Water Extract of <i>Allium Victorialis</i> L. Prevents Doxorubicin-Induced Cardiotoxicity Through Its Antioxidant Property

Doxorubicin (DOX), an anthracycline-based anticancer drug, is commonly used to treat various cancers, but its prolonged use may lead to cardiotoxicity. Despite extensive research efforts, effective strategies for managing DOX-induced cardiotoxicity (DICT) remain limited. This study investigated the DICT-inhibitory efficacy of the water extract of <i>Allium victorialis</i> L. (AVE) and its underlying mechanism. AVE protected mouse cardiomyocytes, H9c2 cells, from DOX-induced toxicity while not interfering with DOX's cytotoxic effect on the MDA-MB-231 cells, human breast cancer cells. DOX-induced abnormal heart rate, RR interval, cQT prolongation, and segmentation were normalized following AVE supplementation. Also, AVE reduced the serum levels of creatine kinase and lactate dehydrogenase and suppressed myocardial fibrosis and cell death by DICT in the AVE-fed mice group. Moreover, AVE was shown to restore DOX-induced impaired electrophysiological changes in human-induced pluripotent stem cell-derived cardiomyocytes, including reduced total activity and decreased conduction velocity, while also normalizing the beat period irregularity and beat period mean. A total of 57 metabolites were tentatively identified in the AVE sample. Furthermore, PCR microarray and western blot analyses confirmed that AVE reversibly increased the expression of antioxidant-related genes and proteins. Altogether, the antioxidant properties of AVE could be utilized as a new strategy for preventing and treating DICT.