Bee-Derived Antioxidants as a Protective Strategy Against Doxorubicin-Induced Ovarian Damage

Antineoplastic agents can induce tissue damage through oxidative stress mechanisms. Doxorubicin, a widely used chemotherapeutic agent, has been shown to cause permanent damage to reproductive tissues. Antioxidant-rich dietary interventions are considered a promising approach to mitigate oxidative stress-related damage. This study aimed to evaluate the therapeutic potential of an antioxidant-rich bee product mixture (ARPM) in ameliorating doxorubicin-induced ovarian injury. The ARPM, composed of honey, pollen, propolis, and royal jelly, was administered via gavage to female Sprague-Dawley rats (180-200 g) following chronic ovarian damage induced by doxorubicin (6 mg/kg, ip). Oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH), as well as endoplasmic reticulum (ER) stress-related markers such as 78-kDa glucose-regulated protein (GRP78), inositol-requiring enzyme 1 (IRE1), C/EBP homologous protein (CHOP), tumor necrosis factor-alpha (TNF-α), and caspase-3, were simultaneously evaluated. In addition, estradiol (E2) and progesterone levels were measured, and histopathological evaluations were conducted. The mixture, rich in bioactive compounds including chrysin, pinocembrin, caffeic acid, ferulic acid, and coumaric acid, was found to significantly improve ovarian function by reducing ER stress compared to the control group. These findings suggest that ARPM may offer protective effects against doxorubicin-induced ovarian damage through its antioxidative and anti-ER stress properties.