Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat.
J Proteome Res
; 5(7): 1586-601, 2006 Jul.
Article
en En
| MEDLINE
| ID: mdl-16823966
ABSTRACT
Administration of high doses of the histamine antagonist methapyrilene to rats causes periportal liver necrosis. The mechanism of toxicity is ill-defined and here we have utilized an integrated systems approach to understanding the toxic mechanisms by combining proteomics, metabonomics by 1H NMR spectroscopy and genomics by microarray gene expression profiling. Male rats were dosed with methapyrilene for 3 days at 150 mg/kg/day, which was sufficient to induce liver necrosis, or a subtoxic dose of 50 mg/kg/day. Urine was collected over 24 h each day, while blood and liver tissues were obtained at 2 h after the final dose. The resulting data further define the changes that occur in signal transduction and metabolic pathways during methapyrilene hepatotoxicity, revealing modification of expression levels of genes and proteins associated with oxidative stress and a change in energy usage that is reflected in both gene/protein expression patterns and metabolites. The difficulties of combining and interpreting multiomic data are considered.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Genómica
/
Proteómica
/
Enfermedad Hepática Inducida por Sustancias y Drogas
/
Antagonistas de los Receptores Histamínicos H1
/
Hígado
/
Metapirileno
Límite:
Animals
Idioma:
En
Revista:
J Proteome Res
Asunto de la revista:
BIOQUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido