Differential regulation of mitogen-activated protein kinase pathways by acetaminophen and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide in TAMH cells.

ABSTRACT: Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States. 3'-Hydroxyacetanilide (AMAP), a regioisomer of APAP, is useful as a comparative tool for studying APAP-induced toxicity because it is nontoxic relative to APAP. Transforming growth factor-alpha transgenic mouse hepatocytes were treated with both isomers to investigate mitogen-activated protein kinase (MAPK) cascades in order to differentiate their toxicological outcomes. Posttranslational modifications of MAPK signaling were assessed using immunoblotting and Bioplex technology, whereas gene expression changes were measured using Affymetrix Mouse Gene 1.0 ST arrays. APAP treatment led to higher l

SUBMITTER: Stamper BD 

PROVIDER: S-EPMC2886858 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature