Shikonin Ameliorates Doxorubicin-Induced Cardiotoxicity

To explore the roles of shikonin in cardiac function, cardiac injury and survival of DOX-treated mice, mice were subjected to a low-dose DOX treatment with or without shikonin. DOX administration resulted in deterioration of cardiac function in mice, as verified by the decreased ejection fraction (EF), shortening fraction (FS) and pressure decay (dp/dt) in left ventricles, which were all increased in mice treated with shikonin (Fig. 1B–F). Previous studies indicated that DOX application significantly decreased the body weight in cancer patients^{29 (link)}, but intriguingly, we found that shikonin attenuated DOX-induced body weight loss in mice (Fig. 1G), which raises the possibility for its clinical use. Meanwhile, we also found that DOX injection decreased the ratio of heart weight to tibia length (HW/TL), which were significantly alleviated by shikonin administration (Fig. 1H). We measured cTnT, CK-MB, and LDH levels to evaluate cardiac injury and function. These biomarkers are commonly used indicators of myocardial damage and provided valuable information on the protective effects of shikonin against doxorubicin-induced cardiotoxicity. And we observed that shikonin significantly reversed the increased levels cTnT, CK-MB and LDH in DOX-treated mice (Fig. 1I–K). Additionally, we observed that Shikonin treatment led to an increase in the survival rate of the mice and a significant increase in their body weight (Fig. S1A–C). More importantly, we found that administration of shikonin showed no hepatic toxicity in mice, as evaluated by the serum concentrations of liver enzymes (Fig. S1D,E). And shikonin did not affect heart rates (Fig. S1F). Altogether, these findings demonstrate that shikonin protects against DOX-induced myocardial damage and dysfunction.