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Updated: Feb 27, 2026
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Widely Targeted Liver Metabolomics Reveals Potential Biomarkers in Mice with Drug-Induced Liver Injury
Jiangning Peng1, Tingting Zhao2, Xuehong Zhang3
1College of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
Background:
Drug-induced liver injury (DILI), a major type of adverse drug reaction, has become one of the leading causes of acute liver injury and liver failure worldwide. Its clinical significance lies not only in acute hepatocyte necrosis and functional failure but also in its role as a key initiating factor for liver cancer progression. Therefore, early diagnosis of DILI is of great importance.
Methods:
This study employed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to perform widely targeted metabolomics analysis on acetaminophen (APAP)-induced liver injury mice and healthy mice.
Results:
UPLC-QTRAP-MS/MS identified 41 differentially expressed metabolites primarily involved in glycerophospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and glutathione metabolism pathways. The significant elevation of serum and hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) confirmed the successful establishment of the drug-induced liver injury (DILI) model. ROC curve analysis indicated 11 metabolites with AUC values exceeding 0.90 as potential biomarkers, including (R)-2-Hydroxybutyric acid, Glu-Gln, γ-Glu-Gln, 2-Methyllactic acid, L-Serine, Hyodeoxycholic acid, 3-Epideoxycholic acid, and Glycochenodeoxycholic acid 7-sulfate.
Conclusions:
We propose that these differential metabolites may serve as candidate biomarkers for DILI. Our findings provide a novel metabolomic signature derived directly from the injured tissue and offer a theoretical foundation for further research into early diagnosis of drug-induced liver injury.
Insights
This study identified 11 potential metabolite biomarkers for early drug-induced liver injury (DILI) detection using metabolomics. These findings offer a novel approach for diagnosing DILI, a critical factor in liver failure and cancer progression.
Area of Science:
- Biochemistry
- Toxicology
- Metabolomics
Background:
- Drug-induced liver injury (DILI) is a significant global health concern, leading to acute liver injury, liver failure, and cancer progression.
- Early diagnosis of DILI is crucial for effective management and prevention of severe outcomes.
Purpose of the Study:
- To identify novel biomarkers for the early diagnosis of drug-induced liver injury (DILI).
- To investigate the metabolomic alterations associated with acetaminophen-induced liver injury (APAP-DILI).
Main Methods:
- Widely targeted metabolomics analysis using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS).
- Analysis of serum and hepatic samples from APAP-induced liver injury mice and healthy controls.
- Receiver operating characteristic (ROC) curve analysis to identify potential biomarkers.
Main Results:
- Identified 41 differentially expressed metabolites involved in key metabolic pathways, including glycerophospholipid and glutathione metabolism.
- Confirmed successful induction of DILI model by elevated ALT and AST levels.
- Discovered 11 metabolites with AUC > 0.90 as potential biomarkers for DILI.
Conclusions:
- Differential metabolites identified may serve as candidate biomarkers for DILI.
- The study provides a novel metabolomic signature from injured tissue for DILI diagnosis.
- Findings support further research into early DILI detection using metabolomics.
