Fig. 16.

ROS and RNS are commonly thought to induce injury by oxidizing (i.e., damaging) the cellular fabric, including proteins, lipids and nucleotides. There is significant pre-clinical evidence that oxidants are damaging based on protection by antioxidants, but this has not translated though to human studies with large-scale clinical trials often showing no benefit or sometimes adverse outcomes. This could be because antioxidants scavenge oxidants that otherwise initiate protective signaling events. As electron donors, antioxidants have the potential to fuel oxidants generation as shown by the dotted line, which adds further complexity. Another consideration is that oxidized antioxidants can exert biological actions via their pro-oxidant chemistry.