GENERATION OF HYDROXYL RADICALS DURING DISMUTATION OF SUPEROXIDE BY SOD MODEL COMPOUNDS

The reactivities of copper(II) complexes with cimetidine (Cim) and cyc lo(histidylhistidyl) (CyHH), both of which are SOD model compounds, to ward active oxygen species such as superoxide (O-2(-)) and hydrogen pe roxide (H2O2) were investigated by electron spin resonance-spin trappi ng and thiobarbituric acid methods. At physiological pH values, low co ncentrations of Cu(II) complexes (0.025 mM) with Cim and CyHH could sc avenge O-2(-), but high concentrations of these compexes (0.25 mM) yie lded hydroxyl radicals ((OH)-O-.) during dismutation of O-2(-). These Cu(II) complexes could directly react with H2O2 to yield (OH)-O-.. Fro m these results, it is indicated that (OH)-O-. formed during the dismu tation of O-2(-) by high concentration of SOD model compounds may be c aused by the reaction of H2O2 generated form dismutation of O-2 with C u(II) complexes. Further, DNA single-stranded breakage was observed du ring the reactions of H2O2 with these Cu(II) complexes. (C) 1994 Acade mic Press, Inc.