Salsolinol is an endogenous
neurotoxin, known to be involved in the pathogenesis of
neurodegenerative disorders. In this present study, we have attempted to characterize the oxidative damage of
DNA induced by the reaction of
salsolinol with
ferritin. When
DNA was incubated with
salsolinol and
ferritin,
DNA strand breakage occurred.
Hydroxyl radical scavengers and
catalase reduced
salsolinol/
ferritin system-mediated DNA cleavage, whereas
Cu,Zn-superoxide dismutase did not inhibit DNA cleavage. The reaction of
salsolinol with
ferritin resulted in a time-dependent increase in the release of free
iron ions. A strong
iron chelator,
ferrozine, effectively inhibited the
salsolinol/
ferritin system-mediated DNA cleavage.
Ferritin enhanced a mutation of the lacZ' gene in the presence of
salsolinol when measured as a loss of alpha-complementation. These results indicate that
salsolinol/
ferritin system-mediated DNA cleavage and mutation may be attributable to
hydroxyl radical generation via the Fenton-like reaction of free
iron ions released from oxidatively damaged
ferritin. The endogenous
dipeptides,
carnosine and related compounds, are naturally occurring compounds with a multiplicity of neuroprotective properties.
Carnosine,
homocarnosine and
anserine significantly inhibited
salsolinol/
ferritin system-mediated
DNA strand breakage and mutation. These results indicate that
carnosine and related compounds effectively suppressed the
salsolinol/
ferritin system-mediated
DNA strand breakage via
hydroxyl radical scavenging.