Abstract
Oxidative damage is closely involved in the development of doxorubicin- (DOX-) induced cardiotoxicity. It has been reported that tetrandrine can prevent the development of cardiac hypertrophy by suppressing reactive oxygen species- (ROS-) dependent signaling pathways in mice. However, whether tetrandrine could attenuate DOX-related cardiotoxicity remains unclear. To explore the protective effect of tetrandrine, mice were orally given a dose of tetrandrine (50 mg/kg) for 4 days beginning one day before DOX injection. To induce acute cardiac injury, the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg). The data in our study showed that tetrandrine prevented DOX-related whole-body wasting and heart atrophy, decreased markers of cardiac injury, and improved cardiac function in mice. Moreover, tetrandrine supplementation protected the mice against oxidative damage and myocardial apoptotic death. Tetrandrine supplementation also reduced ROS production and improved cell viability after DOX exposure in vitro. We also found that tetrandrine supplementation increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and activity in vivo and in vitro. The protection of tetrandrine supplementation was blocked by Nrf2 deficiency in mice. In conclusion, our study found that tetrandrine could improve cardiac function and prevent the development of DOX-related cardiac injury through activation of Nrf2.
Highlights
Doxorubicin (DOX) is a quinone-containing anthracycline and is widely used in the therapy of solid and hematologic malignancies
We found that the mRNA levels of tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and monocyte chemotactic protein- (MCP-) 1 were significantly increased, and these increases could not be suppressed by tetrandrine treatment (Figure 3(a))
The results from our current study demonstrated that tetrandrine protected against DOX-related cardiac injury in vitro and in vivo
Summary
Doxorubicin (DOX) is a quinone-containing anthracycline and is widely used in the therapy of solid and hematologic malignancies. The precise mechanism of DOX-related cardiac injury is multifactorial, including increased reactive oxygen species (ROS) production, inflammatory response, and apoptotic cardiomyocyte death [4, 5]. It has been reported that the heart is more sensitive to DOX-related oxidative injury [6]. The search for a drug that could reduce oxidative stress in response to DOX is of great clinical importance for the treatment of DOX-related cardiac toxicity. The effects of tetrandrine on DOX-induced cardiac injury, especially acute injury, and the related signaling mechanisms are unclear. We first determined the protective effects of tetrandrine on DOX-induced acute cardiac injury in mice. We found that tetrandrine could suppress the acute toxic effects caused by DOX injection in mice
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