Effect of estrogens on the oxidative damage induced by ferrylmyoglobin.
The effect of estrogens, including estrone (E1), estradiol-17beta (E2), estriol (E3) and 2-hydroxyestradiol (2-OH-E2), on the oxidative damage induced by ferrylmyoglobin (ferrylMb) was investigated. These estrogens inhibited lipid peroxidation induced by ferrylMb. The ability of 2-OH-E2 to inhibit lipid peroxidation was much greater than the other estrogens. Furthermore, 2-OH-E2 trapped 2,2'-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals more rapidly, and among these estrogens only 2-OH-E2 reacted with 2,2-diphenyl-1-picrylhydrazyl. These results suggest that the ability of 2-OH-E2 to inhibit lipid peroxidation is because it scavenges lipid peroxyl and carbon-centered radicals. Estrogens, except for 2-OH-E2, partially prevented the inactivation of alcohol dehydrogenase (ADH) induced by ferrylMb. Of interest, however, the exposure of sulfhydryl (SH) enzymes to ferrylMb in the presence of 2-OH-E2 dramatically increased the inhibition of the enzyme activity. Ascorbic acid (ASA) and reduced glutathione (GSH) strongly inhibited the inactivation of ADH induced by ferrylMb in the presence of 2-OH-E2. During the reaction of ferrylMb with ASA or GSH in the presence of 2-OH-E2, large amounts of oxymyoglobin were formed, suggesting the involvement of the semiquinone from 2-OH-E2 in the reduction of metmyoglobin. Presumably, the semiquinone formed from 2-OH-E2 oxidizes the SH group of enzymes to facilitate the rapid inactivation of the SH enzymes induced by ferrylMb.
Hokkaido College of Pharmacy, Otaru, Japan. miuratos@hit.ac.jp
T
T
Miura
S
S
Muraoka
Y
Y
Fujimoto
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008786:Metmyoglobin / Q000633:toxicity*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D004967:Estrogens; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; C028048:ferrylmyoglobin; D008786:Metmyoglobin; D004970:Estrone; D004958:Estradiol; C001390:2-hydroxyestradiol; D000426:Alcohol Dehydrogenase; D004964:Estriol; D005978:Glutathione; D001205:Ascorbic Acid