Abstract
Chemotherapy-induced cardiotoxicity remains a major clinical concern, with Sorafenib (Sor) being among the agents associated with adverse cardiac effects. Vitamin B17 (VB17), known for its antioxidant and anti-inflammatory properties, has shown promise in mitigating cardiovascular damage. This study investigated the cardioprotective potential of VB17, alone or in combination with Sor, in a mouse model of Ehrlich Ascites Carcinoma (EAC)-induced cardiomyopathy. Seventy-two male Swiss albino mice were divided into 12 groups and treated with VB17, Sor, or their combination via intraperitoneal or oral routes. Assessments included tumor volume, viable EAC cell count, cardiac enzyme levels (cardiac troponin (cTn), CK-MB, LDH), oxidative stress markers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)), gene expression (IL-1β, NF-κB, TGF-β, MMP-9, P53), histological analysis, and molecular docking. Combination therapy significantly reduced tumor burden and EAC cell viability while improving cardiac function. VB17 co-treatment lowered elevated troponin I levels and normalized creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Oxidative stress was reduced, evidenced by a 50% decrease in MDA and increases in GSH and SOD activities. Gene analysis showed reduced expression of pro-inflammatory and fibrotic markers (IL-1β, NF-κB, TGF-β, MMP-9) and enhanced P53 expression. Histopathological findings confirmed reduced myocardial damage in the combination group compared to Sor alone. These findings suggest that VB17 enhances the cardioprotective effects of Sor by modulating key inflammatory and apoptotic pathways. The combination therapy shows promise as a potential strategy to counteract chemotherapy-induced cardiomyopathy. Further research is needed to validate these results and explore clinical applications.