title: Different pattern of brain pro-/anti-oxidant activity between depleted and enriched uranium in chronically exposed rats.
abstract: Uranium is not only a heavy metal but also an alpha particle emitter. The main toxicity of uranium is expected to be due to chemiotoxicity rather than to radiotoxicity. Some studies have demonstrated that uranium induced some neurological disturbances, but without clear explanations. A possible mechanism of this neurotoxicity could be the oxidative stress induced by reactive oxygen species imbalance. The aim of the present study was to determine whether a chronic ingestion of uranium induced anti-oxidative defence mechanisms in the brain of rats. Rats received depleted (DU) or 4% enriched (EU) uranyl nitrate in the drinking water at 2mg(-1)kg(-1)day(-1) for 9 months. Cerebral cortex analyses were made by measuring mRNA and protein levels and enzymatic activities. Lipid peroxidation, an oxidative stress marker, was significantly enhanced after EU exposure, but not after DU. The gene expression or activity of the main antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), increased significantly after chronic exposure to DU. On the contrary, oral EU administration induced a decrease of these antioxidant enzymes. The NO-ergic pathway was almost not perturbed by DU or EU exposure. Finally, DU exposure increased significantly the transporters (Divalent-Metal-Transporter1; DMT1), the storage molecule (ferritin) and the ferroxidase enzyme (ceruloplasmin), but not EU. These results illustrate that oxidative stress plays a key role in the mechanism of uranium neurotoxicity. They showed that chronic exposure to DU, but not EU, seems to induce an increase of several antioxidant agents in order to counteract the oxidative stress. Finally, these results demonstrate the importance of the double toxicity, chemical and radiological, of uranium.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de RadioToxicologie Expérimentale. IRSN, Cedex, France. philippe.lestaevel@irsn.fr
authors.forename: P
authors.initials: P
authors.lastname: Lestaevel
authors.forename: E
authors.initials: E
authors.lastname: Romero
authors.forename: B
authors.initials: B
authors.lastname: Dhieux
authors.forename: H
authors.initials: H
authors.lastname: Ben Soussan
authors.forename: H
authors.initials: H
authors.lastname: Berradi
authors.forename: I
authors.initials: I
authors.lastname: Dublineau
authors.forename: P
authors.initials: P
authors.lastname: Voisin
authors.forename: P
authors.initials: P
authors.lastname: Gourmelon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D004326:Drinking; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005293:Ferritins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014502:Uranyl Nitrate / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D014502:Uranyl Nitrate; D009569:Nitric Oxide; D005293:Ferritins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin