Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production.

Peroxynitrite (ONOO(-)), a potent cytotoxic oxidant formed by the reaction of nitric oxide ((.-)NO) and superoxide radical ((.-)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 (.-)O(2)(-) and (.-)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-kappaB and extracellular signalrelated 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.