Protective effects of polydatin on cyclophosphamide-induced ovarian and uterine damage in rats via modulation of hormonal, oxidative, inflammatory, and histopathological alterations

Cyclophosphamide (Cyclo) is a chemotherapeutic agent whose clinical use is limited by its toxic effects on ovarian and uterine tissues. Polydatin (Poly), a resveratrol derivative with antioxidant and anti-inflammatory properties, was evaluated for its protective potential against Cyclo-induced reproductive toxicity. Female rats were divided into five groups: control, Poly (100 mg/kg), Cyclo, and combination groups (Cyclo + Poly 50 mg/kg, Cyclo + Poly 100 mg/kg). Poly was administered orally and Cyclo was administered intraperitoneally. Serum hormone levels (AMH, FSH, E2, LH), antioxidant parameters (SOD, CAT, GPx, GSH), inflammatory markers (NF-κB, TNF-α, IL-1β), gene expression (Pgr, Esr1, Esr2, Cyp19a1, Foxl2, Amh, Hoxa10, Lhcgr, Hsd3b1, Cyp11a1, Sohlh2), and protein levels (BAX, BCL-2, ERK1/2, CREB) were analyzed using ELISA, RT-PCR, Western blot and immunohistochemistry methods. Histopathological analyses were also performed. The results showed that Cyclo significantly disrupted hormonal balance, reduced antioxidant activity, increased inflammatory markers, and induced apoptosis in ovary and uterine tissues. Poly administered with Cyclo dose-dependently attenuated these changes, restoring hormone levels, gene expressions, antioxidant status, and tissue integrity. Consequently, Poly may be a potential therapeutic agent for alleviating Cyclo-induced reproductive toxicity.