Rosuvastatin mitigates ovarian ischemia-reperfusion injury in rats by modulating oxidative stress, inflammation, and angiogenesis

OBJECTIVE: To investigate the protective effects of rosuvastatin against ovarian ischemia-reperfusion (I/R) injury in a rat model. DESIGN: Controlled experimental study using an induced ovarian torsion-detorsion model. SUBJECTS: Fifty adult female Wistar rats (aged 8-10 weeks, weighing 100-150 g). EXPOSURE: Intraperitoneal administration of rosuvastatin (5 mg/kg) 30 minutes before induction of ischemia in the designated treatment groups. MAIN OUTCOME MEASURES: Ovarian tissue levels of myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT); mRNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-α (TNF-α), and caspase-3; and semiquantitative histopathological scoring of tissue damage. RESULTS: Ischemia and I/R significantly elevated MPO, MDA, VEGF, bFGF, TNF-α, and caspase-3 levels while worsening histological damage. Rosuvastatin pretreatment reduced MPO by 13%-16%, MDA by 9%, VEGF by 7%-14%, bFGF by 14%-37%, TNF-α by 34%-38%, and caspase-3 by 31%-39%; increased TAC by 20%; and markedly improved histopathological scores, including reduced follicular atresia. No significant changes were observed in SOD, GPx, or CAT activities. CONCLUSIONS: Rosuvastatin exerts protective effects against ovarian I/R by attenuating oxidative stress, inflammation, excessive angiogenesis, and apoptosis, independent of major antioxidant enzyme induction. These preclinical findings suggest potential adjunctive utility in limiting reperfusion injury after detorsion; however, protein-level validation, dose-response studies, postischemic administration, long-term fertility outcomes, and safety assessments are required before any clinical translation. TRIAL REGISTRATION: Not applicable. This study is an experimental animal study and was not registered as a clinical trial.