Pinostrobin, a dietary bioflavonoid exerts antioxidant, anti-inflammatory, and anti-apoptotic protective effects against methotrexate-induced ovarian toxicity in rats.

This study investigated the protective activities of pinostrobin (PIN) against methotrexate (MTX)-induced ovarian toxicity. Female rats were administered with PIN (50 mg/kg) for 4 weeks, while MTX was administered from weeks 2-4 of PIN treatment. Serum hormonal profiles, ovarian oxidative stress, inflammatory and apoptotic biomarkers as well as ovarian histomorphometry were evaluated. MTX administration elicited profound deficit in serum progesterone and estrogen (E2) levels, while luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly increased. Additionally, MTX administration was associated with significant increases in ovarian malondialdehyde, nitric oxide, NF-кB, TNF-α, IL-6, IL-1β, iNOS and caspase-3 activity, as well as notable reduction in the activities of glutathione peroxidase, catalase and superoxide dismutase as well as the level of glutathione. Whereas, treatment with PIN significantly decreased serum levels of FSH and LH, as well as ovarian levels of NO, MDA, caspase 3, NF-κB, IL-1β, IL-6, TNF-α and iNOS. PIN also significantly upregulated GSH, GPx, CAT and SOD in the ovarian tissues as well as increased serum E2 and progesterone levels compared to the MTX group. Furthermore, PIN significantly restored altered ovarian histoarchitecture in the treated group. These findings suggests that PIN exerts protective effects against MTX-triggered ovarian damages.