Ethylene glycol generates free radical metabolites in rats: an ESR in vivo spin trapping investigation. 2000

M B Kadiiska, and R P Mason
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Kadiiska@niehs.nih.gov

Ethylene glycol, best known as antifreeze, is most often ingested accidentally or as a substitute for alcochol by chronic alcohol abusers. The toxicity of ethylene glycol poisoning is due to its toxic metabolites rather than to ethylene glycol itself. In this study, electron spin resonance (ESR) spectroscopy has been used to study free radical generation in rats by acute ethylene glycol poisoning. The radical spin trapping technique was applied where the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) reacted with free radical metabolites to form radical adducts in vivo. The radical adducts from ethylene glycol intoxication were detected in both the bile and urine samples of male Sprague-Dawley rats. The identification of the POBN-(.)[(13)C]ethylene glycol radical adduct provides for the first time direct ESR evidence for the generation of the ethylene glycol-derived radicals during acute intoxication by ethylene glycol, suggesting a new metabolic pathway. Simultaneous administration of alcohol dehydrogenase inhibitor 4-methylpyrazole with ethylene glycol resulted in an enhanced free radical generation in the bile. This report is the first evidence of ethylene glycol free radical metabolism in rats with acute ethylene glycol intoxication.

UI MeSH Term Description Entries
D008297 Male Males
D009589 Nitrogen Oxides Inorganic oxides that contain nitrogen. Nitrogen Oxide,Oxide, Nitrogen,Oxides, Nitrogen
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D003676 Deferoxamine Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D004578 Electron Spin Resonance Spectroscopy A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING. ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D013113 Spin Labels Molecules which contain an atom or a group of atoms exhibiting an unpaired electron spin that can be detected by electron spin resonance spectroscopy and can be bonded to another molecule. (McGraw-Hill Dictionary of Chemical and Technical Terms, 4th ed) Spin Label,Label, Spin,Labels, Spin

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