Antioxidant and pro-oxidant effects of Qu in the presence of low and high levels of reduced GSH. The antioxidant and pro-oxidant effects of Qu strongly depend upon the availability of intracellular reduced GSH. During an oxidative stress, in the presence of peroxidases, Qu reacts with H2O2 to form a semiquinone radical that is rapidly oxidized to QQ. QQ has a pro-oxidant effect; its high reactivity towards protein thiols and DNA leads to cell damage and cytotoxicity. QQ is also highly reactive towards thiols, and preferentially reacts with GSH to form relatively stable protein-oxidized Qu adducts such as 6-GSQ and 8-GSQ. The reversibility of this reaction allows the continuous dissociation of GSQ into GSH and QQ. In the presence of high GSH concentrations, QQ reacts with GSH to form GSQ again, and QQ cannot exert its cytotoxic effects, whereas when low levels of GSH are present, QQ reacts with protein thiols, thus leading to cellular damage.
