Propolis Attenuates Cisplatin-Induced Ovarian Injury by Modulating Oxidative Stress, Inflammation, Apoptosis, and GRP78/ATF6/CHOP Pathway

Cisplatin-induced ovarian damage is a significant concern for young women receiving chemotherapy. Although propolis, a polyphenol- and flavonoid-rich natural product, has been proposed as a protective agent, its effects on cisplatin-related ovarian injury remain insufficiently defined. This study aimed to investigate whether propolis mitigates cisplatin-induced ovarian toxicity. In this study, 36 adult female Wistar rats were randomly allocated into six groups: Control, Propolis (50 mg/kg), Propolis (100 mg/kg), Cisplatin (7 mg/kg), Cisplatin + Propolis (50 mg/kg), and Cisplatin + Propolis (100 mg/kg). Cisplatin was administered as a single intraperitoneal dose on day 1, while propolis was given orally by gavage once daily for 14 days. Biochemical, histopathological, and endoplasmic reticulum (ER)-stress-related parameters were evaluated. Histopathologically, cisplatin caused significant vascular congestion, hemorrhage, edema, and follicular degeneration (<i>p</i> < 0.01), accompanied by marked reductions in primordial, primary, secondary, and tertiary follicle counts and a significant increase in atretic follicles. Propolis co-administration significantly ameliorated these lesions and partially preserved follicular counts, particularly at the 100 mg/kg dose (<i>p</i> < 0.01). Cisplatin markedly increased malondialdehyde (MDA) levels and ER stress markers (GRP78, ATF6, and CHOP), while reducing glutathione (GSH). Propolis treatment ameliorated these changes, decreased TNF-α and caspase-3 levels, and attenuated oxidative, inflammatory, and apoptotic responses. Propolis exerts strong antioxidant, anti-inflammatory, anti-apoptotic, and ER-stress-modulating effects that collectively counteract cisplatin-induced ovarian injury.