Mechanistic Insights Into Vincamine's Cardio‐Protection Against Gentamicin Toxicity: Crosstalk Between Nrf2/HO‐1, Klotho, WNT‐4/β‐Catenin, and pERK/NF‐κB Pathways

Gentamicin (GET) is a commonly prescribed aminoglycoside antibiotic used to treat severe bacterial infections, but its therapeutic effectiveness is limited by its cardiotoxicity, which is mainly caused by oxidative damage and inflammation. This study investigated the cardioprotective role of vincamine (VIN) against GET‐induced cardiac injury. Adult male rats were divided into four groups and treated for 7 days with either CMC (control), VIN, GET, or a combination of GET and VIN. Measurements included oxidative stress markers (TAC and MDA), gene expression of inflammatory cytokines and apoptosis markers ( TNF‐α , IL‐6 , Bax , Bcl‐2 ) by qRT‐PCR, protein levels of signaling molecules ( Nrf2 / HO‐1 , WNT‐4, pGSK‐3β, β‐catenin, pERK, Klotho) by qRT‐PCR and ELISA, and NF‐κB protein quantification via Western blot. Cardiac tissue was also examined histologically for structural changes. Results demonstrated that VIN significantly reduced GET‐induced cardiac damage by modulating crucial signaling pathways and markedly diminished the tissue structural alterations caused by GET. These findings suggest that VIN may serve as a promising cardioprotective agent against GET‐induced toxicity through the regulation of pathways including Nrf2 / HO‐1 , pERK/NF‐κB, WNT‐4/pGSK‐3β/β‐catenin, and Bax / Bcl‐2 .