Rezaei-Tazangi F, Fakhredini F, Astaneh M E, Aliakbari F, Khoob Z, Motamed-Jahromi M. The Effects of Rutin on Mitophagy and Oxidative Stress Induced by Bisphenol A in Sertoli Cells (TM4 Cell Line). J Mazandaran Univ Med Sci 2026; 36 (260) :68-81
URL:
http://jmums.mazums.ac.ir/article-1-22793-en.html
Abstract: (28 Views)
Background and purpose: Bisphenol A (BPA) is an endocrine-disrupting chemical associated with oxidative stress and mitochondrial dysfunction in reproductive cells. Rutin, a naturally occurring flavonoid with antioxidant properties, may protect cells against oxidative damage. This study aimed to investigate the protective effects of rutin against BPA-induced oxidative stress and mitochondrial dysfunction and to evaluate changes in the expression of mitophagy-related genes in TM4 Sertoli cells.
Materials and methods: In this experimental study, TM4 Sertoli cells were exposed to BPA alone or in combination with different concentrations of rutin. Cell viability was assessed using the MTT assay, and protein content was determined by the Bradford method. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using a spectrofluorimeter. The expression of PINK1, BNIP3, and Parkin genes was evaluated by real-time PCR. Malondialdehyde (MDA), glutathione (GSH), and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured using spectrophotometric methods.
Results: Rutin significantly reduced MDA levels in BPA-exposed Sertoli cells. Moreover, rutin significantly increased SOD and CAT activities and improved mitochondrial membrane potential in BPA-exposed cells. Rutin also increased GSH and GPx levels, indicating an enhancement of cellular antioxidant defences against BPA-induced damage. Changes in PINK1, BNIP3, and Parkin expression suggested that rutin may modulate mitophagy-related pathways under BPA-induced stress.
Conclusion: Rutin may attenuate BPA-induced oxidative and mitochondrial damage in TM4 Sertoli cells and enhance antioxidant defences. The observed changes in mitophagy-related gene expression suggest a potential role for mitophagy-related pathways in rutin-mediated protection. However, protein-level validation and functional assessment of mitophagic flux are needed to confirm this proposed mechanism.