatile organics with aldehyde functionalities. Additionally, reactions of H2O2 with easily oxidisable SVOCs such as glyoxal and pyruvic acid are shown to be competitive to the OH radical conversions when H2O2 is not being strongly depleted by sulphur(IV). References: Herrmann, H.; Tilgner, A.; Barzaghi, P.; Majdik, Z.; Gligorovski, S.; Poulain, L.; Monod, A. Towards a more detailed description of tropospheric aqueous phase organic chemistry: CAPRAM3.0. Atmos. Environ. 2005, 39, 4351-4363. Tilgner, A.; Herrmann, H. Radical-driven carbonyl-to-acid conversion and acid degradation in tropospheric aqueous systems studied by CAPRAM. Atmos. Environ. 2010, submitted for publication.

  16. In vitro free radical scavenging activity of platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Watanabe, Aki; Kajita, Masashi; Kim, Juewon; Kanayama, Atsuhiro; Takahashi, Kyoko; Mashino, Tadahiko; Miyamoto, Yusei

    2009-11-01

    A polyacrylic acid (PAA)-protected platinum nanoparticle species (PAA-Pt) was prepared by alcohol reduction of hexachloroplatinate. The PAA-Pt nanoparticles were well dispersed and homogeneous in size with an average diameter of 2.0 ± 0.4 nm (n = 200). We used electron spin resonance to quantify the residual peroxyl radical (\\mathrm {AOO}^{\\bullet } ) generated from 2,2-azobis (2-aminopropane) dihydrochloride (AAPH) by thermal decomposition in the presence of O2 and a spectrophotometric method to quantify the residual 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. PAA-Pt scavenged these two radicals in a dose-dependent manner. Platinum was the functional component. PAA-Pt reduced the rate of oxygen consumption required for linoleic acid peroxidation initiated by \\mathrm {AOO}^{\\bullet } generated from AAPH, indicating inhibition of the propagation of linolate peroxidation. A thiobarbituric acid test also revealed dose-dependent inhibition of the linolate peroxidation by PAA-Pt. Fifty micromolar platinum, as PAA-Pt, completely quenched 250 µM DPPH radical for 5 min. Even when twice diluted in half, the PAA-Pt still quenched 100% of the 250 µM DPPH radical. The scavenging activity of PAA-Pt is durable. These observations suggest that PAA-Pt is an efficient scavenger of free radicals.

  17. Isolation and structure elucidation of radical scavengers from Thymus vulgaris leaves.

    PubMed

    Dapkevicius, Airidas; van Beek, Teris A; Lelyveld, Gerrit P; van Veldhuizen, Albertus; de Groot, Aede; Linssen, Jozef P H; Venskutonis, Rimantas

    2002-06-01

    2,2-Diphenyl-1-picrylhydrazyl radical (DPPH*) scavenging activity-guided fractionation of a leaf extract of Thymus vulgaris led to the isolation of the radical scavengers rosmarinic acid 1, eriodictyol, taxifolin, luteolin 7-glucuronide, p-cymene 2,3-diol, p-cymene 2,3-diol 6-6'-dimer, carvacrol, thymol, and a new compound, 2. The fractionation was considerably facilitated by using an on-line HPLC detector for radical scavenging activity. In this detector activity is monitored as the disappearance of the color of a postcolumn added stable radical after reacting with radical scavengers in a reaction coil. Compound 2, which consists of rosmarinic and caffeic acid moieties linked via a C-3'-C-8' ' ether bridge, was mainly elucidated by various NMR techniques and CD. Phenylpropanoid trimer 2 was a weaker and stronger radical scavenger than rosmarinic acid 1 in off-line TEAC and DPPH* assays, respectively. PMID:12088434

  18. Pomegranate seed oil: Effect on 3-nitropropionic acid-induced neurotoxicity in PC12 cells and elucidation of unsaturated fatty acids composition.

    PubMed

    Al-Sabahi, Bushra N; Fatope, Majek O; Essa, Musthafa Mohamed; Subash, Selvaraju; Al-Busafi, Saleh N; Al-Kusaibi, Fatma S N; Manivasagam, Thamilarasan

    2014-09-19

    Background Seed oils are used as cosmetics or topical treatment for wounds, allergy, dandruff, and other purposes. Natural antioxidants from plants were recently reported to delay the onset or progress of various neurodegenerative conditions. Over one thousand cultivars of Punica granatum (Punicaceae) are known and some are traditionally used to treat various ailments. Aim The effect of pomegranate oil on 3-nitropropionic acid- (3-NP) induced cytotoxicity in rat pheochromocytoma (PC12) neuronal cells was analyzed in this study. Furthermore, the analysis of unsaturated fatty acid composition of the seed oil of pomegranate by gas chromatography-electron impact mass spectrometry (GC-MS) was done. Results GC-MS study showed the presence of 6,9-octadecadiynoic acid (C18:2(6,9)) as a major component (60%) as 4,4-dimethyloxazoline derivative. The total extractable oil with light petroleum ether by Soxhlet from the dry seed of P. granatum was 4-6%. The oil analyzed for 48.90 ± 1.50 mg gallic acid equivalents/g of oil, and demonstrated radical-scavenging-linked antioxidant activities in various in vitro assays like the DPPH (2,2-diphenyl-l-picrylhydrazyl, % IP = 35.2 ± 0.9%), ABTS (2,2'-azino-bis-3-ethylene benzothiozoline-6-sulfonic acid, % IP 2.2 ± 0.1%), and β-carotene bleaching assay (% IP = 26 ± 3%), respectively, which could be due the possible role of one methylene interrupted diynoic acid system for its radical-scavenging/antioxidant properties of oil. The oil also reduced lipid peroxidation, suppressed reactive oxygen species, extracellular nitric oxide, lactate/pyruvate ratio, and lactase dehydrogenase generated by 3-NP- (100 mM) induced neurotoxicity in PC12 cells, and enhanced the levels of enzymatic and non-enzymatic antioxidants at 40 μg of gallic acid equivalents. Conclusion The protective effect of pomegranate seed oil might be due to the ability of an oil to neutralize ROS or enhance the expression of antioxidant gene. PMID:25238165

  19. Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation*

    PubMed Central

    Doi, Kenichiro; Li, Rongshi; Sung, Shen-Shu; Wu, Hongwei; Liu, Yan; Manieri, Wanda; Krishnegowda, Gowdahalli; Awwad, Andy; Dewey, Alden; Liu, Xin; Amin, Shantu; Cheng, Chunwei; Qin, Yong; Schonbrunn, Ernst; Daughdrill, Gary; Loughran, Thomas P.; Sebti, Said; Wang, Hong-Gang

    2012-01-01

    The anti-apoptotic Bcl-2 family of proteins, including Bcl-2, Bcl-XL and Mcl-1, are well-validated drug targets for cancer treatment. Several small molecules have been designed to interfere with Bcl-2 and its fellow pro-survival family members. While ABT-737 and its orally active analog ABT-263 are the most potent and specific inhibitors to date that bind Bcl-2 and Bcl-XL with high affinity but have a much lower affinity for Mcl-1, they are not very effective as single agents in certain cancer types because of elevated levels of Mcl-1. Accordingly, compounds that specifically target Mcl-1 may overcome this resistance. In this study, we identified and characterized the natural product marinopyrrole A as a novel Mcl-1-specific inhibitor and named it maritoclax. We found that maritoclax binds to Mcl-1, but not Bcl-XL, and is able to disrupt the interaction between Bim and Mcl-1. Moreover, maritoclax induces Mcl-1 degradation via the proteasome system, which is associated with the pro-apoptotic activity of maritoclax. Importantly, maritoclax selectively kills Mcl-1-dependent, but not Bcl-2- or Bcl-XL-dependent, leukemia cells and markedly enhances the efficacy of ABT-737 against hematologic malignancies, including K562, Raji, and multidrug-resistant HL60/VCR, by ∼60- to 2000-fold at 1–2 μm. Taken together, these results suggest that maritoclax represents a new class of Mcl-1 inhibitors, which antagonizes Mcl-1 and overcomes ABT-737 resistance by targeting Mcl-1 for degradation. PMID:22311987

  20. A Modified Method for Studying Behavioral Paradox of Antioxidants and Their Disproportionate Competitive Kinetic Effect to Scavenge the Peroxyl Radical Formation

    PubMed Central

    Masood, Nusrat; Fatima, Kaneez; Luqman, Suaib

    2014-01-01

    We have described a modified method for evaluating inhibitor of peroxyl radicals, a well-recognized and -documented radical involved in cancer initiation and promotion as well as diseases related to oxidative stress and ageing. We are reporting hydrophilic and lipophilic as well as natural and synthetic forms of antioxidants revealing a diversified behaviour to peroxyl radical in a dose-dependent manner (1 nM–10 μM). A simple kinetic model for the competitive oxidation of an indicator molecule (ABTS) and a various antioxidant by a radical (ROO•) is described. The influences of both the concentration of antioxidant and duration of reaction (70 min) on the inhibition of the radical cation absorption are taken into account while determining the activity. The induction time of the reaction was also proposed as a parameter enabling determination of antioxidant content by optimizing and introducing other kinetic parameters in 96-well plate assays. The test evidently improves the original PRTC (peroxyl radical trapping capacity) assay in terms of the amount of chemical used, simultaneous tracking, that is, the generation of the radical taking place continually and the kinetic reduction technique (area under curve, peak value, slope, and Vmax). PMID:24672395

  1. ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli.

    PubMed

    Siddharth, Sumit; Nayak, Deepika; Nayak, Anmada; Das, Sarita; Kundu, Chanakya Nath

    2016-09-01

    PARP inhibitors in combination with other agents are in clinical trial against cancer, but its effect on cancer stem cells (CSCs) is limited. CSCs are responsible for drug resistance, metastasis and cancer relapse due to high DNA repair capacity. Here, we present preclinical effects of Quinacrine (QC) with ABT-888, a PARP inhibitor, on highly metastatic breast cancer stem cells (mBCSCs). An increased level of Adenomatous polyposis coli (APC) was noted after treatment with ABT-888 in QC pre-treated mBCSCs cells. Increased APC physically interacts with PARP-1 and inhibits PARylation causing the non assembly of base excision repair (BER) multiprotein complex, resulting in an irreparable DNA damage and subsequent apoptosis. Knockdown of APC in mBCSCs inhibited DNA damage, increased BER and PARylation, reduces apoptosis while the over-expression of APC in BT20 (APC low expressing) cells reversed the effect. Thus, combination of QC and ABT-888 decreased mBCSCs growth by activating APC and inhibiting BER within the cells. PMID:27334689

  2. Synergistic Induction of Apoptosis in High-Risk DLBCL by BCL2 Inhibition with ABT-199 Combined With Pharmacologic Loss of MCL1

    PubMed Central

    Li, Lingxiao; Pongtornpipat, Praechompoo; Tiutan, Timothy; Kendrick, Samantha L.; Park, Soyoung; Persky, Daniel O.; Rimsza, Lisa M.; Puvvada, Soham D.; Schatz, Jonathan H.

    2015-01-01

    Better treatments are needed for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of failing standard therapy. Avoiding apoptosis is a hallmark of cancer, and in DLBCL the redundantly functioning anti-apoptotic proteins BCL2 and MCL1 are frequently expressed. Here, we explore drugs that cause loss of MCL1, particularly the potent new cyclin-dependent kinase inhibitor dinaciclib, which knocks down MCL1 by inhibiting CDK9. Dinaciclib induces apoptosis in DLBCL cells but is completely overcome by increased activity of BCL2. We find clinical samples have frequent co-expression of MCL1 and BCL2, suggesting therapeutic strategies targeting only one will lead to treatment failures due to activity of the other. The BH3 mimetic ABT-199 potently and specifically targets BCL2. Single-agent ABT-199 had modest anti-tumor activity against most DLBCL lines and resulted in compensatory up-regulation of MCL1 expression. ABT-199 synergized strongly, however, when combined with dinaciclib and with other drugs affecting MCL1, including standard DLBCL chemotherapy drugs. We show potent anti-tumor activities of these combinations in xenografts and in a genetically accurate murine model of MYC-BCL2 double-hit lymphoma. In sum, we reveal a rational treatment paradigm to strip DLBCL of its protection from apoptosis and improve outcomes for high-risk patients. PMID:25882699

  3. Oligorotaxane Radicals under Orders.

    PubMed

    Wang, Yuping; Frasconi, Marco; Liu, Wei-Guang; Sun, Junling; Wu, Yilei; Nassar, Majed S; Botros, Youssry Y; Goddard, William A; Wasielewski, Michael R; Stoddart, J Fraser

    2016-02-24

    A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components-namely oligoviologens-in which different numbers of 4,4'-bipyridinium (BIPY(2+)) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations suggest that the reduced oligopseudorotaxanes fold into highly ordered secondary structures as a result of the formation of BIPY(•+) radical cation pairs. Furthermore, by installing bulky stoppers at each end of the oligopseudorotaxanes by means of Cu-free alkyne-azide cycloadditions, their analogous oligorotaxanes, which retain the same stoichiometries as their progenitors, can be prepared. Solution-state studies of the oligorotaxanes indicate that their mechanically interlocked structures lead to the enforced interactions between the dumbbell and ring components, allowing them to fold (contract) in their reduced states and unfold (expand) in their fully oxidized states as a result of Coulombic repulsions. This electrochemically controlled reversible folding and unfolding process, during which the oligorotaxanes experience length contractions and expansions, is reminiscent of the mechanisms of actuation associated with muscle fibers. PMID:27163033

  4. Oligorotaxane Radicals under Orders

    PubMed Central

    2016-01-01

    A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components—namely oligoviologens—in which different numbers of 4,4′-bipyridinium (BIPY2+) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT4+) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations suggest that the reduced oligopseudorotaxanes fold into highly ordered secondary structures as a result of the formation of BIPY•+ radical cation pairs. Furthermore, by installing bulky stoppers at each end of the oligopseudorotaxanes by means of Cu-free alkyne–azide cycloadditions, their analogous oligorotaxanes, which retain the same stoichiometries as their progenitors, can be prepared. Solution-state studies of the oligorotaxanes indicate that their mechanically interlocked structures lead to the enforced interactions between the dumbbell and ring components, allowing them to fold (contract) in their reduced states and unfold (expand) in their fully oxidized states as a result of Coulombic repulsions. This electrochemically controlled reversible folding and unfolding process, during which the oligorotaxanes experience length contractions and expansions, is reminiscent of the mechanisms of actuation associated with muscle fibers. PMID:27163033

  5. Radically innovative steelmaking technologies

    NASA Astrophysics Data System (ADS)

    Szekely, Julian

    1980-09-01

    The steel industry is faced with serious problems caused by the increasing cost of energy, labor and capital and by tough overseas competition, employing new highly efficient process plants. The very high cost of capital and of capital equipment renders the construction of new green field site plants, exemplifying the best available technology economically unattractive. For this reason, over the long term the development radically innovative steelmaking technologies appears to be the only satisfactory resolution of this dilemma. The purpose of this article is to present a critical review of some of the radically innovative steelmaking technologies that have been proposed during the past few years and to develop the argument that these indeed do deserve serious consideration at the present time. It should be stressed, however, that these innovative technologies can be implemented only as part of a carefully conceived long range plan, which contains as a subset short term solutions, such as trigger prices improved investment credits, and so forth and intermediate term solutions, such as more extensive use of continuous casting, external desulfurization and selective modernization in general.

  6. Influence of Total Anthocyanins from Bitter Melon (Momordica charantia Linn.) as Antidiabetic and Radical Scavenging Agents.

    PubMed

    Güdr, Aytaç

    2016-01-01

    The majority of the antioxidant and antidiabetic activities of fruits are anthocyanins; a group of polyphenolics that are responsible for the color of many fruits, vegetables and flowers. The harvesting time, storage conditions, maturity, extraction steps etc. are very important for the biological activities based on the alteration of chemical composition. The free radical scavenging and antidiabetic activities of total anthocyanins from bitter melon (Momordica charantia Linn) fruit (TAMC) were evaluated by considering four harvesting times. The free radical scavenging activities of the TAMC samples were assessed using DPPH(•), DMPD(•+) and ABTS(•+) assays against BHA, rutin and trolox standards. September as a harvesting period (TAMC-S) had effective DPPH(•) (SC50 2.55 ± 0.08 μg/mL), DMPD(•+) (SC50 2.68 ± 0.09 μg/mL) and ABTS(•+) (SC50 8.19 ± 0.09 μg/mL) scavenging activities compared with other samples and standards. In addition, August (TAMC-A) as a harvesting period showed very influential inhibitory activity against α-amylase (IC50 56.86 ± 1.12 μg/mL) and moderate inhibitory activity against α-glucosidase (IC50 88.19 ± 0.74 μg/mL). In comparison, pharmaceutical active ingredients such as acarbose exhibited anti-amylase and anti-glucosidase activities with IC50 values of 93.07 ± 1.49 μg/mL and 77.25 ± 1.20 μg/mL respectively. These results suggest that the correct selection of harvest period can significantly increase anthocyanin quantity because of the pharmaceutic properties of TAMC. Consequently, TAMC may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia that can be also used as food additives due to its antiradical activity. PMID:27610171

  7. Radical-radical interactions among oxidized guanine bases including guanine radical cation and dehydrogenated guanine radicals.

    PubMed

    Zhao, Jing; Wang, Mei; Yang, Hongfang; Zhang, Meng; Liu, Ping; Bu, Yuxiang

    2013-09-19

    We present here a theoretical investigation of the structural and electronic properties of di-ionized GG base pairs (G(•+)G(•+),G(-H1)(•)G(•+), and G(-H1)(•)G(-H1)(•)) consisting of the guanine cation radical (G(•+)) and/or dehydrogenated guanine radical (G(-H1)(•)) using density functional theory calculations. Different coupling modes (Watson-Crick/WC, Hoogsteen/Hoog, and minor groove/min hydrogen bonding, and π-π stacking modes) are considered. We infer that a series of G(•+)G(•+) complexes can be formed by the high-energy radiation. On the basis of density functional theory and complete active space self-consistent (CASSCF) calculations, we reveal that in the H-bonded and N-N cross-linked modes, (G(•+)G(•+))WC, (G(-H1)(•)G(-H1)(•))WC, (G(-H1)(•)G(-H1)(•))minI, and (G(-H1)(•)G(-H1)(•))minIII have the triplet ground states; (G(•+)G(•+))HoogI, (G(-H1)(•)G(•+))WC, (G(-H1)(•)G(•+))HoogI, (G(-H1)(•)G(•+))minI, (G(-H1)(•)G(•+))minII, and (G(-H1)(•)G(-H1)(•))minII possess open-shell broken-symmetry diradical-characterized singlet ground states; and (G(•+)G(•+))HoogII, (G(•+)G(•+))minI, (G(•+)G(•+))minII, (G(•+)G(•+))minIII, (G(•+)G(•+))HoHo, (G(-H1)(•)G(•+))minIII, (G(-H1)(•)G(•+))HoHo, and (G(-H1)(•)G(-H1)(•))HoHo are the closed-shell systems. For these H-bonded diradical complexes, the magnetic interactions are weak, especially in the diradical G(•+)G(•+) series and G(-H1)(•)G(-H1)(•) series. The magnetic coupling interactions of the diradical systems are controlled by intermolecular interactions (H-bond, electrostatic repulsion, and radical coupling). The radical-radical interaction in the π-π stacked di-ionized GG base pairs ((G(•+)G(•+))ππ, (G(-H1)(•)G(•+))ππ, and (G(-H1)(•)G(-H1)(•))ππ) are also considered, and the magnetic coupling interactions in these π-π stacked base pairs are large. This is the first theoretical prediction that some di

  8. Preparation of Egg White Liquid Hydrolysate (ELH) and Its Radical-Scavenging Activity.

    PubMed

    Noh, Dong Ouk; Suh, Hyung Joo

    2015-09-01

    In the present study, an optimum protease was selected to hydrolyze the egg white liquid protein for the antioxidant peptides. Alcalase treatment yielded the highest amount of α-amino groups (15.27 mg/mL), while the control (no enzymatic hydrolysis) showed the lowest amount of α-amino groups (1.53 mg/mL). Alcalase also gave the highest degree of hydrolysis (DH) value (43.2%) and was more efficient for egg white liquid hydrolysis than the other enzymes. The Alcalase hydrolysate had the highest radical-scavenging activity (82.5%) at a concentration of 5.0 mg/mL. The conditions for enzymatic hydrolysis of egg white liquid with Alcalase were selected as substrate : water ratio of 2:1. Five percent Alacalse treatment did not show significant (P>0.05) increases of DH and α-amino nitrogen content after 24 h-hydrolysis. Thirty two hour-hydrolysis with 5% Alcalase is sufficient to make antioxidative egg white liquid hydrolysate from egg white liquid. DPPH and ABTS radical-scavenging activities were significantly (P<0.05) higher after enzymatic digestion. These results suggest that active peptides released from egg-white protein are effective radical-scavengers. Thus, this approach may be useful for the preparation of potent antioxidant products. PMID:26451355

  9. Preparation of Egg White Liquid Hydrolysate (ELH) and Its Radical-Scavenging Activity

    PubMed Central

    Noh, Dong Ouk; Suh, Hyung Joo

    2015-01-01

    In the present study, an optimum protease was selected to hydrolyze the egg white liquid protein for the antioxidant peptides. Alcalase treatment yielded the highest amount of α-amino groups (15.27 mg/mL), while the control (no enzymatic hydrolysis) showed the lowest amount of α-amino groups (1.53 mg/mL). Alcalase also gave the highest degree of hydrolysis (DH) value (43.2%) and was more efficient for egg white liquid hydrolysis than the other enzymes. The Alcalase hydrolysate had the highest radical-scavenging activity (82.5%) at a concentration of 5.0 mg/mL. The conditions for enzymatic hydrolysis of egg white liquid with Alcalase were selected as substrate : water ratio of 2:1. Five percent Alacalse treatment did not show significant (P>0.05) increases of DH and α-amino nitrogen content after 24 h-hydrolysis. Thirty two hour-hydrolysis with 5% Alcalase is sufficient to make antioxidative egg white liquid hydrolysate from egg white liquid. DPPH and ABTS radical-scavenging activities were significantly (P<0.05) higher after enzymatic digestion. These results suggest that active peptides released from egg-white protein are effective radical-scavengers. Thus, this approach may be useful for the preparation of potent antioxidant products. PMID:26451355

  10. Evaluation of Radical Scavenging Activity of Sempervivum tectorum and Corylus avellana Extracts with Different Phenolic Composition.

    PubMed

    Alberti, Ágnes; Riethmüller, Eszter; Béni, Szabolcs; Kéry, Ágnes

    2016-04-01

    Semnpervivum tectorum L. and Corylus avellana L. are traditional herbal remedies exhibiting antioxidant activity and representing diverse phenolic composition. The aim of this study was to reveal the contribution of certain compounds to total radical scavenging activity by studying S. tectorum and C. avellana extracts prepared with solvents of different selectivity for diverse classes of phenolics. Antioxidant activity of S. tectorum and C. avellana samples was determined in the ABTS and DPPH radical scavenging assays, and phenolic composition was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Correlations between antioxidant activity and phenolic content of houseleek extracts have been revealed. Significant differences regarding antioxidant activity have been shown between S. tectorum 80% (v/v) methanol extract and its fractions. Additionally, synergism among the constituents present together in the whole extract was assumed. Significantly higher radical scavenging activity of hazel extracts has been attributed to the differences in phenolic composition compared with houseleek extracts. PMID:27396195

  11. Free-Radical-Scavenging, Antityrosinase, and Cellular Melanogenesis Inhibitory Activities of Synthetic Isoflavones.

    PubMed

    Lu, Tzy-Ming; Ko, Horng-Huey; Ng, Lean-Teik; Hsieh, Yen-Pin

    2015-06-01

    In this study, we examined the potential of synthetic isoflavones for application in cosmeceuticals. Twenty-five isoflavones were synthesized and their capacities of free-radical-scavenging and mushroom tyrosinase inhibition, as well as their impact on cell viability of B16F10 murine melanoma cells and HaCaT human keratinocytes were evaluated. Isoflavones that showed significant mushroom tyrosinase inhibitory activities were further studied on reduction of cellular melanin formation and antityrosinase activities in B16F10 melanocytes in vitro. Among the isoflavones tested, 6-hydroxydaidzein (2) was the strongest scavenger of both ABTS(.+) and DPPH(.) radicals with SC50 values of 11.3 ± 0.3 and 9.4 ± 0.1 μM, respectively. Texasin (20) exhibited the most potent inhibition of mushroom tyrosinase (IC50 14.9 ± 4.5 μM), whereas retusin (17) showed the most efficient inhibition both of cellular melanin formation and antityrosinase activity in B16F10 melanocytes, respectively. In summary, both retusin (17) and texasin (20) exhibited potent free-radical-scavenging capacities as well as efficient inhibition of cellular melanogenesis, suggesting that they are valuable hit compounds with potential for advanced cosmeceutical development. PMID:26080742

  12. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer

    PubMed Central

    Carducci, Michael A.; Slovin, Susan; Cetnar, Jeremy; Qian, Jiang; McKeegan, Evelyn M.; Refici-Buhr, Marion; Chyla, Brenda; Shepherd, Stacie P.; Giranda, Vincent L.; Alumkal, Joshi J.

    2015-01-01

    Summary Androgen receptor-mediated transcription is directly coupled with the induction of DNA damage, and castration-resistant tumor cells exhibit increased activity of poly (ADP-ribose) polymerase (PARP)-1, a DNA repair enzyme. This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and temozolomide (TMZ) in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot study. Patients with mCRPC progressing on at least one docetaxel-based therapy and prostate specific antigen (PSA) ≥2 ng/mL were treated with veliparib 40 mg twice daily on days 1–7 and TMZ once daily (150 mg/m2/day cycle 1; if well tolerated then 200 mg/m2/day cycle 2 onwards) on days 1–5 q28 days. Patients received 2 (median) treatment cycles (range, 1–9). The primary end-point was confirmed PSA response rate (decline≥30 %). Twenty-six eligible patients were enrolled, 25 evaluable for PSA response. Median baseline PSA was 170 ng/mL. Two patients had a confirmed PSA response (8.0 %; 95 % CI: 1.0– 26.0), 13 stable PSA, and 10 PSA progression. The median progression-free survival was 9 weeks (95 % CI: 7.9–17) and median overall survival 39.6 weeks (95 % CI: 26.6–not estimable). The most frequent treatment-emergent adverse events (AEs) were thrombocytopenia (77 %), anemia (69 %), fatigue (50 %), neutropenia (42 %), nausea (38 %), and constipation (23 %). Grade 3/4 AEs occurring in >10 % of patients were thrombocytopenia (23 %) and anemia (15 %). Veliparib and TMZ combination was well tolerated but with modest activity. Biomarker analysis supported the proof of concept that this combination has some antitumor activity in mCRPC. PMID:24764124

  13. Free radical propulsion concept

    NASA Technical Reports Server (NTRS)

    Hawkins, C. E.; Nakanishi, S.

    1981-01-01

    A free radical propulsion concept utilizing the recombination energy of dissociated low molecular weight gases to produce thrust was examined. The concept offered promise of a propulsion system operating at a theoretical impulse, with hydrogen, as high as 2200 seconds at high thrust to power ratio, thus filling the gas existing between chemical and electrostatic propulsion capabilities. Microwave energy used to dissociate a continuously flowing gas was transferred to the propellant via three body recombination for conversion to propellant kinetic energy. Power absorption by the microwave plasma discharge was in excess of 90 percent over a broad range of pressures. Gas temperatures inferred from gas dynamic equations showed much higher temperatures from microwave heating than from electrothermal heating. Spectroscopic analysis appeared to corroborate the inferred temperatures of one of the gases tested.

  14. Radicals in Berkeley?

    PubMed Central

    Linn, Stuart

    2015-01-01

    In a previous autobiographical sketch for DNA Repair (Linn, S. (2012) Life in the serendipitous lane: excitement and gratification in studying DNA repair. DNA Repair 11, 595–605), I wrote about my involvement in research on mechanisms of DNA repair. In this Reflections, I look back at how I became interested in free radical chemistry and biology and outline some of our bizarre (at the time) observations. Of course, these studies could never have succeeded without the exceptional aid of my mentors: my teachers; the undergraduate and graduate students, postdoctoral fellows, and senior lab visitors in my laboratory; and my faculty and staff colleagues here at Berkeley. I am so indebted to each and every one of these individuals for their efforts to overcome my ignorance and set me on the straight and narrow path to success in research. I regret that I cannot mention and thank each of these mentors individually. PMID:25713083

  15. Radical AdoMet enzymes in complex metal cluster biosynthesis.

    PubMed

    Duffus, Benjamin R; Hamilton, Trinity L; Shepard, Eric M; Boyd, Eric S; Peters, John W; Broderick, Joan B

    2012-11-01

    Radical S-adenosylmethionine (AdoMet) enzymes comprise a large superfamily of proteins that engage in a diverse series of biochemical transformations through generation of the highly reactive 5'-deoxyadenosyl radical intermediate. Recent advances into the biosynthesis of unique iron-sulfur (FeS)-containing cofactors such as the H-cluster in [FeFe]-hydrogenase, the FeMo-co in nitrogenase, as well as the iron-guanylylpyridinol (FeGP) cofactor in [Fe]-hydrogenase have implicated new roles for radical AdoMet enzymes in the biosynthesis of complex inorganic cofactors. Radical AdoMet enzymes in conjunction with scaffold proteins engage in modifying ubiquitous FeS precursors into unique clusters, through novel amino acid decomposition and sulfur insertion reactions. The ability of radical AdoMet enzymes to modify common metal centers to unusual metal cofactors may provide important clues into the stepwise evolution of these and other complex bioinorganic catalysts. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology. PMID:22269887

  16. Myeloperoxidase-induced genomic DNA-centered radicals.

    PubMed

    Gomez-Mejiba, Sandra E; Zhai, Zili; Gimenez, Maria S; Ashby, Michael T; Chilakapati, Jaya; Kitchin, Kirk; Mason, Ronald P; Ramirez, Dario C

    2010-06-25

    Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis. PMID:20406811

  17. [Research progress on free radicals in human body].

    PubMed

    Wang, Q B; Xu, F P; Wei, C X; Peng, J; Dong, X D

    2016-08-10

    Free radicals are the intermediates of metabolism, widely exist in the human bodies. Under normal circumstances, the free radicals play an important role in the metabolic process on human body, cell signal pathway, gene regulation, induction of cell proliferation and apoptosis, so as to maintain the normal growth and development of human body and to inhibit the growth of bacteria, virus and cancer. However, when organic lesion occurs affected by external factors or when equilibrium of the free radicals is tipped in the human body, the free radicals will respond integratedly with lipids, protein or nucleic acid which may jeopardize the health of human bodies. This paper summarizes the research progress of the free radicals conducted in recent years, in relations to the perspective of the types, origins, test methods of the free radicals and their relationship with human's health. In addition, the possible mechanisms of environmental pollutants (such as polycyclic aromatic hydrocarbons) mediating oxidative stress and free radicals scavenging in the body were also summarized. PMID:27539355

  18. Myeloperoxidase-induced Genomic DNA-centered Radicals*

    PubMed Central

    Gomez-Mejiba, Sandra E.; Zhai, Zili; Gimenez, Maria S.; Ashby, Michael T.; Chilakapati, Jaya; Kitchin, Kirk; Mason, Ronald P.; Ramirez, Dario C.

    2010-01-01

    Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis. PMID:20406811

  19. Free Radical Reactions in Aqueous Solutions: Examples from Advanced Oxidation Processes for Wastewater from the Chemistry in Airborne Water Droplets

    NASA Astrophysics Data System (ADS)

    Baird, N. Colin

    1997-07-01

    Inorganic chemistry involving free radicals in aqueous solutions can be important in environmental processes. A common free radical reaction in aqueous solution is electron transfer, especially to the hydroxyl radical and to ozone. Hydrogen peroxide and free radicals related to it act as weak acids, so both their neutral and deprotonated forms must be considered in reactions. In Advanced Oxidation Processes, the hydroxyl radical concentration in water is greatly increased by reactions involving ozone and/or ultraviolet light. Irradiation of solid titanium dioxide can also be used to generate the radicals. The hydroxyl radicals are used in the Processes to initiate the oxidation of dissolved organic pollutants. Free radical reactions also play an important role in the chemistry of water droplets suspended in air in clouds and fogs. The radicals arise indirectly from the photoionization of dissolved organic compounds such as aldehydes and from the iron-catalyzed decomposition of dissolved hydrogen peroxide. They oxidize dissolved sulfur dioxide and certain organic compounds.

  20. Involvement of free radicals in excitotoxicity in vivo.

    PubMed

    Schulz, J B; Henshaw, D R; Siwek, D; Jenkins, B G; Ferrante, R J; Cipolloni, P B; Kowall, N W; Rosen, B R; Beal, M F

    1995-05-01

    Recent evidence has linked excitotoxicity with the generation of free radicals. We examined whether free radical spin traps can attenuate excitotoxic lesions in vivo. Pretreatment with N-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) significantly attenuated striatal excitotoxic lesions in rats produced by N-methyl-D-aspartate (NMDA), kainic acid, and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). In a similar manner, striatal lesions produced by 1-methyl-4-phenylpyridinium (MPP+), malonate, and 3-acetylpyridine were significantly attenuated by either S-PBN or alpha-phenyl-N-tert-butylnitrone (PBN) treatment. Administration of S-PBN in combination with the NMDA antagonist MK-801 produced additive effects against malonate and 3-acetylpyridine toxicity. Malonate injections resulted in increased production of hydroxyl free radicals (.OH) as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid (DHBA). This increase was significantly attenuated by S-PBN, consistent with a free radical scavenging effect. S-PBN had no effects on malonate-induced ATP depletions and had no significant effect on spontaneous striatal electrophysiologic activity. These results provide the first direct in vivo evidence for the involvement of free radicals in excitotoxicity and suggest that antioxidants may be useful in treating neurologic illnesses in which excitotoxic mechanisms have been implicated. PMID:7536809

  1. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species.

    PubMed

    Chandrasekara, Anoma; Shahidi, Fereidoon

    2011-01-12

    Oxidative stress, caused by reactive oxygen species (ROS), is responsible for modulating several pathological conditions and aging. Soluble and bound phenolic extracts of commonly consumed millets, namely, kodo, finger (Ravi), finger (local), foxtail, proso, little, and pearl, were investigated for their phenolic content and inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS, namely, hydroxyl radical, peroxyl radical, hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl), and singlet oxygen ((1)O(2)). Inhibition of DPPH and hydroxyl radicals was detrmined using electron paramagnetic resonance (EPR) spectroscopy. The peroxyl radical inhibitory activity was measured using the oxygen radical absorbance capacity (ORAC) assay. The scavenging of H(2)O(2), HOCl, and (1)O(2) was evaluated using colorimetric methods. The results were expressed as micromoles of ferulic acid equivalents (FAE) per gram of grain on a dry weight basis. In addition, major hydroxycinnamic acids were identified and quantified using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (MS). All millet varieties displayed effective radical and ROS inhibition activities, which generally positively correlated with phenolic contents, except for hydroxyl radical. HPLC analysis revealed the presence of ferulic and p-coumaric acids as major hydroxycinnamic acids in phenolic extract and responsible for the observed effects. Bound extracts of millet contributed 38-99% to ROS scavenging, depending on the variety and the test system employed. Hence, bound phenolics must be included in the evaluation of the antioxidant activity of millets and other cereals. PMID:21133411

  2. Synthesis, molecular modeling and biological evaluation of novel 2-allyl amino 4-methyl sulfanyl butyric acid as α-amylase and α-glucosidase inhibitor

    NASA Astrophysics Data System (ADS)

    Balan, Kannan; Perumal, Perumal; Sundarabaalaji, Narayanan; Palvannan, Thayumanavan

    2015-02-01

    In the present study 2-allyl amino 4-methyl sulfanyl butyric acid (AMSB) was synthesized in good yield. AMSB was characterized by Fourier transforms infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR) (1H and 13C) and Liquid chromatography mass spectrometry (LCMS). The radical scavenging activity and reducing power assay of AMSB was assessed using 1-1-diphenyl 2-picryl hydrazyl (DPPH), 2,2‧-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power assay (FRAP) and was found to be 44.1, 34.71 and 41.7 μg/ml respectively. The compound showed effective inhibition against α-amylase and α-glucosidase. AMSB was identified to be a reversible mixed noncompetitive inhibitor of α-amylase and α-glucosidase. The molecular docking study was carried out to evaluate the specific groove binding properties and affords valuable information of AMSB binding mode in the active site of α-glucosidase the study may lead to the which leads to the rational design of new class of antidiabetic drugs targeting α-glucosidase based on AMSB in near future.

  3. Enhancement of anti arthritic effect of quercetin using thioglycolic acid-capped cadmium telluride quantum dots as nanocarrier in adjuvant induced arthritic Wistar rats.

    PubMed

    Jeyadevi, R; Sivasudha, T; Rameshkumar, A; Ananth, D Arul; Aseervatham, G Smilin Bell; Kumaresan, K; Kumar, L Dinesh; Jagadeeswari, S; Renganathan, R

    2013-12-01

    In this present study, we investigated thio glycolic acid-capped cadmium telluride quantum dots (TGA-CdTe QDs) as nano carrier to study the antiarthritic activity of quercetin on adjuvant induced arthritic Wistar rats. The free radical scavenging activity of QDs-QE complex was evaluated by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide anion scavenging assays. Fifteen days after adjuvant induction, arthritic rats received QDs-QE complex orally at the dose of 0.2 and 0.4mg/kg daily for 3 weeks. Diclofenac sodium (DF) was used as a reference drug. Administration of QDs-QE complex showed a significant reduction in inflammation and improvement in cartilage regeneration. Treatment with QDs-QE complex significantly (P<0.05) reduced the expressions lipid peroxidation and showed significant (P<0.05) increase in activities of antioxidant enzymes such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) catalase (CAT) levels in paw tissue. C-reactive protein (CRP), rheumatoid factor (RF), red blood cells (RBC) and white blood cells (WBC) count and erythrocyte sedimentation rate (ESR) of experimental animals were also estimated. Histology of hind limb tissue in experimental groups confirmed the complete cartilage regeneration in arthritis induced rats treated with QDs-QE complex. Based on our findings, we suggest that the QDs act as nano carrier for the drugs used in the treatment of various degenerative diseases. PMID:23994749

  4. Detection of hydroxyl radical in plasma reaction on toluene removal.

    PubMed

    Guo, Yufang; Liao, Xiaobin; Ye, Daiqi

    2008-01-01

    A new method was introduced to detect the concentration of OH radical in dielectric barrier discharge (DBD) reaction. A film, which was impregnated with salicylic acid, was used to detect OH radical in plasma reaction at room temperature and atmospheric pressure. Salicylic acid reacts with OH radical and produces 2,5-dihydroxybenzoic acid (2,5-DHBA). Then, a high performance liquid chromatography (HPLC) was carried out to detect the concentration of 2,5-DHBA. Therefore, OH radical in nonthermal plasma reaction could be calculated. In this plasma reaction, the applied voltage was controlled at 10 kV, the initial concentration of toluene was 400 mg/m3, and the gas flow rate was 300 ml/min. It was observed that when the film was placed away from the plasma area, 2,5-DHBA could not be detected by HPLC, although the sampling time lasted for 48 h. On the other hand, when the film was placed in the plasma area and the sampling time being too long (> 4 h), the concentration of 2,5-DHBA was also below detection limit, and it could not be detected by HPLC. However, when the film was placed in the plasma reaction field with the sampling time being 3 h, the concentration of OH radical was calculated to be 10.54 x 10(12) cm(-3). In addition, concentration of OH radical was investigated under different humidity, such as 0.2%, 0.4%, 0.6%, 0.8%, and 1.0%. The results showed that the amount of OH radical stayed at order of magnitude of 10(12) cm(-3) and increased with the increase of humidity. PMID:19209627

  5. Formation of free radicals in the photochemical modification of antifrictional plastic compositions

    SciTech Connect

    Klimov, E.S.; Vakar, A.A.; Sokolov, V.P.; Okhlobystin, O.Yu.

    1987-09-20

    Using ESR spectroscopy the authors investigated the photolysis and radical composition of a plastic lubricant composed of polyethylene, perfluoroalkylpolyester 240, oleic acid, mineral oil, and benzophenone. The spectra are comprehensively analyzed. Hyperfine structure and spin trapping are given for the polyalkyl radicals. The photochemical modification of the lubricant leading to these radicals, and their reaction with oxygen, are determined to be responsible for the enhanced adhesion of the plasticizers to the polymer.

  6. Addressing Free Radical Oxidation in Acne Vulgaris

    PubMed Central

    Criscito, Maressa C.; Schlesinger, Todd E.; Verdicchio, Robert; Szoke, Ernest

    2016-01-01

    Objective: Comparatively little attention has been paid to the role of free radical oxidation in acne vulgaris. Here, using the traditional abnormalities cited for acne, the authors address the role of free radical oxidation throughout the pathogenesis by detailing the chemistry that may contribute to clinical changes. To probe the effects of free radical oxidation and test an antioxidant, they conducted a preliminary study of topically applied vitamin E. Methods: Seventeen patients with mild-to-moderate acne vulgaris were evaluated over an eight-week period in two private dermatology practices in this open-label study. All patients enrolled were on the same baseline regimen of salicylic acid and benzoyl peroxide. This regimen was then supplemented with topical vitamin E in sunflower seed oil. Results: At the end of the eight-week period, all patients demonstrated clinical improvement, as indicated by a reduction in the number of lesions and global mean difference. A statistically significant reduction was noted as early as Week 2. Enrolled patients also expressed a positive experience due to good tolerability and easy application. Conclusion: Although the exact pathogenesis of acne vulgaris remains unknown, the presence of excessive reactive oxygen species can be implicated in each of the major abnormalities involved. This presence, along with the positive results of the authors’ preliminary study, demonstrates the need for more exploration on the use of topical antioxidants in limiting free radical oxidation in the acne model. This paper is designed to stimulate academic discussion regarding a new way of thinking about the disease state of acne. PMID:26962389

  7. Competitive reduction of perferrylmyoglobin radicals by protein thiols and plant phenols.

    PubMed

    Jongberg, Sisse; Lund, Marianne N; Skibsted, Leif H; Davies, Michael J

    2014-11-19

    Radical transfer from perferrylmyoglobin to other target species (myofibrillar proteins, MPI) and bovine serum albumin (BSA), extracts from green tea (GTE), maté (ME), and rosemary (RE), and three phenolic compounds, catechin, caffeic acid, and carnosic acid) was investigated by electron paramagnetic resonance (EPR) spectroscopy to determine the concentrations of plant extracts required to protect against protein oxidation. Blocking of MPI thiol groups by N-ethylmaleimide was found to reduce the rate of reaction of MPI with perferrylmyoglobin radicals, signifying the importance of protein thiols as radical scavengers. GTE had the highest phenolic content of the three extracts and was most effective as a radical scavenger. IC50 values indicated that the molar ratio between phenols in plant extract and MPI thiols needs to be >15 in order to obtain efficient protection against protein-to-protein radical transfer in meat. Caffeic acid was found most effective among the plant phenols. PMID:25343706

  8. In vivo copper-mediated free radical production: an ESR spin-trapping study

    NASA Astrophysics Data System (ADS)

    Kadiiska, Maria B.; Mason, Ronald P.

    2002-04-01

    Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the electron spin resonance (ESR) spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid or paraquat. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl- N- t-butyl- nitrone (PBN). In contrast, lipid derived radical was detected in vivo in copper-challenged, vitamin E and selenium-deficient rats. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. Since copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stablilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts generated ex vivo could be mistaken for radical adducts produced in vivo and excreted into the bile.

  9. Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of liver cells.

    PubMed

    Borovic, Suzana; Tirzitis, Gunars; Tirzite, Dace; Cipak, Ana; Khoschsorur, Gholam A; Waeg, Georg; Tatzber, Franz; Scukanec-Spoljar, Mira; Zarkovic, Neven

    2006-05-10

    1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely related to derivatives of 1,4-dihydropyridine, a well-known calcium channel antagonists. 1,4-DHINA we used were derived from a well-known antioxidant Diludin. Although some compounds have neuromodulatory or antimutagenic properties, their activity mechanisms are not well known. This study was performed to obtain data on antioxidant and bioprotective activities of: 2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydroisonicotinic acid (Ia); sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)glutamate (Ib) and sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)ethane-sulphate (Ic). 1,4-DHINA's activities were studied in comparison to Trolox by: N,N-Diphenyl-N'-picrylhydrazyl (DPPH*), deoxyribose degradation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging and antioxidative capacity assays; copper-induced lipid peroxidation of cultured rat liver cells (malondialdehyde determination by high performance liquid chromatography and 4-hydroxynonenal-protein conjugates by dot-blot); (3)H-thymidine incorporation and trypan blue assay for liver cells growth and viability. In all assays used Ia was the most potent antioxidant. Ia was also a potent antioxidant at non-toxic concentrations for liver cell cultures. It completely abolished, while Ic only slightly decreased copper-induced lipid peroxidation of liver cells. Thus, antioxidant capacities are important activity principle of Ia, which was even superior to Trolox in the cell cultures used, while activity principles of Ic and Ib remain yet to be determined. PMID:16600211

  10. Structure and radical scavenging activity relationships of pyrolytic lignins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This work deals with antioxidant properties of pyrolytic lignins against two free radicals, the 1,1-diphenyl-2-picrylhydrazyl and the 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid). Pyrolytic lignins produced by the thermal pyrolysis of the Etek lignin were extracted from the liquid pyrolysi...

  11. Free Radical Scavenging Activity of Scoparia dulcis Extract.

    PubMed

    Babincová, M.; Sourivong, P.

    2001-01-01

    We studied the scavenging capabilities of an extract of Scoparia dulcis (a cosmopolitan weed widespread in Laos and Vietnam) for 1-diphenyl-2-picrylhydrazyl and measured hemoglobin-catalyzed linoleic acid peroxidation with an oxygen electrode. Our results demonstrated strong antioxidant activity corresponding to mitigation of the generation of hydroxyl radicals, a possible rationale for the observed therapeutic effects of this weed. PMID:12639412

  12. Hydroxyl radical induced degradation of salicylates in aerated aqueous solution

    NASA Astrophysics Data System (ADS)

    Szabó, László; Tóth, Tünde; Homlok, Renáta; Rácz, Gergely; Takács, Erzsébet; Wojnárovits, László

    2014-04-01

    Ionizing radiation induced degradation of acetylsalicylic acid, its hydrolysis product salicylic acid and a salicylic acid derivative 5-sulpho-salicylic acid, was investigated in dilute aqueous solutions by UV-vis spectrophotometry, HPLC separation and diode-array or MS/MS detection, chemical oxygen demand, total organic carbon content and by Vibrio fischeri toxicity measurements. Hydroxyl radicals were shown to degrade these molecules readily, and first degradation products were hydroxylated derivatives in all cases. Due to the by-products, among them hydrogen peroxide, the toxicity first increased and then decreased with the absorbed dose. With prolonged irradiation complete mineralization was achieved.

  13. Investigation of the free radical scavenging activity of Ginkgo biloba L. leaves.

    PubMed

    Ellnain-Wojtaszek, M; Kruczyński, Z; Kasprzak, J

    2003-02-01

    The free radical scavenging activity of methanolic, ethanolic and aqueous extracts from Ginkgo biloba leaves, has been determined by EPR (electron paramagnetic resonance) using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. The investigation has also included selected constituents of G. biloba leaves, protocatechuic and p-coumaric acids, quercetin, rutin, isoginkgetin and (+)-catechin. PMID:12628386

  14. Peroxy radical partitioning during the AMMA radical intercomparison exercise

    NASA Astrophysics Data System (ADS)

    Andrés-Hernández, M. D.; Stone, D.; Brookes, D. M.; Commane, R.; Reeves, C. E.; Huntrieser, H.; Heard, D. E.; Monks, P. S.; Burrows, J. P.; Schlager, H.; Kartal, D.; Evans, M. J.; Floquet, C. F. A.; Ingham, T.; Methven, J.; Parker, A. E.

    2010-11-01

    Peroxy radicals were measured onboard two scientific aircrafts during the AMMA (African Monsoon Multidisciplinary Analysis) campaign in summer 2006. This paper reports results from the flight on 16 August 2006 during which measurements of HO2 by laser induced fluorescence spectroscopy at low pressure (LIF-FAGE) and total peroxy radicals (RO2* = HO2+ΣRO2, R = organic chain) by two similar instruments based on the peroxy radical chemical amplification (PeRCA) technique were subject of a blind intercomparison. The German DLR-Falcon and the British FAAM-BAe-146 flew wing tip to wing tip for about 30 min making concurrent measurements on 2 horizontal level runs at 697 and 485 hPa over the same geographical area in Burkina Faso. A full set of supporting measurements comprising photolysis frequencies, and relevant trace gases like CO, NO, NO2, NOy, O3 and a wider range of VOCs were collected simultaneously. Results are discussed on the basis of the characteristics and limitations of the different instruments used. Generally, no data bias are identified and the RO2* data available agree quite reasonably within the instrumental errors. The [RO2*]/[HO2] ratios, which vary between 1:1 and 3:1, as well as the peroxy radical variability, concur with variations in photolysis rates and in other potential radical precursors. Model results provide additional information about dominant radical formation and loss processes.

  15. Peroxy radical partitioning during the AMMA radical intercomparison exercise

    NASA Astrophysics Data System (ADS)

    Andrés-Hernández, M. D.; Stone, D.; Brookes, D. M.; Commane, R.; Reeves, C. E.; Huntrieser, H.; Heard, D. E.; Monks, P. S.; Burrows, J. P.; Schlager, H.; Kartal, D.; Evans, M. J.; Floquet, C. F. A.; Ingham, T.; Methven, J.; Parker, A. E.

    2010-04-01

    Peroxy radicals were measured onboard two scientific aircrafts during the AMMA (African Monsoon Multidisciplinary Analysis) campaign in summer 2006. This paper reports results from the flight on 16 August 2006 during which measurements of HO2 by laser induced fluorescence spectroscopy at low pressure (LIF-FAGE) and total peroxy radicals (RO2*=HO2+ΣRO2, R= organic chain) by two similar instruments based on the peroxy radical chemical amplification (PerCA) technique were subject of a blind intercomparison. The German DLR-Falcon and the British FAAM-BAe-146 flew wing tip to wing tip for about 30 min making concurrent measurements on 2 horizontal level runs at 697 and 485 hPa over the same geographical area in Burkina Faso. A full set of supporting measurements comprising photolysis frequencies, and relevant trace gases like CO, NO, NO2, NOy, O3 and a wider range of VOCs were collected simultaneously. Results are discussed on the basis of the characteristics and limitations of the different instruments used. Generally, no data bias are identified and the RO2* data available agree quite reasonably within the instrumental errors. The [RO2*]/[HO2] ratios, which vary between 1:1 and 3:1, as well as the peroxy radical variability, concur with variations in photolysis rates and in other potential radical precursors. Model results provide additional information about dominant radical formation and loss processes.

  16. Assessment of phenolic content, free-radical-scavenging capacity genotoxic and anti-genotoxic effect of aqueous extract prepared from Moricandia arvensis leaves.

    PubMed

    Skandrani, I; Limem, I; Neffati, A; Boubaker, J; Ben Sghaier, M; Bhouri, W; Bouhlel, I; Kilani, S; Ghedira, K; Chekir-Ghedira, L

    2010-02-01

    The present study was undertaken to provide a set of data on the safety of an aqueous extract (AQE) from Moricandia arvensis. For this reason, Escherichia coli tested strains PQ35 and PQ37 were used to detect induction of DNA lesions by AQE. The SOS Chromotest showed that AQE induced a marginally genotoxic effect, as expressed by the induction factor (IF) value only with E. coli PQ37 tested strain (IF=1.77 at a dose of 250 microg/assay). The measurement of the anti-genotoxic activity of the AQE was also studied by inhibition of beta-galactosidase induction. A significant anti-genotoxic effect was observed with different tested doses of AQE, which suggests that M. arvensis extract has the potential to protect DNA from the action of nitrofurantoïn (NF) and free radicals generated by hydrogen peroxide (H2O2). In addition to anti-genotoxic activity, AQE showed a free-radical-scavenging capacity towards ABTS+* and DPPH*. Total phenolic content was also evaluated following Folin-Ciocalteu method and results indicated high correlation between total phenol content and anti-genotoxic and antioxidant activities for AQE, but the highest correlation was showed with its capacity to stabilize ABTS+* (R2=0.9944). PMID:19951736

  17. New knowledge on the antiglycoxidative mechanism of chlorogenic acid.

    PubMed

    Fernandez-Gomez, Beatriz; Ullate, Monica; Picariello, Gianluca; Ferranti, Pasquale; Mesa, Maria Dolores; del Castillo, Maria Dolores

    2015-06-01

    The role of chlorogenic acid (CGA) in the formation of advanced glycation end-products (AGEs) (glycoxidation reaction) was studied. Model systems composed of bovine serum albumin (BSA) (1 mg mL(-1)) and methylglyoxal (5 mM) under mimicked physiological conditions (pH 7.4, 37 °C) were used to evaluate the antiglycoxidative effect of CGA (10 mM). The stability of CGA under reaction conditions was assayed by HPLC and MALDI-TOF MS. The glycoxidation reaction was estimated by analysis of free amino groups by the OPA assay, spectral analysis of fluorescent AGEs and total AGEs by ELISA, and colour formation by absorbance at 420 nm. Structural changes in protein were evaluated by analysis of phenol bound to the protein backbone using the Folin reaction, UV-Vis spectral analysis and MALDI-TOF-MS, while changes in protein function were measured by determining the antioxidant capacity using the ABTS radical cation decolourisation assay. CGA was isomerised and oxidised under our experimental conditions. Evidence of binding between BSA and multiple CGA and/or its derivative molecules (isomers and oxidation products) was found. CGA inhibited (p < 0.05) the formation of fluorescent and total AGEs at 72 h of reaction by 91.2 and 69.7%, respectively. The binding of phenols to BSA significantly increased (p < 0.001) its antioxidant capacity. Correlations between free amino group content, phenol bound to protein and antioxidant capacity were found. Results indicate that CGA simultaneously inhibits the formation of potentially harmful compounds (AGEs) and promotes the generation of neoantioxidant structures. PMID:26037734

  18. Free Radical Scavenging and Antioxidant Activities of Silymarin Components

    PubMed Central

    Anthony, Kevin P.; Saleh, Mahmoud A.

    2013-01-01

    Silymarin is an over the counter food supplement that is sold as a liver enhancement and liver protection preparation. It is a major constituent of the seeds of Silybum marianum which is composed of a mixture of seven major components and several minor compounds. The seven major components: taxifolin, silychristin, silydianin, silybin A, silybin B, iso-silybin A and iso-silybin B were isolated and purified from the crude mixture of silymarin using preparative high performance liquid chromatography to determine which were the most effective for liver protection. Free radical scavenging, hydroxyl radical antioxidant capacity, oxygen radical antioxidant capacity, trolox-equivalent antioxidant capacity and total antioxidant capacity antioxidant activities were determined for each of the individual purified components as well as the crude silymarin mixture. Taxifolin was the most effective component for scavenging free radicals in the DPPH assay with an EC50 of 32 µM far more effective than all other components which showed EC50 ranging from 115 to 855 µM. Taxifolin was also found to be the most effective antioxidant in the oxygen radical antioxidant capacity (ORAC) assay with a trolox equivalent of 2.43 and the second most effective in the hydroxyl radical antioxidant capacity (HORAC) assay with a gallic acid equivalent of 0.57. Other antioxidants assays did not show significant differences between samples. PMID:26784472

  19. Measurements of hydroxyl and hydroperoxy radicals during CalNex-LA: Model comparisons and radical budgets

    NASA Astrophysics Data System (ADS)

    Griffith, S. M.; Hansen, R. F.; Dusanter, S.; Michoud, V.; Gilman, J. B.; Kuster, W. C.; Veres, P. R.; Graus, M.; Gouw, J. A.; Roberts, J.; Young, C.; Washenfelder, R.; Brown, S. S.; Thalman, R.; Waxman, E.; Volkamer, R.; Tsai, C.; Stutz, J.; Flynn, J. H.; Grossberg, N.; Lefer, B.; Alvarez, S. L.; Rappenglueck, B.; Mielke, L. H.; Osthoff, H. D.; Stevens, P. S.

    2016-04-01

    Measurements of hydroxyl (OH) and hydroperoxy (HO2*) radical concentrations were made at the Pasadena ground site during the CalNex-LA 2010 campaign using the laser-induced fluorescence-fluorescence assay by gas expansion technique. The measured concentrations of OH and HO2* exhibited a distinct weekend effect, with higher radical concentrations observed on the weekends corresponding to lower levels of nitrogen oxides (NOx). The radical measurements were compared to results from a zero-dimensional model using the Regional Atmospheric Chemical Mechanism-2 constrained by NOx and other measured trace gases. The chemical model overpredicted measured OH concentrations during the weekends by a factor of approximately 1.4 ± 0.3 (1σ), but the agreement was better during the weekdays (ratio of 1.0 ± 0.2). Model predicted HO2* concentrations underpredicted by a factor of 1.3 ± 0.2 on the weekends, while measured weekday concentrations were underpredicted by a factor of 3.0 ± 0.5. However, increasing the modeled OH reactivity to match the measured total OH reactivity improved the overall agreement for both OH and HO2* on all days. A radical budget analysis suggests that photolysis of carbonyls and formaldehyde together accounted for approximately 40% of radical initiation with photolysis of nitrous acid accounting for 30% at the measurement height and ozone photolysis contributing less than 20%. An analysis of the ozone production sensitivity reveals that during the week, ozone production was limited by volatile organic compounds throughout the day during the campaign but NOx limited during the afternoon on the weekends.

  20. Biophysical Property and Broad Anti-HIV Activity of Albuvirtide, a 3-Maleimimidopropionic Acid-Modified Peptide Fusion Inhibitor

    PubMed Central

    Chong, Huihui; Yao, Xue; Zhang, Chao; Cai, Lifeng; Cui, Sheng; Wang, Youchun; He, Yuxian

    2012-01-01

    Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugate to serum albumin. Previous studies demonstrated its in vivo long half-life and potent anti-HIV activity. Here, we focused to characterize its biophysical properties and evaluate its antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to form a stable α-helical conformation with the target sequence and block the fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation. The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B′, CRF07_BC and CRF01_AE recombinants that are currently circulating in China. Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20. Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor. PMID:22403678

  1. School Finance-Radical Departure.

    ERIC Educational Resources Information Center

    Kimple, James

    1983-01-01

    It is proposed that New Jersey assume approximately 70 percent of the cost of its public schools. Several other proposals are presented, all a radical departure from current school funding practices. (BW)

  2. Free radical inactivation of pepsin

    NASA Astrophysics Data System (ADS)

    Josimović, Lj; Ruvarac, I.; Janković, I.; Jovanović, S. V.

    1994-06-01

    Alkylperoxy radicals containing one, two or three chlorine atoms, CO -2, O 2 - were reacted with pepsin in aqueous solutions. It was found that only Cl 3COO and CO -2 inactive pepsin, attacking preferentially the disulfide bridge. Transient spectra obtained upon completion of the Cl 3COO + pepsin reaction at pH 5 indicate that 20% of initially produced Cl 3COO radicals oxidizes tryptophan residues, and 40% disulfide bridges. The inactivation induced by the Cl 3COO radical increases at lower pH, and the maximal inactivation, Gin = 5.8, was observed at pH 1.5. The inactivation of pepsin by CO -2 radicals depends on the absorbed dose. The maximal inactivation, Gin = 4.5, was determined in the dose range from 38 to 53 Gy.

  3. Redox Properties of Free Radicals.

    ERIC Educational Resources Information Center

    Neta, P.

    1981-01-01

    Describes pulse radiolysis as a useful means in studing one-electron redox potentials. This method allows the production of radicals and the determination of their concentration and rates of reaction. (CS)

  4. [Alcohol and free oxygen radicals].

    PubMed

    Mira, M L; Manso, C F

    1993-05-01

    Oxygen free radicals may be generated during ethanol metabolization by cytochrome P450, or due to the formation of xanthine oxidase by ethanol effect on xanthine dehydrogenase. After transformation into acetaldehyde, the metabolism of this compound by xanthine oxidase or by aldehyde oxidase also generates oxygen radicals. We present the hypothesis of a vicious cycle during ethanol metabolization by aldehyde oxidase, which would amplify the process and be responsible for an increased degree of lipid peroxidation. PMID:8393265

  5. The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

    PubMed Central

    2013-01-01

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. PMID:24900652

  6. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

    PubMed

    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. PMID:24900652

  7. Mechanisms of radical formation in beef and chicken meat during high pressure processing evaluated by electron spin resonance detection and the addition of antioxidants.

    PubMed

    Bolumar, Tomas; Andersen, Mogens L; Orlien, Vibeke

    2014-05-01

    The generation of radicals during high pressure (HP) processing of beef loin and chicken breast was studied by spin trapping and electron spin resonance detection. The pressurization resulted in a higher level of spin adducts in the beef loin than in the chicken breast. It was shown that radicals were formed in the sarcoplasmic and myofibrillar fractions as well as in the non-soluble protein fraction due to the HP treatment, indicating that other radicals than iron-derived radicals were formed, and most likely protein-derived radicals. The addition of iron as well as the natural antioxidants caffeic acid, rosemary extract, and ascorbic acid resulted in an increased formation of radicals during the HP treatment, whereas addition of ethylendiamintetraacetic acid (EDTA) reduced the radical formation. This suggests that iron-species (protein-bound or free) catalyses the formation of radicals when meat systems are submitted to HP. PMID:24360471

  8. Persistent free radical ESR signals in marine bivalve tissues

    SciTech Connect

    Mehlorn, R.J.; Mendez, A.T.; Higashi, R.; Fan, T.

    1992-08-01

    Freeze-dried homogenates of the oyster Crassostrea rhizophorae collected from waters in Puerto Rico near urban and industrial sites as well as at relatively pristine locations yielded electron spin resonance (ESR) spectra characteristic of free radicals as well as spectral components of transition metal ions, dominated by manganese. The magnitudes of these ESR signals and the concentrations of trace elements (determined by X-ray fluorescence) varied considerably among oyster samples, masking any potential correlation with polluted waters. Laboratory studies were initiated to identify the factors controlling the magnitudes of the tissue free radical ESR signals. Another mollusc, Mytilus californianus collected at the Bodega Marine laboratory in northern California, was fractionated into goneds and remaining tissue. Freeze-dried homogenates of both fractions exhibited ESR signals that increased gradually with time. ESR signals were observed in freeze-dried perchloric acid (PCA) precipitates of the homogenates, delipidated PCA precipitates, and in chloroform extracts of these precipitates. Acid hydrolysis to degrade proteins to amino acids produced a residue, which yielded much larger ESR free radical signals after freeze-drying. Freshly thawed homogenates of Crassostrea rhizophorae also exhibited ESR signals. A laboratory model of copper stress in Crassostrea rhizophorae was developed to study the effect of this transition metal on dssue free radicals. Preliminary results suggested that sublethal copper exposure had little effect on tissue fire radicals, except possibly for a signal enhancement in an oyster fraction that was enriched in kidney granules. Since kidney granules are known to accumulate heavy metals in mussels and probably other marine bivalves, this signal enhancement may prove to be an indicator of free radical processes associated with heavy metal deposition in molluscs.

  9. Isolation and Bioactivity Analysis of Ethyl Acetate Extract from Acer tegmentosum Using In Vitro Assay and On-Line Screening HPLC-ABTS+ System

    PubMed Central

    Song, Na-Young; Oh, You Chang; Cho, Won-Kyung; Ma, Jin Yeul

    2014-01-01

    The Acer tegmentosum (3 kg) was extracted using hot water, and the freeze-dried extract powder was partitioned successively using dichloromethane (DCM), ethyl acetate (EA), butyl alcohol (n-BuOH), and water. From the EA extract fraction (1.24 g), five phenolic compounds were isolated by the silica gel, octadecyl silica gel, and Sephadex LH-20 column chromatography. Based on spectroscopic methods such as 1H-NMR, 13C-NMR, and LC/MS the chemical structures of the compounds were confirmed as feniculin (1), avicularin (2), (+)-catechin (3), (−)-epicatechin (4), and 6′-O-galloyl salidroside (5). Moreover, a rapid on-line screening HPLC-ABTS+ system for individual bioactivity of the EA-soluble fraction (five phenolic compounds) was developed. The results indicated that compounds 1 and 2 were first isolated from the A. tegmentosum. The anti-inflammatory activities and on-line screening HPLC-ABTS+ assay method of these compounds in LPS-stimulated murine macrophages were rapid and efficient for the investigation of bioactivity of A. tegmentosum. PMID:25386382

  10. A comparison of glucose oxidase and aldose dehydrogenase as mediated anodes in printed glucose/oxygen enzymatic fuel cells using ABTS/laccase cathodes.

    PubMed

    Jenkins, Peter; Tuurala, Saara; Vaari, Anu; Valkiainen, Matti; Smolander, Maria; Leech, Dónal

    2012-10-01

    Current generation by mediated enzyme electron transfer at electrode surfaces can be harnessed to provide biosensors and redox reactions in enzymatic fuel cells. A glucose/oxygen enzymatic fuel cell can provide power for portable and implantable electronic devices. High volume production of enzymatic fuel cell prototypes will likely require printing of electrode and catalytic materials. Here we report on preparation and performance of, completely enzymatic, printed glucose/oxygen biofuel cells. The cells are based on filter paper coated with conducting carbon inks, enzyme and mediator. A comparison of cell performance using a range of mediators for either glucose oxidase (GOx) or aldose dehydrogenase (ALDH) oxidation of glucose at the anode and ABTS and a fungal laccase, for reduction of oxygen at the cathode, is reported. Highest power output, although of limited stability, is observed for ALDH anodes mediated by an osmium complex, providing a maximum power density of 3.5 μW cm(-2) at 0.34 V, when coupled to a laccase/ABTS cathode. The stability of cell voltage in a biobattery format, above a threshold of 200 mV under a moderate 75 kΩ load, is used to benchmark printed fuel cell performance. Highest stability is obtained for printed fuel cells using ALDH, providing cell voltages over the threshold for up to 74 h, compared to only 2 h for cells with anodes using GOx. These results provide promising directions for further development of mass-producible, completely enzymatic, printed biofuel cells. PMID:22200380

  11. Radical Scavenging Activities of Tannin Extracted from Amaranth (Amaranthus caudatus L.).

    PubMed

    Jo, Hyeon-Ju; Chung, Kang-Hyun; Yoon, Jin A; Lee, Kwon-Jai; Song, Byeong Chun; An, Jeung Hee

    2015-06-01

    This study investigates the bioactivity of tannin from amaranth (Amaranthus caudatus L.) extracts. The antioxidant activities of the extracts from amaranth leaves, flowers, and seeds were evaluated. Tannin from leaves of amaranth has been evaluated for superoxide scavenging activity by using DPPH and ABTS(+) analysis, reducing power, protective effect against H2O2-induced oxidative damage in L-132 and BNL-CL2 cells, and inhibition of superoxide radical effects on HL-60 cells. At a concentration of 100 μg/ml, tannin showed protective effects and restored cell survival to 69.2% and 41.8% for L-132 and BNL-CL2 cells, respectively. Furthermore, at the same concentration, tannin inhibited 41% of the activity of the superoxide radical on HL-60 cells and 43.4% of the increase in nitric oxide levels in RAW 264.7 cells. The expression levels of the antioxidant-associated protein SOD-1 were significantly increased in a concentration-dependent manner in RAW 264.7 cells treated with tannin from amaranth leaves. These results suggest that tannin from the leaves of Amaranthus caudatus L. is a promising source of antioxidant component that can be used as a food preservative or nutraceutical. PMID:25639718

  12. Radical scavenging and antioxidant effects of Matricaria chamomilla polyphenolic-polysaccharide conjugates.

    PubMed

    Kolodziejczyk-Czepas, Joanna; Bijak, Michal; Saluk, Joanna; Ponczek, Michal B; Zbikowska, Halina M; Nowak, Pawel; Tsirigotis-Maniecka, Marta; Pawlaczyk, Izabela

    2015-01-01

    Matricaria chamomilla L. (MC), a member of the Asteraceae family, is one of the oldest medicinal plants, widely used worldwide for a variety of healing applications. Its recommendations, derived from both traditional and modern medicine, include numerous disorders such as inflammation, ulcers, wounds, gastrointestinal disorders, stomach ache, pharyngitis, rheumatic pain, as well as the other ailments. This work is focused on another aspect of the biological activity of chamomile polyphenolic-polysaccharide conjugates--their antioxidant properties in the protection of blood plasma components against in vitro oxidative stress. Measurements of DPPH and ABTS radical scavenging indicated considerable anti-free radical action of MC. Pre-incubation of blood plasma with MC considerably diminished the extent of ONOO(-)-induced oxidative modifications such as protein carbonyl groups, SH groups, 3-nitrotyrosine, as well as the formation of lipid hydroperoxides. The analysis of the FRAP assay result shows a considerable increase of ferric reducing ability of blood plasma in the presence of MC. The results obtained in this study indicate that polyphenolic-polysaccharide conjugates isolated from M. chamomilla substances possess antioxidant properties. The M. chamomilla macromolecular glycoconjugates may be useful in the creation of new natural-based medications or dietary supplements, helpful in the prevention and treatment of oxidative stress-mediated disorders. PMID:25285848

  13. Mechano-chemical radical formation and polymerization initiation during wet grinding of alumina.

    PubMed

    Damm, C; Peukert, W

    2011-11-01

    The formation of free radicals during wet grinding of alumina in a stirred media mill was studied by using the test radical 2,2-diphenyl-1-picrylhydracyl (DPPH). The kinetics of mechano-chemical radical formation follows a zeroth-order rate law. Particle breakage as well as mechanical activation of the surface of the alumina particles contributes to the radical formation. The rate constants of the radical formation due to mechanical activation of the particle surface k(A) and due to particle breakage k(B) depend on the milling process parameters. The radical formation during wet grinding of alumina was exploited to initiate mechano-chemical polymerization reactions of acrylic acid and acryl amide, respectively. In this way nanoparticles functionalized with polyacrylic acid and polyacryl amide, respectively, are obtained. The influence of the milling process parameters on the kinetics of mechano-chemical radical formation and on the grafted amount of polymer is discussed on the basis of stress energy and number of stress events in the mill. A correlation between the grafted amount of polyacryl amide on the alumina particles and the total radical formation rate was found showing that the concentration of mechano-chemically formed free radicals governs the efficacy of a chemical reaction at activated particle surfaces. PMID:21820123

  14. Crystalline bipyridinium radical complexes and uses thereof

    DOEpatents

    Fahrenbach, Albert C.; Barnes, Jonathan C.; Li, Hao; Stoddart, J. Fraser; Basuray, Ashish Neil; Sampath, Srinivasan

    2015-09-01

    Described herein are methods of generating 4,4'-bipyridinium radical cations (BIPY.sup..cndot.+), and methods for utilizing the radical-radical interactions between two or more BIPY.sup..cndot.+ radical cations that ensue for the creation of novel materials for applications in nanotechnology. Synthetic methodologies, crystallographic engineering techniques, methods of physical characterization, and end uses are described.

  15. Formation of bromate in sulfate radical based oxidation: mechanistic aspects and suppression by dissolved organic matter.

    PubMed

    Lutze, Holger V; Bakkour, Rani; Kerlin, Nils; von Sonntag, Clemens; Schmidt, Torsten C

    2014-04-15

    Sulfate radical based oxidation is discussed being a potential alternative to hydroxyl radical based oxidation for pollutant control in water treatment. However, formation of undesired by-products, has hardly been addressed in the current literature, which is an issue in other oxidative processes such as bromate formation in ozonation of bromide containing water (US-EPA and EU drinking water standard of bromate: 10 μg L(-1)). Sulfate radicals react fast with bromide (k = 3.5 × 10(9) M(-1) s(-1)) which could also yield bromate as final product. The mechanism of bromate formation in aqueous solution in presence of sulfate radicals has been investigated in the present paper. Further experiments were performed in presence of humic acids and in surface water for investigating the relevance of bromate formation in context of pollutant control. The formation of bromate by sulfate radicals resembles the well described mechanism of the hydroxyl radical based bromate formation. In both cases hypobromous acid is a requisite intermediate. In presence of organic matter formation of bromate is effectively suppressed. That can be explained by formation of superoxide formed in the reaction of sulfate radicals plus aromatic moieties of organic matter, since superoxide reduces hypobromous acid yielding bromine atoms and bromide. Hence formation of bromate can be neglected in sulfate radical based oxidation at typical conditions of water treatment. PMID:24565691

  16. Standard Electrode Potentials Involving Radicals in Aqueous Solution: Inorganic Radicals

    SciTech Connect

    Armstrong, David A.; Huie, Robert E.; Koppenol, Willem H.; Lymar, Sergei V.; Merenyi, Gabor; Neta, Pedatsur; Ruscic, Branko; Stanbury, David M.; Steenken, Steen; Wardman, Peter

    2015-12-01

    Recommendations are made for standard potentials involving select inorganic radicals in aqueous solution at 25 °C. These recommendations are based on a critical and thorough literature review and also by performing derivations from various literature reports. The recommended data are summarized in tables of standard potentials, Gibbs energies of formation, radical pKa’s, and hemicolligation equilibrium constants. In all cases, current best estimates of the uncertainties are provided. An extensive set of Data Sheets is appended that provide original literature references, summarize the experimental results, and describe the decisions and procedures leading to each of the recommendations

  17. Mechanically Stabilized Tetrathiafulvalene Radical Dimers

    SciTech Connect

    Coskun, Ali; Spruell, Jason M.; Barin, Gokhan; Fahrenbach, Albert C.; Forgan, Ross S.; Colvin, Michael T.; Carmieli, Raanan; Benitez, Diego; Tkatchouk, Ekaterina; Friedman, Douglas C.; Sarjeant, Amy A.; Wasielewski, Michael R.; Goddard, William A.; Stoddart, J. Fraser

    2011-01-01

    Two donor-acceptor [3]catenanes—composed of a tetracationic molecular square, cyclobis(paraquat-4,4'-biphenylene), as the π-electron deficient ring and either two tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) containing macrocycles or two TTF-butadiyne-containing macrocycles as the π-electron rich components—have been investigated in order to study their ability to form TTF radical dimers. It has been proven that the mechanically interlocked nature of the [3]catenanes facilitates the formation of the TTF radical dimers under redox control, allowing an investigation to be performed on these intermolecular interactions in a so-called “molecular flask” under ambient conditions in considerable detail. In addition, it has also been shown that the stability of the TTF radical-cation dimers can be tuned by varying the secondary binding motifs in the [3]catenanes. By replacing the DNP station with a butadiyne group, the distribution of the TTF radical-cation dimer can be changed from 60% to 100%. These findings have been established by several techniques including cyclic voltammetry, spectroelectrochemistry and UV-vis-NIR and EPR spectroscopies, as well as with X-ray diffraction analysis which has provided a range of solid-state crystal structures. The experimental data are also supported by high-level DFT calculations. The results contribute significantly to our fundamental understanding of the interactions within the TTF radical dimers.

  18. Observation of OH radicals produced by pulsed discharges on the surface of a liquid

    NASA Astrophysics Data System (ADS)

    Kanazawa, Seiji; Kawano, Hirokazu; Watanabe, Satoshi; Furuki, Takashi; Akamine, Shuichi; Ichiki, Ryuta; Ohkubo, Toshikazu; Kocik, Marek; Mizeraczyk, Jerzy

    2011-06-01

    The hydroxyl radical (OH) plays an important role in plasma chemistry at atmospheric pressure. OH radicals have a higher oxidation potential compared with other oxidative species such as free radical O, atomic oxygen, hydroperoxyl radical (HO2), hydrogen peroxide(H2O2) and ozone. In this study, surface discharges on liquids (water and its solutions) were investigated experimentally. A pulsed streamer discharge was generated on the liquid surface using a point-to-plane electrode geometry. The primary generation process of OH radicals is closely related to the streamer propagation, and the subsequent secondary process after the discharge has an influence on the chemical reaction. Taking into account the timescale of these processes, we investigated the behavior of OH radicals using two different diagnostic methods. Time evolution of the ground-state OH radicals above the liquid surface after the discharge was observed by a laser-induced fluorescence (LIF) technique. In order to observe the ground-state OH, an OH [A 2∑+(v' = 1) <-- X 2Π(v'' = 0)] system at 282 nm was used. As the secondary process, a portion of OH radicals diffused from gas phase to the liquid surface and dissolved in the liquid. These dissolved OH radicals were measured by a chemical probe method. Terephthalic acid was used as an OH radical trap and fluorescence of the resulting 2-hydroxyterephthalic acid was measured. This paper directly presents visualization of OH radicals over the liquid surface by means of LIF, and indirectly describes OH radicals dissolved in water by means of a chemical method.

  19. Review: Free radicals, antioxidants, and the immune system.

    PubMed

    Knight, J A

    2000-04-01

    Oxygen-derived free radicals are important in both natural and acquired immunity. Neutrophil and macrophage phagocytosis stimulates various cellular processes including the "respiratory burst" whereby increased cellular oxygen uptake results in the production of the potent oxidant bactericidal agents, hypochlorous acid and hydroxyl radical. In addition, nitric oxide, a gaseous radical produced by macrophages, reacts with superoxide to form peroxynitrite, also a potent bactericidal agent. Conversely, oxidative stress may be detrimental in acquired immunity by activation of nuclear factor kappa B, which governs gene expression involving various cytokines, chemokines, and cell adhesion molecules, among others. However, antioxidant supplementation essentially reverses several age-associated immune deficiencies, resulting in increased levels of interleukin-2, elevated numbers of total lymphocytes and T-cell subsets, enhanced mitogen responsiveness, increased killer cell activity, augmented antibody response to antigen stimulation, decreased lipid peroxidation, and decreased prostaglandin synthesis. PMID:10807157

  20. Radical-Mediated Enzymatic Polymerizations

    PubMed Central

    Zavada, Scott R.; Battsengel, Tsatsral; Scott, Timothy F.

    2016-01-01

    Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes―catalytic proteins―owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol–ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

  1. Epistemological barriers to radical behaviorism

    PubMed Central

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  2. Free radical decay in adamantane

    SciTech Connect

    Tegowski, A.T.; Pratt, D.W.

    1984-01-11

    Kinetic electron paramagnetic resonance (EPR) techniques have been used to characterize the decay behavior of the ''stable'' free radical 2-cyclohexanonyl in the plastic crystal phase f an adamantane matrix over the temperature range 257-313 K. Typical plots of the EPR signal intensity as a function of time are biexponential in nature, suggesting the existence of at least two channels for free radical decay. The activation parameters for both processes have been measured in both protonated and deuterated samples. A comparison of these results with those in other systems suggests that the host does, as expected, considerably reduce the pre-exponential factors for decay of the radical by bimolecular processes but has relatively little influence on the corresponding activation energies. 3 figures.

  3. Radical-Mediated Enzymatic Polymerizations.

    PubMed

    Zavada, Scott R; Battsengel, Tsatsral; Scott, Timothy F

    2016-01-01

    Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes--catalytic proteins--owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol-ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

  4. Dinaciclib, a Cyclin-Dependent Kinase Inhibitor Promotes Proteasomal Degradation of Mcl-1 and Enhances ABT-737-Mediated Cell Death in Malignant Human Glioma Cell Lines.

    PubMed

    Jane, Esther P; Premkumar, Daniel R; Cavaleri, Jonathon M; Sutera, Philip A; Rajasekar, Thatchana; Pollack, Ian F

    2016-02-01

    The prognosis for malignant glioma, the most common brain tumor, is still poor, underscoring the need to develop novel treatment strategies. Because glioma cells commonly exhibit genomic alterations involving genes that regulate cell-cycle control, there is a strong rationale for examining the potential efficacy of strategies to counteract this process. In this study, we examined the antiproliferative effects of the cyclin-dependent kinase inhibitor dinaciclib in malignant human glioma cell lines, with intact, deleted, or mutated p53 or phosphatase and tensin homolog on chromosome 10; intact or deleted or p14ARF or wild-type or amplified epidermal growth factor receptor. Dinaciclib inhibited cell proliferation and induced cell-cycle arrest at the G2/M checkpoint, independent of p53 mutational status. In a standard 72-hour 3-[4,5-dimethylthiazol- 2yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H, tetrazolium (MTS) assay, at clinically relevant concentrations, dose-dependent antiproliferative effects were observed, but cell death was not induced. Moreover, the combination of conventional chemotherapeutic agents and various growth-signaling inhibitors with dinaciclib did not yield synergistic cytotoxicity. In contrast, combination of the Bcl-2/Bcl-xL inhibitors ABT-263 (4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide) or ABT-737 (4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide) with dinaciclib potentiated the apoptotic response induced by each single drug. The synergistic killing by ABT-737 with dinaciclib led to cell death accompanied by the hallmarks of apoptosis, including an early loss of the mitochondrial transmembrane potential; the release of cytochrome c, smac/DIABLO, and apoptosis-inducing factor

  5. Free radical facilitated damage of ungual keratin.

    PubMed

    Khengar, Rajeshree H; Brown, Marc B; Turner, Rob B; Traynor, Matthew J; Holt, Katherine B; Jones, Stuart A

    2010-09-01

    Thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) are thought to disrupt alpha-keratin disulfide links in the nail. However, optimal clinical use of these agents to improve the treatment of nail disorders is currently hindered by a lack of fundamental data to support their mechanism of action. The aim of this study was to investigate how the redox environment of ungual keratin, when manipulated by TA and urea H(2)O(2), influenced the properties of the nail barrier. Potentiometric and voltammetric measurements demonstrated that urea H(2)O(2) obeyed the Nernst equation for a proton coupled one-electron transfer redox process while TA underwent a series of redox reactions that was complicated by electrode adsorption and dimer formation. The functional studies demonstrated that nail permeability, measured through TBF penetration (38.51+/-10.94 microg/cm(2)/h) and nail swelling (244.10+/-14.99% weight increase), was greatest when relatively low concentrations of the thiolate ion were present in the applied solution. Limiting the thiolate ion to low levels in the solution retards thiolate dimerisation and generates thiyl free radicals. It appeared that this free radical generation was fundamental in facilitating the redox-mediated keratin disruption of the ungual membrane. PMID:20550963

  6. Halogen radicals contribute to photooxidation in coastal and estuarine waters

    NASA Astrophysics Data System (ADS)

    Parker, Kimberly M.; Mitch, William A.

    2016-05-01

    Although halogen radicals are recognized to form as products of hydroxyl radical (•OH) scavenging by halides, their contribution to the phototransformation of marine organic compounds has received little attention. We demonstrate that, relative to freshwater conditions, seawater halides can increase photodegradation rates of domoic acid, a marine algal toxin, and dimethyl sulfide, a volatile precursor to cloud condensation nuclei, up to fivefold. Using synthetic seawater solutions, we show that the increased photodegradation is specific to dissolved organic matter (DOM) and halides, rather than other seawater salt constituents (e.g., carbonates) or photoactive species (e.g., iron and nitrate). Experiments in synthetic and natural coastal and estuarine water samples demonstrate that the halide-specific increase in photodegradation could be attributed to photochemically generated halogen radicals rather than other photoproduced reactive intermediates [e.g., excited-state triplet DOM (3DOM*), reactive oxygen species]. Computational kinetic modeling indicates that seawater halogen radical concentrations are two to three orders of magnitude greater than freshwater •OH concentrations and sufficient to account for the observed halide-specific increase in photodegradation. Dark •OH generation by gamma radiolysis demonstrates that halogen radical production via •OH scavenging by halides is insufficient to explain the observed effect. Using sensitizer models for DOM chromophores, we show that halogen radicals are formed predominantly by direct oxidation of Cl‑ and Br‑ by 3DOM*, an •OH-independent pathway. Our results indicate that halogen radicals significantly contribute to the phototransformation of algal products in coastal or estuarine surface waters.

  7. Halogen radicals contribute to photooxidation in coastal and estuarine waters.

    PubMed

    Parker, Kimberly M; Mitch, William A

    2016-05-24

    Although halogen radicals are recognized to form as products of hydroxyl radical ((•)OH) scavenging by halides, their contribution to the phototransformation of marine organic compounds has received little attention. We demonstrate that, relative to freshwater conditions, seawater halides can increase photodegradation rates of domoic acid, a marine algal toxin, and dimethyl sulfide, a volatile precursor to cloud condensation nuclei, up to fivefold. Using synthetic seawater solutions, we show that the increased photodegradation is specific to dissolved organic matter (DOM) and halides, rather than other seawater salt constituents (e.g., carbonates) or photoactive species (e.g., iron and nitrate). Experiments in synthetic and natural coastal and estuarine water samples demonstrate that the halide-specific increase in photodegradation could be attributed to photochemically generated halogen radicals rather than other photoproduced reactive intermediates [e.g., excited-state triplet DOM ((3)DOM*), reactive oxygen species]. Computational kinetic modeling indicates that seawater halogen radical concentrations are two to three orders of magnitude greater than freshwater (•)OH concentrations and sufficient to account for the observed halide-specific increase in photodegradation. Dark (•)OH generation by gamma radiolysis demonstrates that halogen radical production via (•)OH scavenging by halides is insufficient to explain the observed effect. Using sensitizer models for DOM chromophores, we show that halogen radicals are formed predominantly by direct oxidation of Cl(-) and Br(-) by (3)DOM*, an (•)OH-independent pathway. Our results indicate that halogen radicals significantly contribute to the phototransformation of algal products in coastal or estuarine surface waters. PMID:27162335

  8. Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761.

    PubMed

    Maitra, I; Marcocci, L; Droy-Lefaix, M T; Packer, L

    1995-05-26

    Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B-phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis-parinaric acid with peroxyl radicals generated from 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha-tocopherol and beta-carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761. PMID:7786306

  9. Donor free radical explosive composition

    DOEpatents

    Walker, Franklin E. [15 Way Points Rd., Danville, CA 94526; Wasley, Richard J. [4290 Colgate Way, Livermore, CA 94550

    1980-04-01

    An improved explosive composition is disclosed and comprises a major portion of an explosive having a detonation velocity between about 1500 and 10,000 meters per second and a minor amount of a donor additive comprising an organic compound or mixture of organic compounds capable of releasing low molecular weight free radicals or ions under mechanical or electrical shock conditions and which is not an explosive, or an inorganic compound or mixture of inorganic compounds capable of releasing low molecular weight free radicals or ions under mechanical or electrical shock conditions and selected from ammonium or alkali metal persulfates.

  10. Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase.

    PubMed

    Sicoli, Giuseppe; Mouesca, Jean-Marie; Zeppieri, Laura; Amara, Patricia; Martin, Lydie; Barra, Anne-Laure; Fontecilla-Camps, Juan C; Gambarelli, Serge; Nicolet, Yvain

    2016-03-18

    The radical S-adenosyl-L-methionine tryptophan lyase NosL converts L-tryptophan into 3-methylindolic acid, which is a precursor in the synthesis of the thiopeptide antibiotic nosiheptide. Using electron paramagnetic resonance spectroscopy and multiple L-tryptophan isotopologues, we trapped and characterized radical intermediates that indicate a carboxyl fragment migration mechanism for NosL. This is in contrast to a proposed fragmentation-recombination mechanism that implied Cα-Cβ bond cleavage of L-tryptophan. Although NosL resembles related tyrosine lyases, subtle substrate motions in its active site are responsible for a fine-tuned radical chemistry, which selects the Cα-C bond for disruption. This mechanism highlights evolutionary adaptation to structural constraints in proteins as a route to alternative enzyme function. PMID:26989252

  11. Effect of polar solvents on beta-carotene radical precursor.

    PubMed

    Tian, Yu-Xi; Han, Rui-Min; Zhang, Jian-Ping; Skibsted, Leif H

    2008-03-01

    Beta-carotene forms radicals in chloroform upon photo-excitation (i) in the femtosecond time-scale by direct electron ejection into chloroform and (ii) in the microsecond time-scale by secondary reactions with chloroform radicals formed in the faster reactions. The precursor for beta-carotene radical cation decays in a second-order reaction in the mixed solvents, with a rate decreasing for increasing dielectric constant of cosolvent (acetic acid < ethanol < acetonitrile approximately methanol). The precursor is assigned as an ion pair from which the beta-carotene radical cation is formed in neat chloroform, but in more polar solvents it reacts at least partly through disproportionation in a bimolecular reaction promoted by the presence of ions. The stabilization of the radical precursor by increased solvent polarity, allowing for deactivation of the precursor by an alternative reaction channel, is discussed in relation to the balance of pro- and antioxidative properties of beta-carotene at lipid/water interfaces. PMID:18344123

  12. Free-Radical Polymer Science Structural Cancer Model: A Review

    PubMed Central

    Petersen, Richard C.

    2013-01-01

    Polymer free-radical lipid alkene chain-growth biological models particularly for hypoxic cellular mitochondrial metabolic waste can be used to better understand abnormal cancer cell morphology and invasive metastasis. Without oxygen as the final electron acceptor for mitochondrial energy synthesis, protons cannot combine to form water and instead mitochondria produce free radicals and acid during hypoxia. Nonuniform bond-length shrinkage of membranes related to erratic free-radical covalent crosslinking can explain cancer-cell pleomorphism with epithelial-mesenchymal transition for irregular membrane borders that “ruffle” and warp over stiff underlying actin fibers. Further, mitochondrial hypoxic conditions produce acid that can cause molecular degradation. Subsequent low pH-activated enzymes then provide paths for invasive cell movement through tissue and eventually blood-born metastasis. Although free-radical crosslinking creates irregularly shaped membranes with structural actin-polymerized fiber extensions as filopodia and lamellipodia, due to rapid cell division the overall cell modulus (approximately stiffness) is lower than normal cells. When combined with low pH-activated enzymes and lower modulus cells, smaller cancer stem cells subsequently have a large advantage to follow molecular destructive pathways and leave the central tumor. In addition, forward structural spike-like lamellipodia protrusions can leverage to force lower-modulus cancer cells through narrow openings. By squeezing and deforming even smaller to allow for easier movement through difficult passageways, cancer cells can travel into adjacent tissues or possibly metastasize through the blood to new tissue. PMID:24278767

  13. Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L.

    PubMed

    Beevi, Syed Sultan; Narasu, Mangamoori Lakshmi; Gowda, Bandi Boje

    2010-03-01

    Aerial parts (leaves and stem) of Raphanus sativus, which are usually discarded were found to possess potent antioxidant and radical scavenging activity, as measured by standard antioxidant assays. Methanolic and acetone extracts of R. sativus leaves had total polyphenolic content of 86.16 and 78.77 mg/g dry extract, which were comparable to the traditional rich sources such as green tea and black tea. HPLC identification of polyphenolics indicated the presence of catechin, protocatechuic acid, syringic acid, vanillic acid, ferulic acid, sinapic acid, o-coumaric acid, myricetin, and quercetin in leaves and stem. Among the different extraction solvents, methanolic extract of leaves and stem showed potent reductive capacity, significantly inhibited linoleic acid peroxidation and displayed metal chelating activity. Further, they scavenged free radicals effectively with IC50 (half maximal inhibitory concentration) of 31 and 42 microg/ml for DPPH radical, 23 and 52 microg/ml for superoxide radical, 67 and 197 microg/ml for hydrogen peroxide,and 56 and 62 microg/ml for nitric oxide, respectively. Leaves showed most potent antioxidant and radical scavenging activity as compared to stem, which may be accounted for the high polyphenolic content. Leaves and stem of R. sativus,often under-utilized part of this vegetable, thus possessed considerable amount of polyphenolics. Hence, it should be egarded as a potential source of natural antioxidants and could be effectively employed as an ingredient in health or in functional food. PMID:20072818

  14. Students' Ideas and Radical Constructivism

    ERIC Educational Resources Information Center

    Sánchez Gómez, Pedro J.

    2016-01-01

    In this article, I study, from the point of view of the analytic philosophy of mind, the compatibility of students' ideas studies (SIS) with radical constructivism (RC). I demonstrate that RC is based on a psychology of "narrow mental states"; that is, the idea that the mental content of an individual can be fully characterised without…

  15. Robot-assisted radical cystectomy.

    PubMed

    Kurpad, Raj; Woods, Michael

    2015-12-01

    Robot-assisted radical cystectomy (RARC) has rapidly penetrated the field of urology since its inception in 2003. Several observational studies, retrospective reports, and three randomized controlled trials (RCT) have preliminarily demonstrated the safety and efficacy of (RARC). Additionally, results from the RAZOR RCT will be available in 2016-2017 to better substantiate the use of (RARC). PMID:26310514

  16. Radical Coupling Mechanisms in Lignification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechansim by which lignification, the polymerization process by which lignins are formed, is via combinatorial radical coupling reactions. Understanding such reactions allows the range of structures in lignins to be understood, and the ability of lignins to accommodate various phenolic precursor...

  17. The Other Women: Radicalizing Feminism.

    ERIC Educational Resources Information Center

    Puigvert, Lidia; Darder, Antonia; Merrill, Barbara; de los Reyes, Eileen; Stromquist, Nelly

    A recent international symposium on radicalizing feminism explored ways of developing a dialogic feminism that emphasizes working in different settings under the common goal of including women who have been invisible in the dominant feminist literature by furthering theories and practices based on the principles of dialogic feminism. The seminar…

  18. Semiquinone and ascorbyl radicals in the gut fluids of caterpillars measured with EPR spectrometry.

    PubMed

    Barbehenn, R V; Poopat, U; Spencer, B

    2003-01-01

    The biological activity of phenolic compounds ingested by caterpillars is commonly believed to result from their oxidation, although the products of oxidation have been well-characterized in only a few cases. The initial oxidation products of phenols (semiquinone or phenoxyl radicals) can be measured with electron paramagnetic resonance (EPR) spectrometry. In this study semiquinone radicals formed from tannic acid and gallic acid in the gut fluids of two species of caterpillars were measured. In Orgyia leucostigma, in which ingested phenols are not oxidized, semiquinone radicals were absent or at very low intensities. By contrast, in Malacosoma disstria, in which ingested phenols are oxidized, high semiquinone radical intensities were measured. In the absence of detectable levels of semiquinone radicals, ascorbyl radicals were detected in the EPR spectra instead. High molar ratios of ascorbate to phenols in an artificial diet produced ascorbyl radicals in the midgut fluids of both species, while diets containing low molar ratios produced semiquinone radicals. Similar results were obtained in M. disstria fed the leaves of red oak or sugar maple. The results of this study provide further evidence that ascorbate is an essential antioxidant that prevents the oxidation of phenols in the gut fluids of caterpillars, and demonstrate that EPR spectrometry is a valuable method for determining the degree of oxidative activation of phenols ingested by herbivorous insects. PMID:12459207

  19. Comparing the gas-phase fragmentation reactions of protonated and radical cations of the tripeptides GXR

    NASA Astrophysics Data System (ADS)

    Wee, Sheena; O'Hair, Richard A. J.; McFadyen, W. David

    2004-05-01

    Electrospray ionization (ESI) mass spectrometry of methanolic solutions of mixtures of the copper salt (2,2':6',2''-terpyridine)copper(II) nitrate monohydrate ([Cu(II)(tpy)(NO3)2].H2O) and a tripeptide GXR (where X = 1 of the 20 naturally occurring amino acids) yielded [Cu(II)(tpy)(GXR)][radical sign]2+ ions, which were then subjected to collision induced dissociation (CID). In all but one case (GRR), these [Cu(II)(tpy)(GXR)][radical sign]2+ ions fragment to form odd electron GXR[radical sign]+ radical cations with sufficient abundance to examine their gas-phase fragmentation reactions. The GXR[radical sign]+ radical cations undergo a diverse range of fragmentation reactions which depend on the nature of the side chain of X. Many of these reactions can be rationalized as arising from the intermediacy of isomeric distonic ions in which the charge (i.e. proton) is sequestered by the highly basic arginine side chain and the radical site is located at various positions on the tripeptide including the peptide back bone and side chains. The radical sites in these distonic ions often direct the fragmentation reactions via the expulsion of small radicals (to yield even electron ions) or small neutrals (to form radical cations). Both classes of reaction can yield useful structural information, allowing for example, distinction between leucine and isoleucine residues. The gas-phase fragmentation reactions of the GXR[radical sign]+ radical cations are also compared to their even electron [GXR+H]+ and [GXR+2H]2+ counterparts. The [GXR+H]+ ions give fewer sequence ions and more small molecule losses while the [GXR+2H]2+ ions yield more sequence information, consistent with the [`]mobile proton model' described in previous studies. In general, all three classes of ions give complementary structural information, but the GXR[radical sign]+ radical cations exhibit a more diverse loss of small species (radicals and neutrals). Finally, links between these gas-phase results and key

  20. The formation of a novel free radical metabolite from CCl4 in the perfused rat liver and in vivo.

    PubMed

    Connor, H D; Thurman, R G; Galizi, M D; Mason, R P

    1986-04-01

    Electron spin resonance spectroscopy has been used to monitor free radicals formed during CCl4 metabolism by perfused livers from phenobarbital-treated rats. Livers were perfused simultaneously with the spin trap phenyl N-t-butylnitrone and with either 12CCl4 or 13CCl4. Perfusate samples and CHCl3:CH3OH extracts of perfusate and liver samples were analyzed for phenyl N-t-butylnitrone radical adducts of reactive free radicals. In the organic extracts, hyperfine coupling constants and 13C isotope effects observed in the ESR spectra indicated the presence of the radical adduct of the trichloromethyl radical. Surprisingly, an additional free radical signal about two orders of magnitude more intense than that of the phenyl N-t-butylnitrone/CCl.3 radical adduct was observed in the aqueous liver perfusate. This adduct was also detected by ESR in rat urine 2 h after intragastric addition of spin trap and CCl4. This radical adduct had hyperfine coupling constants and 13C isotope effects identical with the radical adduct of the carbon dioxide anion radical (CO2-.). Analysis of the pH dependence of the coupling constants yielded a pK alpha of 2.8 for the CO2-. radical adduct formed either in the perfused liver or chemically. Carbon tetrachloride is converted into CCl.3 by cytochrome P-450 through a reductive dehalogenation. The trichloromethyl free radical reacts with oxygen to form the trichloromethyl peroxyl radical, CCl3OO., which may be converted into .COCl and then trapped. This radical adduct would hydrolyze to the carboxylic acid form, which is detected spectroscopically. Alternatively, the carbon dioxide anion free radical could form through complete dechlorination and then react with the spin trap to give the CO2-. radical adduct directly. PMID:3007463