Increased microsomal interaction with iron and oxygen radical generation after chronic acetone treatment.
In vivo administration of acetone influences a variety of reactions catalyzed by rat liver microsomes. The effect of chronic treatment with acetone (1% acetone in the water for 10-12 days) on interaction with iron and subsequent oxygen radical generation by liver microsomes was evaluated. Microsomes from the acetone-treated rats displayed elevated rates of H2O2 generation, an increase in iron-dependent lipid peroxidation, and enhanced chemiluminescence upon the addition of t-butylhydroperoxide. The ferric EDTA-catalyzed production of formaldehyde from DMSO or of ethylene from 2-keto-4-thiomethylbutyrate was increased 2-fold after acetone treatment. This increase in hydroxyl radical generation was accompanied by a corresponding increase in NADPH utilization and was sensitive to inhibition by catalase and a competitive scavenger, ethanol, but not to superoxide dismutase. In vitro addition of acetone to microsomes had no effect on oxygen radical generation. Associated with the chronic acetone treatment was a 2-fold increase in the microsomal content of cytochrome P-450 and in the activity of NADPH-cytochrome-P-450 reductase. It appears that increased oxygen radical generation by microsomes after chronic acetone treatment reflects the increase in the major enzyme components which comprise the mixed-function oxidase system.
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010545:Peroxides; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D008054:Lipid Peroxides; D010545:Peroxides; D000096:Acetone; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase