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Drug-induced oxidative stress in rat liver from a toxicogenomics perspective
- Source :
-
Toxicology & Applied Pharmacology . Sep2005 Supplement 1, Vol. 207, p171-178. 8p. - Publication Year :
- 2005
-
Abstract
- Abstract: Macrophage activators (MA), peroxisome proliferators (PP), and oxidative stressors/reactive metabolites (OS/RM) all produce oxidative stress and hepatotoxicity in rats. However, these three classes of hepatotoxicants give three distinct gene transcriptional profiles on cDNA microarrays, an indication that rat hepatocytes respond/adapt quite differently to these three classes of oxidative stressors. The differential gene responses largely reflect differential activation of transcription factors: MA activate Stat-3 and NFkB, PP activate PPARa, and OS/RM activate Nrf2. We have used gene signature profiles for each of these three classes of hepatotoxicants to categorize over 100 paradigm (and 50+ in-house proprietary) compounds as to their oxidative stress potential in rat liver. In addition to a role for microarrays in predictive toxicology, analyses of small subsets of these signature profiles, genes within a specific pathway, or even single genes often provide important insights into possible mechanisms involved in the toxicities of these compounds. [Copyright &y& Elsevier]
- Subjects :
- *TOXICOLOGY
*OXIDATIVE stress
*LIVER cells
*LABORATORY rats
Subjects
Details
- Language :
- English
- ISSN :
- 0041008X
- Volume :
- 207
- Database :
- Academic Search Index
- Journal :
- Toxicology & Applied Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19484689
- Full Text :
- https://doi.org/10.1016/j.taap.2005.02.031