Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production

Peroxynitrite (ONOO-), a potent cytotoxic oxidant formed by the reaction of nitric oxide (center dot NO) and superoxide radical (center dot O-2(-)), may be rapidly lethal in a cellular milieu due to oxidization and nitration processes. In the present study, hydroquinone displayed strong ONOO- scavenging activity and inhibitory effect on NO production in murine macrophage RAW264.7 cells. Hydroquinone strongly scavenged ONOO- induced dihydrorhodamine 123 oxidation in a dose-dependent manner compared with other reactive species such as center dot O-2(-) and center dot NO. Hydroquinone also decreased levels of ONOO induced nitrotyrosine of glutathione reductase and consequently prevented the enzyme from ONOO- induced damage. Furthermore, hydroquinone suppressed NO production, a cellular pathway for ONOO- formation, in lipopolysaccharide-activated RAW264.7 cells via inhibition of inducible NO synthase expression. The inhibitory effect by hydroquinone seems to be mediated by interruption of lipopolysaccharide-induced signalling such as activation of nuclear factor-kappa B and extracellular signal-related kinases 1 and 2. The results suggest that hydroquinone may potently modulate reactivity of ONOO- and may therefore be a useful agent against ONOO- mediated diseases.