Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH cytochrome P-450 reductase.
Formation of free radical intermediates from 1--methyl-4-phenylpyridinium ion(MPP+) has been studied using spin-trapping techniques. Incubation of MPP+ with purified NADPH cytochrome P-450 reductase and NADPH under anaerobic conditions failed to produce any detectable radical intermediates. However, in the presence of air and a spin-trap, a significant stimulation of superoxide and hydroxyl radicals was detected. Formation of these toxic radicals from MPP+ was inhibited by superoxide dismutase, catalase, and ethanol. Under identical conditions, however, considerably less of these radicals were formed with MPP+ in comparison to paraquat, a lung toxin containing two pyridinium moieties.
D015655:1-Methyl-4-phenylpyridinium; D000693:Anaerobiosis; D001711:Biotransformation; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010269:Paraquat / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D006878:Hydroxides; D011726:Pyridinium Compounds; D013481:Superoxides; D017665:Hydroxyl Radical; D009251:NADPH-Ferrihemoprotein Reductase; D010269:Paraquat; D015655:1-Methyl-4-phenylpyridinium