Cistanche deserticola Polysaccharides Protect Against Doxorubicin-Induced Cardiotoxicity via Antioxidant and Mitochondrial Mechanisms

Doxorubicin (DOX), a clinical broad-spectrum anthracycline chemotherapeutic agent, induces dose-dependent cardiotoxicity that progresses to heart failure (HF), thereby severely limiting its clinical application. Mitochondrial dysfunction and oxidative stress dysregulation are core pathological mechanisms underlying DOX-induced myocardial injury. This study aimed to investigate the protective effect and underlying mechanism of <i>Cistanche deserticola</i> polysaccharides (CDPs) against DOX-induced cardiotoxicity in C57BL/6J mice. Compared with the DOX model group, CDPs significantly increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduced the activities of serum creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Additionally, CDPs notably decreased the malondialdehyde (MDA) levels in serum and myocardial tissue, while significantly enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, CDPs ameliorated mitochondrial swelling and crista fracture, upregulated the expression of mitochondrial respiratory chain complex-related genes, and increased adenosine triphosphate (ATP) production. In conclusion, CDPs alleviate DOX-induced cardiotoxicity and protect cardiac function by inhibiting myocardial oxidative stress and improving mitochondrial function, which provides a potential therapeutic strategy for preventing DOX-related cardiotoxicity.