Oxygen is the key factor associated with the difference between in vivo and in vitro effects of antioxidants

Antioxidants have received much attention as food factors and drugs. Fox et al. (1) reported that antioxidants induced DNA damage response and cell death in cultured cells. I believe that their study has exceptional importance; however, at the same time, we must be very careful in evaluating antioxidants on the basis of experiments performed under air exposure. The oxygen (O2) concentration in water at 37 °C is ∼200 μM, and O2 also dissolves from the air above the culture medium. Antioxidants easily reduce O2 and generate hydrogen peroxide (H2O2) almost quantitatively, as evidenced by the fact that H2O2 is industrially produced by the reaction between O2 and anthrahydroquinone derivative. Resveratrol, genistein, and baicalein share the same structure with anthrahydroquinone in having two or more hydroxyl groups at the aromatic ring. Therefore, most antioxidants behave as prooxidants when exposed to air. Because the rate of H2O2 formation depends on the antioxidant, each antioxidant behaves differently. Many studies have shown that antioxidants, including polyphenols and even vitamin C, induced apoptosis in cultured cells. I think that H2O2, having extremely high biological activity, is the key factor that explains these effects.