Abstract
The use of doxorubicin (DOX) can result in depression of cardiac function and refractory cardiomyopathy. Currently, there are no effective approaches to prevent DOX-related cardiac complications. Asiatic acid (AA) has been reported to provide cardioprotection against several cardiovascular diseases. However, whether AA could attenuate DOX-related cardiac injury remains unclear. DOX (15 mg/kg) was injected intraperitoneally into the mice to mimic acute cardiac injury, and the mice were given AA (10 mg/kg or 30 mg/kg) for 2 weeks for protection. The data in our study found that AA-treated mice exhibited attenuated cardiac injury and improved cardiac function in response to DOX injection. AA also suppressed myocardial oxidative damage and apoptosis without affecting cardiac inflammation in DOX-treated mice. AA also provided protection in DOX-challenged cardiomyocytes, improved cell viability, and suppressed intracellular reactive oxygen species (ROS) in vitro. Detection of signaling pathways showed that AA activated protein kinase B (AKT) signaling pathway in vivo and in vitro. Furthermore, we found that AA lost its protective effects in the heart with AKT inactivation. In conclusion, our results found that AA could attenuate DOX-induced myocardial oxidative stress and apoptosis via activation of the AKT signaling pathway.
Highlights
Anthracyclines are the primary choice in patients with severe leukemias, lymphomas, and solid tumors [1]
We investigated the effect of Asiatic acid (AA) on DOX-induced cardiotoxicity
Our results showed that AA treatment protected against DOX-induced cardiac injury, oxidative stress, and cell death without affecting inflammation
Summary
Anthracyclines are the primary choice in patients with severe leukemias, lymphomas, and solid tumors [1]. Previous studies demonstrated that cardiac dysfunction even occurs at a very low therapeutic dose of DOX [4, 5]. It is of great importance to find drugs that could protect against DOX-induced cardiac injury. A previous study found that oxidative stress and subsequent lipid peroxidation could be detected in DOXtreated hearts even at three hours after DOX administration [8]. Prevention of oxidative stress may be a promising method against DOX-induced cell loss and cardiac dysfunction. We determined the effect of AA on DOX-induced cardiotoxicity and investigate the underlying mechanisms. Results of our study indicate that DOXinduced cardiac injury can be reduced by AA administration with concomitant activation of protein kinase B (AKT)
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