Study on the Protective Effect of Sodium Ferulate Against Doxorubicin-Induced Cardiotoxicity in Zebrafish

Doxorubicin (DOX) is a widely used first-line chemotherapeutic agent with potent antitumor efficacy. However, its irreversible and dose-dependent cardiotoxicity severely limits its clinical application. Sodium ferulate (SF), a bioactive ingredient extracted from traditional Chinese medicinal herbs such as Rheum palmatum L., Cimicifuga foetida L., and Ligusticum chuanxiong Hort., possesses antioxidant and antithrombotic properties, suggesting potential cardioprotective effects. In this study, a DOX-induced cardiotoxicity model was established using transgenic zebrafish, and the protective effects of SF were systematically evaluated through transcriptomic profiling, histopathological examination, and molecular validation.The results demonstrated that DOX exposure reduced the survival rate of zebrafish, triggered cardiac dysfunction characterized by decreased heart rate and pericardial edema, and caused myocardial structural damage and cardiomyocyte death. Notably, SF intervention significantly alleviated the above DOX-induced cardiotoxic phenotypes, including myocardial pathological damage and cardiomyocyte loss. Transcriptomic profiling revealed that DOX disrupted pathway related to oxidative stress, apoptosis, cardiac contraction, and PPAR signaling, while SF intervention effectively reversed these altertions. Quantitative PCR further confirmed that SF upregulated antioxidant genes (Nrf2, HO-1, and Sod2), downregulated pro-apoptotic genes (Bax, Caspase 3, andp53), and restored expression of key myocardial structural genes (Vmhc, Cmlc2, and Tnnt2).Collectively, SF protects against DOX-induced cardiotoxicity by modulating oxidative stress and apoptotic signaling pathways, offering a promising therapeutic strategy for chemotherapy-associated cardiac injury.