Acrolein-induced oxygen radical formation.
The mechanism of acrolein-induced lipid peroxidation is unknown. This study found that acrolein and its glutathione adduct, glutathionylpropionaldehyde, induce oxygen radical formation. These oxygen radicals may be responsible for the induction of lipid peroxidation by acrolein. The enzymes xanthine oxidase and aldehyde dehydrogenase were found to interact with glutathionylpropionaldehyde to produce O2.- and HO(.). Acrolein was oxidized by xanthine oxidase to produce acroleinyl radical and O2(.-). Aldehyde dehydrogenase metabolized acrolein to form O2.- but not acroleinyl radical. The fact that glutathionylpropionaldehyde is a more potent stimulator of oxygen radical formation than acrolein indicates that glutathionylpropionaldehyde is a toxic metabolite of acrolein and may be responsible for some of the in vivo toxicity of acrolein.
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
J D
JD
Adams
L K
LK
Klaidman
D000171:Acrolein / Q000737:chemistry / Q000494:pharmacology*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D006878:Hydroxides; D013481:Superoxides; C061284:S-(2-aldehydoethyl)glutathione; D017665:Hydroxyl Radical; D000171:Acrolein; D014969:Xanthine Oxidase; D000444:Aldehyde Dehydrogenase; D005978:Glutathione; D010100:Oxygen