title: Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives.
abstract: Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.
authors.affiliation: Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takebayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kaji
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichiyama
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Makino
authors.forename: Eiichi
authors.initials: E
authors.lastname: Gohda
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
mesh_terms: D000578:Amidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects*; D012756:Sheep / Q000097:blood; D013997:Time Factors
chemical_list: D000578:Amidines; D000975:Antioxidants; D005609:Free Radicals; C011669:ascorbate-2-phosphate; C001956:ascorbic acid 2-sulfate; C065378:ascorbic acid 2-O-glucoside; C046728:2,2'-azobis(2-amidinopropane); D001205:Ascorbic Acid