Cardioprotective Potential of Bergenin against Doxorubicin-induced Cardiotoxicity by Targeting Oxidative Stress and Inflammatory Pathways in Rats

Introduction: Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic agents for the treatment of various cancers. However, its clinical use is limited due to its cardiotoxic effects. DOX-induced cardiotoxicity results from excessive generation of reactive oxygen species (ROS), lipid peroxidation, and inflammation in cardiac tissue. Bergenin is a plant-derived molecule isolated from Bergenia ligulata (Haw) Sternb that has potent antioxidant and anti-inflammatory properties. The present study was designed to investigate the cardioprotective effect of bergenin (Berg) against DOX-induced cardiotoxicity and its underlying mechanisms. Methods: Sprague Dawley rats (male) were assigned to five groups: vehicle control, DOX 15 mg/kg single i.p. injection, amlodipine (Amlo) + DOX, Berg 30 mg/kg/animal + DOX, and Berg 60 mg/kg/animal + DOX. Cardiac injury was assessed by measuring serum biomarkers, including troponin-I, CK-MB, LDH, and CPK. Cardiac histology was determined using H&E and trichome staining. Inflammatory markers were evaluated using ELISA, immunohistochemistry (IHC), and PCR. Results: The results revealed that DOX significantly increased cardiac serum biomarkers, indicating tissue damage. Berg pretreatment, especially at 60 mg/kg, led to a significant reduction in troponin I, CK-MB, LDH, and CPK levels compared to DOX alone. Histopathology analysis also demonstrated that Bergmitigated the DOX-induced variations. Furthermore, Berg pretreatment increased Nrf2 and reduced iNOS, NF-κB, TNF-α, and Caspase 3 expression. IHC and RT-PCR also confirmed reduced inflammation and oxidative stress in Berg-treated cardiac tissues. Conclusion: The present study indicated the reduction in cardiac serum biomarkers, inflammatory markers, and histological variations, suggesting that Berg co-administration could mitigate the adverse cardiac effects of DOX. conclusion: Present study indicated the reduction in cardiac serum biomarkers, inflammatory markers, and histological variations suggesting that Bergenin co-administration could mitigate the adverse cardiac effects of doxorubicin.