Oxidative stress and apoptosis serve an essential role in
cisplatin-induced
cardiotoxicity, which limits its clinical use, and increases the risk of
cardiovascular disease. As a natural
drug, the
antioxidant and antitumor effects of
cyanidin have been recognized, but its protective effect on
cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with
cisplatin (1-40 µM) in the presence or absence of
cyanidin (40-80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that
cyanidin was able to dose-dependently reverse
cisplatin-induced cell damage and apoptosis, attenuate the accumulation of
reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of
caspase 3,
caspase 9, but not
caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in
cisplatin-induced apoptosis.
Cyanidin was able to block the translocation of Bax and reduce the release of
cytochrome c from cytoplasm. These data indicate that
cyanidin attenuates
cisplatin-induced
cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated
kinase signaling pathways may also serve important roles.