Quercetin ameliorates cytotoxic effects of zinc oxide nanoparticles on sertoli cells by enhancing autophagy and suppressing oxidative stress

Previous studies have demonstrated the toxic impacts of zinc oxide nanoparticles (ZO-NPs) on male reproductive cells. The effect of quercetin (QCT) on ZO-NPs-induced mouse Sertoli cell (TM4 cell line) toxicity and its underlying mechanisms were investigated in this study. The TM4 cells were exposed to ZO-NPs or QCT in different groups for 24 hr. The TM4 cells pre-treated with 3MA (3-Methyladenine, an autophagy inhibitor) to evaluate the autophagy role of QCT and ZO-NPs in the TM4 cells. ZO-NPs significantly reduced the viability percentage of the TM4 cells. The apoptosis percentage and Bax/Bcl-2 ratio of the ZO-NPs group were significantly increased, while the expression of autophagy-related genes was considerably downregulated. ZO-NPs also induced oxidative stress in the TM4 cells through increasing malondialdehyde contents and reactive oxygen species levels (ROS) and reducing antioxidant factors including superoxide dismutase, catalase, glutathione and glutathione peroxidase. In QCT + ZO-NPs group, these events were considerably reversed. 3MA could significantly decrease the cell viability of TM4 cells exposed to the QCT and ZO-NPs in comparison with the untreated 3MA groups. According to these results, the protective effects of QCT on ZO-NPs-exposed TM4 cells are related to inducing autophagy, prevention apoptosis and suppressing oxidative stress.