title: Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.
abstract: 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, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/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 3h 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.
authors.affiliation: Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP no. 17, F-92262 Fontenay-aux-Roses Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouas
authors.forename: Maâmar
authors.initials: M
authors.lastname: Souidi
authors.forename: Line
authors.initials: L
authors.lastname: Grandcolas
authors.forename: Stephane
authors.initials: S
authors.lastname: Grison
authors.forename: Cedric
authors.initials: C
authors.lastname: Baudelin
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.forename: Yann
authors.initials: Y
authors.lastname: Gueguen