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

Doxorubicin is an effective chemotherapeutic agent widely used in the treatment of solid tumors and hematologic malignancies. The clinical use of doxorubicin is greatly restricted due to its serious cardiotoxic side effects. The present study aimed to investigate the possible protective effects and molecular mechanisms of myricetin against doxorubicin-induced cardiotoxicity in the cultured H9C2 cardiomyocyte cell line. H9C2 cells were incubated with 1 µM doxorubicin for 24 h to establish a model of doxorubicin‑induced cardiac injury. MTT assay was performed to measure cell viability. The cells were pretreated with myricetin (0.25, 0.5, and 1 µM) before doxorubicin treatment. The levels of reactive oxygen species, lipid peroxidation, total thiol molecules, total antioxidant capacity, tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were determined. mRNA expression of BAX and BCL2 was determined using real-time PCR. Moreover, cleaved caspase-3 protein expression was assessed by western blotting. Our results indicated that treatment of H9C2 cardiac myoblasts with doxorubicin decreased cell viability, whereas myricetin increased cell viability upon exposure. Doxorubicin markedly elevated ROS, TNF-α, and IL-1β levels while decreasing total thiol levels and total antioxidant capacity. In addition, myricetin prevented the changes described above. Furthermore, treatment of the cells with myricetin resulted in a significant decrease in the BAX/BCL2 mRNA ratio and in cleaved caspase-3 expression. In conclusion, the findings presented in this study suggest that myricetin pretreatment may be a promising therapeutic approach against doxorubicin-induced cardiotoxicity, in part by enhancing intracellular antioxidant defense and reducing inflammatory markers and the apoptotic pathway.