期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/ijms24065269
关键词
cardiomyocytes; doxorubicin-induced cardiotoxicity; BGP-15; oxidative stress; autophagy; apoptosis; mitochondrial dysfunction
In this study, it was found that pretreatment with BGP-15 can significantly improve the cardiomyocyte damage caused by DOX. This is mainly achieved by preserving mitochondrial function, reducing mitochondrial ROS production, and modulating the autophagy process.
Doxorubicin (DOX) is an efficacious and commonly used chemotherapeutic agent. However, its clinical use is limited due to dose-dependent cardiotoxicity. Several mechanisms have been proposed to play a role in DOX-induced cardiotoxicity, such as free radical generation, oxidative stress, mitochondrial dysfunction, altered apoptosis, and autophagy dysregulation. BGP-15 has a wide range of cytoprotective effects, including mitochondrial protection, but up to now, there is no information about any of its beneficial effects on DOX-induced cardiotoxicity. In this study, we investigated whether the protective effects of BGP-15 pretreatment are predominantly via preserving mitochondrial function, reducing mitochondrial ROS production, and if it has an influence on autophagy processes. H9c2 cardiomyocytes were pretreated with 50 mu M of BGP-15 prior to different concentrations (0.1; 1; 3 mu M) of DOX exposure. We found that BGP-15 pretreatment significantly improved the cell viability after 12 and 24 h DOX exposure. BGP-15 ameliorated lactate dehydrogenase (LDH) release and cell apoptosis induced by DOX. Additionally, BGP-15 pretreatment attenuated the level of mitochondrial oxidative stress and the loss of mitochondrial membrane potential. Moreover, BGP-15 further slightly modulated the autophagic flux, which was measurably decreased by DOX treatment. Hence, our findings clearly revealed that BGP-15 might be a promising agent for alleviating the cardiotoxicity of DOX. This critical mechanism appears to be given by the protective effect of BGP-15 on mitochondria.
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