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Sample records for acid abts radical

  1. Isolation and Characterization of the 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) Radical Cation-Scavenging Reaction Products of Arbutin.

    PubMed

    Tai, Akihiro; Ohno, Asako; Ito, Hideyuki

    2016-09-28

    Arbutin, a glucoside of hydroquinone, has shown strong 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation-scavenging activity, especially in reaction stoichiometry. This study investigated the reaction mechanism of arbutin against ABTS radical cation that caused high stoichiometry of arbutin in an ABTS radical cation-scavenging assay. HPLC analysis of the reaction mixture of arbutin and ABTS radical cation indicated the existence of two reaction products. The two reaction products were purified and identified to be a covalent adduct of arbutin with an ABTS degradation fragment and 3-ethyl-6-sulfonate benzothiazolone. A time-course study of the radical-scavenging reactions of arbutin and the two reaction products suggested that one molecule of arbutin scavenges three ABTS radical cation molecules to generate an arbutin-ABTS fragment adduct as a final reaction product. The results suggest that one molecule of arbutin reduced two ABTS radical cation molecules to ABTS and then cleaved the third ABTS radical cation molecule to generate two products, an arbutin-ABTS fragment adduct and 3-ethyl-6-sulfonate benzothiazolone.

  2. Isolation and Characterization of the 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) Radical Cation-Scavenging Reaction Products of Arbutin.

    PubMed

    Tai, Akihiro; Ohno, Asako; Ito, Hideyuki

    2016-09-28

    Arbutin, a glucoside of hydroquinone, has shown strong 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation-scavenging activity, especially in reaction stoichiometry. This study investigated the reaction mechanism of arbutin against ABTS radical cation that caused high stoichiometry of arbutin in an ABTS radical cation-scavenging assay. HPLC analysis of the reaction mixture of arbutin and ABTS radical cation indicated the existence of two reaction products. The two reaction products were purified and identified to be a covalent adduct of arbutin with an ABTS degradation fragment and 3-ethyl-6-sulfonate benzothiazolone. A time-course study of the radical-scavenging reactions of arbutin and the two reaction products suggested that one molecule of arbutin scavenges three ABTS radical cation molecules to generate an arbutin-ABTS fragment adduct as a final reaction product. The results suggest that one molecule of arbutin reduced two ABTS radical cation molecules to ABTS and then cleaved the third ABTS radical cation molecule to generate two products, an arbutin-ABTS fragment adduct and 3-ethyl-6-sulfonate benzothiazolone. PMID:27607833

  3. A simple, post-additional antioxidant capacity assay using adenosine triphosphate-stabilized 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical cation in a G-quadruplex DNAzyme catalyzed ABTS-H2O2 system.

    PubMed

    Jia, Shu-Min; Liu, Xiao-Fei; Kong, De-Ming; Shen, Han-Xi

    2012-05-15

    The scavenging of 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical cation (ABTS(+)) by antioxidants has been widely used in antioxidant capacity assay. Because of ABTS(+) disproportionation, however, this radical cannot be prepared on a large scale and stored long-term, making it unsuitable for high-throughput detection and screening of antioxidants. We developed a modified "post-additional" antioxidant capacity assay. This method possessed two remarkable features: First, instead of natural peroxidases, an artificial enzyme, G-quadruplex DNAzyme, was used for the preparation of ABTS(+), thus greatly reducing the cost of the assay, and eliminating the strict demand for the storage of enzymes. Second, an ABTS(+) stabilizer, adenosine triphosphate (ATP), was used. In the presence of ATP, the disproportionation of ABTS(+) was effectively inhibited, and the lifetime of this radical cation was prolonged about 6-fold (12 days versus 2 days), making the large-scale preparation of ABTS(+) possible. Utilizing this method, the antioxidant capacities of individual antioxidants and real samples can be quantified and compared easily. In addition, this method can be developed as a high-throughput screening method for antioxidants. The screening results could even be judged by the naked eye, eliminating the need for expensive instruments.

  4. Radical Scavenging by Acetone: A New Perspective to Understand Laccase/ABTS Inactivation and to Recover Redox Mediator.

    PubMed

    Liu, Hao; Zhou, Pandeng; Wu, Xing; Sun, Jianliang; Chen, Shicheng

    2015-11-04

    The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone on the kinetic constants of laccase were determined and the results showed Km and Vmax varied exponentially with increasing acetone content. Acetone as well as some other cosolvents could transform ABTS radicals into its reductive form. The content of acetone in media significantly affected the radical scavenging rates. Up to 95% of the oxidized ABTS was successfully recovered in 80% (v/v) acetone in 60 min. This allows ABTS recycles at least six times with 70%-75% of active radicals recovered after each cycle. This solvent-based recovery strategy may help improve the economic feasibility of laccase/ABTS system in biosynthesis.

  5. Doxorubicin inhibits oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) by a lactoperoxidase/H(2)O(2) system by reacting with ABTS-derived radical.

    PubMed

    Reszka, Krzysztof J; Britigan, Bradley E

    2007-10-15

    The effect of doxorubicin on oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) by lactoperoxidase and hydrogen peroxide has been investigated. It was found that: (1) oxidation of ABTS to its radical cation (ABTS*(+)) is inhibited by doxorubicin as evidenced by its induction of a lag period, duration of which depends on doxorubicin concentration; (2) the inhibition is due to doxorubicin hydroquinone reducing the ABTS*(+) radical (stoichiometry 1: 1.8); (3) concomitant with the ABTS*(+) reduction is oxidation of doxorubicin; only when the doxorubicin concentration decreases to a near zero level, net oxidation of ABTS could be detected; (4) oxidation of doxorubicin leads to its degradation to 3-methoxysalicylic acid and 3-methoxyphthalic acid; (5) the efficacy of doxorubicin to quench ABTS*(+) is similar to the efficacy of p-hydroquinone, glutathione and Trolox C. These observations support the assertion that under certain conditions doxorubicin can function as an antioxidant. They also suggest that interaction of doxorubicin with oxidants may lead to its oxidative degradation.

  6. 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

  7. Kinetics of ABTS derived radical cation scavenging by bucillamine, cysteine, and glutathione. Catalytic effect of Cu(2+) ions.

    PubMed

    Valent, Ivan; Topolská, Dominika; Valachová, Katarína; Bujdák, Juraj; Šoltés, Ladislav

    2016-05-01

    Kinetics of reduction of the stable radical cation derived from 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) in reaction with the anti-rheumatic drug bucillamine (BUC) and two reference thiols - cysteine (Cys) and glutathione (GSH) was followed spectrophotometrically in acidic medium with 10-fold molar excess of the reductant. Decay of the radical is governed by pseudo-first order kinetics with small deviation in the case of GSH. H(+) ions displayed second order inhibition of the reaction with all the studied compounds. The reaction of BUC exhibits zero order kinetics to the radical at lower acidities with a moderate acceleration of the reaction rate by H(+) ions. A significant catalytic effect of Cu(2+) ions on the reactions with all the reductants was observed. The most sensitive to Cu(2+)-catalysis was the reaction of BUC with the radical cation, while Cu(2+) ions showed much lower effect on the reaction with GSH. The presence of EDTA strongly inhibited the reactions and equalized the reaction rates for all the reductants. A Cu(I) selective chelator bathocuproine disulfonate reduced the reaction rate with Cys, but accelerated the reaction with BUC at the lower acidities. The experimental results were rationalized in the framework of the mechanism of reductive chelation. The conclusions may have important consequences for interpretation of antioxidant capacity assays, such as TEAC, utilizing the ABTS derived radical cation.

  8. Comprehensive two-dimensional liquid chromatography coupled to the ABTS radical scavenging assay: a powerful method for the analysis of phenolic antioxidants.

    PubMed

    Kalili, Kathithileni M; De Smet, Seppe; van Hoeylandt, Tim; Lynen, Frédéric; de Villiers, André

    2014-07-01

    The on-line combination of comprehensive two-dimensional liquid chromatography (LC × LC) with the 2,2'-azino-bis(3-ethylbenzothiazoline)-6 sulphonic acid (ABTS) radical scavenging assay was investigated as a powerful method to determine the free radical scavenging activities of individual phenolics in natural products. The combination of hydrophilic interaction chromatography (HILIC) separation according to polarity and reversed-phase liquid chromatography (RP-LC) separation according to hydrophobicity is shown to provide much higher resolving power than one-dimensional separations, which, combined with on-line ABTS detection, allows the detailed characterisation of antioxidants in complex samples. Careful optimisation of the ABTS reaction conditions was required to maintain the chromatographic separation in the antioxidant detection process. Both on-line and off-line HILIC × RP-LC-ABTS methods were developed, with the former offering higher throughput and the latter higher resolution. Even for the fast analyses used in the second dimension of on-line HILIC × RP-LC, good performance for the ABTS assay was obtained. The combination of LC × LC separation with an on-line radical scavenging assay increases the likelihood of identifying individual radical scavenging species compared to conventional LC-ABTS assays. The applicability of the approach was demonstrated for cocoa, red grape seed and green tea phenolics. PMID:24817360

  9. Screening of free radical scavengers from Erigeron breviscapus using on-line HPLC-ABTS/DPPH based assay and mass spectrometer detection.

    PubMed

    Li, Fei; Zhang, Lin-Dong; Li, Bao-Cai; Yang, Jian; Yu, Hua; Wan, Jian-Bo; Wang, Yi-Tao; Li, Peng

    2012-03-01

    Erigeron breviscapus is a well-known traditional Chinese herbal medicine. In this study, on-line HPLC-ABTS/DPPH assay coupled with MS detection were applied to screen and identify the free radical scavengers in 70% methanol extracts of E. breviscapus. Using on-line HPLC-ABTS-MS and HPLC-DPPH-MS assay, 13 radical scavengers (including 4-O-caffeoylquinic acid (4-CQA) (1), 9-caffeoyl-2,7-anhydro-2-octulosonic acid (9-COA) (2), 3-caffeoyl-2,7-anhydro-3-deoxy-2-octulopyranosonic acid (3-CDOA) (3), erigeside I (4), quercetin-3-O-glucuronide (5), eriodictyol-7-O-glucuronide (6), scutellarin (7), 1,4-di-O-caffeoylquinic acid (1,4-di-CQA) (8), 3,5-di-CQA (9), 1-malonyl-3,5-di-CQA (10), erigoster B (11), 4,5-di-CQA (12) and 4,9-di-CDOA (13)) and 9 radical scavengers (including 1, 4, 7, 8, 9, 10, 11, 12 and 13) were discovered, respectively. Furthermore, the anti-oxidative activities of 4 compounds, including 7, 9, 11 and 12 were evaluated. Reverse anti-oxidative activity order of scutellarin and 3,5-di-CQA was observed in on-line HPLC-ABTS assay and on-line HPLC-DPPH assay. To validate their anti-oxidative activities, the off-line ABTS and DPPH assays were performed. Given sufficient reaction time, 3,5-di-CQA showed higher activity than scutellarin, which was consistent with the order obtained in on-line HPLC-ABTS assay. These results revealed that on-line HPLC-ABTS assay is a more sensitive method for screening and determining free radical scavengers, especially more suitable for those compounds with slower reaction kinetics.

  10. Tetrahydro-beta-carboline alkaloids that occur in foods and biological systems act as radical scavengers and antioxidants in the ABTS assay.

    PubMed

    Herraiz, Tomas; Galisteo, Juan

    2002-08-01

    Tetrahydro-beta-carboline alkaloids that occur in foods such as wine, seasonings, vinegar and fruit products juices, jams) acted as good radical scavengers (hydrogen- or electron donating) in the ABTS (2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) assay, and therefore, they could contribute to the beneficial antioxidant capacity attributed to foods. In contrast, the fully aromatic beta-carbolines norharman and harman did not show any radical scavenger activity in the same assay. During the reaction with ABTS.+ radical cation, tetrahydro-beta-carboline-3-carboxylic acid such as 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1,3-dicarboxylic acid (MTCA-COOH) were converted to harman, whereas 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (THCA) and 1,2,3,4-tetrahydro-beta-carboline-1,3-dicarboxylic acid (THCA-COOH) afforded norharman. These results suggest that food and naturally-occurring tetrahydro-beta-carboline alkaloids if accumulated in tissues, as reported elsewhere, might exhibit antioxidant activity.

  11. Kinetics of oxidation of benzyl alcohols by the dication and radical cation of ABTS. Comparison with laccase-ABTS oxidations: an apparent paradox.

    PubMed

    Branchi, Barbara; Galli, Carlo; Gentili, Patrizia

    2005-07-21

    Laccase, a blue copper oxidase, in view of its moderate redox potential can oxidise only phenolic compounds by electron-transfer. However, in the presence of ABTS (2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) as a redox mediator, laccase reacts with the more difficult to oxidise non-phenolic substrates, such as benzyl alcohols. The role of ABTS in these mediated oxidations is investigated. Redox interaction with laccase could produce in situ two reactive intermediates from ABTS, namely ABTS++ or ABTS*+. These species have been independently generated by oxidation with Ce(iv) or Co(iii) salts, respectively, and their efficiency as monoelectronic oxidants tested in a kinetic study towards a series of non-phenolic substrates; a Marcus treatment is provided in the case of ABTS++. On these grounds, intervention of ABTS++ as a reactive intermediate in laccase-ABTS oxidations appears unlikely, because the experimental conditions under which ABTS++ is unambiguously generated, and survives long enough to serve as a diffusible mediator, are too harsh (2 M H2SO4 solution) and incompatible with the operation of the enzyme. Likewise, ABTS*+ seems an intermediate of limited importance in laccase-ABTS oxidations, because this weaker monoelectronic oxidant is unable to react directly with many of the non-phenolic substrates that laccase-ABTS can oxidise. To solve this paradox, it is alternatively suggested that degradation by-products of either ABTS++ or ABTS*+ are formed in situ by hydrolysis during the laccase-ABTS reactions, and may be responsible for the observed oxidation of non-phenolics.

  12. 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.

  13. Sequestering ability of butylated hydroxytoluene, propyl gallate, resveratrol, and vitamins C and E against ABTS, DPPH, and hydroxyl free radicals in chemical and biological systems.

    PubMed

    Soares, Daniele G; Andreazza, Ana C; Salvador, Mirian

    2003-02-12

    The antioxidant capacity of butylated hydroxytoluene (BHT; 2,6-di-tert-butyl-p-cresol), propyl gallate (3,4,5-trihydroxybenzoic acid n-propyl ester), resveratrol (trans-3,4',5-trihydroxystilbene), and vitamins C (l-ascorbic acid) and E [(+)-alpha-tocopherol] was studied in chemical and biological systems. The chemical assays evaluated the capacity of these antioxidants to sequester 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.) and 1,1 diphenyl-2-picrylhydrazyl (DPPH.). A new colorimetric method to determine hydroxyl radical scavenging is also described. The biological tests use the eucaryotic cells of Saccharomyces cerevisiae treated with the antioxidants in the presence of the stressing agents apomorphine, hydrogen peroxide, and paraquat dichloride (methylviologen; 1,1'-dimethyl-4,4'-bipyridinium dichloride). The results in chemical systems showed that all of the antioxidants were able to significantly inhibit the oxidation of beta-carotene by hydroxyl free radicals. The assays in yeast showed that the antioxidant activity of the tested compounds depended on the stressing agent used and the mechanism of action of the antioxidant.

  14. Re-evaluation of ABTS*+ Assay for Total Antioxidant Capacity of Natural Products.

    PubMed

    Dong, Jian-Wei; Cai, Le; Xing, Yun; Yu, Jing; Ding, Zhong-Tao

    2015-12-01

    2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS*+) is a stable free radical frequently used for estimating the total antioxidant capacity (TAC) of natural products. The existing methods for ABTS*+ radical-scavenging activity assays are diverse in pre-diluting solvents and reaction time, which lead to errors in the TAC estimations. To develop an effective and universal method for estimating the ABTS*+ capacity accurately and reasonably, five pre-dilution solvents [methanol, ethanol, phosphate buffer (Na2HPO4-NaH2PO4, 200 mM, pH = 7.4), PBS buffer (Na2HPO4-NaH2PO4- NaCl, 200 mM, pH = 7.4), and distilled water] and different reaction times were investigated in ABTS*+ assays of five typical antioxidants. The results showed that the solvent effects were very significant. When using different pre-diluting solvents, different detection wavelengths should be selected. ABTS*+ assay could be measured within 2-10 min to obtain a rough result, which was mostly 6 min in the literature. However, full and accurate evaluation of antioxidant reactivity rather than capacity requires recording ABTS*+ loss continuously during the whole reaction period. The present study makes a recommendation for estimating the ABTS*+ capacity accurately and reasonably. PMID:26882692

  15. Re-evaluation of ABTS*+ Assay for Total Antioxidant Capacity of Natural Products.

    PubMed

    Dong, Jian-Wei; Cai, Le; Xing, Yun; Yu, Jing; Ding, Zhong-Tao

    2015-12-01

    2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS*+) is a stable free radical frequently used for estimating the total antioxidant capacity (TAC) of natural products. The existing methods for ABTS*+ radical-scavenging activity assays are diverse in pre-diluting solvents and reaction time, which lead to errors in the TAC estimations. To develop an effective and universal method for estimating the ABTS*+ capacity accurately and reasonably, five pre-dilution solvents [methanol, ethanol, phosphate buffer (Na2HPO4-NaH2PO4, 200 mM, pH = 7.4), PBS buffer (Na2HPO4-NaH2PO4- NaCl, 200 mM, pH = 7.4), and distilled water] and different reaction times were investigated in ABTS*+ assays of five typical antioxidants. The results showed that the solvent effects were very significant. When using different pre-diluting solvents, different detection wavelengths should be selected. ABTS*+ assay could be measured within 2-10 min to obtain a rough result, which was mostly 6 min in the literature. However, full and accurate evaluation of antioxidant reactivity rather than capacity requires recording ABTS*+ loss continuously during the whole reaction period. The present study makes a recommendation for estimating the ABTS*+ capacity accurately and reasonably.

  16. Practical problems when using ABTS assay to assess the radical-scavenging activity of peptides: Importance of controlling reaction pH and time.

    PubMed

    Zheng, Lin; Zhao, Mouming; Xiao, Chuqiao; Zhao, Qiangzhong; Su, Guowan

    2016-02-01

    Effects of reaction pH and time on the antioxidant behaviors of Tyr, Trp, Cys, and their related peptides (Tyr-Gly, Tyr-Glu, Tyr-Lys, Trp-Gly, Trp-Glu, Trp-Lys, Cys-Gly and Cys-Gly) in ABTS assay were investigated. Results showed that all these amino acids and peptides displayed a biphasic kinetic pattern with a fast initial step and a slow secondary step. The initial reaction rates of Tyr, Trp and their related peptides were strongly dependent on pH, while those of Cys and Cys-containing peptides were unaffected by pH. They failed to reach equilibrium over the short incubation period of 6-10 min typically used in this assay. Longer incubation time was needed for most of the peptides to approach equilibrium at lower pH. The observed biphasic kinetic pattern as well as the high TEAC values for these amino acids and peptides, could be a result of combined antioxidant behaviors of themselves plus the generated reaction products.

  17. 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

  18. 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

  19. 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

    Kenzom, T; Srivastava, P; Mishra, S

    2014-12-01

    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.

  20. 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

    Kenzom, T; Srivastava, P; Mishra, S

    2014-12-01

    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

  1. 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

  2. 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.

  3. 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.

  4. Coupling interactions between sulfurous acid and the hydroperoxyl radical.

    PubMed

    Li, Ping; Ma, Zhi-Ying; Wang, Wei-Hua; Shen, Zhi-Tao; Bi, Si-Wei; Sun, Hai-Tao; Bu, Yu-Xiang

    2010-02-22

    Radical-molecule complexes associated with the hydroperoxyl radical (HOO) play an important role in atmospheric chemistry. Herein, the nature of the coupling interactions between sulfurous acid (H(2)SO(3)) and the HOO radical is systematically investigated at the B3LYP/6-311++G(3df,3pd) level of theory in combination with the atoms in molecules (AIM) theory, the natural bond orbital (NBO) method, and energy decomposition analyses (EDA). Eight stable stationary points possessing double H-bonding features were located on the H(2)SO(3)...HOO potential energy surface. The largest binding energies of -12.27 and -11.72 kcal mol(-1) are observed for the two most stable complexes, where both of them possess strong double intermolecular H-bonds of partially covalence. Moreover, the characteristics of the IR spectra for the two most stable complexes are discussed to provide some help for their possible experimental identification. PMID:20041456

  5. 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

  6. Inhibition of lactoperoxidase-catalyzed 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and tyrosine oxidation by tyrosine-containing random amino acid copolymers.

    PubMed

    Clausen, Morten R; Skibsted, Leif H; Stagsted, Jan

    2008-09-24

    Oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) by lactoperoxidase was found to be inhibited by tyrosine-containing random amino acid copolymers but not by tyrosine. Both electrostatic effects and polymer size were found to be important by comparison of negatively and positively charged copolymers of varying lengths, with poly(Glu, Tyr)4:1 ([E 4Y 1] approximately 40) as the strongest competitive inhibitor (EC 50 approximately 20 nM). This polymer did not form dityrosine in the presence of lactoperoxidase (LPO) and peroxide. Furthermore, incubation with tert-butyl hydroperoxide, as opposed to hydrogen peroxide, resulted in a peculiar long lag phase of the reaction between the redox intermediate compound II and [E 4Y 1] approximately 40, indicating a very tight association between enzyme and inhibitor. We propose that interactions between multiple positively charged areas on the surface of LPO and the polymer are required for optimal inhibition.

  7. Radical scavenging activity and phenolic compounds in persimmon (Diospyros kaki L. cv. Mopan).

    PubMed

    Chen, X N; Fan, J F; Yue, X; Wu, X R; Li, L T

    2008-01-01

    The Mopan persimmon (Diospyros kaki L. cv. Mopan) is the major cultivar of astringent persimmon in northern China. This study investigates the radical scavenging activity against ABTS and DPPH radical, and the content of total and individual phenolics (catechin, epicatechin, epigallocatechin, chlorogenic acid, caffeic acid, and gallic acid) with apple, grape, and tomato as controls. The radical scavenging activities against ABTS and DPPH radicals of the Mopan persimmon are 23.575 and 22.597 microm trolox eq/g f.w., respectively. These findings suggest that the Mopan persimmon's antioxidant activity is significantly (P < 0.05) stronger than that of reference materials. The Mopan persimmon showed the highest content of total phenolics among the 4 materials tested. Significant correlations (R(2)= 0.993, P < 0.05, ABTS radical; R(2)= 0.980, P < 0.05, DPPH radical) are found between the total phenolics and the radical scavenging activities. The total content of these 6 kinds of phenolics (catechin, epicatechin, epigallocatechin, chlorogenic acid, caffeic acid, and gallic acid) is significantly correlated (R(2)= 0.831, P < 0.05, ABTS radical; R(2)= 0.745, P < 0.05, DPPH radical) with the individual radical scavenging activity of the 4 materials, although the total content of the 6 phenolics accounts for no more than 20% of the total phenolics in the Mopan persimmon. Gallic acid exhibits the strongest antioxidant activity in all 6 kinds of phenolics and its content is the largest in the Mopan persimmon, presumably being responsible for its much higher antioxidant activity as compared to apple, grape, and tomato.

  8. Carminic acid-promoted oxygen radical damage to lipid and carbohydrate.

    PubMed

    Gutteridge, J M; Quinlan, G J

    1986-01-01

    The food colouring carminic acid redox cycles to produce free radicals. These radicals, in the presence of trace amounts of iron salts, readily damage membrane lipid and degrade the carbohydrate deoxyribose. Damage to membrane lipid appears to involve mainly organic oxygen radicals such as alkoxy and peroxy radicals, whereas that to deoxyribose implicates the hydroxyl radical formed in a Fenton-type reaction. Antioxidants and iron chelators prevent such damage. PMID:3803637

  9. 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.

  10. 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.

  11. Formation of hydroxyl radical from the photolysis of salicylic acid.

    PubMed

    Zhou, Can-Hua; Cheng, Shi-Bo; Yin, Hong-Ming; He, Guo-Zhong

    2011-05-26

    Photodissociation dynamics of salicylic acid (SA) in the gas phase at different photolysis wavelengths (266, 315-317 nm) is investigated by probing the nascent OH photoproduct employing the single-photon laser-induced fluorescence (LIF) technique. At all the photolysis wavelengths it is found that the nascent OH radicals are produced mostly in a vibrationally ground state (υ'' = 0) and have similar rotational state distributions. The two spin-orbit and Λ-doublet states of the OH fragment formed in the dissociation are measured to have a nonstatistical distribution at each photolysis wavelength. The LIF signal of the OH could be observed upon photolysis at 317 nm but not at 317.5 nm. The threshold of OH formation from SA photodissociation is estimated to be 98.2 ± 0.9 kcal/mol. The effect of the phenolic OH group on the dissociation of SA is discussed.

  12. 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.

  13. Gas-phase acidities of o-, m- and p-dehydrobenzoic acid radicals. Determination of the substituent constants for a phenyl radical site

    NASA Astrophysics Data System (ADS)

    Wenthold, Paul G.; Squires, Robert R.

    1998-05-01

    Reaction of CO2 with o-, m-, and p-benzyne radical anions in the gas phase produces o-, m-, and p-dehydrobenzoate radical anions, respectively. The (oxygen) gas-phase basicities of these ions, which are equivalent to the gas-phase acidities of the corresponding dehydrobenzoic acid radicals, [Delta]Gacid(o-, m-, or p-C6H4CO2-H), have been determined with a flowing afterglowtriple quadrupole apparatus by means of the kinetic method. The measured values are (in kcal mol-1): [Delta]Gacid(o-C6H4CO2H) = 330.4 +/- 0.4, [Delta]Gacid(m-C6H4CO2H) = 330.2 +/- 0.4, and [Delta]Gacid(p-C6H4CO2H) = 331.6 +/- 0.4 kcal mol-1. All three radicals are more acidic than benzoic acid ([Delta]Gacid = 333.1 +/- 2.0 kcal mol-1). The measured gas-phase acidities for the meta and para isomers suggest values for the resonance-effect substituent constant, [sigma]R, and the field/inductive effect substituent constant, [sigma]F, for a phenyl radical site of - 0.47 and 0.57, respectively. This classifies a phenyl radical site as a strong inductive withdrawing, and strong resonance donating substituent. Density functional calculations of the gas-phase acidities of dehydrobenzoic acids are in good agreement with the experimental results. The increased acidities of the dehydrobenzoic acids are shown to arise from a balance between the electron withdrawing effect of the electronegative radical site, and a compensating polarization of the [pi] system which mimics the effect of a resonance donor group located at the radical carbon.

  14. 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.

  15. 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.

  16. Endogenous released ascorbic acid suppresses ethanol-induced hydroxyl radical production in rat striatum.

    PubMed

    Huang, Mei; Liu, Wen; Li, Qiang; Wu, Chun Fu

    2002-07-19

    Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid release in the striatum. However, the pharmacological implications of ethanol-induced striatal ascorbic acid release are unclear. In the present study, ethanol-induced extracellular changes of ascorbic acid and hydroxyl radical levels were detected in rat striatum by using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection. It was found that both in male and female rats, ethanol (3.0 g/kg, i.p.) increased striatal ascorbic acid release in the first 60 min after ethanol administration. Meanwhile, the extracellular hydroxyl radical levels, detected as 2,3- and 2,5-DHBA, were significantly decreased. However, when the ascorbic acid levels returned to the baseline, hydroxyl radical levels rebounded. Administration of DL-fenfluramine (20 mg/kg, i.p.) had no effect on the basal levels of ascorbic acid and hydroxyl radical, but significantly blocked ethanol-induced ascorbic acid release and increased hydroxyl radical levels significantly. Exogenous administration of ascorbic acid (20 mg/kg, s.c.) increased the extracellular levels of ascorbic acid in the striatum, and inhibited the increase of 2,3- and 2,5-DHBA in DL-fenfluramine plus ethanol group. These results provide first evidence that release of endogenous ascorbic acid in the striatum plays an important role in preventing oxidative stress by trapping hydroxyl radical in the central nervous system.

  17. 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

  18. Reactivity of substituted charged phenyl radicals toward components of nucleic acids.

    PubMed

    Ramírez-Arizmendi, Luis E; Heidbrink, Jenny L; Guler, Leonard P; Kenttämaa, Hilkka I

    2003-02-26

    Reactions of differently substituted phenyl radicals with components of nucleic acids have been investigated in the gas phase. A positively charged group located meta with respect to the radical site was employed to allow manipulation of the radicals in a Fourier-transform ion cyclotron resonance mass spectrometer. All of these electrophilic radicals react with sugars via exclusive hydrogen atom abstraction, with adenine and uracil almost exclusively via addition (likely at the C8 and C5 carbons, respectively), and with the nucleoside thymidine by hydrogen atom abstraction and addition at C5 in the base moiety (followed by elimination of (*)CH(3)). These findings parallel the reactivity of the phenyl radical with components of nucleic acids in solution, except that the selectivity for addition is different. Like HO(*), the electrophilic charged phenyl radicals appear to favor addition to the C5-end of the C5-C6 double bond of thymine and thymidine, whereas the phenyl radical preferentially adds to C6. The charged phenyl radicals do not predominantly add to thymine, as the neutral phenyl radical and HO(*), but mainly react by hydrogen atom abstraction from the methyl group (some addition to C5 in the base followed by loss of (*)CH(3) also occurs). Adenine appears to be the preferred target among the nucleobases, while uracil is the least favored. A systematic increase in the electrophilicity of the radicals by modification of the radicals' structures was found to facilitate all reactions, but the addition even more than hydrogen atom abstraction. Therefore, the least reactive radicals are most selective toward hydrogen atom abstraction, while the most reactive radicals also efficiently add to the base. Traditional enthalpy arguments do not rationalize the rate variations. Instead, the rates reflect the radicals' electron affinities used as a measure for their ability to polarize the transition state of each reaction.

  19. Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid.

    PubMed

    Lü, Jian-Ming; Weakley, Sarah M; Yang, Zhen; Hu, Ming; Yao, Qizhi; Chen, Changyi

    2012-01-01

    Reactive oxygen species (ROS) have been implicated in a variety of inflammatory diseases including cardiovascular disease (CVD), cancer, diabetes, Alzheimer's disease, autism, cataracts and aging. When endogenous mechanisms for the maintenance of redox homeostasis are overwhelmed, dietary intake of antioxidants contributes substantially to balancing the body's oxidant/antioxidant status. Ginsenosides are thought to be primarily responsible for the pharmacological effect of P. ginseng root extracts on oxidative stress and inflammation. However, little is known about the underlying antioxidant mechanisms of individual ginsenoside; specifically, the reactivity of ginsenoside Rb1 with ROS has not been well studied. We found that Rb1 can significantly and selectively reduce hydroxyl radical (●OH) and hypochlorous acid (HOCl), two of the strongest ROS, with unique molecular mechanisms in a cell-free system. Rb1 directly scavenges the ●OH and protects plasmid DNA from damage induced by ●OH. ●OH likely attacks the double bond on the side chain of Rb1 as well as hydrogen atoms adjacent to the -OH groups, including those of sugar moieties. Rb1 also shows a high reactivity to HOCl and effectively inhibits HOCl-induced tyrosine chlorination in a cell free system. HOCl is added to the double bond of Rb1; the -Cl group and -OH group of HOCl possibly bond at C-24 and C-25 of Rb1 based on the regioselectivity of Markovnikov's Rule. To our knowledge, this is the first demonstration that ginsenoside Rb1 scavenges HOCl and protects tyrosine from HOCl-induced chlorination. Thus, this study reveals unique antioxidant mechanisms of individual ginsenoside Rb1, which may contribute to the pharmacological effect of P. ginseng and to the development of effective strategies for clinical applications of ginsenosides.

  20. Oxidative Radical Addition-Cyclization of Sulfonyl Hydrazones with Simple Olefins by Binary Acid Catalysis.

    PubMed

    Zhong, Xingren; Lv, Jian; Luo, Sanzhong

    2016-07-01

    An unprecedented binary acid accelerated oxidative radical annulation of sulfonyl hydrazones with simple olefins is described. Notably, this method provides a novel oxidative radical cycloaddition for the construction of six-member heterocycles. It offers a rapid and efficient approach to tetrahydropyridazines which are key structural motifs in pharmaceutically active compounds.

  1. High-performance liquid chromatographic determination of linoleic acid peroxide-derived radicals using electrochemical detection.

    PubMed

    Iwahashi, H

    2000-12-29

    High-performance liquid chromatography-electrochemical detection (HPLC-ED) was applied to detect 13-hydroperoxide octadecadienoic acid (13-HPODE)-derived radicals such as the pentyl radical and octanoic acid radical. The 13-HPODE-derived radicals were successfully detected using HPLC-ED by the combined use of the spin-trapping technique with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN). The 4-POBN-pentyl radical adduct was detected at the retention time of 18.2 +/- 0.3 min on the elution profile of HPLC-ED with an ODS column (15 cm x 4.6 mm I.D.) using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 29% (v/v) aqueous acetonitrile. The 4-POBN-octanoic acid radical adduct was also detected at the retention time of 13.7 +/- 0.7 min using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 14% (v/v) aqueous acetonitrile. The concentrations of the 4-POBN radical adducts were determined using HPLC-ED without an internal standard. HPLC-ED is 100 times as sensitive as HPLC-electron spin resonance (ESR) under the ESR and ED conditions employed here. Even 1.8 pmol of the 4-POBN-pentyl (or octanoic acid) radical adduct was detectable using PMID:11204234

  2. Radical scavenging activity of lipophilized products from transesterification of flaxseed oil with cinnamic acid or ferulic acid.

    PubMed

    Choo, Wee-Sim; Birch, Edward John; Stewart, Ian

    2009-09-01

    Lipase-catalyzed transesterification of flaxseed oil with cinnamic acid (CA) or ferulic acid (FA) using an immobilized lipase from Candida antarctica (E.C. 3.1.1.3) was conducted to evaluate whether the lipophilized products provided enhanced antioxidant activity in the oil. Lipase-catalyzed transesterification of flaxseed oil with CA or FA produced a variety of lipophilized products (identified using ESI-MS-MS) such as monocinnamoyl/feruloyl-diacylglycerol, dicinnamoyl-monoacylglycerol and monocinnamoyl-monoacylglycerol. The free radical scavenging activity of the lipophilized products of lipase-catalyzed transesterification of flaxseed oil with CA or FA toward 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) were both examined in ethanol and ethyl acetate. The polarity of the solvents proved important in determining the radical scavenging activity of the substrates. Unesterified FA showed the highest free radical scavenging activity among all substrates tested while CA had negligible activity. The esterification of CA or FA with flaxseed oil resulted in significant increase and decrease in the radical scavenging activity compared with the native phenolic acid, respectively. Based on the ratio of a substrate to DPPH. concentration, lipophilized FA was a much more efficient free radical scavenger compared to lipophilized CA and was able to provide enhanced antioxidant activity in the flaxseed oil. Lipophilized cinnamic acid did not provide enhanced radical scavenging activity in the flaxseed oil as the presence of natural hydrophilic antioxidants in the oil had much greater radical scavenging activity.

  3. Chemoselective Conversion from α-Hydroxy Acids to α-Keto Acids Enabled by Nitroxyl-Radical-Catalyzed Aerobic Oxidation.

    PubMed

    Furukawa, Keisuke; Inada, Haruki; Shibuya, Masatoshi; Yamamoto, Yoshihiko

    2016-09-01

    The chemoselective oxidation of α-hydroxy acids to α-keto acids catalyzed by 2-azaadamantane N-oxyl (AZADO), a nitroxyl radical catalyst, is described. Although α-keto acids are labile and can easily release CO2 under oxidation conditions, the use of molecular oxygen as a cooxidant enables the desired chemoselective oxidation. PMID:27533283

  4. Presence of Hydrogen Peroxide, a Source of Hydroxyl Radicals, in Acid Electrolyzed Water

    PubMed Central

    Mokudai, Takayuki; Nakamura, Keisuke; Kanno, Taro; Niwano, Yoshimi

    2012-01-01

    Background Acid electrolyzed water (AEW), which is produced through the electrolysis of dilute sodium chloride (NaCl) or potassium chloride solution, is used as a disinfectant in various fields because of its potent antimicrobial activity. The hydroxyl radical, an oxygen radical species, is often suggested as a putative active ingredient for AEW antimicrobial activity. Methodology/Principal Findings The aim of the present study is to detect hydroxyl radicals in AEW. The hydroxyl radicals in AEW prepared under different conditions were determined using an electron spin resonance (ESR) technique. A signal from 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-OH, an adduct of DMPO and the hydroxyl radical, was detected in AEW prepared by double or triple electrolyses of 1% NaCl but not of 0.1% NaCl solution. Then the presence of hydrogen peroxide as a proposed source of hydroxyl radicals was examined using a combination of ESR and a Fenton reaction. The DMPO-OH signal was clearly detected, even in AEW prepared by single electrolysis of 0.1% NaCl solution, when ferrous sulfate was added to induce a Fenton reaction, indicating the presence of hydrogen peroxide in the AEW. Since sodium formate, a hydroxyl radical scavenger, did not affect the bactericidal activity of AEW, it is concluded that the radical is unlikely to contribute to the antimicrobial activity of AEW, although a small amount of the radical is produced from hydrogen peroxide. Dimethyl sulfoxide, the other hydroxyl radical scavenger used in the present study, canceled the bactericidal activity of AEW, accompanied by complete depletion of free available chlorine, suggesting that hypochlorous acid is probably a major contributor to the antimicrobial activity. Conclusions It is strongly suggested that although hydrogen peroxide is present in AEW as a source of hydroxyl radicals, the antimicrobial activity of AEW does not depend on these radicals. PMID:23029505

  5. Mapping nucleic acid structure by hydroxyl radical cleavage.

    PubMed

    Tullius, Thomas D; Greenbaum, Jason A

    2005-04-01

    Hydroxyl radical footprinting is a widely used method for following the folding of RNA molecules in solution. This method has the unique ability to provide experimental information on the solvent accessibility of each nucleotide in an RNA molecule, so that the folding of all domains of the RNA species can be followed simultaneously at single-nucleotide resolution. In recent work, hydroxyl radical footprinting has been used, often in combination with other global measures of structure, to work out detailed folding pathways and three-dimensional structures for increasingly large and complicated RNA molecules. These include synthetic ribozymes, and group I and group II ribozymes, from yeast, the Azoarcus cyanobacterium and Tetrahymena thermophila. Advances have been made in methods for analysis of hydroxyl radical data, so that the large datasets that result from kinetic folding experiments can be analyzed in a semi-automated and quantitative manner.

  6. Structure and behaviour of the free radicals generated in gamma irradiated amino acid and iminodiacetic acid derivatives.

    PubMed

    Osmanoğlu, Semsettin; Aydın, Murat; Osmanoğlu, Y Emre; Dicle, I Yeşim; Başkan, M Halim

    2011-05-01

    An EPR study has been carried out to investigate the structure and behaviour of the free radical formed γ-irradiated l-alaninamide hydrochloride, dl-glutamic acid monohydrate and N-(2-carboxyethyl) iminodiacetic acid powders at room temperature. The observed paramagnetic species have been attributed to the CH(3)ĊHCONH(2), HOOCCH(2)CH(2)ĊHCOOH and HOOCCH(2)CH(2)NĊHCH(2)(COOH)(2) radicals, respectively. Some spectroscopic properties and suggestions concerning possible structure of the radicals were also discussed in this study. PMID:21393055

  7. Measurement of antioxidant activity with trifluoperazine dihydrochloride radical cation.

    PubMed

    Asghar, M N; Khan, I U

    2008-06-01

    A novel, rapid and cost-effective trifluoperazine dihydrochloride (TFPH) decolorization assay is described for the screening of antioxidant activity. A chromogenic reaction between TFPH and potassium persulfate at low pH produces an orange-red radical cation with maximum absorption at 502 nm in its first-order derivative spectrum. TFPH was dissolved in distilled water to give a 100 mM solution. The TFPH radical cation solution was made by reacting 0.5 mL of the solution with K2S2O8 (final concentration: 0.1 mM) and diluting to 100 mL with 4 M H2SO4 solution. A linear inhibition of color production was observed with linearly increasing amounts of antioxidants, with correlation coefficients (R(2)) ranging from 0.999 to 0.983. The antioxidant capacity of standard solutions of an antioxidant was evaluated by comparing with the inhibition curve using Trolox as the standard. Comparison of antioxidant capacity determined with this newly developed TFPH assay and with the well-known 2,2'-azinobis-[3-ethylbenzthiazoline-6-sulfonic acid] (ABTS)-persulfate decolorization assay indicated the efficacy and sensitivity of the procedure. The proposed assay is less expensive (costs about US$4 per 100 assays) and requires only 20 min for preparation of radical cation solution in comparison with ABTS assay, in which almost 12-16 h are required for preparation of a stable ABTS radical cation solution. The present assay has the advantage over ABTS assay that it can be used to measure the antioxidant activity of the samples, which are naturally found at a pH as low as 1, because the radical cation itself has been stabilized at low pH.

  8. 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.

  9. Discriminating D-amino acid-containing peptide epimers by radical-directed dissociation mass spectrometry.

    PubMed

    Tao, Yuanqi; Quebbemann, Neil R; Julian, Ryan R

    2012-08-01

    The presence of a single D-amino acid in a peptide is very difficult to detect. Mass spectrometry-based approaches rely on differences in fragmentation between all L-amino acid-containing peptides and single D-amino acid-containing peptides (which are epimers) for identification. The success of this approach is dependent on the structural sensitivity of the fragmentation method. Recently, experiments have demonstrated that fragmentation initiated by radical chemistry, or radical-directed dissociation (RDD), is particularly sensitive to the structure of the ion being fragmented. Herein, RDD is used to identify the presence of D-serine, D-alanine, or D-aspartic acid in eight biologically relevant peptides. It is demonstrated that chiral disambiguation by RDD is dependent on both the initial radical site and subsequent radical migration. Fortuitously, RDD can be initiated by a variety of different radical precursors which can be associated with the peptide via covalent or noncovalent means, and RDD can be examined in all observable charge states (both positive and negative). This diversity enables numerous initial radical sites and migration pathways to be explored. For all but one of the peptides that were examined, RDD provides significantly better chiral discrimination than CID. Quantitation of peptide epimers by RDD is also described.

  10. Radical stability directs electron capture and transfer dissociation of β-amino acids in peptides.

    PubMed

    Ben Hamidane, Hisham; Vorobyev, Aleksey; Larregola, Maud; Lukaszuk, Aneta; Tourwé, Dirk; Lavielle, Solange; Karoyan, Philippe; Tsybin, Yury O

    2010-04-19

    We report on the characteristics of the radical-ion-driven dissociation of a diverse array of β-amino acids incorporated into α-peptides, as probed by tandem electron-capture and electron-transfer dissociation (ECD/ETD) mass spectrometry. The reported results demonstrate a stronger ECD/ETD dependence on the nature of the amino acid side chain for β-amino acids than for their α-form counterparts. In particular, only aromatic (e.g., β-Phe), and to a substantially lower extent, carbonyl-containing (e.g., β-Glu and β-Gln) amino acid side chains, lead to N-Cβ bond cleavage in the corresponding β-amino acids. We conclude that radical stabilization must be provided by the side chain to enable the radical-driven fragmentation from the nearby backbone carbonyl carbon to proceed. In contrast with the cleavage of backbones derived from α-amino acids, ECD of peptides composed mainly of β-amino acids reveals a shift in cleavage priority from the N-Cβ to the Cα-C bond. The incorporation of CH2 groups into the peptide backbone may thus drastically influence the backbone charge solvation preference. The characteristics of radical-driven β-amino acid dissociation described herein are of particular importance to methods development, applications in peptide sequencing, and peptide and protein modification (e.g., deamidation and isomerization) analysis in life science research.

  11. 40 CFR 1037.730 - ABT reports.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false ABT reports. 1037.730 Section 1037.730 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW HEAVY-DUTY MOTOR VEHICLES Averaging, Banking, and Trading for Certification §...

  12. Reactions of charged phenyl radicals with aliphatic amino acids in the gas phase.

    PubMed

    Huang, Yiqun; Guler, Leo; Heidbrink, Jenny; Kenttämaa, Hilkka

    2005-03-23

    Gas-phase reactivity of five differently substituted positively charged phenyl radicals was examined toward six amino acids by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR). The reactivity of the radicals studied was determined by the electrophilicity of the radical, which can be characterized by the radical's electron affinity (EA). The larger the electron affinity of the radical, the higher the overall reaction rate. In addition to the expected H-atom abstraction, several unprecedented reaction pathways were observed, including NH2 abstraction, SH abstraction, and SCH3 abstraction. These reaction pathways dominate for the most electrophilic radicals, and they may not follow radical but rather nucleophilic addition-elimination mechanisms. Hydrogen abstraction from glycine was also investigated theoretically. The results indicate that hydrogen abstraction from alphaC of glycine is both kinetically and thermodynamically favored over the NH2 group. The ordering of transition state energies for hydrogen abstraction from the alphaC and NH2 groups was found to reflect the radicals' EA ordering.

  13. Test for antioxidant ability by scavenging long-lived mutagenic radicals in mammalian cells and by blood test with intentional radicals: an application of gallic acid

    NASA Astrophysics Data System (ADS)

    Kumagai, Jun; Kawaura, Tomoko; Miyazaki, Tetsuo; Prost, Michel; Prost, Emmanuelle; Watanabe, Masami; Quetin-Leclercq, Joëlle

    2003-01-01

    Antioxidant ability of gallic acid (GA) are determined both by electron spin resonance measurement of long-lived radicals produced in γ-ray irradiated Syrian golden hamster embryo cells with GA and by hemolysis measurement with GA when blood cells are submitted to radicals. Scavenging properties of GA are determined by the reaction rate constant with long-lived mutagenic radicals in the cells while the blood test allows to analyze the global effects of this compound: radical scavenger+metal ion chelator+regeneration of intra- and extra-cellular antioxidant.

  14. Polyphenolic acids from mint (the aerial of Mentha haplocalyx Briq.) with DPPH radical scavenging activity.

    PubMed

    She, G-M; Xu, C; Liu, B; Shi, R-B

    2010-05-01

    Vegetables of mint (the aerial part of Mentha haplocalyx) contain a significant amount of polyphenols with many health benefits. The crude aqueous acetone extract exhibited high antioxidant activity (IC(50)= 45.67 mug/mL) in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. The activity-guided separation of chlorophyll removal fraction on column chromatography afforded 8 polyphenolic acids, including a new compound, cis-salvianolic acid J (1), and 7 known compounds, salvianolic acid J (2), lithospermic acid (3), rosmarinic acid (4), lithospermic acid B (5), magnesium lithospermate B (6), sodium lithospermate B (7), and danshensu (8), respectively. Their structural elucidations of all the compounds were based on extensive spectroscopic methods, including HRESIMS and 2D NMR experiments (HSQC, HMBC, and ROESY) and by comparison with reference values. Compounds 2, 3, and 5 to 8 were isolated from Mentha genus for the 1st time. The DPPH radical scavenging activities of all the isolated compounds were evaluated.

  15. Antioxidant activity measured in different solvent fractions obtained from Mentha spicata Linn.: an analysis by ABTS*+ decolorization assay.

    PubMed

    Arumugam, Ponnan; Ramamurthy, Perumal; Santhiya, Sathiyavedu Thyagarajan; Ramesh, Arabandi

    2006-01-01

    Antioxidant compounds are abundantly available in plants and play an important role in scavenging free radicals, thus providing protection to humans against oxidative DNA damage. Mentha spicata Linn., commonly called spearmint, belongs to the family lamiaceae. It was selected in the present study because Mentha extracts have antioxidant properties due to the presence of eugenol, caffeic acid, rosmarinic acid and alpha-tocopherol. Four solvent fractions (hexane, chloroform, ethyl acetate and water) of ethanolic extract of dried leaves powder of M. spicata were analyzed for total antioxidant activity (TAA) and relative antioxidant activity (RAA) and compared with standard antioxidants such as Quercetin, beta-carotene, L-ascorbic acid and glutathione using ABTS*+ decolorization assay (ABTS/Potassium persulphate). The antioxidant activity was assumed to be from the total phenolic content of the ethanolic extract. Total phenolics are found to be highest in ethyl acetate fraction (54 mg/g) and least in hexane fraction (13 mg/g) and more or less similar in water and chloroform fractions (30-32 mg/g). TAA is found to be less in hexane and chloroform fractions (<53% at 50 microg/ml) and highest in ethyl acetate (95% at 20 microg/ml) and water (84% at 30 microg/ml) fractions. The RAA of ethyl acetate fraction is 1.1 compared to quercetin (at 5 microM/ml), but greater when compared to beta-carotene (15 microM/ml), L-ascorbic acid (15 microM/ml) and glutathione (15 microM/ml). The RAAs with these antioxidants are in the range of 1.31 -1.6. The values of RAAs for water fraction also show similar trend and are in the range of 1.0-1.4. The antioxidant activities of the solvent factions are closely related to the content of total phenolics present in them.

  16. Concerted effects in the reaction of rad OH radicals with aromatics: radiolytic oxidation of salicylic acid

    NASA Astrophysics Data System (ADS)

    Albarran, G.; Schuler, R. H.

    2003-06-01

    Liquid chromatographic and capillary electrophoretic studies have been used to resolve the products produced in the radiolytic oxidation of salicylic acid in aqueous solution. These studies have shown that, as in the case of phenol, rad OH radicals preferentially add to the positions ortho and para to the OH substituent. However, in contrast to its reaction with phenol, addition at the ortho position is favored over addition at the para position. Because rad OH radical is a strong electrophile this difference suggests that the electron population at the ortho position in the salicylate anion is enhanced as a result of the hydrogen bonding in salicylic acid.

  17. [Effects of ascorbic acid on the free radical formations of isoniazid and its metabolites].

    PubMed

    Matsuki, Y; Akazawa, M; Tsuchiya, K; Sakurai, H; Kiwada, H; Goromaru, T

    1991-10-01

    By the use of electron spin resonance (ESR) spectroscopy and of spin-trapping technique, the effects of ascorbic acid on the formation of the free radical intermediates due to isoniazid (INAH) and its metabolites were investigated with a microsomal system. When alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (4-POBN) was used as a spin trapping agent, the ESR signal due to hydrazine (Hy) was formed to be most intensive among others. Therefore, it was presumed that Hy is a potent intermediate to cause an INAH-induced hepatic injury. In the presence of ascorbic acid (AA), the free radical formation of Hy, INAH and acetyl hydrazine was significantly inhibited, suggesting that AA may affect the INAH-hepatitis. By the addition of inhibitors of cytochrome P-450 like metyrapone and CO, the generation of the radical from Hy decreased, confirming that the radical is formed by the cytochrome P-450 dependent microsome systems. The 4-POBN-trapped radical species generated from Hy was presumed to be the hydrazyl radical by the results of mass spectrometry.

  18. Radical scavenging activity of lipophilized products from lipase-catalyzed transesterification of triolein with cinnamic and ferulic acids.

    PubMed

    Choo, Wee-Sim; Birch, Edward John

    2009-02-01

    Lipase-catalyzed transesterification of triolein with cinnamic and ferulic acids using an immobilized lipase from Candida antarctica (E.C. 3.1.1.3) was conducted to evaluate the antioxidant activity of the lipophilized products as model systems for enhanced protection of unsaturated oil. The lipophilized products were identified using ESI-MS. Free radical scavenging activity was determined using the DPPH radical method. The polarity of the solvents proved important in determining the radical scavenging activity of the substrates. Ferulic acid showed much higher radical scavenging activity than cinnamic acid, which has limited activity. The esterification of cinnamic acid and ferulic acid with triolein resulted in significant increase and decrease in the radical scavenging activity, respectively. These opposite effects were due to the effect of addition of electron-donating alkyl groups on the predominant mechanism of reaction (hydrogen atom transfer or electron transfer) of a species with DPPH. The effect of esterification of cinnamic acid was confirmed using ethyl cinnamate which greatly enhances the radical scavenging activity. Although, compared to the lipophilized cinnamic acid product, the activity was lower. The radical scavenging activity of the main component isolated from lipophilized cinnamic acid product using solid phase extraction, monocinnamoyl dioleoyl glycerol, was as good as the unseparated mixture of lipophilized product. Based on the ratio of a substrate to DPPH concentration, lipophilized ferulic acid was a much more efficient radical scavenger than lipophilized cinnamic acid.

  19. Influence of different free radicals on scavenging potency of gallic acid.

    PubMed

    Đorović, Jelena; Marković, Jasmina M Dimitrić; Stepanić, Višnja; Begović, Nebojša; Amić, Dragan; Marković, Zoran

    2014-07-01

    The M05-2X/6-311++G(d,p) and B3LYP-D2/6-311++G(d,p) models are used to evaluate scavenging potency of gallic acid. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms of gallic acid with some radicals ((•)OO(-), (•)OH, and CH3OO(•)) were investigated using the corresponding thermodynamic quantities: bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA). Namely, the ΔHBDE, ΔHIP, and ΔHPA values of the corresponding reactions in some solvents (water, DMSO, pentylethanoate, and benzene) are investigated using an implicit solvation model (SMD). An approach based on the reactions enthalpies related to the examined mechanisms is applied. This approach shows that a thermodynamically favored mechanism depends on the polarity of reaction media and properties of free radical reactive species. The most acidic 4-OH group of gallic acid is the active site for radical inactivation. The results of this investigation indicate that the SPLET mechanism can be a favored reaction pathway for all three radicals in all solvents, except for (•)OH in the aqueous solution. In water, gallic acid can inactivate (•)OH by the HAT mechanism.

  20. How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

    PubMed Central

    Speijer, D.; Manjeri, G. R.; Szklarczyk, R.

    2014-01-01

    Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH2 or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH2 in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings. PMID:24864314

  1. Radical scavenging capacity of methanolic Phillyrea latifolia L. extract: anthocyanin and phenolic acids composition of fruits.

    PubMed

    Ayranci, Erol; Erkan, Naciye

    2013-01-01

    Radical scavenging capacity of a crude methanolic extract from the fruits of Phillyrea latifolia L., commonly known as green olive tree or mock privet, was investigated with reference to anthocyanin standards, as flavonoids, and phenolic acid standards, as phenylpropanoids. Characterization with high performance liquid chromatography-diode array detection (HPLC-DAD) indicated the presence of keracyanin, kuromanin, cyanidin, ferulic acid, caffeic acid and rosmarinic acid at amounts of 289.1, 90.4, 191.4, 225.2, 221.2 and 190.1 mg/100 g fresh weight (FW) of fruits, respectively. Chlorogenic and p-coumaric acids were found to exist in lower amounts. Trolox equivalent antioxidant capacity (TEAC) and IC(50) values of the plant extract were found to be 1.8 mM Trolox equivalents (TE)/g FW of fruits and 69.4 µg/mL, respectively, indicating the close radical scavenging activity of the extract to those of keracyanin and p-coumaric acid. The crude methanolic P. latifolia L. fruit extract was seen to be fairly potent in radical scavenging. Total phenolic content (TPC) of the plant extract was found to be 1652.9 mg gallic acid equivalent (GAE)/100 g FW of fruits. PMID:23364751

  2. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions.

    PubMed

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G

    2013-12-16

    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  3. 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}.

  4. Copper-catalyzed trifluoromethylation of aryl- and vinylboronic acids with generation of CF3-radicals.

    PubMed

    Li, Yang; Wu, Lipeng; Neumann, Helfried; Beller, Matthias

    2013-04-01

    The selective trifluoromethylation of aryl- and vinylboronic acids proceeds smoothly with CF3SO2Na (Langlois reagent) in the presence of copper catalysts and t-BuOOH. Therefore, the method relies both on transition metal catalysis and selective radical reactions. Advantageously, the protocol can be performed at room temperature under an air atmosphere and avoids the issue of poor regioselectivity. PMID:23431556

  5. Enantioselective conjugate additions of α-amino radicals via cooperative photoredox and Lewis acid catalysis.

    PubMed

    Ruiz Espelt, Laura; McPherson, Iain S; Wiensch, Eric M; Yoon, Tehshik P

    2015-02-25

    We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

  6. A Free-Radical-Promoted Stereospecific Decarboxylative Silylation of α,β-Unsaturated Acids with Silanes.

    PubMed

    Zhang, Lizhi; Hang, Zhaojia; Liu, Zhong-Quan

    2016-01-01

    A stereospecific decarboxylative silylation of acrylic and propiolic acids with silanes was developed. This reaction represents the first example of decarboxylative C-Si bond formation and provides an efficient and convenient approach to various synthetically useful alkenyl and alkynyl organosilicon compounds through the reaction of α,β-unsaturated acids with silanes. Spin-trapping and EPR experiments support a radical addition/elimination process. PMID:26582425

  7. Free radicals from 1-palmitoyl-2-arachidonoylphosphatidylcholine liposomes in Fe2+/ascorbic acid solution.

    PubMed

    Yoshida, T; Otake, H; Aramaki, Y; Hara, T; Tsuchiya, S; Hamada, A; Utsumi, H

    1996-06-01

    The generation of free radicals during the lipid peroxidation of liposomes composed of 1-palmitoyl-2-arachidonoylphosphatidylcholine (PAPC-liposome) in Fe2+/ascorbic acid (AsA) solution was studied by the ESR spin trapping technique. A carbon-centered radical adduct was observed using alpha-(4-pyridyl-1-oxide)-N-tert-butyl-nitorone (4-POBN) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), but no oxygen-centered radicals such as .OH, LO., and LOO. were observed. The lipid peroxidation evaluated as 2-thiobarbituric acid reactive substances was inhibited by the addition of 4-POBN. The intensity of this inhibitory effect was dependent on the time when 4-POBN was added to the mixture of PAPC-liposomes and Fe2+/AsA solution, and no inhibitory effect could be observed after 4 min. The signal intensity of the carbon-centered radical adduct was dependent on the lipid concentration of PAPC-liposomes. These results suggest that the alkyl radicals generated from PAPC-liposome peroxidation induced by Fe2+/AsA were trapped by DMPO or 4-POBN at an earlier stage of lipid peroxidation. PMID:8799472

  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.

  9. 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

  10. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid and methylglyoxal

    NASA Astrophysics Data System (ADS)

    Tan, Y.; Lim, Y. B.; Altieri, K. E.; Seitzinger, S. P.; Turpin, B. J.

    2012-01-01

    Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including pyruvate, oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA). Acetic acid plays a central role in the aqueous oxidation of methylglyoxal and it is a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid (20 μM-10 mM) was oxidized by OH radicals, and pyruvic acid and methylglyoxal experimental samples were analyzed using new analytical methods, in order to better understand the formation of SOA from acetic acid and methylglyoxal. Glyoxylic, glycolic, and oxalic acids formed from acetic acid and OH radicals. In contrast to the aqueous OH radical oxidation of methylglyoxal, the aqueous OH radical oxidation of acetic acid did not produce succinic acid and oligomers. This suggests that the methylgloxal-derived oligomers do not form through the acid catalyzed esterification pathway proposed previously. Using results from these experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  11. 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

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  14. Catalytic effect of water, formic acid, or sulfuric acid on the reaction of formaldehyde with OH radicals.

    PubMed

    Zhang, Weichao; Du, Benni; Qin, Zhenglong

    2014-07-01

    In this paper, for the hydrogen abstraction reaction of HCHO by OH radicals assisted by water, formic acid, or sulfur acid, the possible reaction mechanisms and kinetics have been investigated theoretically using quantum chemistry methods and transition-state theory. The potential energy surfaces calculated at the CCSD(T)/6-311++G(df,pd)//MP2(full)/6-311++G(df,pd) levels of theory reveal that, due to the formation of strong hydrogen bond(s), the relative energies of the transition states involving catalyst are significantly reduced compared to that reaction without catalyst. However, the kinetics calculations show that the rate constants are smaller by about 3, 9, or 10 orders of magnitude for water, formic acid, or sulfur acid assisted reactions than that uncatalyzed reaction, respectively. Consequently, none of the water, formic acid, or sulfur acid can accelerate the title reaction in the atmosphere.

  15. 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.

  16. 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

  17. 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

  18. Peroxynitrite-mediated formation of free radicals in human plasma: EPR detection of ascorbyl, albumin-thiyl and uric acid-derived free radicals.

    PubMed Central

    Vásquez-Vivar, J; Santos, A M; Junqueira, V B; Augusto, O

    1996-01-01

    Formation of peroxynitrite by the fast reaction between nitric oxide and superoxide anion may represent a critical control point in cells producing both species, leading to either down-regulation of the physiological effects of superoxide anion and nitric oxide by forming an inert product, nitrate, or to potentiation of their toxic effects by oxidation of nearby molecules by peroxynitrite. (The term peroxynitrite is used to refer to the sum of all possible forms of peroxynitrite anion and peroxynitrous acid unless otherwise specified.) In this report we demonstrate that, in spite of all the antioxidant defences present in human plasma, its interaction with peroxynitrite leads to generation of free radical intermediates such as (i) the ascorbyl radical, detected by direct EPR, (ii) the albumin-thiyl radical, detected by spin-trapping experiments with both N-tert-butyl-alpha-phenylnitrone and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and (iii) a uric acid-derived free radical, detected as the DMPO radical adduct in plasma whose thiol groups were previously blocked with 5,5-dithiobis-(2-nitrobenzoic acid). The identity of the latter adduct was confirmed by parallel experiments demonstrating that it is not detectable in plasma pretreated with uricase, whereas it is formed in incubations of peroxynitrite with uric acid. Peroxynitrite-mediated oxidations were also followed by oxygen consumption and ascorbate and plasma-thiol depletion. Our results support the view that peroxynitrite-mediated one-electron oxidation of biomolecules may be an important event in its cytotoxic mechanism. In addition, the data have methodological implications by providing support for the use of EPR methodologies for monitoring both free radical reactions and ascorbate concentrations in biological fluids. PMID:8615782

  19. Silver-Catalyzed Decarboxylative Radical Azidation of Aliphatic Carboxylic Acids in Aqueous Solution.

    PubMed

    Liu, Chao; Wang, Xiaoqing; Li, Zhaodong; Cui, Lei; Li, Chaozhong

    2015-08-12

    We report herein an efficient and general method for the decarboxylative azidation of aliphatic carboxylic acids. Thus, with AgNO3 as the catalyst and K2S2O8 as the oxidant, the reactions of various aliphatic carboxylic acids with tosyl azide or pyridine-3-sulfonyl azide in aqueous CH3CN solution afforded the corresponding alkyl azides under mild conditions. A broad substrate scope and wide functional group compatibility were observed. A radical mechanism is proposed for this site-specific azidation.

  20. 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

  1. 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

  2. In vitro antioxidant and radical-scavenging capacities of Citrullus colocynthes (L) and Artemisia absinthium extracts using promethazine hydrochloride radical cation and contemporary assays.

    PubMed

    Asghar, M Nadeem; Khan, I Ullah; Bano, N

    2011-10-01

    A new, quick and economical decolorization assay based upon the generation of a radical cation made from promethazine hydrochloride (PMZH) is described for screening of antioxidant activity of plants/herbal extracts. PMZH radical cations, produced through a reaction between PMZH and potassium persulfate (K(2)S(2)O(8)) in phosphoric acid medium, have maximum absorption at 515 nm in their first-order derivative spectrum. Theconcentrations of chromagen and K(2)S(2)O(8) were optimized (final concentration of PMZH and K₂S₂O₈ were 0.166 mM and 0.11 mM, respectively) for better stability and sensitivity of the radical cation produced. Agood linear correlation was found between the percentage inhibition and the increasing amounts of standard antioxidants, with correlation coefficients ranging from 0.989 to 0.999. The newly developed assay was employed to evaluate the antioxidant capacity of Citrullus colocynthes L. and Artemisia absinthium extracts. The proposed assay involved a more stable radical cation and required only 1 h for preparation of a working solution in comparison to the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation decolorizaion assay, which was reported to be less sensitive at low pH and almost 12-16 h were required for preparation of a working ABTS solution. Other assays employed to evaluate the antioxidant potential andradical-scavenging capacities of the extracts were the ferric-reducing antioxidant power, 2,2'-diphenyl-1-picrylhydrazyl radical scavenging, total phenolic contents assay, total flavonoid contents and metal-chelating activity assays, and the lipid peroxidation value in linoleic acid emulsion systems. The results indicate that boththe plants have potent free radical-scavenging activity and the ability to prevent lipid peroxidation and radical chain reactions.

  3. 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.

  4. Radical formation of amino acid precursors in interstellar regions? Ser, Cys and Asp.

    PubMed

    Knowles, Daniel J; Wang, Tianfang; Bowie, John H

    2010-11-01

    It is proposed that the glycine precursor NH(2)CH(2)CN may be synthesised in interstellar dust clouds by the radical combination reactions NH(2)˙ + ˙CH(2)CN → NH(2)CH(2)CN (ΔG = -302 kJ mol(-1)) and/or NH(2)CH(2)˙ + ˙CN → NH(2)CH(2)CN (ΔG = -414 kJ mol(-1)). All calculations at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31+G(d) level of theory. This paper extends that concept to radical/radical coupling reactions to form Ser, Cys and Asp precursor nitriles. The hydrogen abstraction process NH(2)CH(2)CN + HO˙→ NH(2)˙CHCN + H(2)O (ΔG = -130 kJ mol(-1)) is suggested to precede the radical coupling reactions NH(2)˙CHCN + R˙→ NH(2)CHRCN (R˙ = ˙CH(2)OH, ˙CH(2)SH and ˙CH(2)CN) to form nitrile precursors of the amino acids Ser, Cys and Asp. These three reactions are all favourable (ΔG = -240, -227 and -223 kJ mol(-1)). The radical species ˙CH(2)NH(2), ˙CH(2)OH, ˙CH(2)SH and ˙CH(2)CN are shown to be stable for the microsecond timeframe by a combination of theoretical calculations and the experimental mass spectrometric neutralization/reionization procedure.

  5. 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

  6. 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.

  7. 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

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

    PubMed Central

    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

  9. 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

  10. Aqueous phototransformation of bisphenol S: the competitive radical-attack pathway to p-hydroxybenzenesulfonic acid.

    PubMed

    Wang, Xiaowen; Ma, Jiahai; Wang, Zhenpeng; Guo, Rongrong; Hu, Xuefeng

    2014-01-01

    The kinetics, environmental influencing factors, products and reaction mechanism of aqueous phototransformation of bisphenol S (BPS), as an alternative to bisphenol A, which is of environmental concern, were investigated. p-Hydroxybenzenesulfonic acid, as the major transformation product was confirmed by gas chromatography - mass spectrometry, electrospray ionization, ¹H nuclear magnetic resonance and fluorescence spectrum analysis. A reaction pathway was proposed based on the reactive oxygen species related results by electron paramagnetic resonance and radical traps. The competition of the excited state of BPS between transferring electron to O₂ to •O₂(-) and directly oxidizing H₂O to •OH was revealed.

  11. Formation of peroxides in amino acids and proteins exposed to oxygen free radicals.

    PubMed Central

    Gebicki, S; Gebicki, J M

    1993-01-01

    Dilute aqueous solutions of BSA or lysozyme gave positive tests for peroxides after exposure to reactive oxygen species. The reactive species were generated by gamma-irradiation, reduction of H2O2 with Fe2+ ions or thermal decomposition of an azo compound. Peroxides were assayed by an iodometric method. Identification of the new groups as hydroperoxides was confirmed by their ability to oxidize a range of compounds and by the kinetics of their reaction with iodide. The hydroperoxide groups were bound to the proteins and their yields (G values) corresponded to 1.2 -OOH groups per 100 eV of radiation energy absorbed for BSA, and 0.8 for lysozyme. The oxygen free radicals effective in protein peroxidation were the hydroxyl and organic peroxyl, but not superoxide or its protonated form. The efficiency of BSA peroxidation initiated by the hydroxyl radicals was 40%. Protein peroxides decayed spontaneously with a half-life of about 1.5 days at 20 degrees C. Exposure of the common amino acids to hydroxyl free radicals showed that six of them (glutamate, isoleucine, leucine, lysine, proline and valine) were peroxidized with similar efficiency to the proteins, whereas the rest were inert or much less susceptible. These results suggest that some proteins may be peroxidized by a variety of agents in vivo and that their subsequent reactions with protective agents, such as ascorbate or glutathione, may decrease the antioxidant potential of cells and tissues. PMID:8435071

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. On the reaction of lupulones, hops β-acids, with 1-hydroxyethyl radical.

    PubMed

    de Almeida, Natália E C; do Nascimento, Eduardo S P; Cardoso, Daniel R

    2012-10-24

    Lupulones, hops β-acids, are one of the main constituents of the hops resin and have an important contribution to the overall bacteriostatic activity of hops during beer brewing. The use of lupulones as natural alternatives to antibiotics is increasing in the food industry and also in bioethanol production. However, lupulones are easy oxidizable and have been shown to be very reactive toward 1-hydroxyethyl radical with apparent bimolecular rate constants close to diffusion control k = 2.9 × 10(8) and 2.6 × 10(8) L mol(-1) s(-1) at 25.0 ± 0.2 °C in ethanol-water solution (10% of ethanol (v/v)) as probed by EPR and ESI-IT-MS/MS spin-trapping competitive kinetics, respectively. The free energy change for an electron-transfer mechanism is ΔG° = 106 kJ/mol as calculated from the oxidation peak potential experimentally determined for lupulones (1.1 V vs NHE) by cyclic voltammetry and the reported reduction potential for 1-hydroxyethyl radical. The major reaction products identified by LC-ESI-IT-MS/MS and ultrahigh-resolution accurate mass spectrometry (orbitrap FT-MS) are hydroxylated lupulone derivatives and 1-hydroxyethyl radical adducts. The lack of pH dependence for the reaction rate constant, the calculated free energy change for electron transfer, and the main reaction products strongly suggest the prenyl side chains at the hops β-acids as the reaction centers rather than the β,β'-triketone moiety.

  19. 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

  20. 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.

  1. 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.

  2. A perspective on free radical autoxidation: the physical organic chemistry of polyunsaturated fatty acid and sterol peroxidation.

    PubMed

    Porter, Ned A

    2013-04-19

    This Perspective describes advances from the author's laboratory on the free radical reactions of organic compounds with molecular oxygen. Polyunsaturated fatty acids (PUFAs) and sterols are particularly prone to undergo radical chain oxidation, and evidence suggests that this process, known as lipid peroxidation, occurs in vivo under a variety of conditions that are the result of an oxidative stress. Cyclic peroxides, hydroperoxides, and epoxy alcohols are major products formed from peroxidation, and the basic mechanisms of product formation are now reasonably well understood. These mechanisms include reversible addition of oxygen to carbon radicals, rearrangement and cyclization of allyl and pentadienyl peroxyl radicals, and homolytic substitution of carbon radicals on the peroxide bond. A physical organic approach to the problem of free radicals in biology and medicine is highlighted in this Perspective with stereochemical, kinetic, and extrathermodynamic probes applied to the study of mechanism. A radical clock permits the determination of free radical propagation rate constants, and 7-dehydrocholesterol, the immediate biosynthetic precursor of cholesterol, is found by this clock to be one of the most oxidizable lipids known. The consequences of the extreme reactivity of 7-dehydrocholesterol on human health is the focus of a current research theme in the author's laboratory.

  3. A Perspective on Free Radical Autoxidation: The Physical Organic Chemistry of Polyunsaturated Fatty Acid and Sterol Peroxidation

    PubMed Central

    2013-01-01

    This Perspective describes advances from the author’s laboratory on the free radical reactions of organic compounds with molecular oxygen. Polyunsaturated fatty acids (PUFAs) and sterols are particularly prone to undergo radical chain oxidation and evidence suggests that this process, known as lipid peroxidation, occurs in vivo under a variety of conditions that are the result of an oxidative stress. Cyclic peroxides, hydroperoxides, and epoxy-alcohols are major products formed from peroxidation and the basic mechanisms of product formation are now reasonably well understood. These mechanisms include reversible addition of oxygen to carbon radicals, rearrangement and cyclization of allyl and pentadienyl peroxyl radicals and homolytic substitution of carbon radicals on the peroxide bond. A physical organic approach to the problem of free radicals in biology and medicine is highlighted in this Perspective with stereochemical, kinetic and extrathermodynamic probes applied to the study of mechanism. A radical clock permits the determination of free radical propagation rate constants and 7-dehydrocholesterol, the immediate biosynthetic precursor of cholesterol, is found by this clock to be one of the most oxidizable lipids known. The consequences of the extreme reactivity of 7-dehydrocholesterol on human health is the focus of a current research theme in the author’s laboratory. PMID:23445181

  4. 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

  5. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid

    NASA Astrophysics Data System (ADS)

    Tan, Y.; Lim, Y. B.; Altieri, K. E.; Seitzinger, S. P.; Turpin, B. J.

    2011-06-01

    Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA). Acetic acid is an important intermediate in aqueous methylglyoxal oxidation and a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. Altieri et al. (2008) proposed that acetic acid was the precursor of oligoesters observed in methylglyoxal oxidation. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid at concentrations relevant to atmospheric waters (20 μM-10 mM) was oxidized by OH radical. Products were analyzed by ion chromatography (IC), electrospray ionization mass spectrometry (ESI-MS), and IC-ESI-MS. The formation of glyoxylic, glycolic, and oxalic acids were observed. In contrast to methylglyoxal oxidation, succinic acid and oligomers were not detected. Using results from these and methylglyoxal + OH radical experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  6. 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.

  7. 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.

  8. 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.

  9. The role of alkoxy radicals in the heterogeneous reaction of two structural isomers of dimethylsuccinic acid.

    PubMed

    Cheng, Chiu Tung; Chan, Man Nin; Wilson, Kevin R

    2015-10-14

    A key challenge in understanding the transformation chemistry of organic aerosols is to quantify how changes in molecular structure alter heterogeneous reaction mechanisms. Here we use two model systems to investigate how the relative locations of branched methyl groups control the heterogeneous reaction of OH with two isomers of dimethylsuccinic acid (C6H10O4). 2,2-Dimethylsuccinic acid (2,2-DMSA) and 2,3-dimethylsuccinic acid (2,3-DMSA) differ only in the location of the two branched methyl groups, thus enabling a closer inspection of how the distribution of carbon reaction sites impacts the chemical evolution of the aerosol. The heterogeneous reaction of OH with 2,3-DMSA (reactive OH uptake coefficient, γ = 0.99 ± 0.16) is found to be ∼2 times faster than that of 2,2-DMSA (γ = 0.41 ± 0.07), which is attributed to the larger stability of the tertiary alkyl radical produced by the initial OH abstraction reaction. While changes in the average aerosol oxidation state (OSC) and the carbon number (NC) are similar for both isomers upon reaction, significant differences are observed in the underlying molecular distribution of reaction products. The reaction of OH with the 2,3-DMSA isomer produces two major reaction products: a product containing a new alcohol functional group (C6H10O5) formed by intermolecular hydrogen abstraction and a C5 compound formed via carbon-carbon (C-C) bond scission. Both of these reaction products are explained by the formation and subsequent reaction of a tertiary alkoxy radical. In contrast, the OH reaction with the 2,2-DMSA isomer forms four dominant reaction products, the majority of which are C5 scission products. The difference in the quantity of C-C bond scission products for these two isomers is unexpected since decomposition is assumed to be favored for the isomer with the most tertiary carbon sites (i.e. 2,3-DMSA). For both isomers, there is a much larger abundance of C6 alcohol relative to C6 ketone products, which suggests

  10. 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

  11. Lewis acid-water/alcohol complexes as hydrogen atom donors in radical reactions.

    PubMed

    Povie, Guillaume; Renaud, Philippe

    2013-01-01

    Water or low molecular weight alcohols are, due to their availability, low price and low toxicity ideal reagents for organic synthesis. Recently, it was reported that, despite the very strong BDE of the O-H bond, they can be used as hydrogen atom donors in place of expensive and/or toxic group 14 metal hydrides when boron and titanium(III) Lewis acids are present. This finding represents a considerable innovation and uncovers a new perspective on the paradigm of hydrogen atom transfers to radicals. We discuss here the influence of complex formation and other association processes on the efficacy of the hydrogen transfer step. A delicate balance between activation by complex formation and deactivation by further hydrogen bonding is operative.

  12. A pulse radiolysis study of the dynamics of ascorbic acid free radicals within a liposomal environment.

    PubMed

    Kobayashi, Kazuo; Seike, Yumiko; Saeki, Akinori; Kozawa, Takahiro; Takeuchi, Fusako; Tsubaki, Motonari

    2014-10-01

    The dynamics of free-radical species in a model cellular system are examined by measuring the formation and decay of ascorbate radicals within a liposome with pulse radiolysis techniques. Upon pulse radiolysis of an N2O-saturated aqueous solution containing ascorbate-loaded liposome vesicles, ascorbate radicals are formed by the reaction of OH(·) radicals with ascorbate in unilamellar vesicles exclusively, irrespective of the presence of vesicle lipids. The radicals are found to decay rapidly compared with the decay kinetics in an aqueous solution. The distinct radical reaction kinetics in the vesicles and in bulk solution are characterized, and the kinetic data are analyzed.

  13. In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum.

    PubMed

    Santamaría, A; Jiménez-Capdeville, M E; Camacho, A; Rodríguez-Martínez, E; Flores, A; Galván-Arzate, S

    2001-08-28

    We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo hydroxyl radical (.OH) formation in the striatum of awake rats. Using the microdialysis technique, the generation of.OH was assessed through electrochemical detection of the salicylate hydroxylation product 2,3-dihydroxybenzoic acid (2,3-DHBA). The .OH extracellular levels increased up to 30 times over basal levels after QUIN infusion (240 nmol/microl), returning to the baseline 2 h later. This response was attenuated, but not abolished, by pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min before QUIN infusion. The mitochondrial toxin 3-nitropropionic acid (3-NPA, 500 nmol/microl) had stronger effects than QUIN on .OH generation, as well as on other markers of oxidative stress explored as potential consequences of .OH increased levels. These results support the hypothesis that early .OH generation contributes to the pattern of toxicity elicited by QUIN. The partial protection by MK-801 suggests that QUIN neurotoxicity is not completely explained through NMDA receptor overactivation, but it may also involve intrinsic QUIN oxidative properties.

  14. Examination by EPR spectroscopy of free radicals in melanins isolated from A-375 cells exposed on valproic acid and cisplatin.

    PubMed

    Chodurek, Ewa; Zdybel, Magdalena; Pilawa, Barbara; Dzierzewicz, Zofia

    2012-01-01

    Drug binding by melanin biopolymers influence the effectiveness of the chemotherapy, radiotherapy and photodynamic therapy. Free radicals of melanins take part in formation of their complex with drugs. The aim of this work was to determine the effect of the two compounds: valproic acid (VPA) and cisplatin (CPT) on free radicals properties of melanin isolated from A-375 melanoma cells. Free radicals were examined by an X-band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. EPR spectra were measured for the model synthetic eumelanin - DOPA-melanin, the melanin isolated from the control A-375 cells and these cells treated by VPA, CPT and both VPA and CPT. For all the examined samples broad EPR lines (deltaBpp: 0.48-0.68 mT) with g-factors of 2.0045-2.0060 characteristic for o-semiquinone free radicals were observed. Free radicals concentrations (N) in the tested samples, g-factors, amplitudes (A), integral intensities (I) and linewidths (deltaBpp) of the EPR spectra, were analyzed. The EPR lines were homogeneously broadened. Continuous microwave saturation of the EPR spectra indicated that slow spin-lattice relaxation processes existed in all the tested melanin samples. The relatively slowest spin-lattice relaxation processes characterized melanin isolated from A-375 cells treated with both VPA and CPT. The changes of the EPR spectra with increasing microwave power in the range of 2.2-70 mW were evaluated. Free radicals concentrations in the melanin from A-375 cells were higher than in the synthetic DOPA-melanin. The strong increase of free radicals concentration in the melanin from A-375 cells was observed after their treating by VPA. CPT also caused the increase of free radicals concentrations in the examined natural melanin. The free radicals concentration in melanin isolated from A-375 cells treated with both VPA and CPT was slightly higher than those in melanin from the control cells.

  15. Oxygen radicals shaping evolution: why fatty acid catabolism leads to peroxisomes while neurons do without it: FADH₂/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation.

    PubMed

    Speijer, Dave

    2011-02-01

    Oxygen radical formation in mitochondria is a highly important, but incompletely understood, attribute of eukaryotic cells. I propose a kinetic model in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH is a major determinant in radical formation. During the breakdown of glucose, this ratio is low; during fatty acid breakdown, this ratio is much higher. The longer the fatty acid, the higher the ratio and the higher the level of radical formation. This means that very long chain fatty acids should be broken down without generation of FADH₂ for mitochondria. This is accomplished in peroxisomes, thus explaining their role and evolution. The model explains many recent observations regarding radical formation by the respiratory chain. It also sheds light on the reasons for the lack of neuronal fatty acid (beta-) oxidation and for beneficial aspects of unsaturated fatty acids. Last but not least, it has very important implications for all models describing eukaryotic origins. PMID:21137096

  16. Free radical mediated grafting of chitosan with caffeic and ferulic acids: structures and antioxidant activity.

    PubMed

    Liu, Jun; Wen, Xiao-yuan; Lu, Jian-feng; Kan, Juan; Jin, Chang-hai

    2014-04-01

    In this study, two water soluble chitosan derivatives were synthesized by grafting caffeic acid (CA) and ferulic acid (FA) onto chitosan via a free radical mediated method. The structural characterization, antioxidant activity in vitro and in vivo of chitosan derivatives were determined. Results showed that the UV-vis absorption peaks of chitosan derivatives shifted toward longer wavelengths. FT-IR spectroscopy exhibited the typical phenolic characteristics within 1450-1600 cm(-1). (1)H NMR spectroscopy showed new peaks of phenyl protons at 6.2-7.6 ppm. (13)C NMR spectroscopy showed additional peaks between 110 and 150 ppm assigned to the C=C of phenolic groups. These results all confirmed the successful grafting of CA and FA onto chitosan backbones. The chitosan derivatives had decreased thermal stability and crystallinity as compared to chitosan. In vitro assays showed that the antioxidant activity decreased in the order of CA-g-chitosan>FA-g-chitosan>chitosan. Moreover, administration of the chitosan derivatives could significantly increase antioxidant enzymes activities and decrease malondialdehyde levels in both serums and livers of d-galactose induced aging mice. Our results indicated the potential of CA-g-chitosan and FA-g-chitosan in the development of novel antioxidant agents.

  17. Synthesis of ortho acid ester-type 1,3-dioxolanofullerenes: radical reaction of [60]fullerene with halocarboxylic acids promoted by lead(IV) acetate.

    PubMed

    You, Xun; Li, Fa-Bao; Wang, Guan-Wu

    2014-11-21

    A lead(IV) acetate-promoted radical reaction of [60]fullerene with halocarboxylic acids has been exploited to synthesize rare ortho acid ester-type 1,3-dioxolanofullerenes, the hydroxyl group of which can be further transformed to an ester or ether group. Intriguingly, an ortho acid ester-type 1,3-dioxolanofullerene can also be converted to a 1,4-dioxanonofullerene in the presence of a base or manipulated to another ortho acid ester-type 1,3-dioxolanofullerene by reaction with a stronger halocarboxylic acid. Moreover, two possible reaction pathways leading to the observed products are also proposed.

  18. Caffeoylquinic acid derived free radicals identified during antioxidant reactions of bitter tea (Ilex latifolia and Ilex kudincha).

    PubMed

    Pirker, Katharina Franziska; Goodman, Bernard Albert

    2010-12-01

    In order to provide some insight into the chemical basis for the antioxidant behaviour of bitter tea, the Chinese medicinal beverage derived from leaves of Ilex kudincha or Ilex latifolia, free radicals generated during the oxidation of aqueous extracts of dried leaves have been investigated by electron paramagnetic resonance (EPR) spectroscopy. With both beverages, the major components in the EPR spectra after accelerated autoxidation under alkaline conditions or oxidation with the superoxide anion radical were comparable to those derived from reactions of caffeoylquinic acids. Thus these reaction products have sufficient stability for biological activity, and the present results suggest that such molecules contribute appreciably to the antioxidant chemistry of these beverages.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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).

  4. [Lavoisier and radicals].

    PubMed

    Lafont, Olivier

    2007-01-01

    Lavoisier and his co-workers (Guyton de Morveau, Bertholet, Fourcroy) considered that acids were constituted of oxygen and of something else that they called radicals. These radicals were known in some cases, i.e. nitrogen for nitrous acid, carbon for carbonic acid, phosphorus for phosphoric acid. In the case of sulfur, the sulfuric radical could be associated with different quantities of oxigen leading to sulfuric or sulfurous acids. In other cases radicals remained unknown at the time i.e. muriatic radical for muriatic acid, or benzoyl radical for benzoic acid. It is interesting to notice that Lavoisier evoked the case of compound radicals constituted of different substances such as carbon and hydrogen.

  5. Neutral and acidic products derived from hydroxyl radical-induced oxidation of arabinotriose assessed by electrospray ionisation mass spectrometry.

    PubMed

    Moreira, Ana S P; da Costa, Elisabete V; Evtuguin, Dmitry V; Coimbra, Manuel A; Nunes, Fernando M; Domingues, M Rosário M

    2014-04-01

    The oxidation of α-(1 → 5)-L-arabinotriose (Ara3), an oligosaccharide structurally related to side chains of coffee arabinogalactans, was studied in reaction with hydroxyl radicals generated under conditions of Fenton reaction (Fe(2+)/H2O2). The acidic and neutral oxidation products were separated by ligand exchange/size-exclusion chromatography, subsequently identified by electrospray ionisation mass spectrometry (ESI-MS) and structurally characterised by tandem MS (ESI-MS/MS). In acidic fraction were identified several oxidation products containing an acidic residue at the corresponding reducing end of Ara3, namely arabinonic acid, and erythronic, glyceric and glycolic acids formed by oxidative scission of the furanose ring. In neutral fractions were identified derivatives containing keto, hydroxy and hydroperoxy moieties, as well as derivatives resulting from the ring scission at the reducing end of Ara3. In both acidic and neutral fractions, beyond the trisaccharide derivatives, the corresponding di- and monosaccharide derivatives were identified indicating the occurrence of oxidative depolymerisation. The structural characterisation of these oxidation products by ESI-MS/MS allowed the differentiation of isobaric and isomeric species of acidic and neutral character. The species identified in this study may help in detection of roasting products associated with the free radical-mediated oxidation of coffee arabinogalactans.

  6. 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.

  7. 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

  8. Acid-, base-, and lewis-acid-catalyzed heterolysis of methoxide from an alpha-hydroxy-beta-methoxy radical: models for reactions catalyzed by coenzyme B12-dependent diol dehydratase.

    PubMed

    Xu, Libin; Newcomb, Martin

    2005-11-11

    [Reaction: see text].A model for glycol radicals was employed in laser flash photolysis kinetic studies of catalysis of the fragmentation of a methoxy group adjacent to an alpha-hydroxy radical center. Photolysis of a phenylselenylmethylcyclopropane precursor gave a cyclopropylcarbinyl radical that rapidly ring opened to the target alpha-hydroxy-beta-methoxy radical (3). Heterolysis of the methoxy group in 3 gave an enolyl radical (4a) or an enol ether radical cation (4b), depending upon pH. Radicals 4 contain a 2,2-diphenylcyclopropane reporter group, and they rapidly opened to give UV-observable diphenylalkyl radicals as the final products. No heterolysis was observed for radical 3 under neutral conditions. In basic aqueous acetonitrile solutions, specific base catalysis of the heterolysis was observed; the pK(a) of radical 3 was determined to be 12.5 from kinetic titration plots, and the ketyl radical formed by deprotonation of 3 eliminated methoxide with a rate constant of 5 x 10(7) s(-1). In the presence of carboxylic acids in acetonitrile solutions, radical 3 eliminated methanol in a general acid-catalyzed reaction, and rate constants for protonation of the methoxy group in 3 by several acids were measured. Radical 3 also reacted by fragmentation of methoxide in Lewis-acid-catalyzed heterolysis reactions; ZnBr2, Sc(OTf)3, and BF3 were found to be efficient catalysts. Catalytic rate constants for the heterolysis reactions were in the range of 3 x 10(4) to 2 x 10(6) s(-1). The Lewis-acid-catalyzed heterolysis reactions are fast enough for kinetic competence in coenzyme B12 dependent enzyme-catalyzed reactions of glycols, and Lewis-acid-catalyzed cleavages of beta-ethers in radicals might be applied in synthetic reactions.

  9. 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

  10. 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.

  11. Pulse radiolysis studies of short-lived species in solid amino acids as precursors of radicals and detected by ESR

    NASA Astrophysics Data System (ADS)

    Zagórski, Z. P.; Gładysz, Katarzyna

    1995-06-01

    The aim of the study was to bring closer solid state radiation chemistry and ESR spectroscopy by looking for precursors of free radicals which give ESR signals. It has been performed using time-resolved spectrophotometry (pulse radiolysis of the solid state) and diffuse reflection spectrophotometry. Alanine has been especially considered as the most investigated amino acid, important for radiation dosimetry. Absorption of the transient (Λ maximum at 460 nm) is identified as the species during deamination. The stable absorption spectrum with the Λ maximum at 345 nm is due to the same radical as the one detected by ESR. Other amino acids: valine, threonine, glutamine and arginine show similar behaviour: microsecond spectrum of the intermediate appears always at longer wavelenghts. The transient spectrum changes into stable absorption in UV of a lower wavelenght. Along with the optical spectrum, the ESR spectrum appears, of similar stability. Also, other features indicate that the same radical is responsible for both the electronic and ESR spectrum. Some amino acids, like methionine give intensive transient absorption in the microsecond range but no ESR signal, after completion of consecutive fast reactions. In that case any optical absorption is due to the stable product of radiolysis, i.e. compounds with paired electrons only.

  12. 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

  13. 77 FR 68769 - Access to Confidential Business Information by Abt Associates, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    .... (Abt) of Cambridge, MA, to access information which has been submitted to EPA under section 8 of the...? Under EPA Contract Number EP-W-12-001, contractor Abt of 55 Wheeler Street, Cambridge, MA is assisting... at EPA Headquarters and Abt's Bethesda, MD and Cambridge, MA sites, in accordance with EPA's TSCA...

  14. 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

  15. The rate of decolorization of a radical ion reagent was used to determine the phenolic content of various food extracts.

    PubMed

    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.

  16. 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

  17. Radical generating coordination complexes as tools for rapid and effective fragmentation and fluorescent labeling of nucleic acids for microchip hybridization.

    SciTech Connect

    Kelly, J. J.; Chernov, B. N.; Mirzabekov, A. D.; Bavykin, S. G.; Biochip Technology Center; Northwestern Univ.; Engelhardt Inst. of Molecular Biology

    2002-01-01

    DNA microchip technology is a rapid, high-throughput method for nucleic acid hybridization reactions. This technology requires random fragmentation and fluorescent labeling of target nucleic acids prior to hybridization. Radical-generating coordination complexes, such as 1,10-phenanthroline-Cu(II) (OP-Cu) and Fe(II)-EDTA (Fe-EDTA), have been commonly used as sequence nonspecific 'chemical nucleases' to introduce single-strand breaks in nucleic acids. Here we describe a new method based on these radical-generating complexes for random fragmentation and labeling of both single- and double-stranded forms of RNA and DNA. Nucleic acids labeled with the OP-Cu and the Fe-EDTA protocols revealed high hybridization specificity in hybridization with DNA microchips containing oligonucleotide probes selected for identification of 16S rRNA sequences of the Bacillus group microorganisms.We also demonstrated cDNA- and cRNA-labeling and fragmentation with this method. Both the OP-Cu and Fe-EDTA fragmentation and labeling procedures are quick and inexpensive compared to other commonly used methods. A column-based version of the described method does not require centrifugation and therefore is promising for the automation of sample preparations in DNA microchip technology as well as in other nucleic acid hybridization studies.

  18. Protective effects of hydroxybenzoic acids and their esters on cell damage induced by hydroxyl radicals and hydrogen peroxides.

    PubMed

    Masaki, H; Okamoto, N; Sakaki, S; Sakurai, H

    1997-04-01

    The purpose of this study was to evaluate the hydroxyl radical scavenging activities of hydroxybenzoic acids and their esters from both chemical and biological aspects. These activities of hydroxybenzoic acids and their related compounds were estimated by ESR-spin trapping method, in which 3,4,5-trihydroxybenzoic acid and its ethyl and propyl esters showed the highest activities as estimated by IC50 value (50% inhibition concentration of hydroxyl radicals generated in the system): 78.04 +/- 11.23, 95.95 +/- 2.64, and 86.46 +/- 2.31 microM, respectively. In addition, 3,4,5-trihydroxybenzoic acid (gallic acid) at a concentration of 25 microM, protected against dermal fibroblast cell damage induced by H2O2, and enhanced the survival to 83.8 +/- 3.1%, in which the survival of control was 44.2 +/- 1.0%. Based on these results, the pretreatment effects of 3,4,5-trihydroxybenzoic acid n-alkyl esters on cell damage induced by H2O2 were examined. The survival of fibroblasts pretreated with the esters increased depending on the alkyl chain-length. Both C12 and C16 alkyl esters gave almost complete cell survival of 89.5 +/- 2.0% and 91.3 +/- 1.0%, respectively. The order of the protective effects of the compounds was in good agreement with that of their partition coefficients, suggesting that 3,4,5-trihydroxybenzoic acid alkyl esters are incorporated into fibroblasts, and thus prevent the cells from the toxicity caused by H2O2. In addition, an increase of intracellular peroxide formation in fibroblasts induced by UVA-irradiation, was suppressed to 2.27 +/- 0.41 nmol/10(4) cells by pretreatment with C16 alkyl ester at a concentration of 25 microM. Since 3,4,5-trihydroxybenzoic group has been demonstrated to possess a potent scavenging activity of hydroxyl radicals, this moiety was indicated to be important in preventing cell damage induced by UVA or H2O2: in turn, these produce hydroxyl radicals in the presence of trace metal ions such as iron and copper in cells.

  19. Disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical as a model of reactive oxygen species catalysed by Lewis and/or Brønsted acids.

    PubMed

    Nakanishi, Ikuo; Kawashima, Tomonori; Ohkubo, Kei; Waki, Tsukasa; Uto, Yoshihiro; Kamada, Tadashi; Ozawa, Toshihiko; Matsumoto, Ken-Ichiro; Fukuzumi, Shunichi

    2014-01-25

    Electron-transfer disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) occurred in the presence of Sc(3+) acting as a strong Lewis acid in deaerated acetonitrile. In contrast, in the case of weaker Lewis acids than Sc(3+), such as Mg(2+) and Li(+), external protons from acetic acid were required for the disproportionation of DPPH˙ to occur. PMID:24292255

  20. Uric acid substantially enhances the free radical-induced inactivation of alcohol dehydrogenase.

    PubMed

    Kittridge, K J; Willson, R L

    1984-05-01

    Lactate dehydrogenase (LDH) and yeast alcohol dehydrogenase ( YADH ) are inactivated when attacked by hydroxy free radicals (OH). Organic molecules with a high rate constant of reaction with OH such as ascorbate or urate can compete with the enzymes for these strongly oxidising radicals. However, although 10(-3)M ascorbate can substantially protect both LDH and YADH from OH attack, in the presence of 10(-3)M urate only LDH is protected. In the case of YADH an even greater degree of inactivation than with OH occurs. The extent of inactivation is considerably reduced when oxygen is absent, in agreement with a urate peroxy radical perhaps being partly responsible for the increased inactivation of the enzyme.

  1. EPR studies of free radicals in A-2058 human melanoma cells treated by valproic acid and 5,7-dimethoxycoumarin.

    PubMed

    Zdybel, Magdalena; Chodurek, Ewa; Pilawa, Barbara

    2014-01-01

    Free radicals in A-2058 human melanoma cells were studied by the use of electron paramagnetic resonance (EPR) spectroscopy. The aim of this work was to determine the changes in relative free radical concentrations in tumor A-2058 cells after treatment by valproic acid (VPA) and 5,7-dimethoxycoumarin (DMC). The influences of VPA and DMC on free radicals in A-2058 cells were compared with those for human melanoma malignum A-375 and G-361 cells, which were tested by us earlier. Human malignant melanoma A-2058 cells were exposed to interactions with VPA, DMC, and both VPA and DMC. The tumor cells A-2058 were purchased from LGC Standards (Lomianki, Poland), and they were grown in the standard conditions: at 37°C and in an atmosphere containing 95% air and 5% CO2, in the Minimum Essential Medium Eagle (MEM, Sigma-Aldrich). The A-2058 cells were incubated with VPA (1 mM) and DMC (10 μM) for 4 days. The first-derivative EPR spectra of the control A-2058 cells, and the cells treated with VPA, DMC, and both VPA and DMC, were measured by the electron paramagnetic resonance spectrometer of Radiopan (Poznań, Poland) with microwaves from an X-band (9.3 GHz). The parameters of the EPR lines: amplitudes (A), integral intensities (I), line widths (ΔBpp), and g-factors, were analyzed. The changes of amplitudes and line widths with microwave power increasing from 2.2 to 70 mW were drawn evaluated, o-Semiquinone free radicals of melanin biopolymer are mainly responsible for the EPR lines of A-2058 melanoma malignum cells. The amounts of free radicals in A-2058 cells treated with VPA, and both VPA and DMC, were lower than in the untreated control cells. Application of the tested substances (VPA, and both VPA and DMC) as the antitumor compounds was discussed. DMC without VPA did not decrease free radicals concentration in A-2058 cells. The studies con-firmed that EPR spectroscopy may be used to examine interactions of free radicals with antitumor compounds.

  2. Near-ultraviolet photolysis of beta-phenylpyruvic acid generates free radicals and results in DNA damage.

    PubMed

    Hargreaves, A; Taiwo, F A; Duggan, O; Kirk, S H; Ahmad, S I

    2007-12-14

    Ultraviolet A (UVA) light (315-400 nm) is ubiquitously found in our environment and constitutes about 95% of the total solar UV; all UVC and most UVB being absorbed by the stratospheric ozone layer. Compared with UVB and C, UVA does not show any direct effect on biological systems. Indirect effects of UVA, however, have been recognised overwhelmingly and this includes photosensitization of biological and non-biological compounds and production of free radicals many of which include oxygen and are hence known as reactive oxygen species or ROS. Several types of free radicals have been identified although their impacts on various macro- and micro-biomolecules are yet to be fully elucidated. beta-Phenylpyruvic acid is ubiquitously found in eukaryotic cells as a metabolite of phenylalanine, which is subsequently converted to phenyllactate and/or to 2-hydroxyphenylacetate and mandelate. In patients suffering from phenylketonuria the hydroxylation of phenylalanine to tyrosine is defective due to lack of phenylalanine hydroxylase. These result in accumulation and excretion of this compound in the urine. Here we present evidence that photolysis of beta-phenylpyruvic acid by a skin tanning lamp, emitting 99% UVA (315-400 nm) and 1% UVB (290-315 nm) generates carboxyl radicals (CO(2)(*)) and also possibly causes direct electron transfer (or type 1) reactions. Electron paramagnetic resonance was used to detect the free radicals. To determine the biological effects of this photolytic reaction, T7 was exposed to these photolytic reactive agents and found to lead to high levels of phage inactivation. Damage to DNA and/or components such as tail fibre proteins may be involved in T7 inactivation. In addition, our unpublished data suggest that certain phenylketonuria cell lines are more sensitive to PPA+NUV, lending importance to photolytic studies of this agent.

  3. Extraction and Bioactivity Analysis of Major Flavones Compounds from Scutellaria baicalensis Using In Vitro Assay and Online Screening HPLC-ABTS System

    PubMed Central

    Jung, Pil Mun; Oh, You-Chang; Song, Na-Young; Kim, Taesoo; Ma, Jin Yeul

    2014-01-01

    The extraction efficiency of a number of solvent compositions for the improvement of bioactive compounds yield from S. baicalensis has been investigated. Also, free radical scavengers in the glycoside baicalin (BG), wogonoside (WG), aglycon baicalein (B), and wogonin (W) compounds of S. baicalensis were screened, identified, and quantified using coupled offline ABTS and online screening HPLC-ABTS assay. Increasing ethanol content fractions resulted in decreased extract yield of bioactive compounds. In this case, the best yield of 37.01 mg/g in BG, WG, B, and W compounds was obtained by a dipping method with an extraction time of 4 h. In addition, the yield (43.05%) and IC50 (34.04 μg/mL) determined through ABTS assay of the 60% aqueous ethanol extract were the most satisfactory of all solvent solutions tested. This result shows that an online screening HPLC-ABTS assay can be a powerful technique for the rapid characterization of bioactivity compounds in plant extracts. Moreover, their anti-inflammatory activities were evaluated via analyzed inhibitory effect on NO and inflammatory cytokine production. Furthermore, WG and W exhibited the strong inhibitory effects on inflammatory mediator production including NO, IL-6, and IL-1β in LPS-stimulated RAW 264.7 macrophages. PMID:25258697

  4. Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT-898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-β1 (TGF-β1)

    PubMed Central

    Recouvreux, M. Victoria; Camilletti, M. Andrea; Rifkin, Daniel B.; Becu-Villalobos, Damasia

    2012-01-01

    Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF-β1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF-β1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas. PMID:22700773

  5. ω-Alkynyl Lipid Surrogates for Polyunsaturated Fatty Acids: Free Radical and Enzymatic Oxidations

    PubMed Central

    2015-01-01

    Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated polyunsaturated fatty acids are potentially useful probes for tracking the fate of fatty acid metabolites. The nonenzymatic and enzymatic oxidations of ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were compared to that of linoleic and arachidonic acid. There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce oxygen at different positions in the carbon chains. The rates of oxidation of ω-alkynylated fatty acids were reduced compared to those of the natural fatty acids. Cyclooxygenase-1 and -2 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of arachidonic acid may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the ω-alkyne group causes a conformational change in the fatty acid bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall, ω-alkynyl linoleic acid and ω-alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of polyunsaturated fatty acids when looking at models involving autoxidation and oxidation by lipoxygenases. PMID:25034362

  6. 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.

  7. 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.

  8. 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

  9. Scavenging mechanism of curcumin toward the hydroxyl radical: a theoretical study of reactions producing ferulic acid and vanillin.

    PubMed

    Agnihotri, Neha; Mishra, P C

    2011-12-15

    Curcumin is known to be an antioxidant, as it can scavenge free radicals from biological media. A sequence of H-abstraction and addition reactions involving up to eight OH radicals and curcumin or its degradation products leading to the formation of two other antioxidants, namely, ferulic acid and vanillin, was studied. Single electron transfer from curcumin to an OH radical was also studied. All relevant extrema on the potential energy surfaces were located by optimizing geometries of the reactant and product complexes, as well as those of the transition states, at the BHandHLYP/6-31G(d,p) level of density functional theory in the gas phase. Single-point energy calculations were also performed in the gas phase at the BHandHLYP/aug-cc-pVDZ and B3LYP/aug-cc-pVDZ levels of theory. Solvent effects in aqueous media were treated by performing single-point energy calculations at all of the above-mentioned levels of theory employing the polarizable continuum model and the geometries optimized at the BHandHLYP/6-31G(d,p) level in the gas phase. A few reaction steps were also studied by geometry optimization in aqueous media, and the thus-obtained Gibbs free energy barriers were similar to those obtained by corresponding single-point energy calculations. Our calculations show that the hydrogen atom of the OH group attached to the phenol moiety of curcumin would be most efficiently abstracted by an OH radical, in agreement with experimental observations. Further, our study shows that OH addition would be most favored at the C10 site of the heptadiene chain. It was found that curcumin can serve as an effective antioxidant.

  10. 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

  11. 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.

  12. Exploring water catalysis in the reaction of thioformic acid with hydroxyl radical: a global reaction route mapping perspective.

    PubMed

    Kaur, Gurpreet; Vikas

    2014-06-12

    Hydrogen abstraction pathways, in the gas-phase reaction of tautomers of thioformic acid (TFA), TFA(thiol), and TFA(thione), with hydroxyl radical in the presence and absence of single water molecule acting as a catalyst, is investigated with high-level quantum mechanical calculations at CCSD(T)/6-311++G(2d,2p)//MP2/6-311++G(2d,2p), CCSD(T)/6-311++G(d,p)//DFT/BHandHLYP/6-311++G(d,p), and DFT/B3LYP/6-311++G(2df,2p) levels of the theory. A systematic and automated search of the potential energy surface (PES) for the reaction pathways is performed using the global reaction route mapping (GRRM) method that employs an uphill walking technique to search prereaction complexes and transition states. The computations reveal significant lowering of the PES and substantial reduction in the activation energy for the hydrogen abstraction pathway in the presence of water, thereby proving water as an efficient catalyst in the reaction of both the TFA tautomers with OH radical. The hydrogen-bonding interactions are observed to be responsible for the large catalytic effect of water. Notably, in the case of TFA(thiol), formyl hydrogen abstraction is observed to be kinetically more favorable, while acidic hydrogen abstraction is observed to be thermodynamically more feasible. Interestingly, in the case of TFA(thione), reaction pathways involving only formyl hydrogen abstraction were observed to be feasible. The water-catalyzed hydrogen abstraction reaction of TFA with hydroxyl radical, investigated in this work, can provide significant insights into the corresponding reaction in the biological systems.

  13. Automatic flow system for sequential determination of ABTS*+ scavenging capacity and Folin-Ciocalteu index: a comparative study in food products.

    PubMed

    Magalhães, Luís M; Segundo, Marcela A; Reis, Salette; Lima, José L F C; Tóth, Ildikó V; Rangel, António O S S

    2007-06-01

    In the present work, an automatic flow procedure for the sequential spectrophotometric determination of Folin-Ciocalteu reducing capacity (FC assay) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS*+) scavenging capacity expressed as the trolox equivalent (TEAC assay) is proposed for a comparative study of antioxidant properties in food products. Exploiting the flexibility of flow management associated to the computer control offered by multisyringe flow injection analysis, both methodologies were carried out in the same manifold using gallic acid and trolox as standard compounds. The proposed system configuration allowed the performance of each method separately or in tandem, providing 24 determinations per hour, which accounts for its application in routine analysis. The present methodology was applied to a large number of beverages (n=72), namely red and white wines, herbal and tea infusions, juices and beers. The results obtained showed that FC reducing capacity and TEAC values of red wines were significantly different from those obtained for the other beverages, while tea infusions provided significantly higher TEAC values when compared to white wines, herbal infusions, juices and beers. A good correlation was found between TEAC and FC reducing capacity (R>0.9) for red wines, herbal and tea infusions, and beers. For these beverages, similar slope values were found (106-140 mg L(-1) of gallic acid per mM of Trolox), except for beers that showed a higher response for FC assay. These results provided evidence that the correlation between these assays vary according to the type of sample, reinforcing the idea that more than one method should be used for evaluation of antioxidant capacity.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

    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 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.

  16. 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.

  17. Radical-scavenging compounds from olive tree (Olea europaea L.) wood.

    PubMed

    Pérez-Bonilla, Mercedes; Salido, Sofía; van Beek, Teris A; Altarejos, Joaquín

    2014-01-01

    The purpose of this study was to complete knowledge on the chemical composition and radical-scavenging activity of olive tree wood. Two new monoterpene glycosides, (-)-oleuropeic acid 6'-O-α-D-glucopyranosyl ester (6a) and (-)-perillic acid 1'-O-β-D-primeverosyl ester (8), together with the known compounds (-)-oleuropeic acid (1), (-)-olivil (2), the aldehydic form of oleuropein aglycone (3), (+)-1-hydroxypinoresinol 1-O-β-D-glucopyranoside (4), (-)-oleuropeic acid 1'-O-β-D-glucopyranosyl ester (5), (-)-oleuropeic acid 6'-O-β-D-glucopyranosyl ester (6b), and (-)-olivil 4-O-β-D-glucopyranoside (7) were isolated from an ethyl acetate extract. The radical scavengers found (2-4 and 7) were detected and isolated with the help of the online HPLC-DAD-DPPH/ABTS technique. Compounds 2-4 and 7 displayed a higher antioxidative effect against the free radical DPPH than the reference BHT and lower than hydroxytyrosol, whereas compounds 1, 5, 6a, 6b, and 8 showed no activity.

  18. 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

  19. Dissociations of copper(II)-containing complexes of aromatic amino acids: radical cations of tryptophan, tyrosine, and phenylalanine.

    PubMed

    Siu, Chi-Kit; Ke, Yuyong; Guo, Yuzhu; Hopkinson, Alan C; Siu, K W Michael

    2008-10-14

    The dissociations of two types of copper(II)-containing complexes of tryptophan (Trp), tyrosine (Tyr), or phenylalanine (Phe) are described. The first type is the bis-amino acid complex, [Cu(II)(M)(2)].(2+), where M = Trp, Tyr, or Phe; the second [Cu(II)(4Cl-tpy)(M)].(2+), where 4Cl-tpy is the tridendate ligand 4'-chloro-2,2':6',2''-terpyridine. Dissociations of the Cu(ii) bis-amino acid complexes produce abundant radical cation of the amino acid, M.(+), and/or its secondary products. By contrast, dissociations of the 4Cl-tpy-bearing ternary complexes give abundant M.(+) only for Trp. Density functional theory (DFT) calculations show that for Tyr and Phe, amino-acid displacement reactions by H(2)O and CH(3)OH (giving [Cu(II)(4Cl-tpy)(H(2)O)].(2+) and [Cu(II)(4Cl-tpy)(CH(3)OH)].(2+)) are energetically more favorable than dissociative electron transfer (giving M.(+) and [Cu(I)(4Cl-tpy)](+)). The fragmentation pathway common to all these [Cu(II)(4Cl-tpy)(M)].(2+) ions is the loss of NH(3). DFT calculations show that the loss of NH(3) proceeds via a "phenonium-type" intermediate. Dissociative electron transfer in [Cu(II)(4Cl-tpy)(M-NH(3))].(2+) results in [M-NH(3)].(+). The [Phe-NH(3)] (+) ion dissociates facilely by eliminating CO(2) and giving a metastable phenonium-type ion that rearranges readily into the styrene radical cation.

  20. A mechanism for NaCl inhibition of Reactive Blue 19 decolorization and ABTS oxidation by laccase.

    PubMed

    Champagne, P-P; Nesheim, M E; Ramsay, J A

    2013-07-01

    Laccases produced by white rot fungi have been extensively evaluated for their potential to decolorize textile wastewaters which contain salts like sodium chloride and sodium sulfate. The effect of sodium chloride and sodium sulfate on Trametes versicolor laccase during the decolorization of an anthraquinone dye (Reactive Blue 19) and the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) were evaluated by steady-state kinetic analysis. The results showed that, while sodium sulfate did not affect laccase activity, sodium chloride inhibited both ABTS oxidation and dye decolorization. However, the type of inhibition was substrate-dependent: it was hyperbolic, noncompetitive with ABTS and parabolic, noncompetitive with Reactive Blue 19. Furthermore, the results suggested that two chlorides may bind to laccase in the presence of the dye unlike recent inhibition models which suggest that there is only one inhibition site. This investigation is the first to provide evidence for and to propose a two-site model of laccase inhibition, providing new insight into NaCl inhibition of laccase. The proposed model is also useful to predict decolorization rates in the presence of sodium chloride and to determine operating conditions that will minimize inhibition.

  1. 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

  2. Isolation and purification of salvianolic acid A and salvianolic acid B from Salvia miltiorrhiza by high-speed counter-current chromatography and comparison of their antioxidant activity.

    PubMed

    Sun, Yinshi; Zhu, Haifang; Wang, Jianhua; Liu, Zhengbo; Bi, Jianjie

    2009-03-15

    Water-soluble salvianolic acid A (Sal A) and salvianolic acid B (Sal B) were successfully isolated and purified from the crude extract of Salvia miltiorrhiza by high-speed counter-current chromatography (HSCCC). The solvent system was n-hexane-ethyl acetate-methanol-water (3:6:6:10, v/v/v/v). 4.27 mg of Sal A and 32.09 mg of Sal B were obtained from 260 mg of the crude sample. The purities of Sal A and Sal B were 96.67% and 97.43%, respectively. Their structures were identified by (1)H NMR and (13)C NMR. Antioxidant activities of Sal A and Sal B were also evaluated and compared by the methods of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS(+)) radical cation decolourisation assay. Both Sal A and Sal B showed high radical scavenging activities with their EC(50) values being 1.43+/-0.09 and 1.81+/-0.01 microg/ml in DPPH radical method. The ABTS results showed that Sal A and Sal B exhibited high total antioxidant activities, their EC(50) values were 1.35+/-0.00 and 1.43+/-0.01 microg/ml, respectively.

  3. Effect of ascorbic acid (vitamin C) on the ESR spectra of the red and black hair: pheomelanin free radicals are not always present in red hair.

    PubMed

    Chikvaidze, Eduard; Topeshashvili, Maia

    2015-12-01

    Increased incidence of melanoma in the population with red hair is conditioned by synthesis of pheomelanin pigments in the skin and their phototoxic properties. The recent research has shown that free radicals of pheomelanin are produced not only by the influence of UV irradiation, but also in UV-independent pathways of oxidative stress. It has been ascertained, that the color of the hair is not always determinant of the amount of pheolemanin radicals in red hair. Therefore, in order to evaluate the risk of melanoma in different individuals, it is necessary to define the amount of free radicals of pheomelanin in red hair using ESR spectroscopy method. Besides, it is very important to find effective antioxidant, capable of neutralizing free radicals of pheomelanin. It was proved that ascorbic acid neutralizes free radicals of pheomelanin very effectively. The main goal of our research was to define the presumably optimal concentration of ascorbic acid as an antioxidant and study the kinetics of the influence of this concentration on red and black hair. It has been found out, that ascorbic acid influences the free radicals of red and black hair, and its appropriate optimal concentration is 10 mM. The obtained results can be considered in dermatology and cosmetology.

  4. Kinetic features of the radical species produced in gamma-irradiated dl-tartaric acid and the dosimetric potential of this acid.

    PubMed

    Tuner, H; Korkmaz, M

    2009-07-01

    The room-temperature and high-temperature kinetic features of the radical species produced in solid dl-tartaric acid (dl-TA) gamma-irradiated at room temperature and the dosimetric potential of this acid were investigated in a detailed ESR study. Irradiated dl-TA presents an ESR spectrum with many unresolved resonance lines even at the lowest radiation dose applied (100 Gy). The evolution of the signal intensities associated with induced radical species with microwave power, applied dose and temperature was followed. Three groups of resonance intensities originating from three different radicals exhibiting different spectroscopic features, stabilities at room and high temperatures, and radiation yields were found to take part in the formation of experimental ESR spectrum. These three species were calculated to exhibit spectroscopic features similar to those already reported for X- or gamma-irradiated deuterated single crystals of dl-TA and assigned as I, II and III. The same radical notation was adopted in the present work, and the intensities related to these species were denoted with the names of their corresponding species. Species III, which had the lowest radiation yield and the lowest stability, was observed as a species of four resonance lines. The two inner constituents of these four lines were partially obscured by the two central doublets originating from species I and II. The latter were relatively stable and had activation energies around 35 kJ/mol. The percentage concentrations of the involved species were estimated by comparing experimental and calculated spectra. The reasonably high radical yields of the dl-TA in the dose range of interest, the fairly good stabilities of the species produced (I and II) at room temperature, and the almost linear features of the constructed dose-response curves led us to conclude that the intensities associated with the stable species (I and II) could be used to estimate the applied dose in the dose range of 100 Gy-34

  5. Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC).

    PubMed

    Kikuzaki, Hiroe; Kayano, Shin-ichi; Fukutsuka, Naoko; Aoki, Asuka; Kasamatsu, Kumi; Yamasaki, Yuka; Mitani, Takahiko; Nakatani, Nobuji

    2004-01-28

    Four new abscisic acid related compounds (1-4), together with (+)-abscisic acid (5), (+)-beta-D-glucopyranosyl abscisate (6), (6S,9R)-roseoside (7), and two lignan glucosides ((+)-pinoresinol mono-beta-D-glucopyranoside (8) and 3-(beta-D-glucopyranosyloxymethyl)-2- (4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofuran (9)) were isolated from the antioxidative ethanol extract of prunes (Prunus domestica L.). The structures of 1-4 were elucidated on the basis of NMR and MS spectrometric data to be rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (1), rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid 3'-O-beta-d-glucopyranoside (2), rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (3), and rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxabicyclo[3,2,1]- oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (4). The antioxidant activities of these isolated compounds were evaluated on the basis of oxygen radical absorbance capacity (ORAC). The ORAC values of abscisic acid related compounds (1-7) were very low. Two lignans (8 and 9) were more effective antioxidants whose ORAC values were 1.09 and 2.33 micromol of Trolox equiv/micromol, respectively.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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…

  11. [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

  12. 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.

  13. Enhancement of a Lewis acid-base interaction via solvation: ammonia molecules and the benzene radical cation.

    PubMed

    Chiang, Chi-Tung; Freindorf, Marek; Furlani, Thomas; DeLeon, Robert L; Richard, John P; Garvey, James F

    2007-07-12

    The interaction between ammonia and the benzene radical cation has been investigated by gas-phase studies of mass selected ion clusters {C(6)H(6)-(NH(3))(n=0-8)}(+) via tandem quadrupole mass spectrometry and through calculations. Experiments show a special stability for the cluster ion that contains four ammonias: {C(6)H(6)(NH(3))(4)}(+). Calculations provide evidence that the first ammonia forms a weak dative bond to the cyclohexadienyl radical cation, {C(6)H(6)-NH(3)}(+), where there is a transfer of electrons from ammonia to benzene. Additional solvating ammonia molecules form stabilizing hydrogen bonds to the ring-bound ammonia {C(6)H(6)-NH(3)}(+).(NH(3))(n), which cause cooperative changes in the structure of the cluster complex. Free ammonia is a weak hydrogen bond donor, but electron transfer from NH(3) to the benzene ring that strengthens the dative bond will increase the hydrogen acidity and the strength of the cluster hydrogen bonds to the added ammonia. A progressive "tightening" of this dative bond is observed upon addition of the first, second, and third ammonia to give a cluster stabilized by three N-(+)H x N hydrogen bonds. This shows that the energetic cost of tightening the dative bond is recovered with dividends in the formation of stable cluster hydrogen bonds.

  14. Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer

    PubMed Central

    2013-01-01

    Background New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies. Methods We explored the combination of ABT-737 and chloroquine, an inhibitor of autophagy, in preclinical models of SCLC. These included cell culture analyses of viability and of autophagic and apoptotic pathway induction, as well as in vivo analyses of efficacy in multiple xenograft models. Results Combination treatment of SCLC lines with ABT-737 and chloroquine decreased viability and increased caspase-3 activation over treatment with either single agent. ABT-737 induced several hallmarks of autophagy. However, knockdown of beclin-1, a key regulator of entry into autophagy, diminished the efficacy of ABT-737, suggesting either that the effects of chloroquine were nonspecific or that induction but not completion of autophagy is necessary for the combined effect of ABT-737 and chloroquine. ABT-737 and chloroquine in SCLC cell lines downregulated Mcl-1 and upregulated NOXA, both of which may promote apoptosis. Treatment of tumor-bearing mice demonstrated that chloroquine could enhance ABT-737-mediated tumor growth inhibition against NCI-H209 xenografts, but did not alter ABT-737 response in three primary patient-derived xenograft models. Conclusion These data suggest that although ABT-737 can induce autophagy in SCLC, autophagic inhibition by choroquine does not markedly alter in vivo response to ABT-737 in relevant preclinical models, arguing against this as a treatment strategy for SCLC. PMID:23452820

  15. Electron capture dissociation product ion abundances at the X amino acid in RAAAA-X-AAAAK peptides correlate with amino acid polarity and radical stability.

    PubMed

    Vorobyev, Aleksey; Ben Hamidane, Hisham; Tsybin, Yury O

    2009-12-01

    We present mechanistic studies aimed at improving the understanding of the product ion formation rules in electron capture dissociation (ECD) of peptides and proteins in Fourier transform ion cyclotron resonance mass spectrometry. In particular, we attempted to quantify the recently reported general correlation of ECD product ion abundance (PIA) with amino acid hydrophobicity. The results obtained on a series of model H-RAAAAXAAAAK-OH peptides confirm a direct correlation of ECD PIA with X amino acid hydrophobicity and polarity. The correlation factor (R) exceeds 0.9 for 12 amino acids (Ile, Val, His, Asn, Asp, Glu, Gln, Ser, Thr, Gly, Cys, and Ala). The deviation of ECD PIA for seven outliers (Pro is not taken into consideration) is explained by their specific radical stabilization properties (Phe, Trp, Tyr, Met, and Leu) and amino acid basicity (Lys, Arg). Phosphorylation of Ser, Thr, and Tyr decreases the efficiency of ECD around phosphorylated residues, as expected. The systematic arrangement of amino acids reported here indicates a possible route toward development of a predictive model for quantitative electron capture/transfer dissociation tandem mass spectrometry, with possible applications in proteomics.

  16. Antioxidant potential and radical-scavenging effects of flavonoids from the leaves of Psidium cattleianum grown in French Polynesia.

    PubMed

    Ho, R; Violette, A; Cressend, D; Raharivelomanana, P; Carrupt, P A; Hostettmann, K

    2012-01-01

    Psidium cattleianum J. Sabine (Myrtaceae) is a traditional medicinal plant in French Polynesia. The leaves and roots possess many medicinal properties. These effects may be correlated with the presence of antioxidant compounds. Seven flavonoids along with a benzoic acid were isolated from the leaves of P. cattleianum. The compounds indicated strong antioxidant and radical-scavenging activities in ALP, DPPH(·), ABTS(·-) and ORAC assays. This study demonstrates that the leaves of P. cattleianum possess main compounds with interesting antioxidant and radical-scavenging activities, as clarified by four biological assays. Our findings may justify the use of these leaves in the traditional medicine of French Polynesia. Among the total eight known compounds, reynoutrin and luteolin were isolated for the first time from the genus Psidium.

  17. Evaluation of a technique to measure tropospheric hydroxyl radicals using an aqueous phase salicylic acid scrubbing solution, HPLCseparation and fluorescence detection

    NASA Astrophysics Data System (ADS)

    Salmon, R. A.; Schiller, C. L.; Harris, G. W.

    2003-04-01

    A novel method for monitoring gas phase hydroxyl radicals was examined using a liquid-phase salicylic acid solution to trap tropospheric OH. Quantification occurred following HPLC seperaration and fluorescence detection of one of the products, 2,5-dihydroxy benzoic acid. Although the sensitivity was sufficient to measure typical daytime OH concentrations, the method was hindered by a number of interferences. While most of these were identified and eliminated, an interference from methylperoxy radicals was discovered that could not be removed. The validity of previous reports of OH detection using this method is therefore brought into question.

  18. The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia

    PubMed Central

    Itchaki, Gilad; Brown, Jennifer R.

    2016-01-01

    Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL), it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN. We further strive to contextualize VEN in the current CLL treatment landscape and discuss potential mechanisms of resistance. PMID:27695617

  19. 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

  20. 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

  1. Formation of a cobalt(III)-phenoxyl radical complex by acetic acid promoted aerobic oxidation of a Co(II)salen complex.

    PubMed

    Vinck, Evi; Murphy, Damien M; Fallis, Ian A; Strevens, Robert R; Van Doorslaer, Sabine

    2010-03-01

    The activation of N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II), [Co(II)(1)], by the addition of acetic acid under aerobic conditions has been investigated by a range of spectroscopic techniques including continuous-wave EPR, HYSCORE, pulsed ENDOR, and resonance Raman. These measurements have revealed for the first time the formation of a coordinated cobalt(III)-bound phenoxyl radical labeled [Co(III)(1(*))(OAc)(n)](OAc)(m) (n = m = 1 or n = 2, m = 0). This cobalt(III)-bound phenoxyl radical is characterized by the following spin Hamiltonian parameters: g(x) = 2.0060, g(y) = 2.0031, g(z) = 1.9943, A(x) = 17 MHz, A(y) = 55 MHz, and A(z) = 14 MHz. Although the radical contains coordinated acetate(s), the experiments unambiguously proved that the phenoxyl radical is situated on ligand (1) as opposed to a phenoxyl radical ligated to cobalt in the axial position. Density functional theory computations on different models corroborate the stability of such a phenoxyl radical species and suggest the ligation of one or two acetate molecules to the complex. A mechanism is proposed, which accounts for the formation of this unusual and extremely robust phenoxyl radical, never previously observed for [Co(1)].

  2. [Effect of calcium cations on acid-base properties and free radical oxidation of dopamine and pyrocatechol].

    PubMed

    Lebedev, A V; Ivanova, M V; Timoshin, A A; Ruuge, E K

    2008-01-01

    Ca2+-induced increase in the rate of pyrocatechol and dopamine oxidation by dioxygen and Ca2+-dependent acid-base properties of the catechols were studied by potentiometric titration, UV/Vis-spectrophotometry, EPR-spectroscopy, and by measurement of oxygen consumption. The effect of Ca2+ on the chain reactions of oxidation can be explained by additional deprotonation (decrease in pKai) of the catechols that accelerates one electron transport to dioxygen and formation of calcium semiquinonate, undergoing further oxidation. The described Ca2+-dependent redox-conversion of ortho-phenols proposes that an additional function of calcium in the cell can be its involvement in free radical oxidoreductive reactions at pH > pKai.

  3. 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.

  4. 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.

  5. Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease.

    PubMed

    Shishehbor, Mehdi H; Zhang, Renliang; Medina, Hector; Brennan, Marie-Luise; Brennan, Danielle M; Ellis, Stephen G; Topol, Eric J; Hazen, Stanley L

    2006-12-01

    Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic antioxidant targeted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (>50% stenosis in one or more major coronary vessels) and 54 without CAD (<30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and F(2)-isoprostanes were simultaneously measured by high-performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F(2)-isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 +/- 4 vs 6.8 +/- 4 micromol/mol arachidonate, P = 0.011; and F(2)-isoprostanes, 9.4 +/- 5 vs 6.2 +/- 3 micromol/mol arachidonate, P < 0.001). In multivariable analyses with simultaneous adjustment for Framingham risk score and C-reactive protein, 9-HETE (4th quartile OR = 4.8, 95% CI=1.3 to 17.1; P = 0.016) and F(2)-isoprostanes (4th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F(2)-isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.

  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, 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?...

  9. 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?...

  10. 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?...

  11. Pulse radiolytic and product analysis studies of the reaction of hydroxyl radicals with cinnamic acid. The relative extent of addition to the ring and side chain

    SciTech Connect

    Bobrowski, K.; Raghavan, N.V.

    1982-10-28

    Using pulse radiolysis with optical detection and high-pressure liquid chromatography (HPCL), it has been shown that reaction of OH radicals with cinnamic acid (CA in aqueous solutions leads to addition to both the ring and the olefinic group. The relative extent of the above two pathways was estimated as 3:7, respectively. Benzyl- and hydroxycyclohexadienyl-type radicals were observed with absorption maxima at 320 (310) and 370 (365) nm depending on the pH of the solution. In the pH region 4.9 to 5.7 the absorption at 305 to 315 nm decays during the first 5 ..mu..s after the pulse. The dependence of the rate constants and absorption spectra on pH suggests that this decay is due to an equilibration process between acid-base forms of benzyl-type radicals formed through OH addition to te olefinic group.

  12. 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

  13. Comparison of the contents of the main biochemical compounds and the antioxidant activity of some Spanish olive oils as determined by four different radical scavenging tests.

    PubMed

    Gorinstein, Shela; Martin-Belloso, Olga; Katrich, Elena; Lojek, Antonin; Cíz, Milan; Gligelmo-Miguel, Nuria; Haruenkit, Ratiporn; Park, Yong-Seo; Jung, Soon-Teck; Trakhtenberg, Simon

    2003-03-01

    The aim of this study was to compare the contents of the main biochemical compounds and the antioxidant capacity of five Spanish olive oils by four different antioxidant tests and to find out the most valuable oil for disease preventing diets. Fatty acids, sterols and individual antioxidant compounds in Arbequina, Hojiblanca, Extra Virgin, Picual and Lampante Spanish olive oils were determined. Antioxidant activities were done as well using different radical scavenging activities: total radical-trapping antioxidative potential by ABAP (TRAP-ABAP), radical scavenging activity by DPPH (RSA-DPPH), antioxidant assay by beta-carotene-linoleate model system (AA-beta-carotene) and total antioxidant status by ABTS (TAA-ABTS). The highest content of all studied antioxidant compounds (353; 329; 4.6 and 2.7 mg/kg for tocopherols, tocotrienols, polyphenols and o-diphenols, respectively) was found in Extra Virgin oil. Also the highest antioxidant capacity was observed in Extra Virgin oil (668 nM/ml; 29.4%; 40.4% and 2.64 mM TE/kg for TRAP-ABAP, RSA-DPPH, AA- beta-carotene and TAA-ABTS, respectively). The correlation between total phenols and antioxidant capacities measured by four methods was very high, but the highest for the beta-carotene (R = 0.9958). In conclusion, the best method for determination of the antioxidant capacity of olive oils is the beta-carotene test. Extra Virgin olive oil has high organoleptic properties and the highest antioxidant activity. The above-mentioned makes this oil a preferable choice for diseases preventing diets.

  14. Direct synthesis of sulfonated dihydroisoquinolinones from N-allylbenzamide and arylsulfinic acids via TBHP-promoted cascade radical addition and cyclization.

    PubMed

    Xia, Dong; Li, Yang; Miao, Tao; Li, Pinhua; Wang, Lei

    2016-10-01

    A novel synthesis of sulfonated dihydroisoquinolinones via cascade radical addition and cyclization was developed in the presence of tert-butyl hydroperoxide (TBHP). The reactions generated the desired sulfonated dihydroisoquinolinones in good yields from readily available arylsulfinic acids and N-allylbenzamides under metal-free conditions. PMID:27604055

  15. 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

  16. 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.

  17. Long-chain-substituted uric acid and 5,6-diaminouracil derivatives as novel agents against free radical processes: synthesis and in vitro activity.

    PubMed

    Fraisse, L; Verlhac, J B; Roche, B; Rascle, M C; Rabion, A; Seris, J L

    1993-05-14

    A new series of N-alkylated uric acids (2,6,8-purinetrione) and 5,6-diaminouracils (5,6-diamino-2,4-pyrimidinedione) were synthesized, and their activities against free radicals were evaluated. Long-chain derivatives of both series exhibited a large inhibitory activity against oxygen radical induced lipid peroxidation in bovine heart mitochondria (IC50 lower than 1 microM), compared to the reference antioxidants trolox C or alpha-tocopherol. This activity appeared related to (i) the ability of these compounds to reduce the stable radical 1,1-diphenyl-2-picrylhydrazyl and (ii) their lipophilicity estimated by log P determination. In order to study the scavenging mechanisms of diaminouracils and urate derivatives against lipid radicals, they were also tested against the azo-initiated peroxidation of either methyl linoleate in organic solvents or a liposomal suspension of dilinoleoylphosphatidylcholine. Urate derivatives reacted moderately with lipid radicals and were slowly consumed, significantly affecting the propagation of the peroxidation. Diaminouracils strongly reduced the propagation rate. They were quickly consumed and were able to deactivate about 1 mol of lipid radical per mole of compound in organic solvent. Dodecyl urates and decyl- and dodecyldiaminouracils were chosen for further in vitro investigation and in vivo evaluation.

  18. 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

  19. Vitamin U, a novel free radical scavenger, prevents lens injury in rats administered with valproic acid.

    PubMed

    Tunali, S; Kahraman, S; Yanardag, R

    2015-09-01

    Valproic acid (2-propyl-pentanoic acid, VPA) is the most widely prescribed antiepileptic drug due to its ability to treat a broad spectrum of seizure types. VPA exhibits various side effects such as organ toxicity, teratogenicity, and visual disturbances. S-Methylmethioninesulfonium is a derivative of the amino acid methionine and it is widely referred to as vitamin U (Vit U). This study was aimed to investigate the effects of Vit U on lens damage parameters of rats exposed to VPA. Female Sprague Dawley rats were divided into four groups. Group I comprised control animals. Group II included control rats supplemented with Vit U (50 mg/kg/day) for 15 days. Group III was given only VPA (500 mg/kg/day) for 15 days. Group IV was given VPA + Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals which were fasted overnight were killed. Lens was taken from animals, homogenized in 0.9% saline to make up to 10% (w/v) homogenate. The homogenates were used for protein, glutathione, lipid peroxidation levels, and antioxidant enzymes activities. Lens lipid peroxidation levels and aldose reductase and sorbitol dehydrogenase activities were increased in VPA group. On the other hand, glutathione levels, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and paraoxonase activities were decreased in VPA groups. Treatment with Vit U reversed these effects. This study showed that Vit U exerted antioxidant properties and may prevent lens damage caused by VPA.

  20. ABT-737, a Bcl-2 Selective Inhibitor, and Chloroquine Synergistically Kill Renal Cancer Cells.

    PubMed

    Yin, Pei; Jia, Jinpeng; Li, Jijun; Song, Yan; Zhang, Yiyan; Chen, Fengkun

    2016-01-01

    Renal cell carcinoma (RCC) is the most common malignancy in the kidney in the world, and the 5-year overall survival for patients remains poor due to the lack of effective treatment strategies. Although ABT-737, as a Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic reagent, apoptosis induced by ABT-737 is often blocked in several types of cancer cells. This study investigated whether the combination of the small-molecule BH3 mimetic ABT-737 and the lysosome inhibitor chloroquine was an effective strategy for treating renal cancer cells. We found that the combination of ABT-737 and chloroquine synergistically decreased cell viability when compared to treatment with either single reagent. Cell apoptosis induced by a combined treatment was markedly inhibited by the caspase inhibitors z-DEVD-FMK and z-VAD-FMK. It was also inhibited by cathepsin inhibitor E-64 and CTSI (cathepsin inhibitor), which suggested that apoptosis was dependent on the cascade of caspase activation and cathepsins released from lysosomes. Furthermore, we found that ABT-737 could increase the cell level of ROS, which triggers cathepsin-mediated cell death and augments the role of chloroquine in cell death. So the combination of ABT-737 and chloroquine was an effective strategy for the treatment of renal cancer cells, and this combined strategy may widen the therapeutic window of ABT-737 and chloroquine as well as enhance the clinical efficacy of synergistic drug combinations. PMID:27178823

  1. Synergistic anti-leukemic interactions between ABT-199 and panobinostat in acute myeloid leukemia ex vivo

    PubMed Central

    Schwartz, Jonathan; Niu, Xiaojia; Walton, Eric; Hurley, Laura; Lin, Hai; Edwards, Holly; Taub, Jeffrey W; Wang, Zhihong; Ge, Yubin

    2016-01-01

    Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising preclinical anti-leukemic activities, intrinsic drug resistance remains a problem. In our most recent study, we identified Mcl-1 sequestration of Bim as a mechanism of intrinsic resistance to ABT-199 in AML cells, thus upregulating Bim could overcome such resistance. Histone deacetylase (HDAC) inhibitors (HDACI) are a class of agents that have been confirmed to upregulate Bim. This prompted our hypothesis that combining an HDACI with ABT-199 would overcome intrinsic resistance to ABT-199 and result in synergistic anti-leukemic activity against AML. In this study, we investigated the anti-leukemic activity of panobinostat, a pan-HDACI, in combination with ABT-199 in AML cell lines and primary patient samples. We found that the combined drug treatment resulted in synergistic induction of cell death in both AML cell lines and primary patient samples. Panobinostat treatment resulted in upregulation of Bim, which remained elevated in the presence of ABT-199. In addition, shRNA knockdown of Bim in AML cell lines significantly attenuated apoptosis induced by combined panobinostat and ABT-199. Our results provide compelling evidence that Bim plays a key role in the combined anti-leukemic activity of panobinostat and ABT-199 against AML, and support clinical evaluation of combined panobinostat and ABT-199 in the treatment of AML. PMID:27725868

  2. 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.

  3. In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

    PubMed Central

    Plaza, V.; Prat, J.; Rosellò, J.; Ballester, E.; Ramis, I.; Mullol, J.; Gelpí, E.; Vives-Corrons, J. L.; Picado, C.

    1995-01-01

    BACKGROUND--An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. METHODS--Thirty subjects distributed into three groups were studied: group 1, 10 healthy subjects; group 2, 10 asthmatic patients with aspirin tolerance; and group 3, 10 aspirin-intolerant asthmatics. Platelets were isolated from blood, preincubated with 3H-arachidonic acid for 30 minutes and then incubated for 10 minutes with platelet activating factor (PAF) and aspirin. Cyclo-oxygenase (thromboxane, PGE2, PGF2 alpha, and HHT) and lipoxygenase (12-HETE) arachidonic acid metabolites were measured by high pressure liquid chromatography. Release of oxygen free radicals after incubation with PAF and aspirin was measured by chemiluminescence. Platelet levels of glutathione peroxidase (GSH-Px) were also measured using spectrophotometry. RESULTS--Platelets from aspirin-intolerant asthmatic patients produced higher quantities of arachidonic acid metabolites than the control group at baseline conditions. This increase was significant only for lipoxygenase products. No differences were found amongst the three groups in the response of arachidonic acid metabolism to PAF and aspirin. Incubation with aspirin but not with PAF caused an increase in oxygen-free radical production in aspirin-intolerant patients whereas in aspirin-tolerant patients PAF, rather than aspirin, was the more potent stimulus for oxygen-free radical production. No differences in GSH-Px levels were found amongst the three groups. CONCLUSIONS--These results suggest that the platelet lipoxygenase pathway is activated in aspirin-intolerant patients and that the production of oxygen-free radicals may

  4. Long-lived radical cation-electron pairs generated by anthracene sorption in non Brønsted acidic zeolites.

    PubMed

    Marquis, Séverine; Moissette, Alain; Vezin, Hervé; Brémard, Claude

    2005-03-10

    The sorption of anthracene (ANT) in non Brønsted acidic ZSM-5 zeolite through the mere exposure at room temperature of solid ANT and dehydrated zeolite crystals with Li(3.4)(AlO2)n(SiO2)(96-n) chemical formulas per unit cell generates spontaneous ionization of ANT (IP 7.44 eV in the gas phase). In contrast, ANT was found to be sorbed as an intact molecule in M(3.4)ZSM-5 with M = Na+, K+, Rb+, and Cs+. The radical cation (ANT*+) of the long-lived ANT*+@Li(3.4)ZSM-5*- pair was characterized by conventional diffuse reflectance UV-visible and resonance Raman spectrometry. In contrast, the X-band continuous wave (CW) EPR signal was found to be typical of a weakly coupled spin correlated ion pair. The two-dimension hyperfine sublevel correlation (2D-HYSCORE) spectra provide a detailed description of the microenvironment of the trapped electron of the ANT*+@Li(n)ZSM-5*- pair. The trapped electron appears localized in close proximity of occluded ANT*+, Li+, and the Si-O-Al nearest group of the zeolite framework.

  5. 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.

  6. Forgotten radicals in biology.

    PubMed

    Luc, Rochette; Vergely, Catherine

    2008-12-01

    Redox reactions play key roles in intra- and inter-cellular signaling, and in adaptative processes of tissues towards stress. Among the major free radicals with essential functions in cells are reactive oxygen species (ROS) including superoxide anion (O2 (•-)), hydroxyl radical ((•)OH) and reactive nitrogen species (RNS) such as nitric oxide ((•)NO). In this article, we review the forgotten and new radicals with potential relevance to cardiovascular pathophysiology. Approximately 0.3% of O2 (•-) present in cytosol exists in its protonated form: hydroperoxyl radical (HO2 (•)). Water (H2O) can be split into two free radicals: (•)OH and hydrogen radical (H(•)). Several free radicals, including thiyl radicals (RS(•)) and nitrogen dioxide (NO2 (•)) are known to isomerize double bonds. In the omega-6 series of poly-unsaturated fatty acids (PUFAs), cis-trans isomerization of γ-linolenate and arachidonate catalyzed by RS(•) has been investigated. Evidence is emerging that hydrogen disulphide (H2S) is a signaling molecule in vivo which can be a source of free radicals. The Cu-Zn superoxide dismutase (SOD) enzyme can oxidize the ionized form of H2S to hydro-sulphide radical: HS(•). Recent studies suggest that H2S plays an important function in cardiovascular functions. Carbonate radical, which can be formed when (•)OH reacts with carbonate or bicarbonate ions, is also involved in the activity of Cu-Zn-SOD. Recently, it has been reported that carbonate anion were potentially relevant oxidants of nucleic acids in physiological environments. In conclusion, there is solid evidence supporting the formation of many free radicals by cells leading which may play an important role in their homeostasis. PMID:23675099

  7. In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

    PubMed

    Weiss, K; de Azavedo, J; Restieri, C; Quach, C; Laverdiere, M; Rubin, E; Gourdeau, M; Low, D E

    2001-09-01

    New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

  8. 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

  9. 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

  10. ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope.

    PubMed

    Phillips, Andrew C; Boghaert, Erwin R; Vaidya, Kedar S; Mitten, Michael J; Norvell, Suzanne; Falls, Hugh D; DeVries, Peter J; Cheng, Dong; Meulbroek, Jonathan A; Buchanan, Fritz G; McKay, Laura M; Goodwin, Neal C; Reilly, Edward B

    2016-04-01

    Targeting tumor-overexpressed EGFR with an antibody-drug conjugate (ADC) is an attractive therapeutic strategy; however, normal tissue expression represents a significant toxicity risk. The anti-EGFR antibody ABT-806 targets a unique tumor-specific epitope and exhibits minimal reactivity to EGFR in normal tissue, suggesting its suitability for the development of an ADC. We describe the binding properties and preclinical activity of ABT-414, an ABT-806 monomethyl auristatin F conjugate. In vitro, ABT-414 selectively kills tumor cells overexpressing wild-type or mutant forms of EGFR. ABT-414 inhibits the growth of xenograft tumors with high EGFR expression and causes complete regressions and cures in the most sensitive models. Tumor growth inhibition is also observed in tumor models with EGFR mutations, including activating mutations and those with the exon 2-7 deletion [EGFR variant III (EGFRvIII)], commonly found in glioblastoma multiforme. ABT-414 exhibits potent cytotoxicity against glioblastoma multiforme patient-derived xenograft models expressing either wild-type EGFR or EGFRvIII, with sustained regressions and cures observed at clinically relevant doses. ABT-414 also combines with standard-of-care treatment of radiation and temozolomide, providing significant therapeutic benefit in a glioblastoma multiforme xenograft model. On the basis of these results, ABT-414 has advanced to phase I/II clinical trials, and objective responses have been observed in patients with both amplified wild-type and EGFRvIII-expressing tumors. Mol Cancer Ther; 15(4); 661-9. ©2016 AACR. PMID:26846818

  11. CBLB502, an agonist of Toll-like receptor 5, has antioxidant and scavenging free radicals activities in vitro.

    PubMed

    Li, Weiguang; Ge, Changhui; Yang, Liu; Wang, Ruixue; Lu, Yiming; Gao, Yan; Li, Zhihui; Wu, Yonghong; Zheng, Xiaofei; Wang, Zhaoyan; Zhang, Chenggang

    2016-01-01

    The bacterial protein flagellin is the known agonist of Toll-like receptor 5 (TLR5). It has been reported that CBLB502, a novel agonist of TLR5 derived from Salmonella flagellin, could reduce radiation toxicity in mouse and primate models, protect mice from dermatitis and oral mucositis caused by radiation, inhibit acute renal ischemic failure, and inhibit the growth of A549 lung cancer cell. The property of CBLB502 is able to bind to TLR5 and activates NF-κB signaling. In this study, we investigated the antioxidant potential and free radicals scavenging properties of CBLB502 in vitro. Interestingly, we found that CBLB502 has a direct and distinct antioxidant capacity and can efficiently scavenge a variety of free radicals, including superoxide anion, hydroxyl radical, and ABTS cation (ABTS(+)). Through wave scanning and kinetic evaluation of scavenging ABTS(+), we found that the ABTS(+) scavenging process of CBLB502 is relatively slow, and the ABTS(+) scavenging activity of CBLB502 has a consistently kinetics characteristics. In conclusion, our results suggested that CBLB502 has antioxidant and scavenging free radicals activities in vitro. It is implied that CBLB502 might partially promote the beneficial protective effect through its scavenging free radicals.

  12. Caenorhabditis elegans bicarbonate transporter ABTS-1 is involved in arsenite toxicity and cholinergic signaling.

    PubMed

    Liao, Vivian Hsiu-Chuan; Liu, Jui-Tung; Li, Wen-Hsuan; Yu, Chan-Wei; Hsieh, Yi-Chen

    2010-05-17

    Arsenic poisoning affects millions of people worldwide. Although there is accumulating evidence to suggest that the nervous system is a target of arsenic, relatively little information is known regarding its effects on the nervous system. The effects of arsenite on the nervous system in Caenorhabditis elegans were investigated in the present study. We found that abts-1, which encodes a Na(+)-dependent Cl(-)/HCO(3)(-) transporter, is required to protect C. elegans from arsenite toxicity. The abts-1::GFP transgene is primarily expressed in neurons and the hypodermis, but stronger expression was also observed in the pharynx and body wall muscle cells after exposure to arsenite. The steady-state level of ABTS-1 mRNA increased in response to arsenite exposure. We showed that worms lacking abts-1 are hypersensitive to the paralytic effects of the cholinesterase inhibitor, aldicarb, and the nicotinic acetylcholine receptor agonist, levamisole. We also showed that arsenite enhanced sensitivity to aldicarb and levamisole in abts-1 mutant worms. Our results indicate neuronal effects of arsenite and the ABTS-1 bicarbonate transporter.

  13. 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

  14. Time-resolved EPR investigation of potential model systems for acrylate polymer main chain radicals based on esters of Kemp's tri-acid.

    PubMed

    Lebedeva, Natalia V; Gorelik, Elena V; Magnus-Aryitey, Damaris; Hill, Terence E; Forbes, Malcolm D E

    2009-05-14

    Methyl esters of Kemp's tri-acid and cyclohexanetricarboxylic acid are structurally similar to acrylate polymers, having the same functionalities and stereoregularities as poly(methylmethacrylate) and poly(methylacrylate), respectively. The photochemistry and free radicals from these model systems have been studied using time-resolved electron paramagnetic resonance spectroscopy with laser flash photolysis at 248 nm. Chemically induced electron spin polarization from the triplet mechanism (net emission) is observed. Well-resolved spectra are obtained at all temperatures for the model system radicals, which are determined to be in the slow motion condition, that is, there is no interconversion of chair conformations. The temperature dependence of the spectra is minimal; some hyperfine lines shift as the temperature increases, but without much broadening. Density functional theory calculations are presented and discussed in support of the experimental data.

  15. 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

  16. Solvent polarity effects and limited acid catalysis in rearrangements of model radicals for the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed isomerization reactions.

    PubMed

    Daublain, Pierre; Horner, John H; Kuznetsov, Andriy; Newcomb, Martin

    2004-05-01

    The kinetics of reactions of models for the intermediate radicals formed in the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed rearrangements were studied by laser flash photolysis methods. The aldehyde-containing model analogous to the propanal-3-yl radical reacted via 3-exo cyclization with rate constants that varied with solvent polarity (k in the range 2 x 105 to 1 x 107 s-1). The analogous methyl ketone-containing radical reacted 2 orders of magnitude less rapidly, and the ethylthiocarbonyl-containing radical analogue reacted too slowly for kinetic measurements. No acid catalysis was observed in acetic acid, but the CF3CO2H-complexed radicals reacted 1 order of magnitude faster than the uncomplexed radicals. The results indicate that catalysis of the 3-exo radical cyclizations of the radicals formed in the enzymes by hydrogen bonding to an acid, so-called "partial protonation", is not adequate for acceleration of the reactions to the point of kinetic competence. A dissociative mechanism for the radical rearrangements in nature is considered as an alternative.

  17. Catalytic ozonation of 2,4-dichlorophenoxyacetic acid using alumina in the presence of a radical scavenger.

    PubMed

    Guzman-Perez, Carlos A; Soltan, Jafar; Robertson, Jared

    2012-01-01

    Using a laboratory-scale mixed reactor, the performance of alumina in degrading 2,4-Dichlorophenoxyacetic acid with ozone in the presence of tert-butyl alcohol radical scavenger was studied. The operating variables investigated were the dose of alumina catalyst and solution pH. Results showed that using ozone and alumina leads to a significant increase in 2,4-D removal in comparison to non-catalytic ozonation and adsorption processes. The observed reaction rate constants (k(obs)) for 2,4-D during ozonation were found to increase linearly with increasing catalyst dose. At pH 5, the k(obs) value increased from 19.3 to 26 M(-1) s(-1) and 67 M(-1) s(-1) when varying the alumina dose from 1 to 2 and 4 g L(-1), respectively. As pH was increased, higher reaction rates were observed for both non-catalytic ozonation and catalytic ozonation processes. Thus, at pH 3 and using a catalyst dose of 8 g L(-1), the k(obs) values for non-catalytic ozonation and catalytic ozonation processes were 3.4 and 58.9 M(-1) s(-1), respectively, whereas at pH 5 reaction rate constants of 6.5 and 128.5 M(-1) s(-1) were observed, respectively. Analysis of total organic carbon suggested that catalytic ozonation with alumina achieved a considerable level of mineralization of 2,4-D. Adsorption of 2,4-D on alumina was found to play an important role in the catalytic ozonation process.

  18. 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

  19. Radical-generating coordination complexes as tools for rapid and effective fragmentation and fluorescent labeling of nucleic acids for microchip hybridization.

    SciTech Connect

    Kelly, J. J.; Chernov, B. K.; Tovstanovsky, I.; Mirzabekov, A. D.; Bavykin, S. G.; Biochip Technology Center; Northwestern Univ.; Engelhardt Inst. of Molecular Biology

    2002-12-15

    DNA microchip technology is a rapid, high-throughput method for nucleic acid hybridization reactions. This technology requires random fragmentation and fluorescent labeling of target nucleic acids prior to hybridization. Radical-generating coordination complexes, such as 1,10-phenanthroline-Cu(II) (OP-Cu) and Fe(II)-EDTA (Fe-EDTA), have been commonly used as sequence nonspecific 'chemical nucleases' to introduce single-strand breaks in nucleic acids. Here we describe a new method based on these radical-generating complexes for random fragmentation and labeling of both single- and double-stranded forms of RNA and DNA. Nucleic acids labeled with the OP-Cu and the Fe-EDTA protocols revealed high hybridization specificity in hybridization with DNA microchips containing oligonucleotide probes selected for identification of 16S rRNA sequences of the Bacillus group microorganisms.We also demonstrated cDNA- and cRNA-labeling and fragmentation with this method. Both the OP-Cu and Fe-EDTA fragmentation and labeling procedures are quick and inexpensive compared to other commonly used methods. A column-based version of the described method does not require centrifugation and therefore is promising for the automation of sample preparations in DNA microchip technology as well as in other nucleic acid hybridization studies.

  20. 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

  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. 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

  3. 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.

  4. Intramolecular electron transfer versus substrate oxidation in lactoperoxidase: investigation of radical intermediates by stopped-flow absorption spectrophotometry and (9-285 GHz) electron paramagnetic resonance spectroscopy.

    PubMed

    Fielding, Alistair J; Singh, Rahul; Boscolo, Barbara; Loewen, Peter C; Ghibaudi, Elena M; Ivancich, Anabella

    2008-09-16

    We have combined the information obtained from rapid-scan electronic absorption spectrophotometry and multifrequency (9-295 GHz) electron paramagnetic resonance (EPR) spectroscopy to unequivocally determine the electronic nature of the intermediates in milk lactoperoxidase as a function of pH and to monitor their reactivity with organic substrates selected by their different accessibilities to the heme site. The aim was to address the question of the putative catalytic role of the protein-based radicals. This experimental approach allowed us to discriminate between the protein-based radical intermediates and [Fe(IV)=O] species, as well as to directly detect the oxidation products by EPR. The advantageous resolution of the g anisotropy of the Tyr (*) EPR spectrum at high fields showed that the tyrosine of the [Fe(IV)=O Tyr (*)] intermediate has an electropositive and pH-dependent microenvironment [g(x) value of 2.0077(0) at pH >or= 8.0 and 2.0066(2) at 4.0 radical stability and function. Two types of organic molecules (small aromatic vs bulkier substrates) allowed us to distinguish different mechanisms for substrate oxidation. [Fe(IV)=O Por (*+)] is the oxidizing species of benzohydroxamic acid, o-dianisidine, and o-anisidine via a heme-edge reaction and of mitoxantrone via a long-range electron transfer (favored at pH 8) not involving the tyrosyl radical, the formation of which competed with the substrate oxidation at pH 5. In contrast, the very efficient reaction with ABTS at pH 5 is consistent with [Fe(IV)=O Tyr (*)] being the oxidizing species. Accordingly, the identification of the ABTS binding site by X-ray crystallography may be a valuable tool in rational drug design.

  5. 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.

  6. 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

  7. 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

  8. 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.

  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. Electron microscopic demonstration of Romhányi's aldehyde-bisulphite-toluidine blue (ABT)-topo-optical staining reaction.

    PubMed

    Sótonyi, Peter; Tátrai, Enikö

    2009-01-01

    Romhányi's aldehyde-bisulphite-toluidine blue (ABT) topo-optical reaction was checked electron microscopically. The reaction product was found localized on the sarcolemma membrane and intercalated disc. The findings suggest that the topo-optical ABT-reaction is suitable for molecular analysis. In addition to confirming the electron microscopic suitability of the ABT-reaction it has also offered ultrastructural evidence for the reliability of the topo-optical method.

  11. Second-Generation DBFOX Ligands for the Synthesis of β-Substituted α-Amino Acids via Enantioselective Radical Conjugate Additions

    PubMed Central

    Banerjee, Biplab; Capps, Steven G.; Kang, Junghoon; Robinson, Joshua W.; Castle, Steven L.

    2009-01-01

    A set of second-generation DBFOX ligands possessing extended aryl or benzyl-type groups was synthesized. The requisite amino alcohols were either commercially available (DBFOX/Bn) or constructed via Sharpless asymmetric aminohydroxylation (DBFOX/Nap, DBFOX/t-BuPh, DBFOX/Pip) or phase-transfer-catalyzed asymmetric alkylation (DBFOX/MeNap). Complexes of the ligands with Mg(NTf2)2 were evaluated as promoters of enantioselective radical conjugate additions to α,β-unsaturated α-nitro amides and esters. Reactions employing the DBFOX/Nap ligand exhibited improved enantioselectivity relative to previously published additions mediated by DBFOX/Ph. However, the relatively modest increase in diastereomeric ratio suggests that our substrate–Lewis acid binding model, which was formulated based on results from DBFOX/Ph-promoted radical conjugate additions, is in need of revision. PMID:18947256

  12. Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species: a potential pathway for oxidative damage of retinal proteins in diabetes.

    PubMed

    Pennathur, Subramaniam; Ido, Yasuo; Heller, Jozsef I; Byun, Jaeman; Danda, Ratna; Pergola, Pablo; Williamson, Joseph R; Heinecke, Jay W

    2005-06-17

    The pattern of oxidized amino acids in aortic proteins of nonhuman primates suggests that a species resembling hydroxyl radical damages proteins when blood glucose levels are high. However, recent studies argue strongly against a generalized increase in diabetic oxidative stress, which might instead be confined to the vascular wall. Here, we describe a pathway for glucose-stimulated protein oxidation and provide evidence of its complicity in diabetic microvascular disease. Low density lipoprotein incubated with pathophysiological concentrations of glucose became selectively enriched in ortho-tyrosine and meta-tyrosine, implicating a hydroxyl radical-like species in protein damage. Model system studies demonstrated that the reaction pathway requires both a reactive carbonyl group and a polyunsaturated fatty acid, involves lipid peroxidation, and is blocked by the carbonyl scavenger aminoguanidine. To explore the physiological relevance of the pathway, we used mass spectrometry and high pressure liquid chromatography to quantify oxidation products in control and hyperglycemic rats. Hyperglycemia raised levels of ortho-tyrosine, meta-tyrosine, and oxygenated lipids in the retina, a tissue rich in polyunsaturated fatty acids. Rats that received aminoguanidine did not show this increase in protein and lipid oxidation. In contrast, rats with diet-induced hyperlipidemia in the absence of hyperglycemia failed to exhibit increased protein and lipid oxidation products in the retina. Our observations suggest that generation of a hydroxyl radical-like species by a carbonyl/polyunsaturated fatty acid pathway might promote localized oxidative stress in tissues vulnerable to diabetic damage. This raises the possibility that antioxidant therapies that specifically inhibit the pathway might delay the vascular complications of diabetes.

  13. Scavenging of SO 4- radical anions by mono- and dicarboxylic acids in the Mn(II)-catalyzed S(IV) oxidation in aqueous solution

    NASA Astrophysics Data System (ADS)

    Grgić, Irena; Podkrajšek, Boštjan; Barzaghi, Paolo; Herrmann, Hartmut

    The rate constants for reactions of the SO 4- radical anion with some low molecular weight monocarboxylic acids (MCAs) and dicarboxylic acids (DCAs) and their anions using the laser flash photolysis-long path laser absorption (LFP-LPLA) technique were determined. The present study contains the first measured rate constants for SO 4- reactions with glycolic, lactic, malic and malonic acid. The rate constants are found to be in the range from 10 5 to 10 7 M -1 s -1, with the lower values found for acids and higher values for their respective anions. In addition, the rate constants for scavenging of SO 4- by all investigated organics in the Mn(II)-catalyzed S(IV) autoxidation at pH 4.5 and T=25 °C were determined by means of the reversed rate method. The comparison between these rate constants and the rate constants obtained by direct measurements confirms the proposed inhibiting mechanism for the Mn(II)-catalyzed S(IV) autoxidation in the presence of monocarboxylic acids. In the case of formic acid, which causes the highest inhibition, this mechanism can explain the second part of kinetic traces (i.e. after the induction period). Surprisingly, although dicarboxylic acids are reactive toward SO 4- they do not contribute to the inhibition of S(IV) oxidation (especially malic and malonic acids).

  14. Effect of metal ions on the reactions of the cumyloxyl radical with hydrogen atom donors. Fine control on hydrogen abstraction reactivity determined by Lewis acid-base interactions.

    PubMed

    Salamone, Michela; Mangiacapra, Livia; DiLabio, Gino A; Bietti, Massimo

    2013-01-01

    A time-resolved kinetic study on the effect of metal ions (M(n+)) on hydrogen abstraction reactions from C-H donor substrates by the cumyloxyl radical (CumO(•)) was carried out in acetonitrile. Metal salt addition was observed to increase the CumO(•) β-scission rate constant in the order Li(+) > Mg(2+) > Na(+). These effects were explained in terms of the stabilization of the β-scission transition state determined by Lewis acid-base interactions between M(n+) and the radical. When hydrogen abstraction from 1,4-cyclohexadiene was studied in the presence of LiClO(4) and Mg(ClO(4))(2), a slight increase in rate constant (k(H)) was observed indicating that interaction between M(n+) and CumO(•) can also influence, although to a limited extent, the hydrogen abstraction reactivity of alkoxyl radicals. With Lewis basic C-H donors such as THF and tertiary amines, a decrease in k(H) with increasing Lewis acidity of M(n+) was observed (k(H)(MeCN) > k(H)(Li(+)) > k(H)(Mg(2+))). This behavior was explained in terms of the stronger Lewis acid-base interaction of M(n+) with the substrate as compared to the radical. This interaction reduces the degree of overlap between the α-C-H σ* orbital and a heteroatom lone-pair, increasing the C-H BDE and destabilizing the carbon centered radical formed after abstraction. With tertiary amines, a >2-order of magnitude decrease in k(H) was measured after Mg(ClO(4))(2) addition up to a 1.5:1 amine/Mg(ClO(4))(2) ratio. At higher amine concentrations, very similar k(H) values were measured with and without Mg(ClO(4))(2). These results clearly show that with strong Lewis basic substrates variations in the nature and concentration of M(n+) can dramatically influence k(H), allowing for a fine control of the substrate hydrogen atom donor ability, thus providing a convenient method for C-H deactivation. The implications and generality of these findings are discussed.

  15. 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.

  16. 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

  17. Effects of chloride ion on degradation of Acid Orange 7 by sulfate radical-based advanced oxidation process: implications for formation of chlorinated aromatic compounds.

    PubMed

    Yuan, Ruixia; Ramjaun, Sadiqua N; Wang, Zhaohui; Liu, Jianshe

    2011-11-30

    Sodium chloride is a common salt used during textile wet processes. Here a dual effect of chloride (i.e. inhibitory and accelerating effect) on azo dye (Acid Orange 7, AO7) degradation in an emerging cobalt/peroxymonosulfate (Co/PMS) advanced oxidation process (AOP) was reported. Compared to OH-based AOPs, high concentrations of chloride (>5mM) can significantly enhance dye decoloration independent of the presence of the Co(2+) catalyst, but did greatly inhibit dye mineralization to an extent which was closely dependent upon the chloride content. Both UV-vis absorbance spectra and AOX determination indicated the formation of some refractory byproducts. Some chlorinated aromatic compounds, including 3-chloroisocoumain, 2-chloro-7-hydroxynaphthalene, 1,3,5-trichloro-2-nitrobenzene and tetrachlorohydroquione, were identified by GC-MS measurement in both Co/PMS/Cl(-) and PMS/Cl(-) reaction systems. Based on those experimental results, two possible branched (SO(4)(-)radical-based and non-radical) reaction pathways are proposed. This is one of the very few studies dealing with chlorinated organic intermediates formed via chlorine radical/active chlorine species (HOCl/Cl(2)) attack on dye compounds. Therefore, this finding may have significant technical implications for utilizing Co/PMS regent to detoxify chloride-rich azo dyes wastewater.

  18. 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

  19. Subcritical water extraction and antioxidant activity evaluation with on-line HPLC-ABTS(·+) assay of phenolic compounds from marigold (Tagetes erecta L.) flower residues.

    PubMed

    Xu, Honggao; Wang, Weiyou; Jiang, Junping; Yuan, Fang; Gao, Yanxiang

    2015-06-01

    Subcritical water extraction (SWE) of phenolics was investigated from marigold (Tagetes erecta L.) flower residues. The total phenolics content (TPC), total flavonoids content (TFC) and antioxidant capacities of extracts were determined, furthermore, antioxidant activities of individual compounds were evaluated with on-line HPLC-ABTS(•+) system. The optimum SWE time was 45 min, solid-to-liquid ratio was 1:50, and the highest TPC and TFC were obtained at 220 °C respectively. The effect of SWE temperature on TPC and TFC was significant (p < 0.05), and TPC was ranged from 28.42 ± 0.94 to 124.27 ± 1.94 (mg GAE/g), and TFC ranged from 34.21 ± 0.36 to 133.22 ± 1.57 (mg GAE/g) between 80 and 220 °C. On-line HPLC-ABTS(•+) profiles revealed that quercetagetin from SWE at 200 °C had nearly twofold radical scavenging activities than that by leaching extraction. PMID:26028765

  20. 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

    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.

  1. 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

  2. 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

    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

  3. Oil, protein, antioxidants and free radical scavenging activity of stone from wild olive trees (Olea europaea L.).

    PubMed

    Hannachi, Hédia; Elfalleh, Walid; Marzouk, Sizaiem

    2013-05-01

    The wild olive trees or oleaster (var. sylvestris) and the cultivated olive trees (var. europaea) constitute the two botanical varieties of Olea europaea L. from Mediterranean. In this study, a partial chemical profile was conducted including the total lipids, the fatty acid profiles, soluble proteins, polyphenols, flavanoids contents and antioxidants activities of stone from six oleaster trees. The comparison was made by two olive cultivars cultivated in the same region. The oleaster and cultivar stones were richer in oil content having an average of 8.99 and 7.38 % dry weight basis (DW), respectively. Qualitatively, all studied oils have the same fatty acids profile with the oleic acid C18:1n-9 as the major fatty acid. The oleaster stone oils were richer in monounsaturated fatty acids having an average of 64.87%. They, also, richer in protein content with an average of 198.86 mg/g DW.The globulin is the major fraction, followed by the albumin, the prolamin and the glutemin fractions. The oleaster stone extracts contain polyphenols, flavonoids with an average of 151.14 and 11.91 mg gallic acid equivalent/100g of DW, respectively. The studied extracts showed antioxidant activity using the free radical scavenging activity determined by DPPH and ABTS. The unexploited oleaster stone seems to be a source of oil with good fatty acids balance, in protein and antioxidants metabolites and would be useful for the formulation of supplements and/or pharmaceutical ingredients.

  4. Inhibition of radical reactions for an improved potassium tert-butoxide-promoted (11) C-methylation strategy for the synthesis of α-(11) C-methyl amino acids.

    PubMed

    Suzuki, Chie; Kato, Koichi; Tsuji, Atsushi B; Zhang, Ming-Rong; Arano, Yasushi; Saga, Tsuneo

    2015-03-01

    α-(11) C-Methyl amino acids are useful tools for biological imaging studies. However, a robust procedure for the labeling of amino acids has not yet been established. In this study, the (11) C-methylation of Schiff-base-activated α-amino acid derivatives has been optimized for the radiosynthesis of various α-(11) C-methyl amino acids. The benzophenone imine analog of methyl 2-amino butyrate was (11) C-methylated with [(11) C]methyl iodide following its initial deprotonation with potassium tert-butoxide (KOtBu). The use of an alternative base such as tetrabutylammonium fluoride, triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene did not result in the (11) C-methylated product. Furthermore, the KOtBu-promoted (11) C-methylation of the Schiff-base-activated amino acid analog was enhanced by the addition of 1,2,4,5-tetramethoxybenzene or 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and inhibited by the addition of 1,10-phenanthroline. These results suggest that inhibition of radical generation induced by KOtBu improves the α-(11) C-methylation of the Schiff-base-activated amino acids. The addition of a mixture of KOtBu and TEMPO to a solution of Schiff-base-activated amino acid ester and [(11) C]methyl iodide provided optimal results, and the tert-butyl ester and benzophenone imine groups could be readily hydrolyzed to give the desired α-(11) C-methyl amino acids with a high radiochemical conversion. This strategy could be readily applied to the synthesis of other α-(11) C-methyl amino acids.

  5. 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...

  6. 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

  7. Aqueous-phase photolysis of biacetyl (An α-dicarbonyl compound): A sink for biacetyl, and a source of acetic acid, peroxyacetic acid, hydrogen peroxide, and the highly oxidizing acetylperoxyl radical in aqueous aerosols, fogs, and clouds

    NASA Astrophysics Data System (ADS)

    Faust, Bruce C.; Powell, Kendall; Rao, C. Janakiram; Anastasio, Cort

    Aqueous-phase photolysis of biacetyl represents a heretofore uncharacterized sink for biacetyl and source of organic acids and peroxides to aqueous aerosols, and fog and cloud drops. The photolysis half-life of aqueous-phase biacetyl is approximately 1.0-1.6 h for a solar zenith angle of 36° (midday equinox sunlight in Durham, NC). Major products of aqueous biacetyl photolysis are acetic acid, peroxyacetic acid, and hydrogen peroxide. Pyruvic acid and methylhydroperoxide are minor photoproducts. Common atmospheric reductants (H-atom donors), such as formate, formaldehyde, glyoxal, phenol (as a model for phenolic compounds) and α- D-glucose (as a model for carbohydrates), substantially increase the quantum yields of peroxyacetic acid Formate also significantly increases the quantum yields of hydrogen peroxide. The highly oxidizing acetylperoxyl radical is proposed as a key intermediate in the photolysis of aqueous biacetyl. The sources and reactions of acetylperoxyl radicals in aqueous aerosols, fogs, and clouds should be investigated in future studies of atmospheric water-drop chemistry.

  8. 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.

  9. Antioxidant and bile acid binding activity of buckwheat protein in vitro digests.

    PubMed

    Ma, Yuanyuan; Xiong, Youling L

    2009-05-27

    The objective of the study was to assess the antioxidant and bile acid removing potential of buckwheat protein (BWP) during a two-stage in vitro digestion (1 h of pepsin followed by 2 h of pancreatin). Antioxidant activity of the digests was analyzed by determining: (1) Fe(2+) chelation, (2) reducing power, (3) 2,2'-azinobis (3-ethylbenzothiszoline-6-sulfonic acid) (ABTS(+•)) radical scavenging capacity, and (4) TBARS formation in a liposome system. The initial pepsin digestion decreased the BWP antioxidant activity; however, subsequent pancreatin digestion fully recovered the reducing power and increased (P < 0.05) the ability to chelate Fe(2+) (45%), scavenge ABTS(+•) (87%), and curtail lipid peroxidation (45%) when compared with intact BWP. The final BWP digest exhibited a 67% increase (P < 0.05) in cholic acid binding capability over that of the nondigested BWP control but was comparable to the control in binding chenodeoxycholic and deoxycholic acids. Digestion-resistant peptides were largely responsible for bile acid elimination. PMID:19320435

  10. 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

  11. 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, ...

  12. 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

  13. Free radical scavenging, α-glucosidase inhibitory and anti-inflammatory constituents from Indian sedges, Cyperus scariosus R.Br and Cyperus rotundus L.

    PubMed Central

    Kakarla, Lavanya; Katragadda, Suresh Babu; Tiwari, Ashok K; Kotamraju, K Srigiridhar; Madhusudana, K; Kumar, D Anand; Botlagunta, Mahendran

    2016-01-01

    Background: Cyperus scariosus R. Br and Cyperus rotundus L are widely used in ayurvedic preparation for the treatment of diabetes and other diseases. The early literature, so far, does not indicate the presence of any bioactive principle isolated from these plants. Objective: To identify free radical scavenging, anti-diabetic and anti- inflammatory principles from these two species. Materials and Methods: The bioassay guided fractionation and isolation of active constituents was done by chromatographic techniques. They also evaluated their anti-oxidant activity by DPPH and ABTS. The anti-diabetic activity was screened by α- glucosidase and α- amylase assays. Also, the further evaluation of in vitro anti-inflammatory activity using THP-1 monocytic cells and in vivo anti- inflammatory activity, was confirmed by carrageenan induced rat paw edema as model. Results: The activity guided isolation led to isolation of twelve compounds Which are: Stigmasterol[1], β- sitosterol[2], Lupeol[3], Gallic acid[4], Quercetin[5], β- amyrin[6], Oleanolic acid[7], β- amyrin acetate[8], 4- hydroxyl butyl cinnamate[9], 4- hydroxyl cinnamic acid[10], Caffeic acid,[11] and Kaempferol[12] respectively. Among the isolates, the compounds 4 and 5 displayed potent radical scavenging activity with an IC50 values of 0.43 and 0.067 ΅g/ml. The compounds 4, 5 and 10 showed significant anti-diabetic activities. while lupeol[3] showed potent IL-1 β activity inhibition in THP-1 monocytic cells and also displayed significant (p<0.0025) in vivo anti-inflammatory activity. Conclusion: Inbrief, we isolated twelve compounds from both the species. Collectively, our results suggested that aromatic compounds showed good anti-oxidant and anti-diabetic activities. SUMMARY The study investigates the free radical scavenging, α-glucosidase inhibitory and anti-inflammatory effects of constituents isolated from Indian sedges viz. C. scariosus and C. rotundus. The results indicated that phenolic compounds

  14. Antiradical activity of gallic acid included in lipid interphases.

    PubMed

    Salcedo, C L; Frías, M A; Cutro, A C; Nazareno, M A; Disalvo, E A

    2014-10-01

    Polyphenols are well known as antioxidant agents and by their effects on the hydration layers of lipid interphases. Among them, gallic acid and its derivatives are able to decrease the dipole potential and to act in water as a strong antioxidant. In this work we have studied both effects on lipid interphases in monolayers and bilayers of dimyristoylphosphatidylcholine. The results show that gallic acid (GA) increases the negative surface charges of large unilamellar vesicles (LUVs) and decreases the dipole potential of the lipid interphase. As a result, positively charged radical species such as ABTS(+) are able to penetrate the membrane forming an association with GA. These results allow discussing the antiradical activity (ARA) of GA at the membrane phase which may be taking place in water spaces between the lipids.

  15. Dihydroasparagusic acid: antioxidant and tyrosinase inhibitory activities and improved synthesis.

    PubMed

    Venditti, Alessandro; Mandrone, Manuela; Serrilli, Anna Maria; Bianco, Armandodoriano; Iannello, Carmelina; Poli, Ferruccio; Antognoni, Fabiana

    2013-07-17

    Dihydroasparagusic acid (DHAA) is the reduced form of asparagusic acid, a sulfur-containing flavor component produced by Asparagus plants. In this work, DHAA was synthetically produced by modifying some published protocols, and the synthesized molecule was tested in several in vitro assays (DPPH, ABTS, FRAP-ferrozine, BCB, deoxyribose assays) to evaluate its radical scavenging activity. Results show that DHAA is endowed with a significant in vitro antioxidant activity, comparable to that of Trolox. DHAA was also evaluated for its inhibitory activity toward tyrosinase, an enzyme involved, among others, in melanogenesis and in browning processes of plant-derived foods. DHAA was shown to exert an inhibitory effect on tyrosinase activity, and the inhibitor kinetics, analyzed by a Lineweaver-Burk plot, exhibited a competitive mechanism. Taken together, these results suggest that DHAA may be considered as a potentially active molecule for use in various fields of application, such as pharmaceutical, cosmetics, agronomic and food. PMID:23790134

  16. Cascade dissociations of peptide cation-radicals. Part 1. Scope and effects of amino acid residues in penta-, nona-, and decapeptides.

    PubMed

    Chung, Thomas W; Hui, Renjie; Ledvina, Aaron; Coon, Joshua J; Tureček, Frantisek

    2012-08-01

    Amino acid residue-specific backbone and side-chain dissociations of peptide z ions in MS(3) spectra were elucidated for over 40 pentapeptides with arginine C-terminated sequences of the AAXAR and AAHXR type, nonapeptides of the AAHAAXX"AR and AAHAXAX"AR type, and AAHAAXX"AAR decapeptides. Peptide z(n) ions containing amino acid residues with readily transferrable benzylic or tertiary β-hydrogen atoms (Phe, Tyr, His, Trp, Val) underwent facile backbone cleavages to form dominant z(n-2) or z(n-3) ions. These backbone cleavages are thought to be triggered by a side-chain β-hydrogen atom transfer to the z ion C(α) radical site followed by homolytic dissociation of the adjacent C(α)-CO bond, forming x(n-2) cation-radicals that spontaneously dissociate by loss of HNCO. Amino acid residues that do not have readily transferrable β-hydrogen atoms (Gly, Ala) do not undergo the z(n) → z(n-2) dissociations. The backbone cleavages compete with side-chain dissociations in z ions containing Asp and Asn residues. Side-chain dissociations are thought to be triggered by α-hydrogen atom transfers that activate the C(β)-C(γ) or C(β)-heteroatom bonds for dissociations that dominate the MS(3) spectra of z ions from peptides containing Leu, Cys, Lys, Met, Ser, Arg, Glu, and Gln residues. The Lys, Arg, Gln, and Glu residues also participate in γ-hydrogen atom transfers that trigger other side-chain dissociations. PMID:22669761

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. FORMATION OF CARBONIC ACID (H{sub 2}CO{sub 3}) BY SURFACE REACTIONS OF NON-ENERGETIC OH RADICALS WITH CO MOLECULES AT LOW TEMPERATURES

    SciTech Connect

    Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira; Hama, Tetsuya; Pirronello, Valerio

    2010-10-20

    We present the experimental results of carbonic acid (H{sub 2}CO{sub 3}) formation through surface reactions of CO molecules with non-energetic hydroxyl (OH) radicals at 10-40 K. The formation of H{sub 2}CO{sub 3} was clearly identified both in the IR spectra and in the thermally programmed desorption mass spectra. The H{sub 2}CO{sub 3} yield was rather high, amounting to approximately 40%-70% relative to that of CO{sub 2} formed by the reaction of CO with OH. The structure of H{sub 2}CO{sub 3} formed by reactions of CO with OH may differ from that formed by energetic processes such as UV irradiation, ion irradiation, and electron irradiation of H{sub 2}O/CO{sub 2} binary ices. In this paper, we envisage some of the possible roles H{sub 2}CO{sub 3} may have in the interstellar medium, such as enriching grain mantles of new molecules via acid-base reactions with basic species and contributing to the formation of the unidentified band at 6.8 {mu}m; we suggest possible reasons for its non-detection yet and discuss the restoration of carbonic acid molecules in the gas phase.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Selective BCL-2 Inhibition by ABT-199 Causes On Target Cell Death in Acute Myeloid Leukemia

    PubMed Central

    Pan, Rongqing; Hogdal, Leah J.; Benito, Juliana M; Bucci, Donna; Han, Lina; Borthakur, Gautam; Cortes, Jorge; DeAngelo, Daniel J.; Debose, LaKeisha; Mu, Hong; Döhner, Hartmut; Gaidzik, Verena I.; Galinsky, Ilene; Golfman, Leonard S.; Haferlach, Torsten; Harutyunyan, Karine G.; Hu, Jianhua; Leverson, Joel D; Marcucci, Guido; Müschen, Markus; Newman, Rachel; Park, Eugene; Ruvolo, Peter P.; Ruvolo, Vivian; Ryan, Jeremy; Schindela, Sonja; Zweidler-McKay, Patrick; Stone, Richard M.; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina; Letai, Anthony G.

    2014-01-01

    B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nM, and cell death occurred within 2 h. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia (CLL), a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML. PMID:24346116

  13. 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.

  14. 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.

  15. Mass spectrometric detection of cross-linked fatty acids formed during radical-induced lesion of lipid membranes.

    PubMed Central

    Frank, H; Thiel, D; MacLeod, J

    1989-01-01

    A mass spectrometric method is described for the quantitative determination of dimers of polyunsaturated fatty acids (PUFA) formed in the hepatic endoplasmic reticulum of rats upon inhalation of tetrachloromethane. The results show that dimers account for a considerable fraction of microsomal PUFA which disappear during CCl4 metabolism. Cross-linking of the membrane lipids of the endoplasmic reticulum seems to be a significant process with respect to cell toxicity. PMID:2764908

  16. [The effect of fenofibrate on expression of genes involved in fatty acids beta-oxidation and associated free-radical processes].

    PubMed

    Gureev, A P; Shmatkova, M L; Bashmakov, V Yu; Starkov, A A; Popov, V N

    2016-05-01

    Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered. PMID:27562996

  17. [The effect of fenofibrate on expression of genes involved in fatty acids beta-oxidation and associated free-radical processes].

    PubMed

    Gureev, A P; Shmatkova, M L; Bashmakov, V Yu; Starkov, A A; Popov, V N

    2016-05-01

    Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered.

  18. Plasma thiobarbituric acid reactivity: reaction conditions and the role of iron, antioxidants and lipid peroxy radicals on the quantitation of plasma lipid peroxides

    SciTech Connect

    Wade, C.R.; van Rij, A.M.

    1988-01-01

    The effects of Fe/sup 3 +/, lipid peroxy radicals and the antioxidant butylated hydroxytoluene on the 2-thiobarbituric (TBA) acid quantitation of plasma lipid peroxides were investigated. Whole plasma and plasma fractions prepared by trichloroacetic acid (TCA) protein precipitation and lipid extraction, demonstrated markedly differing TBA reactivities in the presence or absence of added Fe/sup 3 +/. Examination of the spectral profiles of the TBA reacted whole plasma and TCA precipitated fractions demonstrated the presence of interfering compounds which gave rise to an artifactual increase in lipid peroxide concentrations. In contrast the TBA reacted lipid extracts had low levels of interfering compounds that could be removed by our previously described high pressure liquid chromatographic method. Further characterization of the TBA reactivity of the lipid extract showed that Fe/sup 3 +/ at an optimal concentration of 0.5 mM was necessary for the quantitative decomposition of the lipid peroxides to the TBA reactive product malondialdehyde (MDA). However the presence of Fe/sup 3 +/ resulted in further peroxidation of any unsaturated lipids present.

  19. Myristic Acid, A Side Chain of Phorbol Myristate Acetate (PMA), Can Activate Human Polymorphonuclear Leukocytes to Produce Oxygen Radicals More Potently than PMA

    PubMed Central

    Tada, Mika; Ichiishi, Eiichiro; Saito, Rumiko; Emoto, Natsumi; Niwano, Yoshimi; Kohno, Masahiro

    2009-01-01

    Myristic acid (MyA), which is a saturated fatty acid (C14:0) and a side chain of phorbol 12-myristate 13-acetate (PMA), was examined if MyA stimulates human polymorphonuclear leukocytes (PMNs) to release oxygen radicals comparable to PMA by applying electron paramagnetic resonance (EPR)-spin-trapping method. When MyA was added to isolated human PMNs, spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH and DMPO-OOH were time-dependently observed. The amounts of these spin adducts were larger than those of PMNs stimulated by PMA. These results clearly show that MyA is more potent agent to prime human PMNs than PMA, in a point of view of not only O2·− but also ·OH production. This fact calls attention that too much intake of MyA that is known to be contained vegetable oils can lead to crippling effect through uncontrolled production of reactive oxygen species. PMID:19902021

  20. Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury.

    PubMed

    Newaz, M A; Yousefipour, Z; Nawal, N N A

    2005-08-01

    End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2

  1. 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

  2. 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 Central

    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

  3. 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

  4. The isolation and identification of two compounds with predominant radical scavenging activity in hempseed (seed of Cannabis sativa L.).

    PubMed

    Chen, Tianpeng; He, Jinfeng; Zhang, Jianchun; Li, Xiaohui; Zhang, Hua; Hao, Jianxiong; Li, Lite

    2012-09-15

    Forty samples were extracted from defatted kernels and hulls of two varieties of hempseed (Bama and Yunma No. 1) using 10 different polar solvent systems. The radical scavenging capacity of the extracts was evaluated using 2,2-diphenyl-1-pikrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the total phenolic content was determined by Folin-Ciocalteu's phenol reagent. The correlation analysis indicated that the antioxidants in hempseed belonged to phenolic and DPPH() assay was suitable for evaluating the radical scavenging activity. Two compounds, with predominant antiradical activity, were isolated in 60% ethanol extract of hempseed hull using macroporous resin absorption, LH-20 gel chromatography, and high performance liquid chromatography methods, which were identified as N-trans-caffeoyltyramine and cannabisin B by high-resolution mass spectra, nuclear magnetic resonance spectra, and ultraviolet data. The two compounds exhibited significant high DPPH() scavenging activity and protective effect against in vitro oxidation of human low-density lipoprotein compared with extracts from flaxseed, grape seed, and soybean. This suggests that hempseed hull extract is a potential source of natural antioxidants, which could be added to dietary supplements to help prevent oxidative stress.

  5. Protective Effect of Sinapine against Hydroxyl Radical-Induced Damage to Mesenchymal Stem Cells and Possible Mechanisms.

    PubMed

    Li, Xican; Han, Lu; Li, Yunrong; Zhang, Jing; Chen, Jiemin; Lu, Wenbiao; Zhao, Xiaojun; Lai, Yingtao; Chen, Dongfeng; Wei, Gang

    2016-01-01

    As a phenolic alkaloid occurring in Cruciferous plants, sinapine was observed to protect mesenchymal stem cells (MSCs) against ·OH-induced damage in this study. It was also found to prevent DNA from damage, to scavenge various free radicals (·OH, ·O2(-), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt) (ABTS)(+·), and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)), and to reduce Cu(2+) to Cu(+). To further explore the mechanism, the end-product of sinapine reaction with DPPH· was determined using HPLC-electrospray ionization (ESI)-MS/MS and HPLC-diode array detector (DAD). Four molecular ion peaks (m/z 701, 702, 703, and 351) in HPLC-ESI-MS/MS analysis indicated a radical adduct formation (RAF) pathway; while a bathochromic shift (λ(max) 334→475 nm) in HPLC-DAD indicated the formation of quinone as the oxidized product of the phenolic -OH group. Based on these results, it may be concluded that, (i) sinapine can effectively protect against ·OH-induced damage to DNA and MSCs; such protective effect may provide evidence for a potential role for sinapine in MSC transplantation therapy, and be responsible for the beneficial effects of Cruciferous plants. (ii) The possible mechanism for sinapine to protect against ·OH-induced oxidative damage is radical-scavenging, which is thought to be via hydrogen atom (H·) transfer (HAT) (or sequential electron (e) proton transfer (SEPT))→RAF pathways.

  6. 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.

  7. Radical-scavenging capacity of phenol fractions in the brown seaweed Ascophyllum nodosum: an electrochemical approach.

    PubMed

    Blanc, Nathalie; Hauchard, Didier; Audibert, Laetitia; Gall, Erwan Ar

    2011-04-15

    In this article, the radical-scavenging capacity of phenol fractions extracted from the brown seaweed Ascophyllum nodosum was assessed using in parallel colorimetric methods (ABTS and DPPH) and electrochemistry (cyclic voltammetry). Results obtained by the three methods correlated in the case of global fractions, whereas only ABTS and DPPH correlated when activities were expressed on a phenol basis. The successive fractions separated by both their average molecular size and their polarity exhibited activities largely dependent on their phenol content, suggesting that phlorotannins are the main anti-oxidant molecules in hydro-alcoholic extracts of A. nodosum. In addition, phenol fractions of relative low molecular weight were clearly more active than others. This work opens new opportunities to better evaluate the radical-scavenging potential of phenol pools in algae using both bi-parametric fractionating and electrochemistry. PMID:21376981

  8. 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 1.57 mg 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 (28.06 mg QE/g and 7.42 mg CE/g DW, respectively) compared to hexanic extract (0.71 mg QE/g and 0.29 mg 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 (2.13-45.54 μg/mL and 1.2-43.82 μg/mL, respectively). All plant extracts showed ovicidal activity at all tested concentrations. Fruit methanolic (IC50=2.76mg/mL) and aqueous (IC50=2.08 mg/mL) extracts showed higher inhibitory effects than chloroformic (IC50=7.62 mg/mL) and hexanic (IC50=12.93 mg/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

  9. Radical scavengers as ribonucleotide reductase inhibitors.

    PubMed

    Basu, Arijit; Sinha, Barij Nayan

    2012-01-01

    This paper compiled all the previous reports on radical scavengers, an interesting class of ribonucleotide reductase inhibitors. We have highlighted three key research areas: chemical classification of radical scavengers, structural and functional aspects of the radical site, and progress in drug designing for radical scavengers. Under the chemical classification section, we have recorded the discovery of hydroxyurea followed by discussions on hydroxamic acids, amidoximes, hydroxyguanidines, and phenolic compounds. In the next section, we have compiled the structural information for the radical site obtained from different crystallographic and theoretical studies. Finally, we have included the reported ligand based and structure based drug-designing studies.

  10. 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).

  11. Transient effects of 2,4-dichlorophenoxyacetic acid (2,4-D) exposure on some metabolic and free radical processes in goldfish white muscle.

    PubMed

    Kubrak, Olga I; Atamaniuk, Tetiana M; Husak, Viktor V; Lushchak, Volodymyr I

    2013-09-01

    This study aims to assess effects of 96 h goldfish exposure to 1, 10 and 100 mg/L of the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), on metabolic indices and free radical process markers in white muscle of a commercial fish, the goldfish Carassius auratus L. Most oxidative stress markers and antioxidant enzymes were not affected at 2,4-D fish treatment. 2,4-D fish exposure induced the elevated levels of total (by 46% and 40%) and reduced (by 77% and 73%) glutathione in muscles of goldfish of 10 mg/L 2,4-D and recovery (after 100 mg/L of 2,4-D exposure) groups, respectively. However, in muscles of 100 mg/L 2,4-D exposed goldfish these parameters were depleted (by 47% and 64%). None of investigated parameters of protein and carbohydrate metabolisms changed in white muscles of 2,4-D exposed fish, with exception of lactate dehydrogenase activity, which was slightly (by 11-15%) elevated in muscles of goldfish exposed to 10-100 mg/L of 2,4-D, but also recovered. Thus, the short term exposure of goldfish to the selected concentrations of 2,4-D does not substantially affect their white muscle, suggesting the absence of any effect under the environmentally relevant concentrations. PMID:23806294

  12. Gallic acid ester derivatives induce apoptosis and cell adhesion inhibition in melanoma cells: The relationship between free radical generation, glutathione depletion and cell death.

    PubMed

    Locatelli, Claudriana; Leal, Paulo C; Yunes, Rosendo A; Nunes, Ricardo J; Creczynski-Pasa, Tânia B

    2009-10-01

    Malignant melanoma is a lethal disease, and the incidence and mortality associated with it are increasing worldwide. It has a significant tendency to develop both metastasis and resistance to chemotherapy. The tumor cells show abnormal redox regulation, and although the molecular mechanisms involved are not well characterized, they seem to be related to oxidative stress. In a previous study, we showed the antitumoral properties of gallic acid ester derivatives in leukemia cells. Here, we show the effect of octyl, decyl, dodecyl and tetradecyl gallates on B16F10 cells, a melanoma cell line. All compounds induced cytotoxic effects, and the IC(50) values obtained were between 7microM and 17microM after 48h of incubation. Cell death occurred through apoptosis, as demonstrated by the genomic DNA fragmentation pattern. The gallates were able to induce significant production of free radicals, deplete both glutathione and ATP, activate NF-kappaB and promote the inhibition of cell adhesion under the experimental conditions. The glutathione depletion induced by these compounds was related to the inhibition of gamma-glutamylcysteine synthase activity. These results suggest that gallates induce tumoral cell death through apoptosis as a consequence of oxidative stress, though they use different mechanisms to do so. These findings are important since melanoma cells are resistant to death because of their high level of antioxidant defense, adhesion capability and propensity to metastasize.

  13. 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

  14. 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.

  15. 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.

  16. Transient effects of 2,4-dichlorophenoxyacetic acid (2,4-D) exposure on some metabolic and free radical processes in goldfish white muscle.

    PubMed

    Kubrak, Olga I; Atamaniuk, Tetiana M; Husak, Viktor V; Lushchak, Volodymyr I

    2013-09-01

    This study aims to assess effects of 96 h goldfish exposure to 1, 10 and 100 mg/L of the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), on metabolic indices and free radical process markers in white muscle of a commercial fish, the goldfish Carassius auratus L. Most oxidative stress markers and antioxidant enzymes were not affected at 2,4-D fish treatment. 2,4-D fish exposure induced the elevated levels of total (by 46% and 40%) and reduced (by 77% and 73%) glutathione in muscles of goldfish of 10 mg/L 2,4-D and recovery (after 100 mg/L of 2,4-D exposure) groups, respectively. However, in muscles of 100 mg/L 2,4-D exposed goldfish these parameters were depleted (by 47% and 64%). None of investigated parameters of protein and carbohydrate metabolisms changed in white muscles of 2,4-D exposed fish, with exception of lactate dehydrogenase activity, which was slightly (by 11-15%) elevated in muscles of goldfish exposed to 10-100 mg/L of 2,4-D, but also recovered. Thus, the short term exposure of goldfish to the selected concentrations of 2,4-D does not substantially affect their white muscle, suggesting the absence of any effect under the environmentally relevant concentrations.

  17. 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

  18. 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

  19. Phytochemical analysis and in vitro free-radical-scavenging activities of the essential oils from leaf and fruit of Melaleuca leucadendra L.

    PubMed

    Pino, Jorge A; Regalado, Erik L; Rodríguez, José L; Fernández, Miguel D

    2010-09-01

    The phytochemical profile of Melaleuca leucadendra L. leaf and fruit oils from Cuba was investigated by GC and GC/MS. Forty-one and sixty-four volatile compounds were identified and quantified, accounting for 99.2 and 99.5% of the leaf-oil and fruit-oil total composition, respectively. The main components were 1,8-cineol (43.0%), viridiflorol (24.2%), α-terpineol (7.0%), α-pinene (5.3%), and limonene (4.8%) in the leaf oil, and viridiflorol (47.6%), globulol (5.8%), guaiol (5.3%), and α-pinene (4.5%) in the fruit oil. The antioxidant capacity of these essential oils was determined by three different in vitro assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, thiobarbituric acid reactive species (TBARS), and 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation), and significant activities were evidenced for all of them.

  20. L-tryptophan reacts with naturally occurring and food-occurring phenolic aldehydes to give phenolic tetrahydro-beta-carboline alkaloids: activity as antioxidants and free radical scavengers.

    PubMed

    Herraiz, Tomas; Galisteo, Juan; Chamorro, Cristina

    2003-04-01

    The reaction between the essential amino acid l-tryptophan and flavoring or naturally occurring phenyl and phenolic aldehydes was studied, and the alkaloidal reaction products were characterized by NMR and HPLC-MS. Benzaldehyde, vanillin, syringaldehyde, salicylaldehyde, and anisaldehyde condensed with l-tryptophan in aqueous-acidic media affording the corresponding phenolic tetrahydro-beta-carboline-3-carboxylic acid as two diastereoisomers, 1S,3S-cis and 1R,3S-trans. With the exception of benzaldehyde, the rest of the aldehydes needed heating conditions (70 degrees C) to significantly form tetrahydro-beta-carbolines over time with the cyclization highly favored at low pH. This suggests a likely formation of these compounds under conditions that may occur in foods, food processing, or cooking. The new phenolic tetrahydro-beta-carboline alkaloids were assayed, for the first time, for their activity as free radical scavengers and antioxidants and showed good antioxidant properties with Trolox equivalent antioxidant capacity (TEAC) values much higher than those of ascorbic acid and the water soluble vitamin E analogue, Trolox, in the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) assay.

  1. Quantification of lipid alkyl radicals trapped with nitroxyl radical via HPLC with postcolumn thermal decomposition.

    PubMed

    Koshiishi, Ichiro; Tsuchida, Kazunori; Takajo, Tokuko; Komatsu, Makiko

    2005-11-01

    Lipid alkyl radicals generated from polyunsaturated fatty acids via chemical or enzymatic H-abstraction have been a pathologically important target to quantify. In the present study, we established a novel method for the quantification of lipid alkyl radicals via nitroxyl radical spin-trapping. These labile lipid alkyl radicals were converted into nitroxyl radical-lipid alkyl radical adducts using 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (CmdeltaP) (a partition coefficient between octanol and water is approximately 3) as a spin-trapping agent. The resulting CmdeltaP-lipid alkyl radical adducts were determined by HPLC with postcolumn online thermal decomposition, in which the adducts were degraded into nitroxyl radicals by heating at 100 degrees C for 2 min. The resulting nitroxyl radicals were selectively and sensitively detected by electrochemical detection. With the present method, we, for the first time, determined the lipid alkyl radicals generated from linoleic acid, linolenic acid, and arachidonic acid via soybean lipoxygenase-1 or the radical initiator 2,2'-azobis(2,4-dimethyl-valeronitrile).

  2. Antiedematogenic and free radical scavenging activity of swertiamarin isolated from Enicostemma axillare.

    PubMed

    Vaijanathappa, Jaishree; Badami, Shrishailappa

    2009-01-01

    Swertiamarin, a secoiridoid isolated from the ethyl acetate extract of Enicostemma axillare, was evaluated for antiedematogenic activity using carrageenan-, formalin-, and histamine-induced paw edema methods in rats. In the carrageenan-induced method, the percentages of edema inhibition obtained after 5 h induction were 38.60, 52.50, and 45.44, respectively, for 100 and 200 mg/kg bw swertiamarin and 100 mg/kg bw of standard diclofenac sodium given orally. The activity of swertiamarin at 200 mg/kg bw was found to be superior to that of standard diclofenac sodium in all these methods. Swertiamarin was also screened for IN VITRO antioxidant activity using seven different methods: good activity was observed in ABTS and hydrogen peroxide methods, and moderate activity was observed in hydroxyl radical by deoxyribose and lipid peroxidation methods, with IC50 values of 2.83, 5.70, 52.56, and 78.33 microg/mL, respectively. The total antioxidant capacity was found to be 4.51 mM of ascorbic acid per gram of swertiamarin. Swertiamarin possesses antiedematogenic and in vitro antioxidant activities, and it may be the active constituent responsible for the anti-inflammatory activity of E. AXILLARE.

  3. Pharmacological and protein profiling suggest venetoclax (ABT-199) as optimal partner with ibrutinib in chronic lymphocytic leukemia

    PubMed Central

    Cervantes-Gomez, Fabiola; Lamothe, Betty; Woyach, Jennifer A.; Wierda, William G.; Keating, Michael J.; Balakrishnan, Kumudha; Gandhi, Varsha

    2015-01-01

    Purpose Bruton’s tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain. Though ibrutinib results in impressive clinical activity in chronic lymphocytic leukemia (CLL), most patients achieve only partial remission due to residual disease. We performed a pharmacologic profiling of residual circulating CLL cells from patients receiving ibrutinib to identify optimal agents that could induce cell death of these lymphocytes. Experimental design Ex vivo serial samples of CLL cells from patients on ibrutinib were obtained prior and after (weeks 2, 4, and 12) the start of treatment. These cells were incubated with PI3K inhibitors (idelalisib or IPI-145), bendamustine, additional ibrutinib, or BCL-2 antagonists (ABT-737 or ABT-199) and cell death was measured. In vitro investigations complemented ex vivo studies. Immunoblots for BTK signaling pathway and antiapoptotic proteins were performed. Results The BCL-2 antagonists, especially ABT-199, induced high cell death during ex vivo incubations. In concert with the ex vivo data, in vitro combinations also resulted highly cytotoxicity. Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs. Among the three BCL-2 family anti-apoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2. Conclusions Our biological and molecular results suggest that ibrutinib and ABT-199 combination should be tested clinically against CLL. PMID:25829398

  4. 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

  5. Cell and Molecular Determinants of In Vivo Efficacy of the BH3 Mimetic ABT-263 Against Pediatric Acute Lymphoblastic Leukemia Xenografts

    PubMed Central

    Suryani, Santi; Carol, Hernan; Chonghaile, Triona Ni; Frismantas, Viktoras; Sarmah, Chintanu; High, Laura; Bornhauser, Beat; Cowley, Mark J; Szymanska, Barbara; Evans, Kathryn; Boehm, Ingrid; Tonna, Elise; Jones, Luke; Manesh, Donya Moradi; Kurmasheva, Raushan T.; Billups, Catherine; Kaplan, Warren; Letai, Anthony; Bourquin, Jean-Pierre; Houghton, Peter J; Smith, Malcolm A; Lock, Richard B

    2014-01-01

    Purpose Predictive biomarkers are required to identify patients who may benefit from the use of BH3 mimetics such as ABT-263. This study investigated the efficacy of ABT-263 against a panel of patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts and utilized cell and molecular approaches to identify biomarkers that predict in vivo ABT-263 sensitivity. Experimental Design The in vivo efficacy of ABT-263 was tested against a panel of 31 patient-derived ALL xenografts comprised of MLL-, BCP- and T-ALL subtypes. Basal gene expression profiles of ALL xenografts were analyzed and confirmed by quantitative RT-PCR, protein expression and BH3 profiling. An in vitro co-culture assay with immortalized human mesenchymal cells was utilized to build a predictive model of in vivo ABT-263 sensitivity. Results ABT-263 demonstrated impressive activity against pediatric ALL xenografts, with 19 of 31 achieving objective responses. Among BCL2 family members, in vivo ABT-263 sensitivity correlated best with low MCL1 mRNA expression levels. BH3 profiling revealed that resistance to ABT-263 correlated with mitochondrial priming by NOXA peptide, suggesting a functional role for MCL1 protein. Using an in vitro co-culture assay, a predictive model of in vivo ABT-263 sensitivity was built. Testing this model against 11 xenografts predicted in vivo ABT-263 responses with high sensitivity (50%) and specificity (100%). Conclusion These results highlight the in vivo efficacy of ABT-263 against a broad range of pediatric ALL subtypes and shows that a combination of in vitro functional assays can be used to predict its in vivo efficacy. PMID:25013123

  6. Strong Inhibition of O-Atom Transfer Reactivity for Mn(IV)(O)(π-Radical-Cation)(Lewis Acid) versus Mn(V)(O) Porphyrinoid Complexes.

    PubMed

    Zaragoza, Jan Paulo T; Baglia, Regina A; Siegler, Maxime A; Goldberg, David P

    2015-05-27

    The oxygen atom transfer (OAT) reactivity of two valence tautomers of a Mn(V)(O) porphyrinoid complex was compared. The OAT kinetics of Mn(V)(O)(TBP8Cz) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato(3-)) reacting with a series of triarylphosphine (PAr3) substrates were monitored by stopped-flow UV-vis spectroscopy, and revealed second-order rate constants ranging from 16(1) to 1.43(6) × 10(4) M(-1) s(-1). Characterization of the OAT transition state analogues Mn(III)(OPPh3)(TBP8Cz) and Mn(III)(OP(o-tolyl)3)(TBP8Cz) was carried out by single-crystal X-ray diffraction (XRD). A valence tautomer of the closed-shell Mn(V)(O)(TBP8Cz) can be stabilized by the addition of Lewis and Brønsted acids, resulting in the open-shell Mn(IV)(O)(TBP8Cz(•+)):LA (LA = Zn(II), B(C6F5)3, H(+)) complexes. These Mn(IV)(O)(π-radical-cation) derivatives exhibit dramatically inhibited rates of OAT with the PAr3 substrates (k = 8.5(2) × 10(-3) - 8.7 M(-1) s(-1)), contrasting the previously observed rate increase of H-atom transfer (HAT) for Mn(IV)(O)(TBP8Cz(•+)):LA with phenols. A Hammett analysis showed that the OAT reactivity for Mn(IV)(O)(TBP8Cz(•+)):LA is influenced by the Lewis acid strength. Spectral redox titration of Mn(IV)(O)(TBP8Cz(•+)):Zn(II) gives Ered = 0.69 V vs SCE, which is nearly +700 mV above its valence tautomer Mn(V)(O)(TBP8Cz) (Ered = -0.05 V). These data suggest that the two-electron electrophilicity of the Mn(O) valence tautomers dominate OAT reactivity and do not follow the trend in one-electron redox potentials, which appear to dominate HAT reactivity. This study provides new fundamental insights regarding the relative OAT and HAT reactivity of valence tautomers such as M(V)(O)(porph) versus M(IV)(O)(porph(•+)) (M = Mn or Fe) found in heme enzymes.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Effects of the Cognition-Enhancing Agent ABT-239 on Fetal Ethanol-Induced Deficits in Dentate Gyrus Synaptic Plasticity

    PubMed Central

    Varaschin, Rafael K.; Akers, Katherine G.; Rosenberg, Martina J.; Hamilton, Derek A.

    2010-01-01

    Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl) benzonitrile (ABT-239), a histamine H3 receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long-Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H3 receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring. PMID:20308329

  12. 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

  13. Oxygen centered radicals in iodine chemical oscillators.

    PubMed

    Stanisavljev, Dragomir R; Milenković, Maja C; Mojović, Milos D; Popović-Bijelić, Ana D

    2011-07-14

    The existence of free radicals in iodine-based oscillatory systems has been debated for some time. Recently, we have reported the presence of reactive oxygen species (ROS) in the iodide-peroxide system in acidic medium, which is common to all iodine--based oscillatory systems ( J. Phys. Chem. A 2011 , 115 , 2247--2249 ). In this work, the goal was to identify the ROS produced in this system using an EPR spin trap which can distinguish between hydroxyl (HO(•)) and hydroperoxyl (HOO(•)) radicals. The formation of the hydroperoxyl radical was observed and a possible explanation for the low EPR signal of hydroxyl radical was proposed. PMID:21692499

  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. 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

  16. Radical scavenging activity of antioxidants evaluated by means of electrogenerated HO radical.

    PubMed

    Oliveira, Raquel; Geraldo, Dulce; Bento, Fátima

    2014-11-01

    A method is proposed and tested concerning the characterization of antioxidants by means of their reaction with electrogenerated HO radicals in galvanostatic assays with simultaneous O2 evolution, using a Pt anode fairly oxidized. The consumption of a set of species with antioxidant activity, ascorbic acid (AA), caffeic acid (CA), gallic acid (GA) and trolox (T), is described by a first order kinetics. The rate of the processes is limited by the kinetics of reaction with HO radicals and by the kinetics of charge transfer. Information regarding the scavenger activity of antioxidants is obtained by the relative value of the rate constant of the reaction between antioxidants and HO radicals, k(AO,HO)/k(O2). The number of HO radicals scavenged per molecule of antioxidant is also estimated and ranged from 260 (ascorbic acid) to 500 (gallic acid). The method is applied successfully in the characterization of the scavenger activity of ascorbic acid in a green-tea based beverage.

  17. EPR parameters of amino acid radicals in P. eryngii versatile peroxidase and its W164Y variant computed at the QM/MM level.

    PubMed

    Bernini, Caterina; Pogni, Rebecca; Ruiz-Dueñas, Francisco J; Martínez, Angel T; Basosi, Riccardo; Sinicropi, Adalgisa

    2011-03-21

    Quantum mechanics/molecular mechanics (QM/MM) methods, employing density functional theory (DFT), have been used to compute the electron paramagnetic resonance (EPR) parameters of tryptophan and tyrosyl radical intermediates involved in the catalytic cycle of Pleurotus eryngii versatile peroxidase (VP) and its W164Y variant, respectively. These radicals have been previously experimentally detected and characterized both in the two-electron and one-electron activated forms of the enzymes. In this work, the well-studied W164 radical in VP has been chosen for calibration purposes because its spectroscopic properties have been extensively studied by multifrequency EPR and ENDOR spectroscopies. Using a B3LYP/CHARMM procedure, appropriately accounting for electrostatic, such as hydrogen bonding, and steric environmental interactions, a good agreement between the calculated and measured EPR parameters for both radicals has been achieved; g-tensors, hyperfine coupling constants (hfcc) and Mulliken spin densities have been correlated to changes in geometries, hydrogen bond networks and electrostatic environment, with the aim of understanding the influence of the protein surroundings on EPR properties. In addition, the present calculations demonstrate, for VP, the formation of a neutral tryptophan radical, hydrogen bonded to the nearby E243, via a stepwise electron and proton transfer with earlier involvement of a short-lived tryptophan cationic species. Instead, for W164Y, the QM/MM dynamics simulation shows that the tyrosine oxidation proceeds via a concerted electron and proton transfer and is accompanied by a significant reorganization of residues and water molecules surrounding the tyrosyl radical.

  18. 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

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

    PubMed

    Zheng, Ruinian; You, Zhijian; Jia, Jun; Lin, Shunhuan; Han, Shuai; Liu, Aixue; Long, Huidong; Wang, Senming

    2016-02-01

    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

  20. 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.

  1. 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

  2. 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

  3. The inhibitory effect of luteolin-7-O-glucoside on the formation of pentyl and 7-carboxyheptyl radicals from 13-hydroperoxy-9,11-octadecadienoic acid in the presence of iron(II) ions.

    PubMed

    Iwahashi, Hideo; Akata, Kayo; Sunaga, Atsuko; Tone, Yoshiko; Yamada, Noriko; Iijima, Keiko

    2004-08-01

    A flavone glucoside, luteolin-7-O-glucoside (luteolin-7-G) inhibited the formation of pentyl and 7-carboxyheptyl radicals in the reaction of 13-hydroperoxy-9,11-octadecadienoic (13-HPODE) acid with iron(II) ions. The inhibitory effect of luteolin-7-G was diminished in the presence of EDTA. These results indicated that the inhibitory effects of luteolin-7-G occur partly through the chelation of iron ions. Measurement of visible spectra also showed that luteolin-7-G chelates iron ions. On the other hand, luteolin-7-G did not inhibit the reaction under anaerobic conditions, suggesting that oxygen molecules participate in the inhibition. Oxygen consumption measurements showed that the luteolin-7-G/iron ion complexes react with oxygen molecules in competition with 13-HPODE acid, and free iron ions exclusively react with 13-HPODE acid. The reaction of luteolin-7-G/iron ion complexes with oxygen molecules possibly diminishes the formation of pentyl and 7-carboxyheptyl radicals. PMID:15493461

  4. BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy.

    PubMed

    Pedro, Jose Manuel Bravo-San; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Zou, Zhongju; Kroemer, Guido; Levine, Beth

    2015-01-01

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

  5. 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

  6. 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.

  7. Mathematical evaluation of the amino acid and polyphenol content and antioxidant activities of fruits from different apricot cultivars.

    PubMed

    Sochor, Jiri; Skutkova, Helena; Babula, Petr; Zitka, Ondrej; Cernei, Natalia; Rop, Otakar; Krska, Boris; Adam, Vojtech; Provazník, Ivo; Kizek, Rene

    2011-09-01

    Functional foods are of interest because of their significant effects on human health, which can be connected with the presence of some biologically important compounds. In this study, we carried out complex analysis of 239 apricot cultivars (Prunus armeniaca L.) cultivated in Lednice (climatic area T4), South Moravia, Czech Republic. Almost all previously published studies have focused only on analysis of certain parameters. However, we focused on detection both primary and secondary metabolites in a selection of apricot cultivars with respect to their biological activity. The contents of thirteen biogenic alpha-L-amino acids (arginine, asparagine, isoleucine, lysine, serine, threonine, valine, leucine, phenylalanine, tryptophan, tyrosine, proline and alanine) were determined using ion exchange chromatography with UV-Vis spectrometry detection. Profile of polyphenols, measured as content of ten polyphenols with significant antioxidant properties (gallic acid, procatechinic acid, p-aminobenzoic acid, chlorogenic acid, caffeic acid, vanillin, p-coumaric acid, rutin, ferrulic acid and quercetrin), was determined by high performance liquid chromatography with spectrometric/electrochemical detection. Moreover, content of total phenolics was determined spectrophotometrically using the Folin-Ciocalteu method. Antioxidant activity was determined using five independent spectrophotometric methods: DPPH assay, DMPD method, ABTS method, FRAP and Free Radicals methods. Considering the complexity of the obtained data, they were processed and correlated using bioinformatics techniques (cluster analysis, principal component analysis). The studied apricot cultivars were clustered according to their common biochemical properties, which has not been done before. The observed similarities and differences were discussed.

  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.

  9. 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

  10. 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

  11. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

    PubMed

    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

  12. Radical prostatectomy - discharge

    MedlinePlus

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

  13. 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).

  14. The predominant polyphenol in the leaves of the resurrection plant Myrothamnus flabellifolius, 3,4,5 tri-O-galloylquinic acid, protects membranes against desiccation and free radical-induced oxidation.

    PubMed

    Moore, John P; Westall, Kim L; Ravenscroft, Neil; Farrant, Jill M; Lindsey, George G; Brandt, Wolf F

    2005-01-01

    The predominant (>90%) low-molecular-mass polyphenol was isolated from the leaves of the resurrection plant Myrothamnus flabellifolius and identified to be 3,4,5 tri-O-galloylquinic acid using 1H and 13C one- and two-dimensional NMR spectroscopy. The structure was confirmed by mass spectrometric analysis. This compound was present at high concentrations, 44% (by weight) in hydrated leaves and 74% (by weight) in dehydrated leaves. Electron microscopy of leaf material fixed with glutaraldehyde and caffeine demonstrated that the polyphenols were localized in large vacuoles in both hydrated and dehydrated leaves. 3,4,5 Tri-O-galloylquinic acid was shown to stabilize an artificial membrane system, liposomes, against desiccation if the polyphenol concentration was between 1 and 2 microg/mug phospholipid. The phase transition of these liposomes observed at 46 degrees C was markedly diminished by the presence of 3,4,5 tri-O-galloylquinic acid, suggesting that the presence of the polyphenol maintained the membranes in the liquid crystalline phase at physiological temperatures. 3,4,5 Tri-O-galloylquinic acid was also shown to protect linoleic acid against free radical-induced oxidation.

  15. The predominant polyphenol in the leaves of the resurrection plant Myrothamnus flabellifolius, 3,4,5 tri-O-galloylquinic acid, protects membranes against desiccation and free radical-induced oxidation

    PubMed Central

    2004-01-01

    The predominant (>90%) low-molecular-mass polyphenol was isolated from the leaves of the resurrection plant Myrothamnus flabellifolius and identified to be 3,4,5 tri-O-galloylquinic acid using 1H and 13C one- and two-dimensional NMR spectroscopy. The structure was confirmed by mass spectrometric analysis. This compound was present at high concentrations, 44% (by weight) in hydrated leaves and 74% (by weight) in dehydrated leaves. Electron microscopy of leaf material fixed with glutaraldehyde and caffeine demonstrated that the polyphenols were localized in large vacuoles in both hydrated and dehydrated leaves. 3,4,5 Tri-O-galloylquinic acid was shown to stabilize an artificial membrane system, liposomes, against desiccation if the polyphenol concentration was between 1 and 2 μg/μg phospholipid. The phase transition of these liposomes observed at 46 °C was markedly diminished by the presence of 3,4,5 tri-O-galloylquinic acid, suggesting that the presence of the polyphenol maintained the membranes in the liquid crystalline phase at physiological temperatures. 3,4,5 Tri-O-galloylquinic acid was also shown to protect linoleic acid against free radical-induced oxidation. PMID:15355309

  16. Inhibition of CHK1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells

    PubMed Central

    Zhao, Jianyun; Niu, Xiaojia; Li, Xinyu; Edwards, Holly; Wang, Guan; Wang, Yue; Taub, Jeffrey W; Lin, Hai; Ge, Yubin

    2016-01-01

    Resistance to standard chemotherapy agents remains a major obstacle for improving treatment outcomes for acute myeloid leukemia (AML). The Bcl-2-selective inhibitor ABT-199 has demonstrated encouraging preclinical results, drug resistance remains a concern. Mcl-1 has been demonstrated to contribute to ABT-199 resistance, thus combining with therapies that target Mcl-1 could overcome such resistance. In this study, we utilized a CHK1 inhibitor, LY2603618, to decrease Mcl-1 and enhance ABT-199 efficacy. We found that LY2603618 treatment resulted in abolishment of the G2/M cell cycle checkpoint and increased DNA damage, which was partially dependent on CDK activity. LY2603618 treatment resulted in decrease of Mcl-1, which coincided with the initiation of apoptosis. Overexpression of Mcl-1 in AML cells significantly attenuated apoptosis induced by LY2603618, confirming the critical role of Mcl-1 in apoptosis induced by the agent. Simultaneous treatment with LY2603618 and ABT-199 resulted in synergistic induction of apoptosis in both AML cell lines and primary patient samples. Our findings provide new insights into overcoming a mechanism of intrinsic ABT-199 resistance in AML cells and support the clinical development of combined ABT-199 and CHK1 inhibition. PMID:27166183

  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.

  18. [Ethanol metabolism and pathobiochemistry of organ damage--1992. II. Relation between ethanol metabolism and free radicals, and the metabolism of saccharides and amino acids. Ethanol as a carcinogen. Drug interactions with ethanol].

    PubMed

    Zima, T

    1993-01-01

    Ethanol metabolism induces formation of free radicals which are responsible for lipid peroxidation of biological membranes with subsequent aldehyde formation (malondialdehyde,4-hydroxy-nonenal). These aldehydes are competitive or mixed inhibitors of aldehyde dehydrogenase, and they cause an increase in hepatocellular toxicity of aldehydes. The activity of antioxidative systems in human body after chronic as well as acute ethanol intake is being reduced. Interference of ethanol metabolism and gluconeogenesis is caused by inhibition of intake substrates or by decrease NADH/NAD+, ratio in hepatocyte. The blood level of glucose decreases, lactate level increases as well as the ration of lactate, pyruvate and NADH/NAD+ which inhibit cytosole pyruvate carboxykinase. An acute ethanol administration reduces the concentration of most amino acids in plasma by ethanol oxidation impacts on increase of NADH/NAD+ ratio or by mechanism mediated by beta-adrenergic receptors. Chronic alcoholics develop tolerance to decreased plasmatic levels of amino acids. Accumulation of proteins in liver may be explained by larger amount of proteins binding to fatty acids, and also by diminished degradation of proteins with decreasing autophagosome and autolysosome formations. Alcohol is one of carcinogenic factors. Ethanol, acetaldehyde and originating free radicals impaired the DNA repairing enzyme. Binding itself to DNA, acetaldehyde changes DNA properties. Ethanol may also function as a co-carcinogen due to its ability to increase disolution and absorption of carcinogens. Chronic alcoholism induces cytochrome P450 which takes part in the activation and metabolism of carcinogens. Mutual interaction of drugs metabolism and ethanol is connected mainly with cytochrome P450-MEOS. Acute ethanol intake inhibits MEOS, as MEOS gives preference to ethanol as a substrate, however, chronic alcoholism induces MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 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

  20. 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

  1. 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

  2. Structural and medium effects on the reactions of the cumyloxyl radical with intramolecular hydrogen bonded phenols. The interplay between hydrogen-bonding and acid-base interactions on the hydrogen atom transfer reactivity and selectivity.

    PubMed

    Salamone, Michela; Amorati, Riccardo; Menichetti, Stefano; Viglianisi, Caterina; Bietti, Massimo

    2014-07-01

    A time-resolved kinetic study on the reactions of the cumyloxyl radical (CumO(•)) with intramolecularly hydrogen bonded 2-(1-piperidinylmethyl)phenol (1) and 4-methoxy-2-(1-piperidinylmethyl)phenol (2) and with 4-methoxy-3-(1-piperidinylmethyl)phenol (3) has been carried out. In acetonitrile, intramolecular hydrogen bonding protects the phenolic O-H of 1 and 2 from attack by CumO(•) and hydrogen atom transfer (HAT) exclusively occurs from the C-H bonds that are α to the piperidine nitrogen (α-C-H bonds). With 3 HAT from both the phenolic O-H and the α-C-H bonds is observed. In the presence of TFA or Mg(ClO4)2, protonation or Mg(2+) complexation of the piperidine nitrogen removes the intramolecular hydrogen bond in 1 and 2 and strongly deactivates the α-C-H bonds of the three substrates. Under these conditions, HAT to CumO(•) exclusively occurs from the phenolic O-H group of 1-3. These results clearly show that in these systems the interplay between intramolecular hydrogen bonding and Brønsted and Lewis acid-base interactions can drastically influence both the HAT reactivity and selectivity. The possible implications of these findings are discussed in the framework of the important role played by tyrosyl radicals in biological systems.

  3. 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

  4. 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

  5. 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

  6. Mechanism of deoxyribonucleic acid breakage induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and copper: role for cuprous ion and oxygen free radicals

    SciTech Connect

    Wong, A.; Huang, C.H.; Crooke, S.T.

    1984-06-19

    4-(9-Acridinylamino)methanesulfon-m-anisidide (mAMSA) interacts with Cu(II) ions, as indicated by changes in the mAMSA absorption spectrum induced by Cu(II). The spectral changes are due to the oxidation of mAMSA by Cu(II), resulting in an oxidized mAMSA product and Cu(I). Cu(I) plays an important role in the mAMSA-Cu(II)-induced DNA breakage, since in the presence of neocuproine the DNA breakage is inhibited. Up to 200 ..mu..M, Cu(I) by itself is virtually ineffective, in contrast to the mixture of mAMSA and Cu(II). This suggests that mAMSA, aside from reducing Cu(II) to Cu(I), may play a role in mediating DNA breakage. The DNA breakage was reduced in partially anaerobic conditions, indicating the involvement of molecular oxygen. Catalase and 4,5-dihydroxy-1,2-benzenedisulfonate inhibited the DNA breakage completely, indicating that hydrogen peroxide and superoxide radicals mediate DNA breakage. 1,3-Diazabicyclo(2.2.2)octane partially inhibited the breakage, suggesting that singlet oxygen is involved. The available evidence supports a mechanism indicating the formation of a DNA x mAMSA x Cu(II) ternary complex and the subsequent oxidation-reduction of the complex to form DNA x mAQDI x Cu(I). The oxidation of the complexed Cu(I) may result in reduction of oxygen to oxygen free radicals which induce DNA breaks.

  7. 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

  8. [Free radicals and eye inflammations].

    PubMed

    Ianopol, N

    1998-01-01

    Free radicals (FR), mainly those oxygen derived (FRO) are considered to be inflammation's mediators. Produced either by photochemical reactions or by synthesis into active phagocytic cells (in the cellular time of inflammation), FRO can determine an inflammatory reaction or they can augment a pre-existed one. These phenomena are produced by synthesis of inflammation's mediators as: prostaglandines, prostaciclines, thromboxane and leucotrienes starting from arachidonic acid, by the generation of some compounds with chemotactic properties and by the activation of phagocytic cells, by the augmentation of the proteolytic activity due to natural protease inhibitors inactivation and, last but not least, by the directly destructive action against different tissue compounds. In the first part of this lecture I presented general data about FR, inflammation, photosensitive agents and radical reactions. In the second part, I presented the pathogenic relation between FR and ocular inflammations from two different point of view: that of inflammation generation by FR, and that of FR generation during a preexistent inflammation.

  9. 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.

  10. 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

  11. 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

  12. Protein hydroperoxides can give rise to reactive free radicals.

    PubMed Central

    Davies, M J; Fu, S; Dean, R T

    1995-01-01

    Proteins damaged by free-radical-generating systems in the presence of oxygen yield relatively long-lived protein hydroperoxides. These hydroperoxides have been shown by e.p.r. spectroscopy to be readily degraded to reactive free radicals on reaction with iron(II) complexes. Comparison of the observed spectra with those obtained with free amino acid hydroperoxides had allowed identification of some of the protein-derived radical species (including a number of carbon-centred radicals, alkoxyl radicals and a species believed to be the CO2 radical anion) and the elucidation of novel fragmentation and rearrangement processes involving amino acid side chains. In particular, degradation of hydroperoxide functions on the side chain of glutamic acid is shown to result in decarboxylation at the side-chain carboxy group via the formation of the CO2 radical anion; the generation of an identical radical from hydroperoxide groups on proteins suggests that a similar process occurs with these molecules. In a number of cases these fragmentation and rearrangement reactions give rise to further reactive free radicals (R., O2-./HO2., CO2-.) which may act as chain-carrying species in protein oxidations. These studies suggest that protein hydroperoxides are capable of initiating further radical chain reactions both intra- and inter-molecularly, and provide information on some of the fundamental mechanisms of protein alteration and side-chain fragmentation. PMID:7832784

  13. HOCO radical chemistry.

    PubMed

    Francisco, Joseph S; Muckerman, James T; Yu, Hua-Gen

    2010-12-21

    Free radicals are important species in atmospheric chemistry, combustion, plasma environments, interstellar clouds, and biochemistry. Therefore, researchers would like to understand the formation mechanism, structure, stability, reactivity, spectroscopy, and dynamics of these chemical species. However, due to the presence of one or more unpaired electrons, radicals are often very reactive and have short lifetimes, which makes it difficult to conduct experiments. The HOCO radical appears in the atmosphere as well as in combustion environments and plays an important role in the conversion of CO to CO(2). Through the interplay between theoretical and experimental investigations, researchers have only recently understood the chemical role of the HOCO radical. In this Account, we systematically describe the current state of knowledge of the HOCO radical based on recent theoretical and experimental studies. This radical's two stable conformers, trans- and cis-HOCO, have been identified by high-level ab initio calculations and experimental spectroscopy. trans-HOCO is more stable by approximately 1.8 kcal/mol. The heat of formation of HOCO (298 K) was determined to be -43.0 ± 0.5 kcal/mol, giving a potential well depth of 30.1 ± 0.5 kcal/mol relative to the asymptote of the reactants OH + CO. The HOCO radical is very reactive. In most reactions between the HOCO radical and atoms, the HOCO radical acts as a hydrogen donor to reaction partners. Generally, the hydrogen is transferred through the formation of an association intermediate, which then proceeds through a molecular elimination step to produce the reaction products. The reaction rates of HOCO with some small radicals fall in the range of 10(-11)-10(-10) cm(3) molecule(-1) s(-1). These results clearly illustrate important features in the reactivity of the HOCO radical with other molecules.

  14. 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

  15. 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

  16. 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

  17. pH dependence and structural interpretation of the reactions of Coprinus cinereus peroxidase with hydrogen peroxide, ferulic acid, and 2,2'-azinobis.

    PubMed

    Abelskov, A K; Smith, A T; Rasmussen, C B; Dunford, H B; Welinder, K G

    1997-08-01

    Steady-state and transient-state analysis of Coprinus cinereus peroxidase, CIP (identical to Arthromyces ramosus peroxidase), was used to characterize the kinetics of the three fundamental steps in heme peroxidase catalysis: compound I (cpd I) formation, cpd I reduction, and compound II (cpd II) reduction. The rate constant k1 for cpd I formation determined by transient-state analysis is (9.9 +/- 0.6) x 10(6) M-1 s-1. The k1 determined by steady-state analysis is (8.8 +/- 0.6) x 10(6) M-1 s-1 in the presence of ferulic acid and (6.7 +/- 0.2) x 10(6) M-1 s-1 in the presence of ABTS. The value of k1 is constant from pH 6 to 11. However, at low pH the value of k1 decreases, corresponding to titration of an enzyme group with a pKa of 5.0. Titration of this group is also detected from cyanide-binding kinetics. Furthermore, titration of this group is linked with marked spectroscopic changes unique to CIP. We ascribe these changes to protonation of proximal His183. A very low pKa is proposed for distal His55 in the resting state of CIP. The rate constants, k2 for cpd I and k3 for cpd II reduction, are very large for both ferulic acid and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). For ferulic acid, transient-state kinetic analysis shows that the values of k2 and k3 are identical at pH 5-6, and the ratio k2/k3 increases to 10 at pH 10. The similar magnitude of k2 and k3 is unusual for a peroxidase. Both k2 and k3 decrease with increasing pH, and both are influenced by two ionizations: one with a pKa value near 7, assumed to reflect the protonation of His55; and the other with pKa of 9.0 +/- 0.7 for k2 and 8.8 +/- 0.4 for k3, perhaps reflecting the phenol-linked deprotonation of ferulic acid. Steady-state analysis at pH 7.0 gave k2k3/(k2 + k3) = (2.2 +/- 0.1) x 10(7) M-1 s-1 for ferulic acid, and (2.0 +/- 0.7) x 10(7) M-1 s-1 for ABTS and revealed a unimolecular step with ku = 1500 s-1, ascribed to slow ABTS radical product release. From transient

  18. Generation and recycling of radicals from phenolic antioxidants.

    PubMed

    Kagan, V E; Serbinova, E A; Packer, L

    1990-07-01

    Hindered phenols are widely used food preservatives. Their pharmacological properties are usually attributed to high antioxidant activity due to efficient scavenging of free radicals. Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) also cause tissue damage. Their toxic effects could be due to the production of phenoxyl radicals. If phenoxyl radicals can be recycled by reductants or electron transport, their potentially harmful side reactions would be minimized. A simple and convenient method to follow phenoxyl radical reactions in liposomes and rat liver microsomes based on an enzymatic (lipoxygenase + linolenic acid) oxidation system was used to generate phenoxyl radicals from BHT and its homologues with substitutents in m- and p-positions. Different BHT-homologues display characteristic ESR signals of their radical species. In a few instances the absence of phenoxyl radical ESR signals was found to be due to inhibition of lipoxygenase by BHT-homologues. In liposome or microsome suspensions addition of ascorbyl palmitate resulted in disappearance of the ESR signal of phenoxyl radicals with concomittant appearance of the ascorbyl radical signal. After exhaustion of ascorbate, the phenoxyl radical signal reappears. Comparison of the rates of ascorbyl radical decay in the presence or absence of BHT-homologues showed that temporary elimination of the phenoxyl radical ESR signal was due to their reduction by ascorbate. Similarly, NADPH or NADH caused temporary elimination of ESR signals as a result of reduction of phenoxyl radicals in microsomes. Since ascorbate and NADPH might generate superoxide in the incubation system used, SOD was tested. SOD shortened the period, during which the phenoxyl radicals ESR signal could not be observed. Both ascorbyl palmitate and NADPH exerted sparing effects on the loss of BHT-homologues during oxidation. These effects were partly diminished by SOD. These data indicate that reduction of phenoxyl radicals was partly

  19. Rational discovery and development of a mitochondria-targeted antioxidant based on cinnamic acid scaffold.

    PubMed

    Teixeira, José; Soares, Pedro; Benfeito, Sofia; Gaspar, Alexandra; Garrido, Jorge; Murphy, Michael P; Borges, Fernanda

    2012-05-01

    A novel mitochondria-targeted antioxidant (TPP-OH) was synthesized by attaching the natural hydrophilic antioxidant caffeic acid to an aliphatic lipophilic carbon chain containing a triphenylphosphonium (TPP) cation. This compound has similar antioxidant activity to caffeic acid as demonstrated by measurement of DPPH/ABTS radical quenching and redox potentials, but is significantly more hydrophobic than its precursor as indicated by the relative partition coefficients. The antioxidant activity of both compounds was intrinsic related to the ortho-catechol system, as the methoxylation of the phenolic functions, namely in TPP-OCH(3) and dimethoxycinnamic acid, gave compounds with negligible antioxidant action. The incorporation of the lipophilic TPP cation to form TTP-OH and TPP-OCH(3) allowed the cinnamic derivatives to accumulate within mitochondria in a process driven by the membrane potential. However, only TPP-OH was an effective antioxidant: TPP-OH protected cells against H(2)O(2) and linoleic acid hydroperoxide-induced oxidative stress. As mitochondrial oxidative damage is associated with a number of clinical disorders, TPP-OH may be a useful lead that could be added to the family of mitochondria-targeted antioxidants that can decrease mitochondrial oxidative damage.

  20. 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).

  1. Glutathione-induced radical formation on lactoperoxidase does not correlate with the enzyme's peroxidase activity.

    PubMed

    Bonini, Marcelo G; Siraki, Arno G; Bhattacharjee, Suchandra; Mason, Ronald P

    2007-04-01

    Lactoperoxidase (LPO) is believed to serve as a mediator of host defense against invading pathogens. The protein is more abundant in body fluids such as milk, saliva, and tears. Lactoperoxidase is known to mediate the oxidation of halides and (pseudo)halides in the presence of hydrogen peroxide to reactive intermediates presumably involved in pathogen killing. More recently, LPO has been shown to oxidize a wide diversity of thiol compounds to thiyl free radicals, which ultimately lead to the formation of a protein radical characterized by DMPO-immunospin trapping. In the same study by our group the authors claimed that a consequence of this protein radical formation was the inactivation of LPO (Guo et al., J. Biol. Chem.279:13272-13283; 2004). Here we demonstrate that although thiyl radical formation does lead to LPO radical production, the formation of this radical is unrelated to the enzyme's activity. We suggest the source of this misleading interpretation to be the binding of GSH to ELISA plates, which interferes with ABTS and guaiacol oxidation. In addition, DMPO-GSH-nitrone adducts bind to ELISA plates, leading to ambiguities of interpretation since we have demonstrated that DMPO-GSH nitrone does not bind to LPO, and only LPO-protein-DMPO-nitrone adducts can be detected by Western blot.

  2. 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

  3. 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

  4. 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

  5. Carbohydrate radicals: from ethylene glycol to DNA strand breakage.

    PubMed

    von Sonntag, Clemens

    2014-06-01

    Radiation-induced DNA strand breakage results from the reactions of radicals formed at the sugar moiety of DNA. In order to elucidate the mechanism of this reaction investigations were first performed on low molecular weight model systems. Results from studies on deoxygenated aqueous solutions of ethylene glycol, 2-deoxy-d-ribose and other carbohydrates and, more relevantly, of d-ribose-5-phosphate have shown that substituents can be eliminated from the β-position of the radical site either proton and base-assisted (as in the case of the OH substituent), or spontaneously (as in the case of the phosphate substituent). In DNA the C(4') radical undergoes strand breakage via this type of reaction. In the presence of oxygen the carbon-centred radicals are rapidly converted into the corresponding peroxyl radicals. Again, low molecular weights models have been investigated to elucidate the key reactions. A typical reaction of DNA peroxyl radicals is the fragmentation of the C(4')-C(S') bond, a reaction not observed in the absence of oxygen. Although OH radicals may be the important direct precursors of the sugar radicals of DNA, results obtained with poly(U) indicate that base radicals may well be of even greater importance. The base radicals, formed by addition of the water radicals (H and OH) to the bases would in their turn attack the sugar moiety to produce sugar radicals which then give rise to strand breakage and base release. For a better understanding of strand break formation it is therefore necessary to investigate in more detail the reactions of the base radicals. For a start, the radiolysis of uracil in oxygenated solutions has been reinvestigated, and it has been shown that the major peroxyl radical in this system undergoes base-catalysed elimination of [Formula: see text], a reaction that involves the proton at N(l). In the nucleic acids the pyrimidines are bound at N(l) to the sugar moiety and this type of reaction can no longer occur. Therefore, with

  6. 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

  7. 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.

  8. Alkoxy radicals: Delta proton hyperfine couplingsa)

    NASA Astrophysics Data System (ADS)

    Budzinski, Edwin E.; Box, Harold C.

    1985-04-01

    Single crystals of rhamnose were x irradiated at 4.2 K and the ESR and ENDOR spectra taken at 1.6 K. A component of the ESR absorption arises from an alkoxy radical exhibiting an unusual delta proton hyperfine coupling. Parallels between the radiation-induced oxidation of certain carbohydrates and that of amino acids are pointed out.

  9. The antioxidant properties of theaflavins and their gallate esters--radical scavengers or metal chelators?

    PubMed

    Miller, N J; Castelluccio, C; Tijburg, L; Rice-Evans, C

    1996-08-19

    The antioxidant properties of theaflavins and their gallate esters were studied by investigating their abilities to scavenge free radicals in the aqueous and lipophilic phases. The total relative antioxidant activities in the aqueous phase were assessed by measuring their direct ABTS.+ radical scavenging abilities, and by their efficacies in inhibiting the degradation of deoxyribose induced by iron. The propensities for enhancing the resistance of LDL to oxidation mediated by Cu2+ were also measured. The results show that the hierarchy of reactivity of these compounds as antioxidants is: theaflavin digallate > 3'-monogallate = 3-monogallate > theaflavin. Spectroscopic studies show that all the compounds chelate iron and copper; enhanced absorbance in the visible region is observed in the case of the iron-digallate complex, but not with copper.

  10. 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

  11. Data on the DNA damaging and mutagenic potential of the BH3-mimetics ABT-263/Navitoclax and TW-37.

    PubMed

    Green, Maja M; Shekhar, Tanmay M; Hawkins, Christine J

    2016-03-01

    Unfortunately, the mutagenic activities of chemotherapy and radiotherapy can provoke development of therapy-induced malignancies in cancer survivors. Non-mutagenic anti-cancer therapies may be less likely to trigger subsequent malignant neoplasms. Here we present data regarding the DNA damaging and mutagenic potential of two drugs that antagonize proteins within the Bcl-2 family: ABT-263/Navitoclax and TW-37. Our data reveal that concentrations of these agents that stimulated Bax/Bak-dependent signaling provoked little DNA damage and failed to trigger mutations in surviving cells. The data supplied in this article is related to the research work entitled "Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells" [1].

  12. 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.

  13. Radical-Mediated Fluoroalkylations.

    PubMed

    Cho, Eun Jin

    2016-02-01

    Recently, the development of eco-friendly radical processes has become of great interest in synthetic chemistry. In particular, visible-light photocatalysis has drawn tremendous attention for its environmental compatibility and versatility in promoting many synthetically important reactions. In addition, inorganic electrides as electron donors have emerged as new eco-friendly tools for radical transformations since they consist of non-toxic and naturally abundant main metals such as calcium. The design of new fluoroalkylation reactions has benefited greatly from recent advances in visible-light photocatalysis and the chemistry of inorganic electrides. Since adding fluoroalkyl groups can dramatically change the physical and chemical properties of organic compounds, using these processes to promote eco-friendly radical fluoroalkylations will have a major impact in areas such as pharmaceuticals, agrochemicals, and material sciences. This Personal Account reviews radical-mediated fluoroalkylations, such as trifluoromethylations and difluoroalkylations, recently developed in our laboratory. PMID:26497950

  14. 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.

  15. Bicarbonate and Alkyl Carbonate Radicals: Structural Integrity and Reactions with Lipid Components.

    PubMed

    Bühl, Michael; DaBell, Peter; Manley, David W; McCaughan, Rory P; Walton, John C

    2015-12-30

    The elusive neutral bicarbonate radical and the carbonate radical anion form an acid/conjugate base pair. We now report experimental studies for a model of bicarbonate radical, namely, methyl carbonate (methoxycarbonyloxyl) radical, complemented by DFT computations at the CAM-B3LYP level applied to the bicarbonate radical itself. Methyl carbonate radicals were generated by UV irradiation of oxime carbonate precursors. Kinetic EPR was employed to measure rate constants and Arrhenius parameters for their dissociation to CO2 and methoxyl radicals. With oleate and cholesterol lipid components, methyl carbonate radicals preferentially added to their double bonds; with linoleate and linolenate substrates, abstraction of the bis-allylic H atoms competed with addition. This contrasts with the behavior of ROS such as hydroxyl radicals that selectively abstract allylic and/or bis-allylic H atoms. The thermodynamic and activation parameters for bicarbonate radical dissociation, obtained from DFT computations, predicted it would indeed have substantial lifetime in gas and nonpolar solvents. The acidity of bicarbonate radicals was also examined by DFT methods. A noteworthy linear relationship was discovered between the known pKa's of strong acids and the computed numbers of microsolvating water molecules needed to bring about their ionization. DFT computations with bicarbonate radicals, solvated with up to eight water molecules, predicted that only five water molecules were needed to bring about its complete ionization. On comparing with the correlation, this indicated a pKa of about -2 units. This marks the bicarbonate radical as the strongest known carboxylic acid.

  16. A lipoxygenase from red alga Pyropia haitanensis, a unique enzyme catalyzing the free radical reactions of polyunsaturated fatty acids with triple ethylenic bonds.

    PubMed

    Zhu, Zhujun; Qian, Feijian; Yang, Rui; Chen, Juanjuan; Luo, Qijun; Chen, Haimin; Yan, Xiaojun

    2015-01-01

    Lipoxygenases (LOXs) are key enzymes to regulate the production of hormones and defensive metabolites in plants, animals and algae. In this research, a full length LOX gene has been cloned and expressed from the red alga Pyropia haitanensis (Bangiales, Rhodophyta) gametophyte (PhLOX2). Subsequent phylogenetic analysis showed that such LOX enzymes are separated at the early stage of evolution, establishing an independent branch. The LOX activity was investigated at the optimal pH of 8.0. It appears that PhLOX2 is a multifunctional enzyme featuring both lipoxygenase and hydroperoxidase activities. Additionally, PhLOX2 exhibits remarkable substrate and position flexibility, and it can catalyze an array of chemical reactions involving various polyunsaturated fatty acids, ranging from C18 to C22. As a matter of fact, mono-hydroperoxy, di-hydroperoxy and hydroxyl products have been obtained from such transformations, and eicosapentaenoic acid seem to be the most preferred substrate. It was found that at least triple ethylenic bonds are required for PhLOX2 to function as a LOX, and the resulting hydroxy products should be originated from the PhLOX2 mediated reduction of mono-hydroperoxides, in which the hydrogen abstraction occurs on the carbon atom between the second and third double bond. Most of the di-hydroperoxides observed seem to be missing their mono-position precursors. The substrate and position flexibility, as well as the function versatility of PhLOXs represent the ancient enzymatic pathway for organisms to control intracellular oxylipins.

  17. A Lipoxygenase from Red Alga Pyropia haitanensis, a Unique Enzyme Catalyzing the Free Radical Reactions of Polyunsaturated Fatty Acids with Triple Ethylenic Bonds

    PubMed Central

    Zhu, Zhujun; Qian, Feijian; Yang, Rui; Chen, Juanjuan; Luo, Qijun; Chen, Haimin; Yan, Xiaojun

    2015-01-01

    Lipoxygenases (LOXs) are key enzymes to regulate the production of hormones and defensive metabolites in plants, animals and algae. In this research, a full length LOX gene has been cloned and expressed from the red alga Pyropia haitanensis (Bangiales, Rhodophyta) gametophyte (PhLOX2). Subsequent phylogenetic analysis showed that such LOX enzymes are separated at the early stage of evolution, establishing an independent branch. The LOX activity was investigated at the optimal pH of 8.0. It appears that PhLOX2 is a multifunctional enzyme featuring both lipoxygenase and hydroperoxidase activities. Additionally, PhLOX2 exhibits remarkable substrate and position flexibility, and it can catalyze an array of chemical reactions involving various polyunsaturated fatty acids, ranging from C18 to C22. As a matter of fact, mono-hydroperoxy, di-hydroperoxy and hydroxyl products have been obtained from such transformations, and eicosapentaenoic acid seem to be the most preferred substrate. It was found that at least triple ethylenic bonds are required for PhLOX2 to function as a LOX, and the resulting hydroxy products should be originated from the PhLOX2 mediated reduction of mono-hydroperoxides, in which the hydrogen abstraction occurs on the carbon atom between the second and third double bond. Most of the di-hydroperoxides observed seem to be missing their mono-position precursors. The substrate and position flexibility, as well as the function versatility of PhLOXs represent the ancient enzymatic pathway for organisms to control intracellular oxylipins. PMID:25658744

  18. 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

  19. 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

  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. Targeting ERK1/2-bim signaling cascades by BH3-mimetic ABT-737 as an alternative therapeutic strategy for oral cancer.

    PubMed

    Shin, Ji-Ae; Kim, Lee-Han; Lee, Sook-Jeong; Jeong, Joseph H; Jung, Ji-Youn; Lee, Hae Nim; Hong, In-Sun; Cho, Sung-Dae

    2015-11-01

    To date, many different chemotherapeutic agents have been widely used as common treatments for oral cancers. However, their therapeutic effects have been disappointing, and these agents may have unwanted side effects. Among the many regulatory factors, overexpression of pro-survival Bcl-2 family members may promote resistance to chemotherapeutic drugs in many tumors. The BH3 domain-only proteins effectively antagonize their apoptotic activities. Therefore, there is substantial interest in developing chemotherapeutic drugs that directly target pro-survival Bcl-2 proteins by mimicking the BH3 domain and unleashing pro-apoptotic molecules in tumor cells. Among the numerous available small molecule BH3 mimetics, ABT-737, a potent small molecule that binds to Bcl-2/Bcl-xL with high affinity, has anti-tumor activity in a wide variety of cancer cells. However, the effects of ABT-737 on human oral cancers and the underlying molecular mechanisms have not previously been elucidated. In the present study, we observed that inactivation of the ERK1/2 signaling pathway using ABT-737 dramatically increased the expression of pro-apoptotic protein Bim via transcriptional and/or posttranslational regulation, in a cell type-dependent manner, inducing mitochondria-mediated apoptosis of human oral cancer cells. To the best of our knowledge, this is the first demonstration of the antitumor effects of ABT-737 on human oral cancers. PMID:26447615

  2. Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.

    PubMed

    Lenz, Robert A; Pritchett, Yili L; Berry, Scott M; Llano, Daniel A; Han, Shu; Berry, Donald A; Sadowsky, Carl H; Abi-Saab, Walid M; Saltarelli, Mario D

    2015-01-01

    ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

  3. 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…

  4. Radical formation in cytochrome c oxidase☆

    PubMed Central

    Yu, Michelle A.; Egawa, Tsuyoshi; Shinzawa-Itoh, Kyoko; Yoshikawa, Shinya; Yeh, Syun-Ru; Rousseau, Denis L.; Gerfen, Gary J.

    2015-01-01

    The formation of radicals in bovine cytochrome c oxidase (bCcO), during the O2 redox chemistry and proton translocation, is an unresolved controversial issue. To determine if radicals are formed in the catalytic reaction of bCcO under single turnover conditions, the reaction of O2 with the enzyme, reduced by either ascorbate or dithionite, was initiated in a custom-built rapid freeze quenching (RFQ) device and the products were trapped at 77 K at reaction times ranging from 50 µs to 6 ms. Additional samples were hand mixed to attain multiple turnover conditions and quenched with a reaction time of minutes. X-band (9 GHz) continuous wave electron paramagnetic resonance (CW-EPR) spectra of the reaction products revealed the formation of a narrow radical with both reductants. D-band (130 GHz) pulsed EPR spectra allowed for the determination of the g-tensor principal values and revealed that when ascorbate was used as the reductant the dominant radical species was localized on the ascorbyl moiety, and when dithionite was used as the reductant the radical was the SO2•− ion. When the contributions from the reductants are subtracted from the spectra, no evidence for a protein-based radical could be found in the reaction of O2 with reduced bCcO. As a surrogate for radicals formed on reaction intermediates, the reaction of hydrogen peroxide (H2O2) with oxidized bCcO was studied at pH 6 and pH 8 by trapping the products at 50 µs with the RFQ device to determine the initial reaction events. For comparison, radicals formed after several minutes of incubation were also examined, and X-band and D-band analysis led to the identification of radicals on Tyr-244 and Tyr-129. In the RFQ measurements, a peroxyl (R – O – O•) species was formed, presumably by the reaction between O2 and an amino acid-based radical. It is postulated that Tyr-129 may play a central role as a proton loading site during proton translocation by ejecting a proton upon formation of the radical

  5. 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

  6. Oxygen radicals stimulate guinea pig gallbladder glycoprotein secretion in vitro

    SciTech Connect

    Hale, W.B.; Turner, B.; LaMont, J.T. )

    1987-11-01

    In several animal models of cholelithiasis, and in humans with gallstones, hypersecretion of gallbladder mucin is observed. This study was undertaken to determine the effect of oxygen radicals on guinea pig gallbladder glycoprotein secretion in organ culture. Mucosal explants were incubated with ({sup 3}H)glucosamine hydrochloride to label glycoproteins, then exposed to oxygen radicals generated by chelated ferric iron and ascorbic acid. Marked stimulation of glycoprotein release was observed after a 30-min exposure to the oxygen radical-generating system, and the effect was inhibited by mannitol. The stimulatory effect of hydroxyl radical was not accompanied by leakage of intracellular lactate dehydrogenase. Parallel experiments with human granulocytes activated with f-Met-Leu-Phe and coincubated with gallbladder explants revealed similar results. These results indicate that oxygen radicals, especially the hydroxyl radical (OH), are capable of stimulating rapid release of mucous-type glycoproteins from gallbladder epithelium.

  7. 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

  8. Development of the radical-stable Coprinus cinereus peroxidase (CiP) by blocking the radical attack.

    PubMed

    Kim, Su Jin; Joo, Jeong Chan; Kim, Han Sang; Kwon, Inchan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

    2014-11-10

    Despite the potential use of peroxidases as industrial biocatalysts, their practical application is often impeded due to suicide inactivation by radicals generated in oxidative reactions. Using a peroxidase from Coprinus cinereus (CiP) as a model enzyme, we revealed a dominant factor for peroxidase inactivation during phenol oxidation, and we engineered radical-stable mutants by site-directed mutagenesis of an amino acid residue susceptible to modification by phenoxyl radical. Mass spectrometry analysis of inactivated CiP identified an adduct between F230 and a phenoxyl radical, and subsequently, the F230 residue was mutated to amino acids that resisted radical coupling. Of the F230 mutants, the F230A mutant showed the highest stability against radical inactivation, retaining 80% of its initial activity, while the wild-type protein was almost completely inactivated. The F230A mutant also exhibited a 16-fold higher turnover of the phenol substrate compared with the wild-type enzyme. Furthermore, the F230A mutant was stable during the oxidation of other phenolic compounds, including m-cresol and 3-methoxyphenol. No structural changes were observed by UV-vis and CD spectra of CiP after radical coupling, implying that the F230-phenol radical adduct inactivated CiP by blocking substrate access to the active site. Our novel strategy can be used to improve the stability of other peroxidases inactivated by radicals.

  9. 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.

  10. Free-radical reactions of glycerolipids and sphingolipids

    NASA Astrophysics Data System (ADS)

    Yurkova, I. L.

    2012-02-01

    Free-radical reactions of glycero- and sphingolipids occurring in their polar moiety (fragmentation) and in their hydrophobic residue (peroxidation) under the action of reactive oxygen species are considered. The main attention is focused on free-radical fragmentation; its mechanism and regularities are discussed. Lipid peroxidation has been shown to modify the residues of polyunsaturated fatty acids, while the free-radical fragmentation results in the cleavage of ester, O-glycosidic and amide bonds in lipid molecules to give glycerophosphatides, ceramides and fatty acid amides functioning as secondary messengers in biosystems. The bibliography includes 132 references.

  11. 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.

  12. 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…

  13. 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

  14. 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

    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

    2015-04-01

    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 PARP inhibition. We evaluated brain penetrance and efficacy of carboplatin ± the PARP inhibitor ABT888, and investigated gene-expression changes in murine intracranial TNBC models stratified by BRCA and molecular subtype status. Athymic mice were inoculated intracerebrally with BRCA-mutant: SUM149 (basal), MDA-MB-436 (claudin-low); or BRCA-wild-type (wt): MDA-MB-468 (basal), MDA-MB-231BR (claudin-low). TNBC cells were treated with PBS control [intraperitoneal (IP), weekly], carboplatin (50 mg/kg/wk, IP), ABT888 (25 mg/kg/d, oral gavage), or their combination. DNA damage (γ-H2AX), apoptosis (cleaved caspase-3, cC3), and gene expression were measured in intracranial tumors. Carboplatin ± ABT888 significantly improved survival in BRCA-mutant intracranial models compared with control, but did not improve survival in BRCA-wt intracranial 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 with control, whereas BRCA-wt 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 intracranial 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

  15. Petroleum films exposed to sunlight produce hydroxyl radical.

    PubMed

    Ray, Phoebe Z; Tarr, Matthew A

    2014-05-01

    Sunlight exposed oil films on seawater or pure water produced substantial amounts of hydroxyl radical as a result of irradiation. Oil was collected from the surface of the Gulf of Mexico following the Deepwater Horizon spill and exposed to simulated sunlight in thin films over water. Photochemical production of hydroxyl radical was measured with benzoic acid as a selective chemical probe in the aqueous layer. Total hydroxyl radical formation was studied using high benzoic acid concentrations and varying exposure time. The total amount of hydroxyl radical produced in 24 h irradiations of thin oil films over Gulf of Mexico water and pure water were 3.7×10(-7) and 4.2×10(-7) moles respectively. Steady state concentrations of hydroxyl radical were measured using a competition kinetics approach. Hydroxyl radical concentrations of 1.2×10(-16) to 2.4×10(-16) M were observed for seawater and pure water under oil films. Titanium dioxide (TiO2) nanomaterials were added to the system in an effort to determine if the photocatalyst would enhance oil photodegradation. The addition of TiO2 nanoparticles dramatically changed the observed formation rate of hydroxyl radical in the systems with NP water at pH 3, showing increased formation rate in many cases. With photocatalyst, the steady state concentration of radical decreased, predominantly due to an increase in the hydroxyl radical scavenging rate with oxide present. This study illustrates that oil is a strong and important source of hydroxyl radical when exposed to sunlight. The fate of oil and other dissolved species following oil spills will be heavily dependent on the formation and fate of hydroxyl radical.

  16. Petroleum films exposed to sunlight produce hydroxyl radical.

    PubMed

    Ray, Phoebe Z; Tarr, Matthew A

    2014-05-01

    Sunlight exposed oil films on seawater or pure water produced substantial amounts of hydroxyl radical as a result of irradiation. Oil was collected from the surface of the Gulf of Mexico following the Deepwater Horizon spill and exposed to simulated sunlight in thin films over water. Photochemical production of hydroxyl radical was measured with benzoic acid as a selective chemical probe in the aqueous layer. Total hydroxyl radical formation was studied using high benzoic acid concentrations and varying exposure time. The total amount of hydroxyl radical produced in 24 h irradiations of thin oil films over Gulf of Mexico water and pure water were 3.7×10(-7) and 4.2×10(-7) moles respectively. Steady state concentrations of hydroxyl radical were measured using a competition kinetics approach. Hydroxyl radical concentrations of 1.2×10(-16) to 2.4×10(-16) M were observed for seawater and pure water under oil films. Titanium dioxide (TiO2) nanomaterials were added to the system in an effort to determine if the photocatalyst would enhance oil photodegradation. The addition of TiO2 nanoparticles dramatically changed the observed formation rate of hydroxyl radical in the systems with NP water at pH 3, showing increased formation rate in many cases. With photocatalyst, the steady state concentration of radical decreased, predominantly due to an increase in the hydroxyl radical scavenging rate with oxide present. This study illustrates that oil is a strong and important source of hydroxyl radical when exposed to sunlight. The fate of oil and other dissolved species following oil spills will be heavily dependent on the formation and fate of hydroxyl radical. PMID:24405967

  17. High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition

    PubMed Central

    Bate-Eya, Laurel T.; den Hartog, Ilona J.M.; van der Ploeg, Ida; Schild, Linda; Koster, Jan; Santo, Evan E.; Westerhout, Ellen M.; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.; Dolman, M. Emmy M.

    2016-01-01

    The anti-apoptotic protein B cell lymphoma/leukaemia 2 (BCL-2) is highly expressed in neuroblastoma and plays an important role in oncogenesis. In this study, the selective BCL-2 inhibitor ABT199 was tested in a panel of neuroblastoma cell lines with diverse expression levels of BCL-2 and other BCL-2 family proteins. ABT199 caused apoptosis more potently in neuroblastoma cell lines expressing high BCL-2 and BIM/BCL-2 complex levels than low expressing cell lines. Effects on cell viability correlated with effects on BIM displacement from BCL-2 and cytochrome c release from the mitochondria. ABT199 treatment of mice with neuroblastoma tumors expressing high BCL-2 levels only resulted in growth inhibition, despite maximum BIM displacement from BCL-2 and the induction of a strong apoptotic response. We showed that neuroblastoma cells might survive ABT199 treatment due to its acute upregulation of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) and BIM sequestration by MCL-1. In vitro inhibition of MCL-1 sensitized neuroblastoma cell lines to ABT199, confirming the pivotal role of MCL-1 in ABT199 resistance. Our findings suggest that neuroblastoma patients with high BCL-2 and BIM/BCL-2 complex levels might benefit from combination treatment with ABT199 and compounds that inhibit MCL-1 expression. PMID:27056887

  18. 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

  19. 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.

  20. Effect of substituents on different channels of rad OH radical reaction with substituted organic sulfides

    NASA Astrophysics Data System (ADS)

    Mohan, Hari; Mittal, Jai P.

    2005-10-01

    Pulse radiolysis technique has been employed to study the nature of rad OH radical reaction in aqueous solutions of substituted organic sulfides. The transient absorption band at 345 nm observed on reaction of rad OH radicals in neutral aqueous solution of 3,3'-thiodipropionitrile is assigned to OH-adduct at sulfur. OH-adduct is observed to have high reactivity with oxygen ( k=8.8×10 8 dm 3 mol -1 s -1). The reaction of rad OH radicals in neutral aqueous solution of methyl propyl sulfide has shown the formation of sulfur-centered dimer radical cation with a small fraction (˜10%) of α-(alkylthio)alkyl radicals. The reaction of rad OH radicals with thiodiglycolic acid showed an absorption band at 285 nm, which is assigned to α -(alkylthio)alkyl radicals. The reaction of rad OH radicals with dimethyl 2,2'-thiodiethanoic acid has been assigned to OH-adduct at sulfur, whereas the transient absorption band at 390 observed with 3,3'-thiodipropionic acid is assigned to intra-molecular radical cation formed on p-orbital overlap of oxidized sulfur with oxygen. In acidic solutions, sulfur-centered dimer radical cation is the only transient species observed with substituted alkyl sulfides. The concentration of acid required to observe the formation of dimer radical cation is found to depend on the electron-withdrawing power of the substituted group. The reaction of rad OH radicals in neutral aqueous solution of substituted aryl sulfides has shown the formation of monomer radical cation and OH-adduct at benzene ring. Sulfur-centered dimer radical cations are not observed even in acidic conditions.

  1. Chemical constituents of two sages with free radical scavenging activity.

    PubMed

    Demirezer, Omur L; Gurbuz, Perihan; Kuruuzum-Uz, Ayşe; Guvenalp, Zuhal; Kazaz, Cavit; Donmez, Ali A

    2012-02-01

    From the aerial parts of Salvia trichoclada Bentham and S. verticillata L. one new and two known phenolic acids, 3-(3',4'-dihydroxyphenyl)-2-hydroxymethyl propionic acid (1), 3-(3',4'-dihydroxyphenyl) lactic acid (2), and rosmarinic acid (3); two flavonoids, apigenin 4'-methyl ether 7-O-glucuronide (4), and luteolin 7-O-beta glucuronide (5); two lupan type triterpene aglycones, lupeol (6), and 30-hydroxylup-20 (29)-en-3-on (7); an oleanane-type triterpene acid, oleanolic acid (8); and an ursan-type triterpene acid, ursolic acid (9) were isolated. The structures of the compounds were elucidated by spectroscopic analysis. Different extracts of the plants were examined for their free radical scavenging activities by DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Some of the polar extracts showed high free radical scavenging activity.

  2. 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.

  3. Coumestan inhibits radical-induced oxidation of DNA: is hydroxyl a necessary functional group?

    PubMed

    Xi, Gao-Lei; Liu, Zai-Qun

    2014-06-18

    Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(•+)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by (•)OH, Cu(2+)/glutathione (GSH), and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit (•)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit (•)OH- and Cu(2+)/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.

  4. 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

  5. Radical-based dephosphorylation and organophosphonate biodegradation

    SciTech Connect

    Frost, J.W.; Loo, S.; Cordeiro, M.L.; Li, D.

    1987-04-01

    Products resulting from the degradation of organophosphonates by Escherichia coli are identified and used as a basis for evaluating mechanisms which may be the chemical basis of the biodegradation. One mechanistic hypothesis which is consistent with the biodegradation products involves radical-based dephosphorylation. Chemical modeling of this process is achieved by the reaction of alkylphosphonic acids with lead(IV) tetraacetate and electrochemical oxidation at a platinum anode.

  6. Free radical scavenging abilities of polypeptide from Chlamys farreri

    NASA Astrophysics Data System (ADS)

    Han, Zhiwu; Chu, Xiao; Liu, Chengjuan; Wang, Yuejun; Mi, Sun; Wang, Chunbo

    2006-09-01

    We investigated the radical scavenging effect and antioxidation property of polypeptide extracted from Chlamys farreri (PCF) in vitro using chemiluminescence and electron spin resonance (ESR) methods. We examined the scavenging effects of PCF on superoxide anions (O{2/-}), hydroxyl radicals (OH·), peroxynitrite (ONOO-) and the inhibiting capacity of PCF on peroxidation of linoleic acid. Our experiment suggested that PCF could scavenge oxygen free radicals including superoxide anions (O{2/-}) (IC50=0.3 mg/ml), hydroxyl radicals (OH·) (IC50=0.2 μg/ml) generated from the reaction systems and effectively inhibit the oxidative activity of ONOO- (IC50=0.2 mg/ml). At 1.25 mg/ml of PCF, the inhibition ratio on lipid peroxidation of linoleic acid was 43%. The scavenging effect of PCF on O{2/-}, OH· and ONOO- free radicals were stronger than those of vitamin C but less on lipid peroxidation of linoleic acid. Thus PCF could scavenge free radicals and inhibit the peroxidation of linoleic acid in vitro. It is an antioxidant from marine products and potential for industrial production in future.

  7. 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

  8. 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.

  9. Trapping of neutral radicals by aromatic and heterocyclic cation radicals

    SciTech Connect

    Shine, H.J.; Soroka, M.

    1986-09-01

    A considerable amount of knowledge has been accrued during the last 15-20 years on the chemistry of polynuclear aromatic and heterocyclic cation radicals. For the most part, the reactions that have been studied have been of cation radicals with neutral and anionic nucleophiles which lead to addition or substitution products. Classic examples among these reactions are, for example, the reaction of water with the cation radical of 9,10-diphenylanthracene and perylene, and that of water with the thianthrene cation radical. Reactions such as these have been among foundation-establishing studies in the scope and mechanism of cation-radical reactions. Cation radicals can also undergo another type reaction with nucleophies, that is, electron transfer. This possibility leads to two far-reaching and connected questions: can addition and substitution reactions of aromatic cation radicals with nucleophiles be preceded by single electron transfer (SET).; and, can such cation radicals trap neutral radicals. These questions are also then related to another question having even greater impact on organic chemistry: can electrophilic aromatic substitution (ArH + E/sup +/ ..-->.. ArE + H/sup +/) be preceded by SET. The authors have been trying to answer the first two questions about SET and trapping of radicals by combining the two possibilities. That is, they have chosen the reaction of the thianthrene cation radical (represented by the symbol S/sup +./) with grignard reagents, for which two possible routes could be anticipated: either direct addition at sulfur or addition preceded by SET.

  10. 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.

  11. Radicalism, Marxism, and medicine.

    PubMed

    Navarro, V

    1983-01-01

    This article presents a critique of recent radical interpretations of medicine and provides an alternative explanation of such interpretations. It analyzes 1) the articulation of medical practices, knowledge, and institutions within specific modes of production and social formations; 2) the dual functions of medicine within capitalist relations of production; 3) the reproduction of power within medicine; and 4) the meaning of capitalist, socialist, and communist medicine. The political practice derived from these analyses is also elaborated.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. [Radical prostatectomy - pro robotic].

    PubMed

    Gillitzer, R

    2012-05-01

    Anatomical radical prostatectomy was introduced in the early 1980s by Walsh and Donker. Elucidation of key anatomical structures led to a significant reduction in the morbidity of this procedure. The strive to achieve similar oncological and functional results to this gold standard open procedure but with further reduction of morbidity through a minimally invasive access led to the establishment of laparoscopic prostatectomy. However, this procedure is complex and difficult and is associated with a long learning curve. The technical advantages of robotically assisted surgery coupled with the intuitive handling of the device led to increased precision and shortening of the learning curve. These main advantages, together with a massive internet presence and aggressive marketing, have resulted in a rapid dissemination of robotic radical prostatectomy and an increasing patient demand. However, superiority of robotic radical prostatectomy in comparison to the other surgical therapeutic options has not yet been proven on a scientific basis. Currently robotic-assisted surgery is an established technique and future technical improvements will certainly further define its role in urological surgery. In the end this technical innovation will have to be balanced against the very high purchase and running costs, which remain the main limitation of this technology.

  18. Silicon based radicals, radical ions, diradicals and diradicaloids.

    PubMed

    Chandra Mondal, Kartik; Roy, Sudipta; Roesky, Herbert W

    2016-02-21

    Radicals are an important class of species which act as intermediates in numerous chemical and biological processes. Most of the radicals have short lifetimes. However, radicals with longer lifetimes can be isolated and stored in a pure form. They are called stable radicals. Over the last five decades, the syntheses of several stable radicals have been reported. Recently, highly unstable radicals have been successfully stabilized via strong σ-donation of singlet carbenes. Cyclic aklyl(amino) carbene (cAAC) is regarded as a stronger σ-donor and a better π-acceptor when compared with that of an N-heterocyclic carbene (NHC). In this article we review preferentially the results of our group to generate stable radical centers on the carbene carbon atoms by employing the so far hidden and unique ability of the cAACs. We focus on the development of new synthetic routes to stable and isolable radicals containing silicon atoms. All the compounds have been well characterized by single crystal X-ray analysis; the mono-radicals have been distinguished by EPR spectroscpy and the ground state of the diradicals has been studied by magnetic susceptibility measurements and theoretical calculations. Many of these compounds are studied by cyclic voltammetry and are often converted to their corresponding radical cations or radical anions via electron abstraction or addition processes. Some of them are stable, having long lifetimes and hence are isolated and characterized thoroughly. Not much information has been obtained on the short lived persistent radical species. Herein, we discuss some of the examples of such a type of species and focus on what kind of chemical reactions are initiated by these short-lived radical species in solution. We also briefly mention the syntheses and charaterization of the so far reported stable silicon centered radicals. PMID:26585359

  19. Total phenolic contents and free-radical scavenging activities of grape (Vitis vinifera L.) and grape products.

    PubMed

    Keser, Serhat; Celik, Sait; Turkoglu, Semra

    2013-03-01

    Grape is one of the world's largest fruit crops, with an approximate annual production of 58 million metric tons, and it is well known that the grape skins, seeds and stems, waste products generated during wine and grape juice processing, are rich sources of polyphenols. It contains flavonoids, phenolic acids and stilbenes. In this study, we tried to determine antioxidant properties and phenolic contents of grape and grape products (fresh fruit, seed, dried fruit, molasses, pestil, vinegar) of ethanol and water extracts. Antioxidant properties of extracts were investigated by DPPH(√), ABTS(√+), superoxide, H(2)O(2) scavenging, reducing power, metal chelating activity and determination of total phenolic contents. The seed extracts revealed highest ABTS(√+), DPPH(√), H(2)O(2) scavenging and reducing power activities. Furthermore, these extracts showed higher total phenolic contents than other grape product extracts.

  20. 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

  1. 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

  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. 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

  4. Radical Cation/Radical Reactions: A Fourier Transform Ion Cyclotron Resonance Study of Allyl Radical Reacting with Aromatic Radical Cations

    PubMed Central

    Russell, Amber L.; Rohrs, Henry W.; Read, David; Giblin, Daryl E.; Gaspar, Peter P.; Gross, Michael L.

    2010-01-01

    A method for the study of reactions of open-shell neutrals (radicals) and radical cations is described. Pyrolysis (25–1500 °C) of thermally labile compounds, such as, 1,5-hexadiene via a Chen nozzle yields a seeded beam of reactive species in helium. The pyrolysis products are then analyzed by electron ionization (EI) or reacted with stored ions. Electron ionization of the pyrolysis products of 1,5-hexadiene shows that both the allyl radical and allene are generated. Reactions of benzene radical cations and the pyrolysis products of 1,5-hexadiene result in carbon-carbon bond formation. Those reactions of allyl radical with the benzene radical cation yield the C7H7+ ion of m/z 91, permitting an unusual entry into arenium ions. The reaction of allene with benzene radical cation in contrast yields C9H10+. and C9H9+. PMID:20401179

  5. New free radical scavenging neolignans from fruits of Piper attenuatum

    PubMed Central

    Reddy, S. Divya; Siva, Bandi; Poornima, B.; Kumar, D. Anand; Tiwari, Ashok K.; Ramesh, U.; Babu, K. Suresh

    2015-01-01

    Objective: The aim was to study and identify free radicals scavenging and antihyperglycemic principles in fruit of Piper attenuatum. Materials and Methods: Bioassay guided identification of extracts possessing potent free radical scavenging activity, and isolation of compounds was done. Chloroform extract of P. attenuatum possessing potent radical scavenging activity was also evaluated for antihyperglycemic activity following oral glucose tolerance test in rats. Results: Nine neolignans namely, denudatin B (1), iso-4’, 5’-dimethoxy-3, 4-methylenedioxy-2’-oxo-Δ3’,5’,8’-8.1’-lignan (2), lancifolin D (3), denudatin A (4), wallichinin (5), piperenone (6), lancifolin C (7), 2-oxo-piperol B (8), piperkadsin A (9) and a crotepoxide (10) was identified in Chloroform extract of P. attenuatum. Neolignans (1-9) displayed potent 2, 2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical and piperkadsin A (9) also displayed 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity. Analysis of structure-activity relationship revealed that presence of furan ring and methoxy groups is an important criterion to influence 2, 2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging potentials. Chloroform extract of P. attenuatum fruit could not display antihyperglycemic activity following oral glucose tolerance test in rats. Conclusion: Neolignans present in P. attenuatum fruits are potent free radical scavengers and this is the first report identifying these compounds and activities in this fruit. PMID:25829760

  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. Free radicals in primary photobiological processes.

    PubMed

    Vladimirov, Y A

    1998-01-01

    Formation of a semiquinone free radical derived from chlorophyll in the reaction of photoreduction has been discovered by A. A. Krasnovsky, Sr. in 1953. This review consider the results obtained in the author's laboratory, concerning the participation of free radicals in photochemical reactions under UV-irradiation of aromatic amino acids, proteins, and lipids, as well as in the reactions of chemiluminescence (CL) in the protein and chlorophyll-containing systems. Free radicals are the very first products of photochemical reactions in all systems studied. The back reactions of radicals are accompanied with photon emission. From the point of view of the molecular energetics, the radiativeless electronic transition in molecules is the most probable event, the transition triplet level is less probable, and the transition to the singlet excited level is virtually impossible. This may explain the low quantum yield of CL, similarity of CL and phosphorescence (rather than fluorescence) spectrum of the reaction products, low quantum yield of CL, and its high temperature coefficient.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. a Free Radical

    NASA Astrophysics Data System (ADS)

    Carrington, Alan

    2001-10-01

    This chapter describes my research career, spanning the period from 1955 to 2000. My initial PhD work at the University of Southampton was concerned with the electronic structure and spectra of transition metal complexes and included studies of the electronic spin resonance (ESR) spectra of magnetically dilute single crystals. After a year at the University of Minnesota, I went to Cambridge University and for the next six years studied the ESR spectra of liquid phase organic free radicals. I commenced work on the microwave magnetic resonance (MMR) spectra of gaseous free radicals in 1965, and this work continued until 1975. I moved from Cambridge to Southampton in 1967. In 1975 I turned to the study of gas phase molecular ions, using ion beam methods. In the earlier years of this period I concentrated on simple fundamental species like H+2, HD+, and H+3. In the later years until my retirement in 1999, I concentrated on the observation and analysis of microwave spectra involving energy levels lying very close to a dissociation asymptote. DEDICATION This chapter is dedicated to the memory of Harry E. Radford, who died while it was being written. Harry was a quiet and shy man, who often worked alone and never indulged in self-promotion. So far as I know, he was never awarded any medals or prizes, nor elected to any academies or learned societies. Nevertheless he was an experimentalist of the highest originality and quality, a theorist of true intellectual depth, and a remarkable pioneer in many of the techniques of studying free radicals that are now commonplace.

  13. Catalysis of Radical Reactions: A Radical Chemistry Perspective.

    PubMed

    Studer, Armido; Curran, Dennis P

    2016-01-01

    The area of catalysis of radical reactions has recently flourished. Various reaction conditions have been discovered and explained in terms of catalytic cycles. These cycles rarely stand alone as unique paths from substrates to products. Instead, most radical reactions have innate chains which form products without any catalyst. How do we know if a species added in "catalytic amounts" is a catalyst, an initiator, or something else? Herein we critically address both catalyst-free and catalytic radical reactions through the lens of radical chemistry. Basic principles of kinetics and thermodynamics are used to address problems of initiation, propagation, and inhibition of radical chains. The catalysis of radical reactions differs from other areas of catalysis. Whereas efficient innate chain reactions are difficult to catalyze because individual steps are fast, both inefficient chain processes and non-chain processes afford diverse opportunities for catalysis, as illustrated with selected examples.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. [Initiation and inhibition of free-radical processes in biochemical peroxidase systems: a review].

    PubMed

    Metelitsa, D I; Karaseva, E I

    2007-01-01

    The role of complexes containing oxygen or peroxide in monooxygenase systems and models thereof, as well as in peroxidase- and quasi-peroxidase-catalyzed processes, has been reviewed. Pathways of conversion of these intermediate complexes involving single-electron (radical) and two-electron (heterolytic) mechanisms are dealt with. Coupled peroxidase-catalyzed oxidation of aromatic amines and phenols is analyzed; inhibition and activation of peroxidase-catalyzed reactions are characterized quantitatively. Oxidation of chromogenic substrates (ABTS, OPD, and TMB) in the presence of phenolic inhibitors or polydisulfides of substituted phenols is characterized by inhibition constants (Ki, micromol). Activation of peroxidase-catalyzed oxidation of the same substrates is characterized by the degree (coefficient) of activation (alpha, M(-1)), which was determined for 2-aminothiazole, melamine, tetrazole, and its 5-substituted derivatives. Examples of applied use of peroxidase-catalyzed enzyme and model systems are given (oxidation of organic compounds, chemical analysis, enzyme immunoassay, tests for antioxidant activity of biological fluids).

  19. Complications Following Radical Nephroureterectomy.

    PubMed

    Raman, Jay D; Jafri, Syed M

    2016-05-01

    Radical nephroureterectomy (RNU) is the gold standard treatment strategy for bulky, high-grade, or muscle-invasive upper tract urothelial carcinoma (UTUC). Many patients with UTUC who require RNU are elderly, comorbid, and at risk for perioperative complications. Recognition of likelihood and extent of such complications guides preoperative counseling, decision-making process for major surgery, and perioperative care. A critical review of such data is essential, given the inevitable impact of complications on hospital duration, need for readmission, resource utilization, and costs associated with management. PMID:26968416

  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. 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.

  2. 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

  3. 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

  4. Bursectomy at radical gastrectomy

    PubMed Central

    Kayaalp, Cuneyt

    2015-01-01

    Radical gastrectomy with extended lymph node dissection and prophylactic resection of the omentum, peritoneum over the posterior lesser sac, pancreas and/or spleen was advocated at the beginning of the 1960s in Japan. In time, prophylactic routine resections of the pancreas and/or spleen were abandoned because of the high incidence of postoperative complications. However, omentectomy and bursectomy continued to be standard parts of traditional radical gastrectomy. The bursa omentalis was thought to be a natural barrier against invasion of cancer cells into the posterior part of the stomach. The theoretical rationale for bursectomy was to reduce the risk of peritoneal recurrences by eliminating the peritoneum over the lesser sac, which might include free cancer cells or micrometastases. Over time, the indication for bursectomy was gradually reduced to only patients with posterior gastric wall tumors penetrating the serosa. Despite its theoretical advantages, its benefit for recurrence or survival has not been proven yet. The possible reasons for this inconsistency are discussed in this review. In conclusion, the value of bursectomy in the treatment of gastric cancer is still under debate and large-scale randomized studies are necessary. Until clear evidence of patient benefit is obtained, its routine use cannot be recommended. PMID:26523213

  5. Bursectomy at radical gastrectomy.

    PubMed

    Kayaalp, Cuneyt

    2015-10-27

    Radical gastrectomy with extended lymph node dissection and prophylactic resection of the omentum, peritoneum over the posterior lesser sac, pancreas and/or spleen was advocated at the beginning of the 1960s in Japan. In time, prophylactic routine resections of the pancreas and/or spleen were abandoned because of the high incidence of postoperative complications. However, omentectomy and bursectomy continued to be standard parts of traditional radical gastrectomy. The bursa omentalis was thought to be a natural barrier against invasion of cancer cells into the posterior part of the stomach. The theoretical rationale for bursectomy was to reduce the risk of peritoneal recurrences by eliminating the peritoneum over the lesser sac, which might include free cancer cells or micrometastases. Over time, the indication for bursectomy was gradually reduced to only patients with posterior gastric wall tumors penetrating the serosa. Despite its theoretical advantages, its benefit for recurrence or survival has not been proven yet. The possible reasons for this inconsistency are discussed in this review. In conclusion, the value of bursectomy in the treatment of gastric cancer is still under debate and large-scale randomized studies are necessary. Until clear evidence of patient benefit is obtained, its routine use cannot be recommended. PMID:26523213

  6. 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.

  7. 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

  8. Radicals in flavoproteins.

    PubMed

    Schleicher, Erik; Weber, Stefan

    2012-01-01

    Current technical and methodical advances in electron paramagnetic resonance (EPR) spectroscopy have proven to be very beneficial for studies of stationary and short-lived paramagnetic states in proteins carrying organic cofactors. In particular, the large number of proteins with flavins as prosthetic groups can be examined splendidly by EPR in all its flavors. To understand how a flavin molecule can be fine-tuned for specific catalysis of different reactions, understanding of its electronic structure mediated by subtle protein-cofactor interactions is of utmost importance. The focus of this chapter is the description of recent research progress from our laboratory on EPR of photoactive flavoproteins. These catalyze a wide variety of important photobiological processes ranging from enzymatic DNA repair to plant phototropism and animal magnetoreception. Whereas increasing structural information on the principal architecture of photoactive flavoproteins is available to date, their primary photochemistry is still largely undetermined. Interestingly, although these proteins carry the same light-active flavin chromophore, their light-driven reactions differ significantly: Formations of photoexcited triplet states and short-lived radical pairs starting out from triplet or singlet-state precursors, as well as generation of stationary radicals have been reported recently. EPR spectroscopy is the method of choice to characterize such paramagnetic intermediates, and hence, to assist in unravelling the mechanisms of these inimitable proteins.

  9. 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

  10. Protonation of water clusters induced by hydroperoxyl radical surface adsorption.

    PubMed

    Torrent-Sucarrat, Miquel; Ruiz-Lopez, Manuel F; Martins-Costa, Marilia; Francisco, Joseph S; Anglada, Josep M

    2011-04-26

    We have investigated the HO(2) adsorption and acid dissociation process on the surface of (H(2)O)(20) and (H(2)O)(21) clusters by using quantum-chemistry calculations. Our results show that the radical forms a stable hydrogen-bond complex on the cluster. The HO(2) acid dissociation is more favorable in the case of the (H(2)O)(21) cluster, for which the inner water molecule plays a crucial role. In fact, acid dissociation of HO(2) is found to occur in two steps. The first step involves H(2) O autoionization in the cluster, and the second one involves the proton transfer from the HO(2) radical to the hydroxide anion. The presence of the HO(2) radicals on the surface of the cluster facilitates water autoionization in the cluster. PMID:21433120

  11. Vertically resolved measurements of nighttime radical reservoirs in Los Angeles and their contribution to the urban radical budget.

    PubMed

    Young, Cora J; Washenfelder, Rebecca A; Roberts, James M; Mielke, Levi H; Osthoff, Hans D; Tsai, Catalina; Pikelnaya, Olga; Stutz, Jochen; Veres, Patrick R; Cochran, Anthony K; VandenBoer, Trevor C; Flynn, James; Grossberg, Nicole; Haman, Christine L; Lefer, Barry; Stark, Harald; Graus, Martin; de Gouw, Joost; Gilman, Jessica B; Kuster, William C; Brown, Steven S

    2012-10-16

    Photolabile nighttime radical reservoirs, such as nitrous acid (HONO) and nitryl chloride (ClNO(2)), contribute to the oxidizing potential of the atmosphere, particularly in early morning. We present the first vertically resolved measurements of ClNO(2), together with vertically resolved measurements of HONO. These measurements were acquired during the California Nexus (CalNex) campaign in the Los Angeles basin in spring 2010. Average profiles of ClNO(2) exhibited no significant dependence on height within the boundary layer and residual layer, although individual vertical profiles did show variability. By contrast, nitrous acid was strongly enhanced near the ground surface with much smaller concentrations aloft. These observations are consistent with a ClNO(2) source from aerosol uptake of N(2)O(5) throughout the boundary layer and a HONO source from dry deposition of NO(2) to the ground surface and subsequent chemical conversion. At ground level, daytime radical formation calculated from nighttime-accumulated HONO and ClNO(2) was approximately equal. Incorporating the different vertical distributions by integrating through the boundary and residual layers demonstrated that nighttime-accumulated ClNO(2) produced nine times as many radicals as nighttime-accumulated HONO. A comprehensive radical budget at ground level demonstrated that nighttime radical reservoirs accounted for 8% of total radicals formed and that they were the dominant radical source between sunrise and 09:00 Pacific daylight time (PDT). These data show that vertical gradients of radical precursors should be taken into account in radical budgets, particularly with respect to HONO.

  12. Antimutagenic and free radical scavenger effects of leaf extracts from Accacia salicina

    PubMed Central

    2011-01-01

    Background Three extracts were prepared from the leaves of Accacia salicina; ethyl acetate (EA), chloroform (Chl) and petroleum ether (PE) extracts and was designed to examine antimutagenic, antioxidant potenty and oxidative DNA damage protecting activity. Methods Antioxidant activity of A. salicina extracts was determined by the ability of each extract to protect against plasmid DNA strand scission induced by hydroxyl radicals. An assay for the ability of these extracts to prevent mutations induced by various oxidants in Salmonella typhimurium TA102 and TA 104 strains was conducted. In addition, nonenzymatic methods were employed to evaluate anti-oxidative effects of tested extracts. Results These extracts from leaf parts of A. salicina showed no mutagenicity either with or without the metabolic enzyme preparation (S9). The highest protections against methylmethanesulfonate induced mutagenicity were observed with all extracts and especially chloroform extract. This extract exhibited the highest inhibitiory level of the Ames response induced by the indirect mutagen 2- aminoanthracene. All extracts exhibited the highest ability to protect plasmid DNA against hydroxyl radicals induced DNA damages. The ethyl acetate (EA) and chloroform (Chl) extracts showed with high TEAC values radical of 0.95 and 0.81 mM respectively, against the ABTS.+. Conclusion The present study revealed the antimutagenic and antioxidant potenty of plant extract from Accacia salicina leaves. PMID:22132863

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Theoretical studies on the coupling interactions in H2SO4···HOO˙···(H2O)n (n = 0-2) clusters: toward understanding the role of water molecules in the uptake of HOO˙ radical by sulfuric acid aerosols.

    PubMed

    Li, Ping; Ma, Zhiying; Wang, Weihua; Zhai, Yazhou; Sun, Haitao; Bi, Siwei; Bu, Yuxiang

    2011-01-21

    A detailed knowledge of coupling interactions among sulfuric acid (H(2)SO(4)), the hydroperoxyl radical (HOO˙), and water molecules (H(2)O) is crucial for the better understanding of the uptake of HOO˙ radicals by sulfuric acid aerosols at different atmospheric humidities. In the present study, the equilibrium structures, binding energies, equilibrium distributions, and the nature of the coupling interactions in H(2)SO(4)···HOO˙···(H(2)O)(n) (n = 0-2) clusters have been systematically investigated at the B3LYP/6-311++G(3df,3pd) level of theory in combination with the atoms in molecules (AIM) theory, natural bond orbital (NBO) method, energy decomposition analyses, and ab initio molecular dynamics. Two binary, five ternary, and twelve tetramer clusters possessing multiple intermolecular H-bonds have been located on their potential energy surfaces. Two different modes for water molecules have been observed to influence the coupling interactions between H(2)SO(4) and HOO˙ through the formations of intermolecular H-bonds with or without breaking the original intermolecular H-bonds in the binary H(2)SO(4)···HOO˙ cluster. It was found that the introduction of one or two water molecules can efficiently enhance the interactions between H(2)SO(4) and HOO˙, implying the positive role of water molecules in the uptake of the HOO˙ radical by sulfuric acid aerosols. Additionally, the coupling interaction modes of the most stable clusters under study have been verified by the ab initio molecular dynamics. PMID:21052607

  19. [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.

  20. [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

  1. ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.

    PubMed

    Shiosaki, K; Jenner, P; Asin, K E; Britton, D R; Lin, C W; Michaelides, M; Smith, L; Bianchi, B; Didomenico, S; Hodges, L; Hong, Y; Mahan, L; Mikusa, J; Miller, T; Nikkel, A; Stashko, M; Witte, D; Williams, M

    1996-01-01

    (-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which

  2. Hydroxyl radical scavenging reactivity of proton pump inhibitors.

    PubMed

    Simon, Wolfgang Alexander; Sturm, Ernst; Hartmann, Hans-Jürgen; Weser, Ulrich

    2006-04-28

    In addition to the established control of acid secretion of the class of proton pump inhibitors (PPI) reactivity from the pyridyl methyl sulphinyl benzimidazole type a second independent anti-inflammatory reactivity was observed in vitro. This inhibitory reactivity was clearly noticed using three different assays where the aggressive hydroxyl radicals were successfully trapped in a concentration dependent manner. There is unequivocal evidence that the proton pump inhibitors having the sulphoxide group are able to scavenge hydroxyl radicals which are generated during a Fenton reaction. By way of contrast, the corresponding thioethers were substantially less active. No detectable effect was seen in the superoxide radical scavenging system. In conclusion, pantoprazole as well as the other proton pump inhibitors have a pronounced inhibitory reactivity towards hydroxyl radicals.

  3. Hydrazyl-nitrones, novel hybrid molecules in free radical research.

    PubMed

    Ionita, Petre

    2006-01-01

    This work describes the synthesis and characterisation of some novel hybrid molecules which contains in the same molecule a free radical moiety of hydrazyl type and a spin-trap moiety of nitrone type. The new compounds synthesized have multiple and easy to follow spectroscopic properties, making them useful as sensors or probes in radical chemistry. The new class of hydrazyl-nitrone molecules can act, in a single step process, as both generator and spin-trap of short-lived radicals. The hybrid molecules can be also involved in acid-base or redox processes, and the chemical processes can be easily monitored by visible or electron paramagnetic resonance spectroscopy. The excellent generator and trap properties recommend them as valuable sensors and probes in radical chemistry.

  4. Spectroscopic characterization of radicals and radical pairs in fruit fly cryptochrome - protonated and nonprotonated flavin radical-states.

    PubMed

    Paulus, Bernd; Bajzath, Csaba; Melin, Frédéric; Heidinger, Lorenz; Kromm, Viktoria; Herkersdorf, Christoph; Benz, Ulrike; Mann, Lisa; Stehle, Patricia; Hellwig, Petra; Weber, Stefan; Schleicher, Erik

    2015-08-01

    Drosophila melanogaster cryptochrome is one of the model proteins for animal blue-light photoreceptors. Using time-resolved and steady-state optical spectroscopy, we studied the mechanism of light-induced radical-pair formation and decay, and the photoreduction of the FAD cofactor. Exact kinetics on a microsecond to minutes timescale could be extracted for the wild-type protein using global analysis. The wild-type exhibits a fast photoreduction reaction from the oxidized FAD to the FAD(•-) state with a very positive midpoint potential of ~ +125 mV, although no further reduction could be observed. We could also demonstrate that the terminal tryptophan of the conserved triad, W342, is directly involved in electron transfer; however, photoreduction could not be completely inhibited in a W342F mutant. The investigation of another mutation close to the FAD cofactor, C416N, rather unexpectedly reveals accumulation of a protonated flavin radical on a timescale of several seconds. The obtained data are critically discussed with the ones obtained from another protein, Escherichia coli photolyase, and we conclude that the amino acid opposite N(5) of the isoalloxazine moiety of FAD is able to (de)stabilize the protonated FAD radical but not to significantly modulate the kinetics of any light-inducted reactions.

  5. Total synthesis of cephalosporolide E via a tandem radical/polar crossover reaction. The use of the radical cations under nonoxidative conditions in total synthesis.

    PubMed

    Cortezano-Arellano, Omar; Quintero, Leticia; Sartillo-Piscil, Fernando

    2015-03-01

    The present work reports the first example of the use of the chemistry of radical cations under nonoxidative conditions in total synthesis. Using a late-stage tandem radical/polar crossover reaction, a highly stereoselective total synthesis of cephalosporolide E (which is typically obtained admixed with cephalosporolide F) was accomplished. The reaction of a phthalimido derivative with triphenyltin radical in refluxing toluene engenders a contact ion-pair (radical cation) that leads, in the first instance, to the cephalosporolide F, which is transformed into the cephalosporolide E via a stereocontrolled spiroketal isomerization promoted by the diphenylphosphate acid that is formed during the tandem transformation.

  6. Time-resolved CIDNP: an NMR way to determine the EPR parameters of elusive radicals.

    PubMed

    Morozova, Olga B; Ivanov, Konstantin L; Kiryutin, Alexey S; Sagdeev, Renad Z; Köchling, Talea; Vieth, Hans-Martin; Yurkovskaya, Alexandra V

    2011-04-14

    Chemically Induced Dynamic Nuclear Polarization (CIDNP) of the diamagnetic products of radical reactions is exploited for the purpose of determination of the hyperfine coupling constants (HFCCs) of the radical intermediates. A simple proportionality relation between geminate CIDNP of a nucleus and its HFCC at the radical stage is established. The applicability range of this relation is determined: the relation is fulfilled in the case of a large difference in g-factor between the radicals involved and for the situation where the number of magnetic nuclei in the system is sufficiently large. The validity of the relation was confirmed by CIDNP experiments on radical pairs with precisely known HFCCs. Using the proportionality relation we were able to measure the HFCCs in various short-lived radicals of the amino acids histidine and tryptophan and of the S-N-centered cyclic radical of methionine derived from the methionine-glycine dipeptide in aqueous solution.

  7. ESR evidence for radical production from the reaction of ozone with unsaturated lipids

    SciTech Connect

    Church, D.F.; McAdams, M.L..; Pryor, W.A. )

    1991-03-15

    The authors report electron spin resonance (ESR) spin trapping evidence for radical production by the reaction of ozone with unsaturated compounds. Soy and egg phosphatidylcholine liposomes, fatty acid emulsions, and homogeneous aqueous solutions of 3-hexenoic acid were treated with ozone in the presence of the spin trap {alpha}-phenyl-N-tert-butyl nitrone (PBN). Under these conditions, they observe spin adducts resulting from the trapping of both organic carbon- and oxygen-centered radicals. When the lipid-soluble antioxidant alpha-tocopherol is included in the liposomal systems, the formation of spin adducts is completely inhibited. The authors suggest that radicals giving rise to these spin adducts arise form the rapid decomposition of the 1,2,3-trioxolane intermediate that is initially formed when ozone reacts with the carbon-carbon double bonds of the substrates. These free radicals are not formed by the decomposition of the Criegee ozonide, since little of the ozonide is formed in the presence of water. Although hydrogen peroxide is the predominate peroxidic product of the ozone/alkene reaction, its decomposition is not responsible for the observed radical production since neither catalase nor iron chelators significantly affect the spin adduct yield. The radical yield is approximately 1%. Since a polyunsaturated fatty acid (PUFA) such as linoleic acid produces much higher concentrations of spin trappable radicals than does the monounsaturated fatty oleic acid, the results also suggest that sites in the lung containing higher levels of PUFA may be an important target for radical formation.

  8. Studies of radiation-produced radicals and radical ions

    SciTech Connect

    Williams, T.F.

    1991-01-01

    The radiolytic oxidation of anti-5-methylbicyclo(2.1.0)pentane gives the 1-methylcyclopentene radical cation as the sole rearrangement product H migration whereas oxidation of its syn isomer results in the highly selective formation of the 3-methylcyclopentene radical cation by methyl group migration. Since exactly the same stereoselectivity of olefin formation was observed in corresponding PET (photosensitized electron transfer) studies in the liquid phase, it is concluded that the rearrangement in this case also occurs through the intermediacy of radical cations. Clearly, the radical cation rearrangement must occur very rapidly (10{sup {minus}8}--10{sup {minus}9}s) under liquid-phase conditions at room temperature to compete with back electron transfer, and therefore the hydrogen (or methyl) migration is a fast process under these conditions. An intramolecular cycloaddition reaction was demonstrated in the radical cation rearrangement of 4-vinylcyclohexene to bicyclo(3.2.1)oct-2-ene. ESR studies show that the radiolytic oxidation of quadricyclane in Freon matrices under conditions of high substrate dilution leads to the bicyclo(3.2.0)hepta-2,6-diene radical cation as well as the previously reported norbornadiene radical cation, the former species predominating at sufficiently low concentrations.

  9. 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.

  10. Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit (Myrciaria dubia).

    PubMed

    Fracassetti, Daniela; Costa, Carlos; Moulay, Leila; Tomás-Barberán, Francisco A

    2013-08-15

    The aims of this study were the evaluation of polyphenols and vitamin C content, and antioxidant capacity of dehydrated pulp powder and the dried flour obtained from the skin and seeds residue remaining after pulp preparation from camu-camu (Myrciaria dudia). Fifty-three different phenolics were characterised by HPLC-DAD-ESI-MS-MS and UPLC-HR-QTOF-MS-MS. The phenolic content of camu-camu flour was higher than that of the pulp powder (4007.95 mg/100 g vs. 48.54 mg/100 g). In both products the flavonol myricetin and conjugates, ellagic acid and conjugates and ellagitannins were detected. Cyanidin 3-glucoside, and quercetin and its glycosides were only found in the pulp powder, while proanthocyanidins were only present in the flour (3.5 g/100 g, mean degree of polymerisation 3). The vitamin C content was lower in pulp powder (3.5%) than in the flour (9.1%). The radical-scavenging capacity of both powders was determined by the DPPH, ABTS and ORAC assays, and was higher for camu-camu flour as could be expected for its higher phenolics and vitamin C content. Comparative analyses with fresh camu-camu berries indicate that some transformations occur during processing. Analysis of fresh berries showed that ellagic acid derivatives and ellagitannins were mainly present in the seeds, while proanthocyanidins were present both in the seeds and skin. PMID:23561148

  11. Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit (Myrciaria dubia).

    PubMed

    Fracassetti, Daniela; Costa, Carlos; Moulay, Leila; Tomás-Barberán, Francisco A

    2013-08-15

    The aims of this study were the evaluation of polyphenols and vitamin C content, and antioxidant capacity of dehydrated pulp powder and the dried flour obtained from the skin and seeds residue remaining after pulp preparation from camu-camu (Myrciaria dudia). Fifty-three different phenolics were characterised by HPLC-DAD-ESI-MS-MS and UPLC-HR-QTOF-MS-MS. The phenolic content of camu-camu flour was higher than that of the pulp powder (4007.95 mg/100 g vs. 48.54 mg/100 g). In both products the flavonol myricetin and conjugates, ellagic acid and conjugates and ellagitannins were detected. Cyanidin 3-glucoside, and quercetin and its glycosides were only found in the pulp powder, while proanthocyanidins were only present in the flour (3.5 g/100 g, mean degree of polymerisation 3). The vitamin C content was lower in pulp powder (3.5%) than in the flour (9.1%). The radical-scavenging capacity of both powders was determined by the DPPH, ABTS and ORAC assays, and was higher for camu-camu flour as could be expected for its higher phenolics and vitamin C content. Comparative analyses with fresh camu-camu berries indicate that some transformations occur during processing. Analysis of fresh berries showed that ellagic acid derivatives and ellagitannins were mainly present in the seeds, while proanthocyanidins were present both in the seeds and skin.

  12. 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