Russell Nahorski; Arnim Ploeger; Lorena Ludovici; Raffaele Marchis; Stephen Eikan; Maria Mckay; Fiorella Gille; Detlef Mazzon
Received October 09, 2016; Accepted February 28, 2017; Published March 29, 2017
http://dx.doi.org/10.18081/2333-5106/017-93-108
Abstract
Worldwide, breast cancer continues to be a major challenge, affecting a large number of women, with approximately 2.1 million cases being reported annually. Doxorubicin is one of the most important natural chemotherapy drugs for the treatment of breast cancer and other solid tumors. However, the cardiotoxic side effects resulting from the poor ability of doxorubicin to discriminate between cancer and healthy cells limit its clinical application. In this work, TLR4/NF-кB stimulated doxorubicin-injured cardiomyocytes were used in vitro to explore potential protective methods associated with myocardial injury induced by doxorubicin. As one of the front-line natural anti-inflammatory agents, AS achieves cardioprotective effects. AS antagonizes doxorubicin-induced myocardial injury by inhibiting the TLR4/NF-кB signaling pathway. However, our data demonstrate the demyelinating properties of doxorubicin in otherwise healthy rat cardiomyocytes, as evidenced by elevated levels of CK-MB, LDH, and cTnT. After treatment with AS, the secretion of heart injury markers was significantly reduced, and the myocardium structure was repaired. Furthermore, the reduced expression of key regulators in the TLR4/NF-кB signaling pathway highlights the related protective mechanism. This work describes the discovery of a new strategy for protecting doxorubicin-damaged hearts and provides evidence that AS inhibits the TLR4/NF-кB signaling pathway. The protective effect of AS could be associated with the dephosphorylation of downstream molecules within the TLR4/NF-кB signaling pathway. In conclusion, AS added to the potential therapy list for myocardial injury induced by doxorubicin and proposed a putative cardioprotective mechanism. Our findings suggest that AS is promising for treating doxorubicin-induced myocardial injury.
Keywords: Astragaloside; Cardiomyopathy; Doxorubicin; Chemotherapy, Cardiotoxicity
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