We examined the ability of horseradish peroxidase (HRP), an analog of
human myeloperoxidase, to protect DNA against oxidative damage caused
by peroxynitrite in the presence of chlorogenic acid (CGA), a naturall
y occurring polyphenol. Chlorogenic acid inhibits the formation of sin
gle strand breaks in supercoiled pBR322 DNA by acting as a scavenger o
f peroxynitrite. Horseradish peroxidase markedly enhances the extent o
f DNA protection by catalyzing the decomposition of peroxynitrite in t
he presence of CGA. Horseradish peroxidase alone does not inhibit pero
xynitrite-induced DNA strand breaks, indicating that CGA is required a
s an electron donor to regenerate the active enzyme. The apparent seco
nd order rate constant for the HRP-mediated oxidation of CGA in the pr
esence of peroxynitrite at pH 6.9 is 3.4 x 10(7) M-1 s(-1). This high
rate suggests that CGA and other dietary polyphenols might efficiently
scavenge peroxynitrite in peroxidase-containing systems in vivo. (C)
1998 Federation of European Biochemical Societies.