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.