Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure
Résumé
The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1 mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50 mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3 h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. © 2009 Elsevier B.V. All rights reserved.
Mots clés
cytochrome P450 3A2
paracetamol
uranium
animal experiment
animal model
animal tissue
area under the curve
article
controlled study
drug blood level
drug half life
drug metabolism
enzyme induction
gene expression
kidney injury
liver injury
long term exposure
male
maximum plasma concentration
nonhuman
nucleotide sequence
priority journal
radiation exposure
radioactive contamination
rat
single drug dose
time to maximum plasma concentration
Rattus