Amelioration of Doxorubicin Induced Cardiotoxicity in Tumor Bearing Mice by Ferulic Acid: a Mechanistic Study at Cellular and Biochemical Level

Doxorubicin (DOX) is one of the most effective anticancer therapeutic but its use is limited by cardiotoxicity. The generation of reactive oxygen species (ROS) and mitochondrial dysfunction have been implicated in DOX-induced cardiotoxicity. Cardiotoxicity was induced in tumor bearing mice by a single dose of DOX (25mg/kg, i.p). Ferulic acid (FA) (100 mg/kg p.o and 200 mg/kg p.o) was administered one hour after DOX administration. The administration of FA significantly protected the myocardium from the toxic effects of DOX by reducing the levels of serum marker enzymes like CK and LDH and other serum enzymes SGOT and SGPT, which were elevated during DOX induced cardiomyopathy. The level of HDL was also significantly increased in FA administered groups compared to DOX control. FA protected the cardiac tissues, whereas it potentiated the anticancer efficacy of DOX in tumor tissues as evident from different antioxidant enzyme levels and the extent of lipid peroxidation. The histopathological observations also supported these results. FA effectively protected cellular DNA in heart tissue preferentially, without offering any protection to the DNA in tumour tissues as evidenced from the comet assay. These results suggest that ferulic acid has a protective effect against cardiotoxicity induced by DOX and it may, therefore improve the chemotherapeutic index of DOX.