ArticleScientific reports2018
Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat.
Article in Scientific reports, 2018. 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, 24 citations in OpenAlex.
- Article
- Quantifying liver-toxic responses from dose-dependent chemical exposures using a rat genome-scale metabolic model.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Transcriptome-based biomarker prediction for Parkinson's disease using genome-scale metabolic modeling.Scientific reports · 2024Article
- Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2.Stem cell research & therapy · 2022Article
- Compartmentalization of metabolism between cell types in multicellular organisms: a computational perspective.Current opinion in systems biology · 2022Article
- The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2.Experimental & molecular medicine · 2021Article
- Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat.Toxicology and applied pharmacology · 2021Article
- Toxicant-Induced Metabolic Alterations in Lipid and Amino Acid Pathways Are Predictive of Acute Liver Toxicity in Rats.International journal of molecular sciences · 2020Article
- Review
- Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure.Toxicologic pathology · 2020Article
- Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Genome-scale metabolic model of the rat liver predicts effects of diet restriction.Scientific reports · 2019Article
- Mechanistic identification of biofluid metabolite changes as markers of acetaminophen-induced liver toxicity in rats.Toxicology and applied pharmacology · 2019Article
- Mining Public Toxicogenomic Data Reveals Insights and Challenges in Delineating Liver Steatosis Adverse Outcome Pathways.Frontiers in genetics · 2019Article
- Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat.Frontiers in physiology · 2019Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
In order to provide timely treatment for organ damage initiated by therapeutic drugs or exposure to environmental toxicants, we first need to identify markers that provide an early diagnosis of potential adverse effects before permanent damage occurs. Specifically, the liver, as a primary organ prone to toxicants-induced injuries, lacks diagnostic markers that are specific and sensitive to the early onset of injury. Here, to identify plasma metabolites as markers of early toxicant-induced injury, we used a constraint-based modeling approach with a genome-scale network reconstruction of rat liver metabolism to incorporate perturbations of gene expression induced by acetaminophen, a known hepatotoxicant. A comparison of the model results against the global metabolic profiling data revealed that our approach satisfactorily predicted altered plasma metabolite levels as early as 5 h after exposure to 2 g/kg of acetaminophen, and that 10 h after treatment the predictions significantly improved when we integrated measured central carbon fluxes. Our approach is solely driven by gene expression and physiological boundary conditions, and does not rely on any toxicant-specific model component. As such, it provides a mechanistic model that serves as a first step in identifying a list of putative plasma metabolites that could change due to toxicant-induced perturbations.
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Registered trials
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