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Article Dans Une Revue Environmental Toxicology and Pharmacology Année : 2009

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.

Dates et versions

hal-02993478 , version 1 (06-11-2020)

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Citer

C. Rouas, M. Souidi, L. Grandcolas, S. Grison, C. Baudelin, et al.. Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure. Environmental Toxicology and Pharmacology, 2009, 28 (3), pp.363-369. ⟨10.1016/j.etap.2009.06.004⟩. ⟨hal-02993478⟩

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