Detection of free radicals as a consequence of dog tracheal epithelial cellular xenobiotic metabolism.
1. Spin-trapping techniques have been used to examine the metabolism of three xenobiotics known to produce free radicals during their metabolism. Reaction with oxygen generated superoxide, the location of which was dependent upon the xenobiotic. 2. Paraquat was metabolized by dog trachea epithelial cells under anaerobiosis to the paraquat free radical, some of which diffused into the extracellular milieu. With the addition of oxygen, superoxide was spin-trapped both intra- and extracellularly. 3. When menadione was metabolized by epithelial cells, superoxide was spin-trapped within the cell and in the surrounding media. However, in this case, extracellular superoxide arose as the result of the disproportionation reaction of menadione and menadiol, resulting from DT-diaphorase reduction of menadione followed by diffusion into extracellular space, to give the menadione semiquinone. Reduction of oxygen resulted in formation of superoxide. 4. For nitrazepam, only intracellular superoxide was generated, resulting from the one-electron reduction of this drug to its corresponding nitro anion free radical. Reaction with oxygen produced superoxide.
Rosen
G M
GM
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Hassett
D J
DJ
Yankaskas
J R
JR
Cohen
M S
MS
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D004848:Epithelium / Q000378:metabolism; D005609:Free Radicals; D009130:Muscle, Smooth / Q000378:metabolism; D009567:Nitrazepam / Q000378:metabolism; D010269:Paraquat / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*; D014812:Vitamin K / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D005609:Free Radicals; D015262:Xenobiotics; D013481:Superoxides; D014812:Vitamin K; D009567:Nitrazepam; D010269:Paraquat