ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Identification of Serum Biomarkers to Distinguish Hazardous and Benign Aminotransferase Elevations.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Spatiotemporally Resolved Protein Tagging for Dynamic and Tissue-Specific Secretome Profiling In Vivo.Angewandte Chemie (International ed. in English) · 2026Article
- Welfare Assessment of Female BALB/c Mice Housed with Different Environmental Enrichment Materials.Animals : an open access journal from MDPI · 2026Article
- Context-dependent contribution of peptidyl arginine deiminase 4 (PAD4) to neutrophil extracellular trap formation and liver injury in acute and chronic hepatotoxicant challenge.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Quantitative analysis of septin Cdc10 & Cdc3-associated proteome during stress response in the fungal pathogen Cryptococcus neoformans.PloS one · 2024Article
- Article
- Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult.Molecular metabolism · 2023Article
- Transcriptional profiling of drug-induced liver injury biomarkers: association of hepatic Srebf1/Pparα signaling and crosstalk of thrombin, alcohol dehydrogenase, MDR and DNA damage regulators.Molecular and cellular biochemistry · 2023Article
- Article
- Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.Nature communications · 2023Article
- Drug Metabolism: A Half-Century Plus of Progress, Continued Needs, and New Opportunities.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Article
- The Challenge of Interpreting Alanine Aminotransferase Elevations in Clinical Trials of New Drug Candidates.Clinical and translational science · 2021Article
- Prognostic Value of Serum Exosomal AHCY Expression in Hepatitis B-Induced Liver Cirrhosis.Frontiers in medicine · 2021Article
- Registered report protocol: Quantitative analysis of septin Cdc10-associated proteome in Cryptococcus neoformans.PloS one · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The standard circulating biomarker of liver injury in both clinical settings and drug safety testing is alanine aminotransferase (ALT). However, ALT elevations sometimes lack specificity for tissue damage. To identify novel serum biomarkers with greater specificity for injury, we combined unique animal models with untargeted proteomics, followed by confirmation with immunoblotting. Using proteomics, we identified 109 proteins in serum from mice with acetaminophen (APAP)-induced liver injury that were not detectable in serum from mice with benign ALT elevations due to high-dose dexamethasone (Dex). We selected 4 (alcohol dehydrogenase 1A1 [Aldh1a1], aldehyde dehydrogenase 1 [Adh1], argininosuccinate synthetase 1 [Ass1], and adenosylhomocysteinase [Ahcy]) with high levels for further evaluation. Importantly, all 4 were specific for injury when using immunoblots to compare serum from Dex-treated mice and mice with similar lower ALT elevations due to milder models of APAP or bromobenzene-induced liver injury. Immunoblotting for ALDH1A1, ADH1, and ASS1 in serum from APAP overdose patients without liver injury and APAP overdose patients with mild liver injury revealed that these candidate biomarkers can be detected in humans with moderate liver injury as well. Interestingly, further experiments with serum from rats with bile duct ligation-induced liver disease indicated that Aldh1a1 and Adh1 are not detectable in serum in cholestasis and may therefore be specific for hepatocellular injury and possibly even drug-induced liver injury, in particular. Overall, our results strongly indicate that ALDH1A1, ADH1, and ASS1 are promising specific biomarkers for liver injury. Adoption of these biomarkers could improve preapproval drug safety assessment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.