Synergistic effects of AgNPs and zileuton on PCOS via ferroptosis and inflammation mitigation
Amira Kamel Eltokhy, Rehab Ahmed Ahmed El‐Shaer, Omnia Safwat El‐Deeb, Eman E. Farghal, Rowida Raafat Ibrahim, Rasha Osama El‐Esawy, Marwa Mahmoud Awad, Radwa Ismail, Shaimaa M. Motawea, Doaa Shatat, Yasser Mostafa Hafez, Hend Ahmed El hanafy, Marwa Mohamed Atef
Abstract
Background: The most prevalent endocrine disorder affecting women is PCOS. Programmed death of ovarian cells has yet to be elucidated. Ferroptosis is a kind of iron-dependent necrosis featured by significantly Fe+2-dependent lipid peroxidation. The ongoing study aimed to reinforce fertility by combining therapy with AgNPs and (Zileuton) in PCOS rats’ model.Methods: The study included 75 adult female rats divided into 5 groups; control, PCOS, PCOS treated with AgNPs, PCOS treated with Zileuton, and PCOS group treated with AgNPs and Zileuton. The study investigated the anti-ferroptotic, anti-inflammatory, antioxidant, antiapoptotic, histopathological and immunohistochemical examinations of COX-2 and VEGF.Results: The combination of AgNPs and Zileuton showed significant reduction of inflammatory mediators (IL-6, TNF-α, NFk-B) compared with diseased group (P-value < 0.05), regression of ferroptosis marks (Panx1 and TLR4 expression, Fe+2 levels) compared with diseased group (P-value < 0.05), depression of apoptotic marker caspase 3 level compared with diseased animals (P-value < 0.05), depression of MDA level, elevation of HO-1, GPx4 activity, and reduction of Cox2 and VEGF as compared with the diseased, AgNPs or zileuton-treated groups (P-value < 0.05).Conclusion: The study showed that the combination of AgNPs and zileuton guards against, inflammation, apoptosis, and ferroptosis in PCO.