Influence of acetaminophen vehicle on regulation of transporter gene expression during hepatotoxicity

Lauren M. Aleksunes, Lisa M. Augustine, Nathan J. Cherrington, José E. Manautou

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Researchers who study acetaminophen (APAP) hepatotoxicity use either a 50% propylene glycol solution or saline as a diluent. Previous studies demonstrated differential expression of hepatobiliary transporter mRNA in mice treated with a toxic dose of APAP dissolved in 50% propylene glycol. The purpose of this study was to determine whether using saline as a diluent for APAP alters regulation of transporter gene expression during hepatotoxicity. Male C57BL/6J mice received acetaminophen (APAP 400 mg/kg, ip in saline) or saline (20 ml/kg). Plasma and liver samples were collected at 24 and 48 h for assessment of alanine aminotransferase (ALT) activity and gene expression. It was determined that plasma ALT activity was elevated at 24 and 48 h after APAP administration. Using the branched DNA signal amplification assay, reductions in organic anion-transporting polypeptides Oatp1a1, Oatp1b2, sodium/taurocholate- cotransporting polypeptide (Ntcp), and bile salt export pump (Bsep) mRNA were observed in APAP-treated mice. In contrast, multidrug resistance-associated proteins Mrp1, Mrp2, Mrp3, and Mrp4, as well as multidrug resistance proteins Mdr1a and Mdr1b genes, were increased following APAP. No changes in Oatp1a4, Mdr2, or breast cancer resistance protein (Bcrp) mRNA were observed. Alterations in transporter gene expression in this study were similar to those reported previously using propylene glycol as diluent. With the exceptions of Oatp1a1, Ntcp, and Mrp1, these data mirror previous results suggesting that the solution used to dissolve APAP may alter the susceptibility of mice to hepatotoxicity, but only minimally change the regulation of transporter gene expression.

Original languageEnglish (US)
Pages (from-to)1870-1872
Number of pages3
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Volume70
Issue number21
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Influence of acetaminophen vehicle on regulation of transporter gene expression during hepatotoxicity'. Together they form a unique fingerprint.

  • Cite this