Abstract
The ability of ten polyphenolic antioxidants to prevent CuO nanoparticle ((NP)CuO) and H(2)O(2)-mediated DNA damage and cytotoxicity was investigated. Five of the polyphenols (MEPCA, PREGA, MEGA, ECG, and EGCG) prevent (NP)CuO/H(2)O(2)-mediated DNA damage (IC(50) values of 7.5-800 μM), three have no effect (PCA, VA, and EC), and two (GA and EGC) result in increased DNA damage. Most polyphenols had similar antioxidant/prooxidant activity in the presence of (NP)CuO or free copper ions. Electron paramagnetic resonance (EPR) spectroscopy of reactive oxygen species (ROS) generated by (NP)CuO/H(2)O(2) in the presence of representative polyphenols correlate with results of DNA damage studies: in the presence of (NP)CuO/H(2)O(2), MEPCA prevents ROS formation, VA has no effect on ROS levels, and EGC increases ROS levels. EPR results with CuO nanoparticles washed to remove dissolved copper in solution ((w)CuO) in the presence of H(2)O(2)/ascorbate suggest that MEPCA prevents ROS formation on the nanoparticle surface in addition to preventing ROS formation from dissolved copper. In mouse fibroblast (L929) cells, combining (NP)CuO with H(2)O(2) results in significantly greater cytotoxicity than observed for either component alone. After 3 h incubation with MEPCA or MEGA, the viability loss in L929 cells induced by (NP)CuO/H(2)O(2) challenge was significantly rescued at physiologically relevant polyphenol levels (1 μM). These studies show that polyphenols can protect DNA and inhibit cytotoxicity generated by (NP)CuO under oxidative stress conditions.