Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH cytochrome P-450 reductase |
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| Authors: | B K Sinha Y Singh G Krishna |
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| Affiliation: | 1. Clinical Oncology Branch, National Cancer Institute National Institutes of Health, Bethesda, Maryland 20892 USA;2. Laboratory of Chemical Pharmacology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 USA;1. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;2. Research Center for Modeling and Simulations, National University of Sciences and Technology, Islamabad, Pakistan;3. Department of Chemistry, University of Gujrat, Gujrat, Pakistan;4. Department of Physics, University of Sargodha, Sargodha, Pakistan;5. Leibniz Institute for Catalysis, Rostock, Germany;1. Yuzuncu Yil University, Faculty of Pharmacy, Department of Analytical Chemistry, 65080 Van, Turkey;2. Yuzuncu Yil University, Faculty of Science, Department of Physical Chemistry, 65080 Van, Turkey;3. Yuzuncu Yil University, Faculty of Science, Department of Analytical Chemistry, 65080 Van, Turkey;1. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia;2. Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, Australia;1. Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands;2. Interfaculty Mass Spectrometry Center, University of Groningen, Groningen, The Netherlands |
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| Abstract: | 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. |
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