Asiatic Acid Protects against Doxorubicin-Induced Cardiotoxicity in Mice

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.</jats:p

miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in doxorubicin- (DOX-) induced cardiotoxicity. MicroRNA-200a (miR-200a) could target Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation. However, the role of miR-200a in DOX-related cardiotoxicity remained unclear. Our study is aimed at investigating the effect of miR-200a on DOX-induced cardiotoxicity in mice. For cardiotropic expression, male mice received an injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or miR-scramble. Four weeks later, mice received a single intraperitoneal injection of DOX at 15 mg/kg. In our study, we found that miR-200a mRNA was the only microRNA that was significantly decreased in DOX-treated mice and H9c2 cells. miR-200a supplementation blocked whole-body wasting and heart atrophy caused by acute DOX injection, decreased the levels of cardiac troponin I and the N-terminal probrain natriuretic peptide, and improved cardiac and adult cardiomyocyte contractile function. Moreover, miR-200a reduced oxidative stress and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory factors in mice with acute DOX injection. miR-200a also attenuated DOX-induced oxidative injury and cell loss in vitro. As expected, we found that miR-200a activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a supplementation in mice. miR-200a also provided cardiac benefits in a chronic model of DOX-induced cardiotoxicity. In conclusion, miR-200a protected against DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway. Our data suggest that miR-200a may represent a new cardioprotective strategy against DOX-induced cardiotoxicity.</jats:p

A growing system closer to the natural conditions for studying root growth and response of Arabidopsis thaliana

Abstract In natural environments, shoot was exposed to sunlight but roots are not directly exposed to light, being buried deep down in the soil and grow in darkness without sucrose addition. However, most current research in root biology has been carried out by growing the Arabidopsis root system in the presence of light and sucrose-added medium since root development is typically studied in traditional agar-plate culture system (TPG, traditional plant-growing). Here, we present a protocol for improved agar-plate culture system (IPG, improved plant-growing), allows the in vitro cultivation of Arabidopsis with the aerial part growing in normal light/dark photoperiod while roots grow in darkness without sucrose addition. IPG provides an efficient system for cultivating a large number of seedlings and easily characterizing root architecture in the dark. We also provide methods for key steps all the way through to seedlings growth.We found that the primary root lengths in TPG were significantly longer than that in IPG, and the root elongation growth is dependent on auxin-triggered acidification of the root apoplast of Arabidopsis . With this protocol, a better understanding of the mechanisms involved in root growth and responses of plants can be easily characterized.</jats:p