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Clarification of the Relationship Between Free Radical Spin Trapping and Carbon Tetrachloride Metabolism in Microsomal Systems |
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| Authors: | H.D Connor R.G Thurman G Chen J.L Poyer E.G Janzen Ronald P Mason |
| Affiliation: | A National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; B Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; C Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Ontario, Canada; D Oklahoma Medical Research Foundation, Oklahoma City, OK, USA |
| Abstract: | It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl radical adduct (PBN/•CCl3) is metabolized to either the C-phenyl-N-tert-butylnitrone/carbon dioxide anion radical adduct (PBN/•CO2−) or the glutathione (GSH) and CCl4-dependent PBN radical adduct (PBN/[GSH-•CCl3]). Inclusion of PBN/•CCl3 in microsomal incubations containing GSH, nicotinamide adenine dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH-•CCl3] or PBN/•CO2− radical adducts. Microsomes alone or with GSH had no effect on the PBN/•CCl3 radical adduct. Addition of NADPH to a microsomal system containing PBN/•CCl3 presumably reduced the radical adduct to its ESR-silent hydroxylamine because no ESR signal was observed. The Folch extract of this system produced an ESR spectrum that was a composite of two radicals, one of which had hyperfine coupling constants identical to those of PBN/•CCl3. We conclude that PBN/•CCl3 is not metabolized into either PBN/[GSH-•CCl3] or PBN/•CO2− in microsomal systems. |
| Keywords: | Free radical Spin-trapping Carbon tetrachloride Trichloromethyl radical Electron spin resonance Glutathione Rat liver microsomes |
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