Myricetin affords protection against peroxynitrite-mediated DNA damage and hydroxyl radical formation

Peroxynitrite has been extensively implicated in the pathogenesis of various forms of neurodegenerative disorders via its cytotoxic effects, this study was undertaken to investigate whether the neuroprotective effect of myricetin is associated with inhibition of peroxynitrite-mediated DNA damage, a critical event leading to peroxynitrite elicited cytotoxicity. We observed that peroxynitrite can cause DNA damage in ϕX-174 plasmid DNA and rat primary astrocytes. The presence of myricetin at physiological concentration was found to significantly inhibit DNA strand breakage induced by both peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1). Moreover, the consumption of oxygen caused by SIN-1 was found to be decreased in the presence of myricetin, indicating that myricetin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy demonstrated that the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from peroxynitrite, and that myricetin inhibited the adduct signal in a concentration-dependent manner. Taken together, these results demonstrate for the first time that myricetin can inhibit peroxynitrite-mediated DNA damage and hydroxyl radical formation.