Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.

ABSTRACT: The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo. The cardioprotective effects and mechanisms of ILA were explored using multi-omics approaches, including single-nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq, and were further validated in Nrf2 knockout mice. The findings revealed that DOX treatment disrupted gut microbiota, significantly reducing the levels of the tryptophan

SUBMITTER: Lian J 

PROVIDER: S-EPMC11756996 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature