Amoura M. Abou-El-Naga
1 
, Aya M. Abd-Elhady
1, Mohamed E. Abdraboh
1 , Yasmin M. Tag
2, Maher Monir Akl
3* 1 Department of Zoology, Faculty of Science, Mansoura University, 35516, Mansoura, Egypt.
2 Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Gamasa, 35516, Egypt.
3 Faculty of Medicine, National Research Lobachevsky State University of Nizhny Novgorod, 603022, Nizhny Novgorod, Russia.
Abstract
Purpose: This study evaluated the protective effects of protodioscin against doxorubicin (DOX)-induced ovarian injury by examining its potential to modulate hormonal alterations and apoptosis-related pathways in a rat model. Methods: Forty female Wistar rats were randomized into four groups: control, protodioscin (10 mg/kg orally for 14 days), DOX (10 mg/kg intraperitoneally on Day 7), and DOX plus protodioscin. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and 17β-estradiol (E2) were quantified using enzyme-linked immunosorbent assay. Ovarian histopathology and immunohistochemistry were performed to evaluate tissue integrity and expression of p53, CDK4, and Survivin. Gene expression of Bax and Bcl-2 was assessed using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: DOX administration significantly reduced ovarian weight by 38.5% and uterine weight by 22.6% (P < 0.01) compared with controls, accompanied by marked hormonal alterations, including increased FSH and decreased LH, AMH, and E2 levels. DOX also increased p53 and Bax expression and decreased Bcl-2 expression, resulting in an elevated Bax/Bcl-2 ratio. Co-treatment with protodioscin significantly attenuated these changes, partially restoring hormonal levels and modulating apoptosis-related markers. Protodioscin reduced p53 and Bax expression while increasing Bcl-2, CDK4, and Survivin levels, leading to a marked reduction in the Bax/Bcl-2 ratio (P < 0.05). Conclusion: Protodioscin exerts a protective effect against DOX-induced ovarian injury, likely through modulation of hormonal disturbances and apoptosis-related pathways. However, these findings should be interpreted with caution due to the absence of estrous cycle synchronization and the use of an acute DOX model.