Differential gene expression analysis of a known hepatotoxin, N-acetyl-p-amino-phenol (APAP) as compared to its non-toxic analog, N-acetyl-m-amino-phenol (AMAP) in mouse liver.

作者: Priyanka Priyadarsiny , Sunil K. Khattar , Renu Malik , Venkatesha Udupa , Arigila Seshaiah

DOI: 10.2131/JTS.33.163

关键词: ToxicogenomicsGamma-glutamyltransferaseBiologyGeneGene expression profilingLiver injuryAcetaminophenHepatotoxinGene expressionPharmacology

摘要: Drug-induced hepatotoxicity is one of the most common adverse events associated with drug withdrawal from market. Elucidating molecular mechanism essential to predict safety a new molecule. To examine genes involved in hepatotoxicity, we have used oligonucleotide CodeLink Bioarrays and determined transcriptional profile mice liver treated hepatotoxic N-acetyl-p-amino-phenol (APAP) as well its non-toxic analog N-acetyl-m-amino-phenol (AMAP). Out 20,000 analyzed, 896 showed differential expression > or = 2-fold (648 upregulated 248 downregulated) within APAP compared control. In comparison AMAP mice, 62 were 70 downregulated after treatment. Functional classification these differentially expressed identified stress response, cell cycle, growth inhibition, death, structural components, signaling inflammation. Gene was further correlated biochemical analysis histopathological lesions. These data show that gene profiling would help better understanding basis drug-induced will lead rational development safer drugs, particularly pre-clinical stages.

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