Renal anemia induced by chronic ingestion of depleted uranium in rats.
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.
Berradi
Hanaâ
H
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.
Bertho
Jean-Marc
JM
Dudoignon
Nicolas
N
Mazur
André
A
Grandcolas
Line
L
Baudelin
Cédric
C
Grison
Stéphane
S
Voisin
Philippe
P
Gourmelon
Patrick
P
Dublineau
Isabelle
I
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
D027682:Cation Transport Proteins; D007501:Iron; D012333:RNA, Messenger; D014501:Uranium; D000099236:Solute Carrier Family 11, Member 2