The peroxidase activity of ADM-Fe(3+) cooperates with lipid peroxidation: The participation of hydroperoxide and hydroxyl radicals in the damage to proteins and DNA.

To investigate the mechanisms of cardiotoxicity induced by adriamycin (ADM), the enzymatic activities of ADM-Fe(3+), including the peroxidase and lipoxygenase (LOX) activity, and participation of active oxygen species in the damage to biological components were examined. ADM-Fe(3+), but not ADM, steadily oxidized tetramethyl-p-phenylenediamine in the presence of peroxides, indicating that ADM-Fe(3+) acts as a peroxidase. However, the activity of ADM-Fe(3+) as peroxidase was very low compared with that of heme peroxidase, but was similar to that of LOX, which has a known peroxidase activity. Conversely, the activity of ADM-Fe(3+) as a LOX was also very low compared with that of LOX itself. However, the lipid hydroperoxides (LOOH) produced by ADM-Fe(3+) were the substrate for ADM-Fe(3+) as a peroxidase. These findings indicate that lipid peroxidation cooperates with the peroxidase activity of ADM-Fe(3+). Hydroxyl radicals (HO) were generated when ADM-Fe(3+) was incubated with H2O2, but not with LOOH. Alcohol dehydrogenase was inactivated by LOOH. Conversely, DNA was mainly damaged by ADM-Fe(3+) with H2O2. A small amount of DNA remained at the starting point on agarose gels during incubation with ADM-Fe(3+) with LOOH and ADM-Fe(3+) with H2O2. It seems that HO and compound I-like species participate in the strand breaks and the aggregation of DNA, respectively.