Muric, Maja (59002523500)Maja (59002523500)MuricSrejovic, Ivan (55754581700)Ivan (55754581700)SrejovicNovakovic, Jovana (58854633200)Jovana (58854633200)NovakovicZivkovic, Vladimir (55352337400)Vladimir (55352337400)ZivkovicJovic, Jovana Joksimovic (59553699800)Jovana Joksimovic (59553699800)JovicSretenovic, Jasmina (56893730400)Jasmina (56893730400)SretenovicNikolic, Marina (58956180400)Marina (58956180400)NikolicLazarevic, Nevena (59248467600)Nevena (59248467600)LazarevicAndjic, Marijana (57214602872)Marijana (57214602872)AndjicKocovic, Aleksandar (57193554378)Aleksandar (57193554378)KocovicUzelac, Jovana Jakovljevic (57210212812)Jovana Jakovljevic (57210212812)UzelacBolevich, Sergey (6603144931)Sergey (6603144931)BolevichJakovljevic, Vladimir (56425747600)Vladimir (56425747600)Jakovljevic2025-07-022025-07-022025https://doi.org/10.1007/s10557-025-07675-4https://www.scopus.com/inward/record.uri?eid=2-s2.0-85217719504&doi=10.1007%2fs10557-025-07675-4&partnerID=40&md5=7f3264a788da0d98411fc887605e33ffhttps://remedy.med.bg.ac.rs/handle/123456789/11478Purpose: The idea behind this study was to assess the effects of empagliflozin and sacubitril/valsartan and their combination on isoproterenol-induced heart failure (HF) and underlying molecular mechanisms. Methods: HF was induced with 7-day isoproterenol (5 mg/kg daily), confirmed by ejection fraction below 55% after 4 weeks. HF rats received empagliflozin, sacubitril/valsartan, or both for 4 weeks. Parameters measured included hemodynamics, cardiac function, redox status, and histomorphology. Results: Isoproterenol impaired hemodynamics and cardiac function, increased oxidative damage, and altered cardiac structure. All treatments were cardioprotective; however, combined empagliflozin and sacubitril/valsartan therapy had the most pronounced effect. Conclusion: Combined empagliflozin and sacubitril/valsartan showed superior cardioprotection in HF, primarily by enhancing antioxidative effects. These findings support early use of both drugs in HF treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.Cardiac functionEmpagliflozinHeart failureOxidative stressSacubitril/valsartan