Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray

J Vet Med Sci. 2004 Nov;66(11):1329-33. doi: 10.1292/jvms.66.1329.

Abstract

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / toxicity
  • Chemical and Drug Induced Liver Injury
  • Clofibrate / toxicity*
  • Dose-Response Relationship, Drug
  • Gemfibrozil / toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Liver / drug effects*
  • Liver / ultrastructure
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Peroxisomes / drug effects
  • Peroxisomes / metabolism
  • Phenytoin / toxicity*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anticonvulsants
  • Phenytoin
  • Clofibrate
  • Gemfibrozil