Xanthosine alleviates myocardial ischemia–reperfusion injury through attenuation of cardiomyocyte ferroptosis

作者：Xu Yang, Wenfeng Zhou, Zhongguo Fan, Yiwei Cheng, Yujia Xiao, Yu Liu, Xinxin Li, Zhenjun Ji, Yi Fan, Genshan Ma · 发表于：Cellular & Molecular Biology Letters · 年份：2025 · DOI：10.1186/s11658-025-00766-y · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Immune cells in cancer、Cardiac Fibrosis and Remodeling

BACKGROUND: Ischemic heart disease remains a leading cause of morbidity and mortality worldwide, with myocardial ischemia-reperfusion (I/R) injury significantly contributing to cardiomyocyte death and poor outcomes post-acute myocardial infarction (AMI). Emerging evidence highlights metabolic changes during myocardial injury, particularly in purine metabolism. This study investigates the protective role of xanthosine (XTS), a purine metabolism intermediate, in alleviating I/R injury. METHODS: Neonatal and adult mouse myocardial tissues post-myocardial infarction (MI) were analyzed using untargeted and targeted metabolomics to explore metabolic profiles. The effects of XTS on I/R injury were evaluated in vivo using a murine I/R model and in vitro with hypoxia/reoxygenation-treated neonatal rat cardiomyocytes (NRCMs). Cardiac function, fibrosis, apoptosis, oxidative stress markers, and ferroptosis-related pathways were assessed via echocardiography, biochemical assays, western blotting, and electron microscopy. Integrated drug affinity responsive target stability (DARTS)-based drug target screening and RNA-seq transcriptomic profiling elucidate XTS-mediated mechanisms against I/R injury. RESULTS: Metabolomics revealed distinct differences in purine metabolism between neonatal and adult mice post-MI, with significant XTS accumulation observed in neonatal hearts. In vivo, XTS treatment in adult mice enhanced left ventricular function, reduced fibrosis, and alleviated lipid peroxi...