3-nitrotyrosine and 2-2--azino-di-(3-ethylbenzothiazoline)-6-sulfonic-acid

Myasthenia gravis (MG) is an autoimmune disease caused by production of antibodies against acetylcholine receptors of the neuromuscular junction (Ab). The aim of this study was to ascertain if oxidative stress accompanies MG by estimation of the several independent parameters of oxidative damage, mainly the levels of oxidative modifications of blood serum proteins. The group studied consisted of 50 MG patients (28 females and 22 males), 24 with ocular MG (OMG) and 26 with generalized MG (GMG), of mean age of 66.7 (30-81)years (y), mean disease duration of 9.5 (0.5-34)y, mean level of Ab of 8.9 (0.1-85)nmol/ml, and 25 age-matched healthy controls. MG patients were stratified into groups according to disease duration (<5y or >5y), Ab level (low, <3 or high, >3nmol/l) as well as symptoms (GMG or OMG). Glycophore fluorescence was increased in OMG

Topics: Adult; Advanced Oxidation Protein Products; Aged; Aged, 80 and over; Autoantibodies; Benzothiazoles; Blood Proteins; Disease Progression; Female; Glycophorins; Humans; Kynurenine; Male; Middle Aged; Myasthenia Gravis; Oxidative Stress; Protein Carbonylation; Receptors, Cholinergic; Sulfonic Acids; Thymectomy; Tyrosine

Stable hydrophilic C60(OH)10 nanoparticles were prepared from 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and applied to the treatment of an acetaminophen overdose induced liver Injury. C60(OH)10 nanoparticles were produced by cogrinding α-CD, β-CD, γ-CD and HP-β-CD and characterized in terms of solubility, mean particle diameter, ζ-potential and long term dispersibility in water. Hydrophilic C60(OH)10 nanoparticles with particle sizes less than 50 nm were effectively produced by cogrinding HP-β-CD with C60(OH)10 at a molar ratio of 1:3 (C60(OH)10:CD). The resulting C60(OH)10/HP-β-CD nanoparticles were stable in water and showed no aggregation over a 1 month period. The C60(OH)10/CDs nanoparticles scavenged not only free radicals (DPPH and ABTS radicals) but also reactive oxygen species (O2(•-) and •OH). When C60(OH)10/HP-β-CD nanoparticles were intraperitoneally administered to mice with a liver injury induced by an overdose of acetaminophen (APAP), the ALT and AST levels were markedly reduced to almost the same level as that for normal mice. Furthermore, the administration of the nanoparticles prolonged the survival rate of liver injured mice, while all of the mice that were treated with APAP died within 40 h. To reveal the mechanism responsible for liver protection by C60(OH)10 nanoparticles, GSH level, CYP2E1 expression and peroxynitrite formation in the liver were assessed. C60(OH)10/HP-β-CD nanoparticles had no effect on CYP2E1 expression and GSH depletion, but suppressed the generation of peroxynitrite in the liver. The findings indicate that the protective effect of C60(OH)10/HP-β-CD nanoparticles was due to the suppression of oxidative stress in mitochondria, as the result of scavenging ROS such as O2(•-), NO and peroxynitrite, which act as critical mediators in the liver injuries.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetaminophen; Animals; Antioxidants; Benzothiazoles; beta-Cyclodextrins; Biphenyl Compounds; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2E1; Drug Overdose; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Fullerenes; Glutathione; Hydrophobic and Hydrophilic Interactions; Hydroxylation; Liver; Male; Mice, Inbred C57BL; Nanoparticles; Nitric Oxide; Oxidative Stress; Particle Size; Peroxynitrous Acid; Picrates; Protective Agents; Solubility; Static Electricity; Sulfonic Acids; Tyrosine

There is considerable interest in the isolation of more potent antioxidant compounds to treat diseases involving oxidative stress. Thirty-three traditional Chinese medicine (TCM) extracts were examined for their antioxidant activity using the 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonate] (ABTS) assay. Five extracts with high activity (Cratoxylum cochinchinense, Cortex magnoliae officinalis, Psoralea corylifolia L, Curculigo orchioides Gaertn, and Glycyrrhiza uralensis Fisch.) were selected for further characterization. C. cochinchinense outperformed other extracts in most of the assays tested except phospholipid peroxidation inhibition, where P. corylifolia L showed higher activity. C. cochinchinense was particularly potent in inhibiting the formation of advanced glycation end products on proteins and strongly inhibited hypochlorous acid-induced DNA damage. We attempted to isolate the active ingredients from C. cochinchinense and obtained an extract (YCT) containing at least 90% mangiferin as identified by HPLC and mass spectrometry. However, YCT showed significantly higher activity in assays of phospholipid peroxidation, inhibition of protein glycation, and superoxide (O(2)(?-)) and peroxynitrite (ONOO(-)) scavenging, as compared with mangiferin, suggesting that the nonmangiferin constituents of YCT contribute to its additional antioxidant activities.

Topics: Antioxidants; Ascorbic Acid; Benzothiazoles; Chromatography, High Pressure Liquid; Clusiaceae; DNA Damage; Dose-Response Relationship, Drug; Hypochlorous Acid; Lipid Peroxidation; Lipids; Mass Spectrometry; Medicine, Chinese Traditional; Models, Chemical; Nitrogen; Peroxynitrous Acid; Phenol; Phospholipids; Sulfonic Acids; Superoxides; Tyrosine; Xanthine Oxidase; Xanthones