Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure

Caroline Rouas; Maâmar Souidi; Line Grandcolas; Stephane Grison; Cedric Baudelin; Patrick Gourmelon; Marc Pallardy; Yann Gueguen

doi:10.1016/j.etap.2009.06.004

Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure

Environ Toxicol Pharmacol. 2009 Nov;28(3):363-9. doi: 10.1016/j.etap.2009.06.004. Epub 2009 Jun 24.

Authors

Caroline Rouas¹, Maâmar Souidi, Line Grandcolas, Stephane Grison, Cedric Baudelin, Patrick Gourmelon, Marc Pallardy, Yann Gueguen

Affiliation

¹ 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.

PMID: 21784028
DOI: 10.1016/j.etap.2009.06.004

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.