Myricetin Prevents Doxorubicin-Induced Oxidative Stress and Mitochondrial Apoptotic Pathway in H9C2 Cardiac Cells

Doxorubicin (DOX) is an effective chemotherapy agent widely used in the treatment of solid tumors and hematologic malignancies. The clinical use of DOX is greatly restricted due to its serious cardiotoxic side effects. The aim of the present study was to investigate possible protective effects and molecular mechanisms of myricetin against DOX-induced cardiotoxicity in the cultured H9C2 cardiomyocyte cell line. H9C2 cells were incubated with 1 µM DOX for 24 h to establish a model of DOX‑induced cardiac injury. MTT assay was performed to measure cell viability. The cells were pretreated with myricetin (0.25, 0.5, and 1µM) before DOX treatment. Oxidative stress mediators including lipid peroxidation (LPO), total thiol molecules (TTM), and total antioxidant capacity (TAC) were determined. mRNA expression of Bax and Bcl-2 was determined using the real-time PCR. Moreover, the protein expression of cleaved caspase-3 was assessed by Western blotting. Our results indicated that treatment of H9C2 cardiac myoblasts with DOX decreased cell viability, while myricetin increased the viability of H9C2 cells in response to DOX exposure. DOX markedly decreased TTM and TAC levels. In addition, those above changes could be prevented by myricetin. Furthermore, treatment of the cells with myricetin revealed a considerable decrease in Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, the findings presented in this study suggest that myricetin pretreatment may be considered as a promising therapeutic approach against DOX-induced cardiotoxicity, in part through enhancement of the intracellular antioxidant defense and reduced apoptotic mitochondria pathway.