Natural Polysaccharide β-Glucan Protects against Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress

Abstract

Doxorubicin (DOXO) can be used to treat a variety of human tumors, but its clinical application is limited due to severe cardiotoxic side effect. Here, we explore the role of β-glucan in DOXO-induced cardiotoxicity in mice and study its underlying mechanism. When co-administered with DOXO, β-glucan was observed to prevent left ventricular dilation and fibrosis. In fact, DOXO reduces the activity of mitochondrial respiratory chain complex and enhances oxidative stress, which in turn impairs heart function. DOXO decreases the ATP production capacity of the heart and increases the ROS content, while β-glucan can restore the heart capacity and reduce oxidative stress. β-glucan also increases the activity of antioxidant enzymes GSH-PX and SOD, and reduces the level of MDA in the serum. In addition, the mRNAs of cardiac dysfunction marker genes ANP, BNP and Myh7 were significantly increased after DOXO induction, however, they did not increase when combined with β-glucan administration. In conclusion, our results indicate that β-glucan can improve the antioxidant capacity of the heart, thereby serving as a potential therapeutic strategy to prevent DOXO-induced cardiotoxicity.