Abstract
PURPOSE: To investigate the protective effects of fisetin on ovarian ischemia-reperfusion injury in rats, focusing on the modulation of the TLR4-MyD88-TRAF6 signaling pathway. METHODS: Wistar rats randomly divided into different groups received oral administration of fisetin (5, 10 and 15 mg/kg). Body weight and ovary weight were measured. Hormones, hematological, antioxidant, cytokines, inflammatory and apoptosis parameters were assessed. Histological and histopathologic evaluations were conducted on ovary tissue. Different mRNA expressions were estimated. RESULTS: Dose dependent treatment significantly improved body and ovary weight along with alteration in hematological parameters such as red blood cells, white blood cells, hemoglobin, platelet, lymphocyte; antioxidant parameters, including malonaldehyde, superoxide dismutase, glutathione, glutathione peroxidase, catalase; cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18); inflammatory parameters such as cyclooxynase-2, inducible nitric oxide synthetase (iNOS), prostaglaindin, nuclear kappa B factor (NF-κB), C reactive protein and apoptosis parameters, including Bcl-2, Bax, and caspase-3. Fisetin treatment significantly (p < 0.001) altered the mRNA expression of TNF-α, IL-6, IL-1β, IL-10, Bax, Bcl-2, caspase-3, toll-like receptor 4, myeloid differentiation primary response protein 88, tumor necrosis factor receptor-associated factor 6, endothelial nitric oxide synthase, iNOS, NF-κB, inhibitor of kappaB kinase alpha, heme oxygenase-1, and nuclear factor erythroid 2-related factor 2. Fisetin treatment altered the hemorrhage, vascular proliferation, polymorphonuclear leukocyte, edema, vascular congestion, and apoptosis. CONCLUSION: Fisetin ameliorated the ovary injury against ovarian ischemia-reperfusion via conquering TLR4-MyD88-TRAF6 signaling pathway.