title: Renal anemia induced by chronic ingestion of depleted uranium in rats.
abstract: Kidney disease is a frequent consequence of heavy metal exposure and renal anemia occurs secondarily to the progression of kidney deterioration into chronic disease. In contrast, little is known about effects on kidney of chronic exposure to low levels of depleted uranium (DU). Study was performed with rats exposed to DU at 40 mg/l by chronic ingestion during 9 months. In the present work, a approximately 20% reduction in red blood cell (RBC) count was observed after DU exposure. Hence, three hypotheses were tested to determinate origin of RBC loss: (1) reduced erythropoiesis, (2) increased RBC degradation, and/or (3) kidney dysfunction. Erythropoiesis was not reduced after exposure to DU as revealed by erythroid progenitors, blood Flt3 ligand and erythropoietin (EPO) blood and kidney levels. Concerning messenger RNA (mRNA) and protein levels of spleen iron recycling markers from RBC degradation (DMT1 [divalent metal transporter 1], iron regulated protein 1, HO1, HO2 [heme oxygenase 1 and 2], cluster of differentiation 36), increase in HO2 and DMT1 mRNA level was induced after chronic exposure to DU. Kidneys of DU-contaminated rats had more frequently high grade tubulo-interstitial and glomerular lesions, accumulated iron more frequently and presented more apoptotic cells. In addition, chronic exposure to DU induced increased gene expression of ceruloplasmin (x12), of DMT1 (x2.5), and decreased mRNA levels of erythropoietin receptor (x0.2). Increased mRNA level of DMT1 was associated to decreased protein level (x0.25). To conclude, a chronic ingestion of DU leads mainly to kidney deterioration that is probably responsible for RBC count decrease in rats. Spleen erythropoiesis and molecules involved in erythrocyte degradation were also modified by chronic DU exposure.
authors: Institut de Radioprotection et de Sûreté Nucléaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidémiologie, F-92262 Fontenay-aux-Roses Cedex, France.
authors: Hanaâ
authors: H
authors: Berradi
authors: Jean-Marc
authors: JM
authors: Bertho
authors: Nicolas
authors: N
authors: Dudoignon
authors: André
authors: A
authors: Mazur
authors: Line
authors: L
authors: Grandcolas
authors: Cédric
authors: C
authors: Baudelin
authors: Stéphane
authors: S
authors: Grison
authors: Philippe
authors: P
authors: Voisin
authors: Patrick
authors: P
authors: Gourmelon
authors: Isabelle
authors: I
authors: Dublineau
mesh_terms: D000284:Administration, Oral; D000740:Anemia / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014501:Uranium / Q000633:toxicity*; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D007501:Iron; D012333:RNA, Messenger; D014501:Uranium; D000099236:Solute Carrier Family 11, Member 2