ascorbic-acid and colchiceine
ascorbic-acid has been researched along with colchiceine* in 1 studies
Other Studies
1 other study(ies) available for ascorbic-acid and colchiceine
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Anti-/pro-oxidant effects of phenolic compounds in cells: are colchicine metabolites chain-breaking antioxidants?
Effective scavenging of reactive radicals and low reactivity of generated secondary antioxidant radicals towards vital intracellular components are two critical requirements for a chain-breaking antioxidant. Tubulin-binding properties aside, colchicine metabolites remain largely untested for other possible biological activities, including antioxidant activity. Mourelle et al. [Life Sci. 45 (1989) 891] proposed that colchiceine (EIN) acts as an antioxidant and protective agent against lipid peroxidation in a rat model of liver injury. Since EIN as well as two other colchicine metabolites, 2-demethylcolchicine (2DM) and 3-demethylcolchicine (3DM), possess a hydroxy-group on their carbon ring that could participate in radical scavenging, we tested whether they can act as chain-breaking antioxidants. Using our fluorescence-HPLC assay with metabolically incorporated oxidation-sensitive cis-parinaric acid (PnA) we studied the effects of colchicine metabolites on peroxidation of different classes of membrane phospholipids in HL-60 cells. None of the colchicine metabolites in concentrations ranging from 10(-6) to 10(-4) M was able to protect phospholipids against peroxidation induced by either azo-initiators of peroxyl radicals or via myeloperoxidase (MPO)-catalyzed reactions in the presence of hydrogen peroxide. However, the metabolites did exhibit dose-dependent depletion of glutathione, resembling the behavior of etoposide, a hindered phenol with antioxidant properties against lipid peroxidation. Electron spin resonance (ESR) experiments demonstrated that in a catalytic system containing horseradish peroxidase (HRP)/H(2)O(2), colchicine metabolites undergo one-electron oxidation to form phenoxyl radicals that, in turn, cause ESR-detectable ascorbate radicals by oxidation of ascorbate. Phenoxyl radicals of colchicine metabolites formed through MPO-catalyzed H(2)O(2)-dependent reactions in HL-60 cells and via HRP/H(2)O(2) in model systems can also oxidize GSH. Thus, colchicine metabolites possess the prerequisites of many antioxidants, i.e. a nucleophilic hydroxy-group on a carbon ring and the ability to scavenge reactive radicals and form a secondary radical. However, the latter retain high reactivity towards critical biomolecules in cells such as lipids, thiols, ascorbate, thereby, rendering colchicine metabolites effective radical scavengers but not effective chain-breaking antioxidants. Topics: Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Colchicine; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Fatty Acids, Unsaturated; Fluorescent Dyes; Free Radical Scavengers; Glutathione; HL-60 Cells; Humans; Lipid Peroxidation; Membrane Lipids; Phospholipids; Reactive Oxygen Species | 2002 |