Fatty acids ameliorate doxorubicin-induced intracellular Ca²⁺ increase and apoptosis in rat cardiomyocytes

Doxorubicin (Dox) is a highly effective anticancer drug but exhibits cumulative dose-dependent cardiomyopathy. In this study, we investigated effects of Magnolia seed extract (MagS) on the Dox-induced cardiotoxicity. The results showed that MagS significantly reduces doxorubicin (Dox)-induced increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i), generation of reactive oxygen species (ROS), and apoptosis in rat cardiomyocytes. Analyses of the bioactive compounds in MagS by thin layer chromatography and gas chromatography/mass spectroscopy revealed that bioactive compounds in MagS are linoleic acid, oleic acid, and palmitic acid. All three fatty acids were able to inhibit the Dox-induced increase in [Ca ²⁺]_i, ROS generation, and apoptosis with a similar potency. Efficacy of MagS was examined in in vivo using a murine Dox-induced cardiomyopathy model. Dox (12 mg/kg, intravenously) was administered to mice and treated with the MagS (2 mg/kg/d, intraperitoneally) or saline for three weeks. Dox-treated mice showed structural disarray in heart tissue, including lymphocyte infiltration and loss of body weight. In contrast, treatment of the MagS substantially attenuated the Dox-induced cardiac damages including the loss of body weight. These results indicate that fatty acids in MagS and other seeds may ameliorate cardiotoxicity of the anticancer drug.