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Gene expression analysis of liver and kidney following methapyrilene treatment in male Sprague-Dawley rats

ABSTRACT: This study was performed to gain insight into the hepatotoxicity of methapyrilene. Gene expression changes in the kidney (non-target tissue for toxicity) were compared to those in the liver (target tissue for toxicity) to attribute gene expression changes to relevant biological processes (i.e. toxic response, non-specific acute response, pharmacological response, etc…). Keywords: Time course, tissue comparison, liver toxicity, hepatotoxicity

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE5381 | GEO | 2007/03/01

SECONDARY ACCESSION(S): PRJNA96287

REPOSITORIES: GEO

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Transcription profiling of rat liver and kidney following methapyrilene treatment in male Sprague-Dawley rats

Project description:This study was performed to gain insight into the hepatotoxicity of methapyrilene. Gene expression changes in the kidney (non-target tissue for toxicity) were compared to those in the liver (target tissue for toxicity) to attribute gene expression changes to relevant biological processes (i.e. toxic response, non-specific acute response, pharmacological response, etcâ¦). Experiment Overall Design: Male Sprague-Dawley rats were treated with methapyrilene at two different doses (10 mg/kg/day and 100 mg/kg/day) for 1, 3, and 7 days. Livers and kidneys were removed 24 hours after the last dose and flash frozen in liquid nitrogen. Five hundred nanograms (500 ng) of total RNA was amplified and labeled using the Agilent Low RNA Input Fluorescent Linear Amplification Kit according to the manufacturerâs protocol. For each two color comparison, 750 ng each of Cy3- and Cy5-labeled cRNA were mixed and fragmented using the Agilent In Situ Hybridization Kit protocol. Hybridizations were performed for 17 hours in a rotating hybridization oven according to the Agilent 60-mer oligo microarray processing protocol prior to washing and scanning with an Agilent Scanner. Data was obtained using the Agilent Feature Extraction software (v. 7.1) using defaults for all parameters. Experiment Overall Design: Equal amounts of RNA was pooled from all of the animals in each group (n=4). Each treated group was hybridized against its pooled time-matched and tissue-matched control group in quadruplicate (2 replicates + 2 fluor reversals).

2008-06-13 | E-GEOD-5381 | biostudies-arrayexpress

Acute Gene Induction by Tienilic Acid in the Male Sprague Dawley Rat: Possible Role for Danger

Project description:Tienilic acid (TA) was withdrawn from the US market due to numerous cases of liver necrosis. Two major hypotheses currently used to understand the mechanisms of idiosyncratic reactions such as TA-induced hepatotoxicity are the hapten and danger hypotheses. Both human cytochrome (CYP) P450 2C9 and the rat ortholog CYP 2C11 metabolize TA, and it was reported that a reactive metabolite of TA binds almost exclusively to these enzymes, thus acting as a mechanism-based inhibitor. TA-induced liver toxicity is associated with antibodies against CYP 2C9, thus TA appears to act as a hapten. However, if the binding were limited to CYP 2C, it is unlikely that this would lead to significant cell stress. Thus, if TA does not cause cell stress it would suggest that a drug does not have to generate a “danger signal” in order to cause an idiosyncratic drug reaction and acting as a hapten is sufficient. In order to test whether TA can cause cell stress, male Sprague Dawley rats were orally dosed with TA, and hepatic gene expression was profiled at 6 and 24 h after drug administration. Results showed that TA induced robust changes in genes involved in oxidative stress (e.g. aldo-keto reductase, glutathione-S-transferase, thioredoxin reductase, epoxide hydrolase), inflammation and cytotoxicity (e.g. IL-1b, interferon regulatory factor 1, macrophage stimulating protein 1, caspase-12), as well as those promoting liver regeneration (e.g. p27Kip1, DUSP6, serine dehydratase, spectrin bII, inhibin bA). These data support the hypothesis that danger signals in the form of cell-stress proteins and the generation of oxidative stress may be involved in initiating the immune response observed in TA-induced toxicity. Other recent data also indicate that the reactive metabolite of TA binds to other proteins in addition to CYP 2C Keywords: time course, stress response

2007-06-23 | GSE8252 | GEO

Sprague Dawley Whole Egg MicroRNA & Total RNA Sequencing

Project description:In order to understand the effects that egg consumption has on tissue-specific microRNA and gene expression, we examined the role of whole egg consumption (20% protein, w/w) on differentially expressed genes (DEGs) between male rat (n =12) transcriptomes in the prefrontal cortex (PFC), liver, kidney and adipose tissue.

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5-Day Gavage Study of Crude 4-Methylcyclohexanemethanol in Male Harlan Sprague Dawley Rats

2015-12-31 | GSE75655 | GEO

Danlu Tongdu Tablets: Safety evaluation and mechanism of hepatotoxicity in Sprague-Dawley rats

Project description:Based on the acute and chronic toxicity study, we further focused on the impact of Danlu Tongdu (DLTD) on the liver. At the end of 26 weeks of administration, 4 male rats were selected from the control group and the high-dose group respectively for transcriptome analysis. The selection criteria were random selection from the control group, the four rats selected from the high-dose. group showed pathological changes in the liver.

2022-08-25 | GSE212036 | GEO

5-Day Gavage Study of Crude 4-Methylcyclohexanemethanol in Male Harlan Sprague Dawley Rats

Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of crude 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 44 samples were evaluated in this study. 27 were from liver and 17 were from kidney. Signficant batch effects were detected with a subset of samples and these were removed from the study prior to data analysis and are therefore not included in this GEO series. 3 (kidney) or 4 (liver) biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 2-4 biological replicates. The groups that contain only 2 or 3 replicates do so due to a number of samples not passing QC as byproduct of batch effects. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.

2015-12-31 | E-GEOD-75655 | biostudies-arrayexpress

Normal gene expression in male and female Sprague-Dawley rat nasal respiratory and olfactory epithelium

Project description:The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity. Human epidemiological investigations and experimental laboratory animal studies show that the nasal olfactory epithelium is selectively damaged by inhalation exposure to several chemicals, including vinyl acetate and hydrogen sulfide. The reason for the relative sensitivity of the nasal olfactory epithelium is not known. To better understand and predict the response of the nasal epithelium to inhaled xenobiotics, gene expression profiles from naїve male and female Sprague-Dawley rats were constructed. Epithelial cells were manually collected from the nasal septum, naso- and maxillo-turbinates, and ethmoid turbinates of 9 male and 9 female rats. Gene expression analysis was performed using the Affymetrix Rat Genome 430 2.0 microarray. Gene ontology enrichment analysis identified several functional categories including xenobiotic metabolism, cell cycle, apoptosis, and ion channel/transport with significantly different expression between tissue types. Surprisingly, there were few gender differences in gene expression. This baseline data will contribute to our understanding of the normal physiology and selectivity of the nasal epithelial cells’ response to inhaled environmental toxicants. Keywords: Comparative

2007-05-01 | GSE5019 | GEO

5-Day Gavage Study of 4-Methylcyclohexanemethanol (CASRN: 34885-03-5) in Male Harlan Sprague Dawley Rats

Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 58 samples were evaluated in this study. 29 were from liver and 29 were from kidney. Five biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 4 biological replicates. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.

2015-12-31 | E-GEOD-75657 | biostudies-arrayexpress

5-Day Gavage Study of 4-Methylcyclohexanemethanol (CASRN: 34885-03-5) in Male Harlan Sprague Dawley Rats

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microRNA profiling of Sprague Dawley organs

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