Metabolomics and Network Analyses Reveal Phenylalanine and Tyrosine as Signatures of Anthracycline-Induced Hepatotoxicity.

ABSTRACT: The chemotherapy drug doxorubicin (DOX) is an anthracycline with over 30% incidence of liver injury in breast cancer patients, yet the mechanism of its hepatotoxicity remains unclear. To identify potential biomarkers for anthracycline-induced hepatotoxicity (AIH), we generated clinically-relevant mouse and rat models administered low-dose, long-term DOX. These models exhibited significant liver damage but no decline in cardiac function. Through untargeted metabolic profiling of the liver, we identified 27 differential metabolites in a mouse model and 28 in a rat model. We then constructed a metabolite-metabolite network for each animal model and computationally identified several potential metabolic markers, with particular emphasis on aromatic amino acids, including phenylalanine, tyrosin

SUBMITTER: Liu P 

PROVIDER: S-EPMC10302024 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature