New Insights into Quercetin Restoring the Impairment of Testicular Angiogenesis Induced by Silicon Dioxide Particles in Food: Inhibiting ROS/PPARγ-Mediated Ferroptosis

Silicon dioxide particles (SiO₂) have been widely used in food additives. Increasing data demonstrate that SiO₂ can cause multisystem damage through oxidative stress. Quercetin (Que) is one of the most popular nutritional antioxidants. Ferroptosis reduces the level of angiogenesis. However, whether Que alleviates the inhibition of testicular angiogenesis by relieving SiO₂-induced ferroptosis via ROS/PPARγ is unclear. Based on this, we established SiO₂-exposed mice testicular and C166 cell models and added oxidative stress activators Sanguinarine chloride (SAN), PPARγ inhibitor GW9662, and ferroptosis activator Erastin to the models in vitro. The results showed that the SiO₂ exposure group had antioxidant dysfunction; PPARγ was significantly downregulated; ferroptosis levels were increased; and angiogenesis was reduced. Que treatment can alleviate these changes. The addition of SAN, GW9662, and Erastin reduced the effects of Que by activating oxidative stress, inhibiting PPARγ, and activating ferroptosis, respectively. In general, Que can alleviate SiO₂-induced ferroptosis through ROS/PPARγ, thus restoring testicular angiogenesis in mice.