Protective Mechanism of Quercetin and Rutin Using Glutathione Metabolism on H 2 O 2 ‐induced Oxidative Stress in HepG2 Cells

The levels of cellular glutathione (GSH) and reactive oxygen species (ROS) simultaneously determined by fluorometric measurement, may provide important information on pro‐oxidative and antioxidative balance. The dual effect of quercetin antioxidant and pro‐oxidant activity was proposed from different studies. Our study demonstrated that quercetin acted as an antioxidant in HepG2 cells when cells were treated with 10 and 100 μmol/L quercetin for 30 min, but quercetin acted as a pro‐oxidant when cells were incubated at 100 μmol/L quercetin for longer periods (12 and 24 h). Quercetin is capable of reducing H 2 O 2 ‐induced oxidative stress of HepG2 cells through different mechanisms, such as detoxification of H 2 O 2, inhibition of ROS generation, and removal of generated ROS. We find that quercetin can block ROS generation through Fenton reaction to produce hydroxyl radicals by chelating with transition metal ions such as Cu 2+ . Evidence that quercetin might exert an antioxidant effect by changing generated ROS into less reactive ROS suggests that when quercetin reacts with ROS, it becomes oxidized, which is less harmful but still reactive, and the oxidized quercetin interacts with thiol compounds as reduced GSH to return to the parent compound quercetin. In contrast, the prolonged treatment of quercetin in high concentrations (100 μmol/L) shows that quercetin may act as a pro‐oxidant rather than as an antioxidant, resulting in cell death (apoptosis).