title: In vivo endotoxin enhances biliary ethanol-dependent free radical generation.
abstract: Endotoxemia is associated with alcoholic liver diseases; however, the effect of endotoxin on the oxidation of ethanol is not known. We tested the hypothesis that endotoxin treatment enhances hepatic ethanol radical production. The generation of free radicals by the liver was studied with spin-trapping technique utilizing the primary trap ethanol (0.8 g/kg) and the secondary trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN; 500 mg/kg). Electron paramagnetic resonance (EPR) spectra of bile showed six-line signals, which were dependent on ethanol, indicating the trapping of ethanol-dependent radicals. Intravenous injections of Escherichia coli lipopolysaccharide (0.5 mg/kg) 0.5 h before 4-POBN plus ethanol treatment caused threefold increases of biliary radical adducts. EPR analyses of bile from [1-13C]ethanol-treated endotoxic rats showed the presence of species attributable to alpha-hydroxyethyl adduct, carbon-centered adducts, and ascorbate radical. The generation of endotoxin-induced increases of ethanol-dependent radicals was suppressed by 50% on GdCl3 (20 mg/kg i.v.) or desferrioxamine mesylate (1 g/kg i.p.) treatment. Our data show that in vivo endotoxin increases biliary ethanol-dependent free radical formation and that these processes are modulated by Kupffer cell activation and catalytic metals.
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chamulitrat
authors.forename: J
authors.initials: J
authors.lastname: Carnal
authors.forename: N M
authors.initials: NM
authors.lastname: Reed
authors.forename: J J
authors.initials: JJ
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism*; D015415:Biomarkers; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007728:Kupffer Cells / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009589:Nitrogen Oxides / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D019097:Spin Trapping
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D005609:Free Radicals; D007502:Iron Chelating Agents; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D016877:Oxidants; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D000431:Ethanol; D003676:Deferoxamine