Antioxidative activity of benzylideneascorbate and its effect on adriamycin-induced cardiotoxicity.
The in vitro antioxidative activity of benzylideneascorbate (SBA) and the in vivo effect on adriamycin (ADR)-induced cardiotoxicity in a mouse model were investigated. The radical-scavenging activity of SBA was assayed in terms of reduction of chemiluminescence induced by O2-, generated in xanthine/xanthine oxidase and macrophage/phorbol myristate acetate reaction systems. SBA showed a strong antioxidative activity (IC50 = 3 to 4 microM) in both assay systems, though its activity was weaker than that of ascorbic acid (Asc). In the assay of the antioxidative activity against auto-oxidation of linolenic acid, SBA was stable and retained its potency for a long period of time in comparison with Asc, 6-palmitoylascorbic acid (6-P-Asc) and cysteamine (CysNH2). Electron spin resonance examination indicated that SBA strongly scavenged both superoxide anion and hydroxy radical. The in vivo protective effect of SBA against ADR-induced cardiotoxicity, in which active oxygen radicals play a role, was examined. The serum creatine phosphokinase activity, a parameter of cardiotoxicity, was remarkably increased from the 3rd day until the 4th day after ADR treatment. This elevation was significantly suppressed by SBA treatment, whereas Asc, 6-P-Asc and CysNH2 were ineffective. SBA could have clinical potential for the treatment of diabetes and other disorders in which active oxygen species play a pathogenic role.
Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
S
S
Kojima
H
H
Iizuka
H
H
Yamaguchi
S
S
Tanuma
M
M
Kochi
Y
Y
Ueno
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D001597:Benzylidene Compounds / Q000627:therapeutic use*; D003543:Cysteamine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D013481:Superoxides / Q000633:toxicity; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D001597:Benzylidene Compounds; D016166:Free Radical Scavengers; D014970:Xanthines; D017962:alpha-Linolenic Acid; D013481:Superoxides; D019820:Xanthine; D003543:Cysteamine; D004317:Doxorubicin; D014969:Xanthine Oxidase; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid; C070680:zilascorb