Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure
| Autor: | Stéphane Grison, Yann Gueguen, Line Grandcolas, Caroline Rouas, Patrick Gourmelon, Maâmar Souidi, C. Baudelin, Marc Pallardy |
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| Přispěvatelé: | Radiobiologie et épidémiologie (DRPH/SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN) |
| Rok vydání: | 2009 |
| Předmět: |
enzyme induction
paracetamol Health Toxicology and Mutagenesis [SDV]Life Sciences [q-bio] radiation exposure Pharmacology Toxicology Basal (phylogenetics) 0302 clinical medicine rat media_common chemistry.chemical_classification 0303 health sciences Kidney Chemistry digestive oral and skin physiology article single drug dose General Medicine Uranium radioactive contamination medicine.anatomical_structure priority journal 030220 oncology & carcinogenesis kidney injury cytochrome P450 3A2 medicine.drug liver injury Drug Chronic exposure area under the curve media_common.quotation_subject animal experiment chemistry.chemical_element animal tissue long term exposure uranium 03 medical and health sciences Pharmacokinetics male medicine controlled study 030304 developmental biology nonhuman maximum plasma concentration Rattus animal model drug half life nucleotide sequence drug metabolism Acetaminophen time to maximum plasma concentration Enzyme drug blood level gene expression |
| Zdroj: | Environmental Toxicology and Pharmacology Environmental Toxicology and Pharmacology, 2009, 28 (3), pp.363-369. ⟨10.1016/j.etap.2009.06.004⟩ |
| ISSN: | 1872-7077 |
| DOI: | 10.1016/j.etap.2009.06.004⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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