The Comparasion of The Effects of Novel Antioxidant Compounds Ebselen, Isorhamnetin, and Genistein on the Cardiovascular System

Purpose: This study evaluated the effects of antioxidants Ebselen (EBS), Isorhamnetin (ISO), and Genistein (GEN) on oxidative stress (OS), hemodynamic parameters, and cardiovascular histopathology in rats. Methods: Forty adult Wistar rats were randomized into four groups (n=8/group): control (vehicle), EBS (15 mg/kg/day), ISO (5 mg/kg/day), and GEN (10 mg/kg/day) for 7 days. Hemodynamic parameters, biochemical markers, and histopathological changes in cardiac and aortic tissues were analyzed. Caspase-3 immunoreactivity assessed apoptosis. Results: EBS significantly increased diastolic and mean blood pressure versus control (p<0.05). All treatments reduced cardiac malondialdehyde, indicating OS attenuation. GEN exhibited the strongest antioxidant effect, with improved glutathione and catalase activity. EBS paradoxically reduced aortic glutathione and increased malondialdehyde, suggesting pro-oxidant potential. Histopathology revealed myocardial degeneration in EBS and ISO groups, while GEN preserved cardiac structure. ISO and GEN enhanced aortic glutathione, but EBS showed mixed effects. Serum alanine aminotransferase elevation in ISO and GEN indicated mild hepatotoxicity. Caspase-3 immunoreactivity was elevated in EBS-treated hearts (p<0.001), implying pro-apoptotic effects. Conclusion: GEN demonstrated robust antioxidant and cardioprotective effects, making it a promising therapeutic candidate. ISO showed vascular benefits but requires further safety evaluation. EBS, despite reducing OS, may induce adverse cardiac effects, warranting caution. These findings underscore the need for targeted antioxidant therapies in cardiovascular diseases, balancing efficacy and safety. Ethics approval An application was made to the Inonu University Faculty of Medicine Animal Experiments Local Ethics Committee for ethical approval, and ethics committee permission was obtained with ethical approval number 2016/A-103. Author’s contributions OO: Supervision, Conceptualization, Software, Visualization, Data curation, Writing- Original draft preparation, Writing-Reviewing and Editing. AA: Supervision, Writing-Reviewing and Editing. AY: Investigation, Methodology, Visualization. NE: Investigation, Methodology, Visualization. BA: Investigation, Data curation, Validation, Investigation, Methodology. NV: Investigation, Data curation, Validation, Investigation, Methodology. CC: Investigation, Methodology, Visualization. MG: Writing-Reviewing and Editing. HP: Supervise, write, review, and Edit. Conflicts of interest/Competing interests The authors have no relevant financial or non-financial interests to disclose. Funding This work was supported by Research Fund of the Inonu University. (Project number: 2016/189 belongs to Haci Ahmet Acet.).