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.
Highlights
DOXO has been used for more than 50 years in the treatment of liver cancer, breast cancer and many other types of malignancies as an effective clinical anti-tumor drug
We aimed to evaluate whether β-glucan can prevent DOXO-induced cardiotoxicity by reducing oxidative stress and enhancing mitochondrial function
DOXO can break the dynamic balance between antioxidant enzymes and ROS in the cell, indirectly cause cell apoptosis and destruction of Ca2+ homeostasis [31,40,41,42,43]
Summary
DOXO has been used for more than 50 years in the treatment of liver cancer, breast cancer and many other types of malignancies as an effective clinical anti-tumor drug. The incidence of cardiotoxicity due to the use of DOXO is as high as 11% [2]. The main strategies to prevent cardiotoxicity caused by DOXO are as follows: (1) Free radical scavengers, antioxidants and anti-inflammatory cytokines can reduce cardiotoxicity [3,4,5]. Liposomes or nanoparticles can preferentially target tumor tissues, thereby reducing the concentration of DOXO exposed to plasma [9]. How to prevent and treat cardiotoxicity caused by DOXO has not yet been accepted clinically. It is urgent to explore and study effective DOXO-induced cardiotoxic protective agents
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