Article
Nitrones as therapeutics.
Experimental Therapeutics Research Program, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Free Radical Biology and Medicine (impact factor:
5.42).
09/2008;
45(10):1361-74.
DOI:10.1016/j.freeradbiomed.2008.08.017
pp.1361-74
Source: PubMed
-
Article: Immuno-spin trapping of DNA radicals.
[show abstract] [hide abstract]
ABSTRACT: The detection of DNA radicals by immuno-spin trapping (IST) is based on the trapping of radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), forming stable nitrone adducts that are then detected using an anti-DMPO serum. DNA radicals are very reactive species, and because they are paramagnetic they have previously been detected only by electron spin resonance (ESR) with or without spin trapping, which is not available in most bioresearch laboratories. IST combines the simplicity, reliability, specificity and sensitivity of spin trapping with heterogeneous immunoassays for the detection of DNA radicals, and complements existing methods for the measurement of oxidatively generated DNA damage. Here we have used IST to demonstrate that DMPO traps Cu(II)-H(2)O(2)-induced DNA radicals in situ and in real time, forming DMPO-DNA nitrone adducts, but preventing both 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation and DNA fragmentation. We also applied IST to detect DNA radicals in rat hepatocytes exposed to Cu(II) and H(2)O(2) under nonlethal conditions.Nature Methods 03/2006; 3(2):123-7. · 19.28 Impact Factor -
Article: ESR spin-trapping studies on the reaction of Fe2+ ions with H2O2-reactive species in oxygen toxicity in biology.
[show abstract] [hide abstract]
ABSTRACT: Using ESR spin-trapping techniques with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), we confirmed the 1:1 stoichiometry for the formation of hydroxyl radicals with Fe2+ in the Fenton reaction under experimental conditions wherein [H2O2] is 90 microM and [Fe2+] is very low, 1 microM or less. The stoichiometry decreased markedly as the Fe2+ concentration was increased. The efficiency of hydroxyl radical generation varied with the nature of the iron chelators used and increased in the order of phosphate alone approximately ADP less than EDTA less than diethylenetriaminepentaacetic acid (DETAPAC). The second order rate constant for the Fenton reaction was measured to be 2.0 x 10(4) M-1 s-1 for phosphate alone, 8.2 x 10(3) M-1 s-1 for ADP, 1.4 x 10(4) M-1 s-1 for EDTA, and 4.1 x 10(2) M-1 s-1 for DETAPAC. Measuring the radicals formed as spins trapped in the presence of ethanol, we estimated the amount of total oxidizing intermediates formed in the Fenton reaction, which we concluded consists of hydroxyl radicals and an iron species. The oxidizing species of iron which might be assigned as ferryl, FeO2+, or Fe(IV) = O was generated effectively in the presence of ADP even at low Fe2+ concentrations. In general, as the Fe2+ concentration was increased, the ferryl species predominated over the hydroxyl radical except for the case of Fe(II)-DETAPAC, which generated only hydroxyl radicals as the oxidizing species. Three possible pathways are proposed for the Fenton reaction, the dominant ones depending very much on the nature of the iron chelator being used.Journal of Biological Chemistry 09/1990; 265(23):13589-94. · 4.77 Impact Factor -
Article: A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma.
[show abstract] [hide abstract]
ABSTRACT: Free radical and calcium buffering mechanisms are implicated in cochlear cell damage that has been induced by sound trauma. Thus in this study we evaluated the therapeutic effect of a novel dual inhibitor of calpains and of lipid peroxidation (BN 82270) on the permanent hearing and hair cell loss induced by sound trauma. Perfusion of BN 82270 into the scala tympani of the guinea pig cochlea prevented the formation of calpain-cleaved fodrin, translocation of cytochrome c, DNA fragmentation and hair cell degeneration caused by sound trauma. This was confirmed by functional tests in vivo, showing a clear dose-dependent reduction of permanent hearing loss (ED50 = 4.07 microM) with almost complete protection at 100 microM. Furthermore, BN82270 still remained effective even when applied onto the round window membrane after sound trauma had occurred, within a therapeutic window of 24 h. This indicates that BN 82270 may be of potential therapeutic value in treating the cochlea after sound trauma.Neuropharmacology 06/2007; 52(6):1426-37. · 4.81 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed.
The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual
current impact factor.
Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence
agreement may be applicable.
Keywords
acute acoustic-noise-induced hearing loss
biochemical systems
cellular processes
cellular signaling processes
chemical systems
conventional notions
experimental animal models
experimental cancer models
experimental models
extensive commercial development
free radical biochemical
free radical trapping biochemistry
free radicals
nitrones
pathologic conditions
PBN-related nitrones
potent biological activity
potent biological anti-inflammatory activity
recent observations nitrones
trap free radicals
