Antioxidant and pro-oxidant actions of flavonoids: Effects on DNA damage induced by nitric oxide, peroxynitrite and nitroxyl anion

Antioxidant and pro-oxidant activities of flavonoids have been reported. We have studied the effects of 18 flavonoids and related phenolic compounds o n DNA damage induced by nitric oxide (NO), peroxynitrite, and nitroxyl anio n (NO-). Similarly to our previous findings with catecholamines and catecho l-estrogens, DNA single-strand breakage was induced synergistically when pB R322 plasmid was incubated in the presence of an NO-releasing compound (die thylamine NONOate) and a flavonoid having an ortho-trihydroxyl group in eit her the B ring (e.g., epigallocatechin gallate) or the A ring (e.g., querce tagetin). Either NO or any of the above flavonoids alone did not induce str and breakage significantly. However, most of the tested flavonoids inhibite d the peroxynitrite-mediated formation of 8-nitroguanine in calf-thymus DNA , measured by a new HPLC-electrochemical detection method, as well as the p eIoxynitrite-induced strand breakage. NO- generated from Angeli's salt caus ed DNA strand breakage, which was also inhibited by flavonoids but at only high concentrations. On the basis of these findings, we propose that NO- an d/or peroxynitrite could be responsible for DNA strand breakage induced by NO and a flavonoid having an ortho-trihydroxyl group. Our results indicate that flavonoids have antioxidant properties, but some act as pro-oxidants i n the presence of NO. (C) 1998 Elsevier Science Inc.