Naringenin ameliorates cytotoxic effects of bisphenol A on mouse Sertoli cells by suppressing oxidative stress and modulating mitophagy: An experimental study

Bisphenol A (BPA), an endocrine-disrupting agent, is widely used as polycarbonate plastics for producing food containers. BPA exposure at environmentally relevant concentrations can cause reproductive disorders. The effect of Naringenin (NG) on BPA-induced Sertoli cell toxicity and its mechanism was examined in the present study. In this experimental-laboratory study, the mouse TM4 cells were treated to BPA (0.8 μM) or NG for 24 hr at concentrations of 10, 20, and 50 μg/ml. Cell viability, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, antioxidant level, and mitochondrial membrane potential (MMP) were examined. The expression of mitophagy-related genes, including Parkin and PTEN-induced putative kinase 1 (Pink1), was also evaluated. BPA significantly lowered the viability of the Sertoli cells (p= 0.004). Pink1 and Parkin levels of the BPA group were significantly increased (p 0.001), while the MMP was considerably decreased (p 0.001). BPA raised MDA and ROS levels (p 0.001) and reduced antioxidant biomarkers (p= 0.003). NG at the 20 and 50 μg/ml concentrations could significantly improve the viability and MMP of TM4 cells (p= 0.034). NG depending on concentration, could decrease Pink1 and Parkin at mRNA and protein levels compared to the BPA group (p = 0.024). NG enhanced antioxidant factors, while ROS and MDA levels were decreased in the BPA-exposed cells. The beneficial impacts of NG on BPA-exposed Sertoli cells are related to the suppression of mitophagy and the reduction of oxidative stress.