EPR studies of nitric oxide interactions of alkoxyl and peroxyl radicals in in vitro and ex vivo model systems.
A model compound of lipid peroxidation, tert-butyl hydroperoxide (tBOOH), was used in vitro to investigate (i) the generation of tBOOH-derived free radicals by hematin or rat enterocytes and (ii) the modulation of cell-generated free radical production by a nitric oxide (NO) donor, or when these cells were primed to produce NO. In hematin-catalyzed decomposition of tBOOH, NO from nitrosoglutathione, or S-nitroso-N-acetylpenicillamine suppressed the generation of peroxyl radicals (measured by direct electron paramagnetic resonance) and tert-butylalkoxyl, methoxyl, and methyl radicals (measured by electron paramagnetic resonance spin trapping). Similarly, co-incubation of S-nitroso-N-acetylpenicillamine or nitrosoglutathione with tBOOH caused significant decreases in tBOOH-derived free radical generation catalyzed by enterocytes. Epithelial cells are the known source of the inducible form of NO synthase in the intestine of rats challenged with lipopolysaccharide (LPS). Enterocytes isolated from LPS-treated rats produced decreased levels of tBOOH-derived radicals. These decreases in free radical production were further decreased when these cells were treated with LPS in vitro. These findings demonstrated that exogenously added or endogenously produced NO could modulate the extent of tBOOH-derived free radical generation in enterocytes. These decreases in free radical production could, at least in part, describe the protective role of NO from hydroperoxide-induced injury.
Chamulitrat
W
W
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112, USA. w.chamulitrat@dkfz-heidelberg.de
D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D004731:Endotoxins / Q000494:pharmacology; D020895:Enterocytes / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide / Q000378:metabolism*
D000438:Alcohols; D004731:Endotoxins; D016166:Free Radical Scavengers; D005609:Free Radicals; D008070:Lipopolysaccharides; D010545:Peroxides; C059688:alkoxyl radical; C049375:perhydroxyl radical; D009569:Nitric Oxide; D006427:Hemin; D020122:tert-Butylhydroperoxide; D010100:Oxygen