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In vitro gene expression analysis of hepatotoxic drugs in rat primary hepatocytes
- Source :
- Journal of Applied Toxicology. 28:227-236
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- The study examined the feasibility of screening for hepatotoxicity by an in vitro gene expression analysis using rat primary hepatocytes and Affymetrix Rat Toxicology U34 arrays. Hepatocytes were exposed for 6 or 24 h to eight drugs, with different mechanisms of hepatotoxicity, at one third of the cytotoxic concentration TC50, i.e. acetaminophen, cyclophosphamide, clofibrate, chlorpromazine, lithocholic acid, cisplatin, diclofenac and disulfiram. The types of transcriptional changes observed in this study were generally consistent with previously reported in vivo data, although there were some differences. In hierarchical cluster analysis, drugs formed clusters depending on their mode of toxicity against cells. The number of transcripts affected by the cholestatic hepatotoxicants (lithocholic acid and chlorpromazine) or the drugs that rarely cause of hepatotoxicity (cisplatin, diclofenac and disulfiram) were limited compared with the other drugs (acetaminophen, clobifibrate and cyclophosphamide), where they did not induce transcriptional changes apparently related to toxicity. It is concluded that in vitro gene expression analysis of hepatocytes using microarray is a useful tool for evaluating the toxicological profile of drugs and in screening for the direct toxicity of drugs against hepatocytes.
- Subjects :
- Male
Drug
Time Factors
Lithocholic acid
Transcription, Genetic
media_common.quotation_subject
Cell Culture Techniques
Pharmacology
Biology
Toxicology
Rats, Sprague-Dawley
chemistry.chemical_compound
In vivo
Toxicity Tests
medicine
Animals
Cluster Analysis
Clofibrate
RNA, Messenger
Cells, Cultured
Acetaminophen
Oligonucleotide Array Sequence Analysis
media_common
Cisplatin
Dose-Response Relationship, Drug
Gene Expression Profiling
Rats
medicine.anatomical_structure
chemistry
Hepatocyte
Disulfiram
Toxicity
Hepatocytes
Feasibility Studies
medicine.drug
Subjects
Details
- ISSN :
- 10991263 and 0260437X
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Toxicology
- Accession number :
- edsair.doi.dedup.....4d7d770a4374877be3fa5dd9f594602e