Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Mouse_APAP

ABSTRACT: Comprehensive cataloging of cell-free circulating RNAs using next generation sequencing technology may open a window to assess drug associated adverse effects at the systems level. To explore this potential, we conducted an RNA profiling study using the well-characterized acetaminophen overdose mouse model on liver and plasma with next generation sequencing platforms.

ORGANISM(S): Mus musculus

SUBMITTER: Hong Li

PROVIDER: E-MTAB-1538 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The spectrum of circulating RNA: a window into systems toxicology.

Wang Kai K Yuan Yue Y Li Hong H Cho Ji-Hoon JH Huang David D Gray Li L Qin Shizhen S Galas David J DJ

Toxicological sciences : an official journal of the Society of Toxicology 20130128 2

Adverse effects caused by therapeutic drugs are a serious and costly health concern. Despite the body's systemic responses to therapeutics, the liver is often the focus of damage and is usually the focus of studies of toxic effects due to its active roles in the metabolism of xenobiotics. It is extremely difficult, however, to assess systemic responses with currently available methods. Comprehensive cataloging of cell-free circulating RNAs using next-generation sequencing technology may open a w ...[more]

PMID: 23358195

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Project description:Reddyhoff2015 - Acetaminophen metabolism and toxicity This model examines acetaminophen metabolism and related hepatotoxicity. Multiple pathways associated with APAP metabolism has been included in the model. Using numerical, sensitivity and timescale analysis, key parameters involved in the toxicity has been identified. The model analysis highlights a critical acetaminophen dose in terms of the model parameters. This model is described in the article: Timescale analysis of a mathematical model of acetaminophen metabolism and toxicity. Reddyhoff D, Ward J, Williams D, Regan S, Webb S J Theor Biol. 2015 Dec 7;386:132-46. Abstract: Acetaminophen is a widespread and commonly used painkiller all over the world. However, it can cause liver damage when taken in large doses or at repeated chronic doses. Current models of acetaminophen metabolism are complex, and limited to numerical investigation though provide results that represent clinical investigation well. We derive a mathematical model based on mass action laws aimed at capturing the main dynamics of acetaminophen metabolism, in particular the contrast between normal and overdose cases, whilst remaining simple enough for detailed mathematical analysis that can identify key parameters and quantify their role in liver toxicity. We use singular perturbation analysis to separate the different timescales describing the sequence of events in acetaminophen metabolism, systematically identifying which parameters dominate during each of the successive stages. Using this approach we determined, in terms of the model parameters, the critical dose between safe and overdose cases, timescales for exhaustion and regeneration of important cofactors for acetaminophen metabolism and total toxin accumulation as a fraction of initial dose. This model is hosted on BioModels Database and identified by: MODEL1603080000. To cite BioModels Database, please use: BioModels: Content, Features, Functionality and Use. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Mouse_APAP

Publications

The spectrum of circulating RNA: a window into systems toxicology.

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