Amino Acid Hepatotoxicity Biomarkers in Human Hepatic Organoids: Promising Standardization of Drug Toxicity Evaluation.

ABSTRACT: Human hepatic organoids (hHOs) are regarded as physiologically relevant in vitro platforms to evaluate hepatotoxicity, a critical step in drug development, but their applications are currently limited by the lack of qualified and standardized evaluation markers. In this study, by leveraging the established reference measurement system of amino acids (AAs), we propose 12 new biomarkers for drug-induced hepatotoxicity evaluation in human induced pluripotent stem cell-derived hHOs. Two orthogonal analytical methods for AAs were developed and validated based on isotope dilution mass spectrometry. Four AAs (aspartic acid, arginine, glutamine, and phenylalanine) and eight ratios of two designated AAs in the media of hHOs showed reliable alteration by drug treatment, which was confirmed by differ

SUBMITTER: Noh H 

PROVIDER: S-EPMC11833729 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature