Prophylactic and Curative Effects of Citrus aurantifolia Peels Extract on Doxorubicin-Induced Ovarian Oxidative Stress and Histopathological Alterations in Female Wistar Rats

Laburpena

Background: Doxorubicin (DOX), a potent chemotherapeutic agent, is widely used in treating various malignancies but is limited by its dose-dependent toxicity, particularly in reproductive organs. Ovarian toxicity resulting from DOX administration leads to oxidative stress, follicular atresia, and impaired fertility. Natural antioxidants from medicinal plants have been explored as protective agents against chemotherapy-induced organ damage. Citrus aurantifolia (lime) peel contains flavonoids, phenolic acids, and vitamin C, which possess strong antioxidant and anti-inflammatory activities. This study investigated the prophylactic and curative effects of Citrus aurantifolia peels extract (CAPE) on DOX-induced ovarian toxicity in female Wistar rats.

Methods: Sixty female Wistar rats were divided into prophylactic and curative experimental models, each with six subgroups (n=5). CAPE (100, 200, and 400 mg/kg) and a reference antioxidant, alpha lipoic acid {ALA}(150 mg/kg), were administered orally for seven days either before or after a single intraperitoneal dose of DOX (15 mg/kg). Ovarian tissues were evaluated for oxidative stress biomarkers, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and vitamin C and examined histologically. Statistical analysis was conducted using ANOVA with significance set at p < 0.05.

Results: DOX administration significantly increased MDA levels while decreasing GSH, SOD, catalase, and vitamin C concentrations. CAPE markedly reversed these alterations in a dose-dependent manner, with the 400 mg/kg dose demonstrating comparable effects to alpha lipoic acid. Histopathological analysis revealed restoration of normal follicular structure, reduced edema, and improved ovarian morphology, especially in prophylactic groups.

Conclusion: CAPE exhibited significant prophylactic and curative antioxidant and histoprotective effects against DOX-induced ovarian damage, suggesting its potential as a natural adjunct for preserving female fertility during chemotherapy.