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The effects of differential gut microbiota on hepatic gene expression

ABSTRACT: Our preliminary data suggest that differential gut microbiota modulates acetaminophen-induced hepatotoxicity (APAP toxicity) in mice model. The goal of our study is to determine whether commensal gut microbiota modulates the hepatic gene expressions potentially responsible for modulating APAP toxicity.

ORGANISM(S): Mus musculus

PROVIDER: GSE125418 | GEO | 2025/01/10

REPOSITORIES: GEO

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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.

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The effects of differential gut microbiota on hepatic gene expression

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