SCAVENGING OF PEROXYNITRITE BY A PHENOLIC PEROXIDASE SYSTEM PREVENTS OXIDATIVE DAMAGE TO DNA/

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.