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Gene expression profiles of amiodarone, valproic acid, and tetracycline induced steatosis in C57BL/6 mice


ABSTRACT: Toxicogenomics (tgx) is used as a tool to identify mechanisms and markers of steatosis in C57BL/6 mice treated by oral gavage using amiodarone (AMD), valproic acid (VPA), and tetracycline (TET). Critical doses for tgx analysis were derived from a 25 day dose range finding study. For tgx analysis, livers of mice were collected after 1, 4, and 11 days of repeated treatment with 6.7, 20, and 60 mg/kg bw for AMD; 125, 250, and 500 mg/kg bw for VPA; and 14.8, 44, and 133 mg/kg bw for TET. For each treatment (compound and vehicle) in the toxicogenomics study samples were as follows: four at the high dose 1 and 4 day time point, and five at the low, medium, and high dose at 11 days. One set of vehicle controls were used for AMD and VPA (PBS), and TET had its own vehicle controls (milli-q water with ascorbic acid). The total number of samples was 95.

ORGANISM(S): Mus musculus

SUBMITTER: Alexa Vitins 

PROVIDER: E-GEOD-48126 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models.

Vitins Alexa P AP   Kienhuis Anne S AS   Speksnijder Ewoud N EN   Roodbergen Marianne M   Luijten Mirjam M   van der Ven Leo T M LT  

Archives of toxicology 20140218 8


Liver injury is the leading cause of drug-induced toxicity. For the evaluation of a chemical compound to induce toxicity, in this case steatosis or fatty liver, it is imperative to identify markers reflective of mechanisms and processes induced upon exposure, as these will be the earliest changes reflective of disease. Therefore, an in vivo mouse toxicogenomics study was completed to identify common pathways, nuclear receptor (NR) binding sites, and genes regulated by three known human steatosis  ...[more]

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