Protective effect of Baicalin against doxorubicin-induced cytotoxic and electrophysiological damage in human iPSC-cardiomyocytes

Abstract

Abstract Doxorubicin (DOX) remains one of the most effective chemotherapeutic agents for a variety of solid tumors and hematological malignancies. Nevertheless, its clinical utility is restricted by DOX-induced cardiotoxicity (DIC), primarily driven by oxidative stress, inflammation, and apoptosis. Baicalin (BAI), a natural compound with antioxidant, anti-inflammatory, and anti-cancer properties, has shown cardioprotective effects in DOX-treated animal cardiac models, but its impact on human cardiomyocytes remains unexplored. This study was designed to assess the cardioprotective effects of BAI against human cardiac DIC using induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were pretreated with BAI and exposed to acute (1 µM for 24 h) and long-term (0.3 µM for 7d) DOX treatments, with or without different BAI concentrations (1 µM, 10 µM, and 25 µM). Multielectrode array (MEA) analysis, Tunel and cleaved-caspase 3 staining, reactive oxygen species (ROS) analysis, and sarcomere protein staining were performed to assess the effects of BAI on human DIC. BAI treatment alleviates DOX-induced cytotoxic injury, reducing apoptosis, oxidative stress, and preventing sarcomere disorganization. Moreover, BAI attenuated the long-term DOX-induced electrophysiological alterations, stabilizing field potential duration, beat rate, spike amplitude, and conduction velocity. These findings suggest the potential protective role of BAI against the DOX-induced human cardiac toxicity, supporting a potential clinical application in cancer patients.