Astaxanthin mitigates doxorubicin-induced cardiotoxicity via inhibiting ferroptosis and autophagy: a study based on bioinformatic analysis and in vivo/vitro experiments

作者：Bowen Yin, Jingyi Ren, Xuanyi Liu, Yadong Zhang, Jinshi Zuo, Wen Rui, Huanting Pei, Miaomiao Lu, Siqi Zhu, Zhenao Zhang, Ziyi Wang, Yanyi Zhai, Yuxia Ma · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1524448 · 被引用次数：11 · 研究领域：Ferroptosis and cancer prognosis、Chemotherapy-induced cardiotoxicity and mitigation、Cancer, Lipids, and Metabolism

Background Doxorubicin (DOX), a widely employed chemotherapeutic agent in cancer treatment, has seen restricted use in recent years owing to its associated cardiotoxicity. Current reports indicate that doxorubicin-induced cardiotoxicity (DIC) is a complex phenomenon involving various modes of cell death. Astaxanthin (ASX), a natural carotenoid pigment, has garnered significant attention for its numerous health benefits. Recent studies have shown that ASX has a broad and effective cardiovascular protective effect. Our study aims to investigate the protective effects of ASX against DIC and elucidate its underlying mechanisms. This has substantial practical significance for the clinical application of DOX. Methods Bioinformatic analyses were conducted using transcriptomic data from the gene expression omnibus (GEO) database to identify key mechanisms underlying DIC. Network pharmacology was employed to predict the potential pathways and targets through which ASX exerts its effects on DIC. In vitro experiments, following pretreatment with ASX, H9C2 cells were exposed to DOX. Cell viability, injury and the protein expression levels associated with ferroptosis and autophagy were assessed. In the animal experiments, rats underwent 4 weeks of gavage treatment with various doses of ASX, followed by intraperitoneal injections of DOX every 2 days during the final week. Histological, serum, and protein analyses were conducted to evaluate the effects of ASX on DIC. Results The bioinformat...