title: Acute methanol intoxication generates free radicals in rats: an ESR spin trapping investigation.
abstract: Electron spin resonance (ESR) spectroscopy has been used to investigate free radical generation in rats with acute methanol poisoning. The spin trapping technique was used where a spin trapping agent, alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), reacted with the corresponding alcohol-derived or alcohol-dependent radical to form radical adducts. One radical adduct was detected in both bile and urine samples 2 h after acute methanol poisoning in male Sprague Dawley rats. The hyperfine coupling constants for the radical adduct from [(13)C]-labeled methanol detected in the bile were a(N) = 15.58, a(beta)(H) = 2.81 G, and a(beta)(13C) = 4.53 G, which unambiguously identified this species as POBN/*CH@OH. The same radical adduct was detected in urine. The identification of a methanol-derived radical adduct in samples from bile and urine provided strong direct evidence for the generation of the alcohol-derived radicals during acute intoxication by methanol. Simultaneous administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole and methanol resulted in an increase in the generation of the free radical metabolite detected in the bile. This is the first ESR evidence of methanol-derived free radical generation in an animal model of acute methanol intoxication.
authors.affiliation: Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. kadiiska@niehs.nih.gov
authors.forename: M B
authors.initials: MB
authors.lastname: Kadiiska
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D000432:Methanol / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D019097:Spin Trapping
chemical_list: D005609:Free Radicals; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D017665:Hydroxyl Radical; D007064:L-Iditol 2-Dehydrogenase; D001219:Aspartate Aminotransferases; D000432:Methanol