Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy.

Li-Fei Luo,Lu-Yun Qin,En-Sheng Ji,Peng Guan,Na Wang,Jian-Xin Wang

doi:10.3389/fphar.2021.669782

Li-Fei Luo, Lu-Yun Qin + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2021.669782

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Abstract

Astragaloside IV (ASIV) is the main active component of Astragalus, and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups (n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway.

Highlights

Adriamycin (ADR) is a powerful antineoplastic agent (Liu et al, 2020) that is widely used to treat high-grade osteosarcoma (Anninga et al, 2011) in the clinic
The expression of p62 (Figure 4F) in the ADR group was decreased, and Astragaloside IV (ASIV) restored the expression of p62. These results proved that ADR increased the autophagic flux in rat cardiomyocytes and that ASIV reversed the abnormal increase in autophagy induced by ADR. mTOR is an important regulator related to protein synthesis and cell survival, and it is an important negative regulator of autophagy
Our study investigated the effect of ASIV on ADR-induced myocardial injury in rats

Summary

Introduction

Adriamycin (ADR) is a powerful antineoplastic agent (Liu et al, 2020) that is widely used to treat high-grade osteosarcoma (Anninga et al, 2011) in the clinic. Cumulative doses of adriamycin can cause severe heart damage (Navarro-Hortal et al, 2020). Adriamycin is a first-line cancer treatment drug, its cardiotoxicity can lead to cardiomyopathy and eventually to heart failure, which substantially limits its clinical application. Previous studies have shown that induction of an abnormal increase in free radical productions is the main mechanism by which adriamycin causes myocardial damage (Sun et al, 2014; Kalyanaraman, 2020). With the gradual increase in the number of studies showing that adriamycin causes myocardial damage through oxidative stress, it was found that inhibiting oxidative stress alone cannot prevent heart failure (Sun et al, 2014; Khadka et al, 2018; Kalyanaraman, 2020). The cardiotoxicity caused by adriamycin through other mechanisms is worth studying

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