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

Background: 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. Objective: The effect of Naringenin (NG) on BPA-induced Sertoli cell toxicity and its mechanism was examined in the present study. Materials and Methods: In this experimental-laboratory study, the mouse TM۴ cells were treated to BPA (۰.۸ μM) or NG for ۲۴ hr at concentrations of ۱۰, ۲۰, and ۵۰ 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 ۱ (Pink۱), was also evaluated. Results: BPA significantly lowered the viability of the Sertoli cells (p = ۰.۰۰۴). Pink۱ and Parkin levels of the BPA group were significantly increased (p < ۰.۰۰۱), while the MMP was considerably decreased (p < ۰.۰۰۱). BPA raised MDA and ROS levels (p < ۰.۰۰۱) and reduced antioxidant biomarkers (p = ۰.۰۰۳). NG at the ۲۰ and ۵۰ μg/ml concentrations could significantly improve the viability and MMP of TM۴ cells (p = ۰.۰۳۴). NG depending on concentration, could decrease Pink۱ and Parkin at mRNA and protein levels compared to the BPA group (p = ۰.۰۲۴). NG enhanced antioxidant factors, while ROS and MDA levels were decreased in the BPA-exposed cells. Conclusion: The beneficial impacts of NG on BPA-exposed Sertoli cells are related to the suppression of mitophagy and the reduction of oxidative stress.

کلیدواژه ها:

Mitophagy ، Naringenin ، Sertoli cells ، Bisphenol A ، Reactive oxygen species ، Pink۱ ، Parkin. ، میتوفاژی ، نارینجنین ، سلول­های سرتولی ، بیسفنل آ ، گونه­های فعال اکسیژن.