Quercetin Ameliorates Methotrexate-Induced Reproductive Toxicity in Sertoli Cells

Methotrexate (MTX) is a chemotherapeutic and immunosuppressive drug that can impair spermatogenesis and lead to male infertility. This study examined the effects of different MTX concentrations on TM۴ Sertoli cells and evaluated the protective role of quercetin (QT), a natural antioxidant, against MTX-induced oxidative stress.TM۴ cells were treated with MTX at the following concentrations: ۱ µg/mL /mL, ۵ µg/mL /mL, and ۱۰ µg/mL /mL for ۲۴ hours, ۴۸ hours, and ۷۲ hours. Our results show that an IC₅₀ value of MTX in these cells was ۷ µg/mL. Quercetin was then applied by itself to the cultures at the following concentrations: ۱۰ µg/mL /mL, ۲۵ µg/mL /mL, and ۵۰ µg/mL /mL, and in combination with MTX at its IC₅₀ concentration, for ۲۴ hours. MTX significantly reduced TM۴ cell viability, whereas quercetin treatment markedly alleviated this cytotoxic effect. Levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were significantly higher in MTX-treated cells compared with controls (p < ۰.۰۰۱ and p < ۰.۰۱, respectively). In contrast, MDA and ROS levels were significantly decreased in quercetin-treated cells (p < ۰.۰۵ and p < ۰.۰۱), further supporting its antioxidant activity. In addition, cotreatment with quercetin significantly restored the total antioxidant capacity suppressed by MTX (p < ۰.۰۱). These findings indicate that quercetin effectively protects TM۴ Sertoli cells against MTX-induced oxidative damage.

کلیدواژه ها:

Methotrexate ، Quercetin ، Sertoli ، TM۴ ، ROS