Cu(I)–Glutathione complex: A potential source of superoxide radicals generation

Abstract

Cu2+ ions and GSH molecules interact to swiftly form the complex Cu(I)–glutathione. We investigated the potential capacity of such complex to reduce molecular oxygen. The addition of SOD to a solution containing Cu(I)–glutathione led to a sustained decline of the basal oxygen level. Such effect was partially reverted by the addition of catalase. The complex was able to induce the reduction of cytochrome c and the oxidation of dyhydroethidium into 2-hydroxyethidium. Both effects were totally blocked by SOD. The ability of the complex to generate superoxide radicals was confirmed by EPR spin-trapping. Cu(I)–glutathione induce no oxidation of fluorescein, a hydroxyl radical-sensitive probe. We conclude that in solutions containing the complex, oxygen is continually reduced into superoxide, and that—in absence of interceptors—the latter radicals are quantitatively re-oxidized into molecular oxygen. We suggest that by functioning as a continuous source of superoxide, the complex could potentially affect a broad range of susceptible biological targets.