The involvement of ethanol in the free radical reaction of 6-hydroxydopamine.
ESR spin trapping technique was used to detect and analyze free radical formation. When 6-hydroxydopamine (6-OHDA) was incubated alone or in the presence of a free radical generating system (H2O2 and FeSO4), hydroxyl free radicals were observed in a concentration-dependent manner. Glutathione was found to be the most effective scavenger of the ESR signal when compared with vitamin E or Mannitol. The addition of ethanol resulted in the formation of the pure hydroxyethyl free radicals. The amount of hydroxyethyl free radicals in the system was dependent upon the concentration of ethanol and the formation of hydroxyethyl free radicals correlated well with the extent of lipid peroxidation and the loss of enzymic activity of the membrane-bound (Na+,K+)-ATPase. We suggest that in the biological system ethanol may potentiate the neurotoxicity of 6-OHDA with the formation of hydroxyethyl free radicals, which are longer-lived and far more damaging to membranes than the hydroxyl radicals. These data lead us to further hypothesize that the neuronal degeneration caused by 6-OHDA and other compounds that generate free radicals could be potentiated in the presence of ethanol.
Oldfield
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Department of Pharmacology, School of Medicine, University of Missouri, Columbia 65212.
Cowan
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Sun
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D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000378:metabolism; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D006892:Hydroxydopamines / Q000378:metabolism*; D017665:Hydroxyl Radical; D015227:Lipid Peroxidation; D008353:Mannitol / Q000494:pharmacology; D016627:Oxidopamine; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013113:Spin Labels; D014810:Vitamin E / Q000494:pharmacology
D003497:Cyclic N-Oxides; D005296:Ferrous Compounds; D005609:Free Radicals; D006878:Hydroxides; D006892:Hydroxydopamines; D013113:Spin Labels; D014810:Vitamin E; C065424:1-hydroxyethyl radical; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D000431:Ethanol; D008353:Mannitol; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione