Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.
Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described.
Linseman
K L
KL
Upjohn Company, Kalamazoo, MI 49001.
Larson
P
P
Braughler
J M
JM
McCall
J M
JM
D000818:Animals; D001923:Brain Chemistry; D002839:Chromans / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology*; D016166:Free Radical Scavengers; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000378:metabolism*
D002839:Chromans; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D008563:Membrane Lipids; D008565:Membrane Proteins; D010879:Piperazines; D000644:Quaternary Ammonium Compounds; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C066382:U 78517F; D014810:Vitamin E; C038178:ammonium ferrous sulfate; D007501:Iron