Protective effects of apricot kernel oil and metformin against BPA-induced ovarian toxicity in rat models of polycystic ovary syndrome: insights into PI3K/AKT and mitochondrial apoptosis pathways

Abstract In this study, the therapeutic synergistic effects of metformin (MET) and Apricot Kernel Oil (AKO) were investigated in an animal model of bisphenol A (BPA)-induced polycystic ovary syndrome (PCOS). BPA disrupts endocrine functions and induces oxidative stress in ovarian tissues, leading to PCOS. AKO and MET target underlying mechanisms associated with PCOS, particularly those related to insulin resistance and oxidative stress, which are critical in the pathology of this condition. Antioxidant activities, total phenolic, and flavonoid contents of AKO were performed. The AKO underwent liquid chromatographic–electrospray ionization tandem mass-spectrometric (LC–ESI-MS/MS) analysis after acetonitrile treatment. PCOS was induced in adult Wistar rats by administering BPA. After 60 days, the 70 rats were divided into seven groups (n = 10/group): Normal, PCOS, MET, AKO, and co-treatment with MET and AKO. On the 22ndday of the study, serum catalase, glutathione peroxidase, superoxide dismutase activity, LH, FSH, progesterone, estrogen, and testosterone hormones alongside inflammatory cytokines (TNF-a, IL-6, CRP, and IL-1β) and nitric oxide levels were measured. Ovarian tissues were isolated for measurements of ferric reducing ability of plasma and thiobarbituric acid reactive substances levels. The expression of genes and proteins related to mitochondrial and PI3K/AKT pathways was analyzed. The results demonstrated that AKO, in synergy with MET, modulated hormone levels, reduced pro-inflammatory cytokines, and enhanced antioxidant properties. AKO, in combination with MET modulated apoptosis via mitochondrial and PI3K/AKT pathways. These findings suggest that AKO holds promise as a potential therapeutic option for women with ovulation disorders, particularly those affected by bisphenol A-induced PCOS.